Miracle-dz/UniFAR-FTUs huggingface dataset:
Anticancer activity of bergenin against cervical cancer cells involves apoptosis, cell cycle arrest, inhibition of cell migration and the STAT3 signalling pathway

Bergenin is a secondary metabolite that may be primarily isolated from Bergenia species. Although it has been found to exhibit significant biological activities, the anticancer activity of bergenin against cervical cancer cells has not been explored. The present study was designed to evaluate the anticancer effects of bergenin on HeLa cervical cancer cells. The results showed that bergenin reduced the cell viability of the HeLa cervical cancer cells in a dose-dependent pattern. However, the anticancer effects of bergenin were found to be comparatively lower on the normal cervical cells. Furthermore, the anticancer effects of bergenin were primarily found to be due to induction of apoptosis in the HeLa cervical cancer cells. Notably, bergenin also enhanced the expression of Bax and decreased the expression of Bcl-2. WThe effect of bergenin on cell cycle phase distribution of HeLa cells was also investigated and it was found that bergenin could induce G0/G1 cell cycle arrest. Furthermore, bergenin could also inhibit the migration of HeLa cancer cells as well as the phosphorylation of STAT3. Taken together, bergenin may be a promising candidate for the management of cervical cancer.
Evaluation of Transforming Growth Factor-β1 and Interleukin-35 Serum Levels in Patients with Placenta Accreta.

OBJECTIVE Placenta accreta is a pregnancy-related disorder with extreme trophoblast invasion and the adherence of the placenta to the uterine wall. This study aimed to investigate the serum level of transforming growth factor-beta 1 (TGF-β1) and interleukin (IL)-35 in patients with placenta accreta. METHODS Thirty-one women with placenta accreta and 57 healthy pregnant women were enrolled. The serum levels of TGF-β1 and IL-35 were measured using the enzyme-linked immunosorbent assay method. RESULTS The serum levels of both TGF-β and IL-35 were significantly higher in the placenta accreta group compared with the group of healthy women (1082.48 pg/mL vs 497.33 pg/mL and 4541.14 pg/mL vs 1306.04 pg/mL; P <.001, respectively). Moreover, the level of TGF-β1 positively correlated with the IL-35 level but other factors such as age, gestations, live births, and abortions did not correlate with IL-35 and TGF-β1 levels. CONCLUSION The serum levels of IL-35 and TGF-β1 may contribute to the pathogenesis of placenta accreta and could be considered as potential targets in clinical and diagnostic approaches.
The functional connectivity study on the brainstem‐cortical/subcortical structures in responders following cervical vagus nerve stimulation

Cervical vagus nerve stimulation (VNS) is an effective neuromodulation therapy for patients with drug‐resistant epilepsy (DRE). The previous studies reported that VNS may reduce seizures by regulating the functional connectivity (FC) between cortical and subcortical regions. However, no studies on brainstem have been done in responders who achieved ≥50% seizure reduction following VNS.
Urodynamic assessment of bladder storage function after radical hysterectomy for cervical cancer

Supplemental Digital Content is available in the text Abstract Background After radical hysterectomy for cervical cancer, the most common complication is lower urinary tract symptoms. Post-operatively, bladder capacity can alter bladder function for a prolonged period. This study aimed to identify factors affecting bladder storage function. Methods A multicenter, retrospective cohort study was conducted. Information of patients with stages IA2 to IIB cervical cancer with urodynamic study results were retrospectively collected from nine hospitals between June 2013 and June 2018 according to the inclusion criteria. Demographic, surgical, and oncological data were collected. The univariate and multivariate logistic regression was used to identify clinical factors associated with bladder storage function. Results Two hundred and three patients with cervical cancer had urodynamic testing post-operatively. Ninety-five (46.8%) patients were diagnosed with stress urinary incontinence (SUI). The incidence of low bladder compliance (LBC) was 23.2%. Twenty-seven (13.3%) patients showed detrusor overactivity (DO). Fifty-seven patients (28.1%) presented with a decreased maximum cystometric capacity (DMCC). The probability of composite bladder storage dysfunction was 68.0%. Multivariate analysis confirmed that laparoscopy represents a protective factor for SUI with an odds ratio of 0.498 (P = 0.034). Patients who underwent a nerve-sparing procedure were less odds to experience SUI (P = 0.014). A significant positive correlation between LBC and DO was observed (P < 0.001). A greater length of the resected vagina and chemoradiotherapy were common risk factors for LBC and DO, while radiotherapy exerted a stronger effect than chemotherapy. Additionally, patients who received chemoradiotherapy frequently developed a DMCC. The follow-up time was not correlated with bladder storage function. Conclusion A nerve-sparing procedure without longer resected vagina is recommended for protecting the bladder storage function.
Using climate‐driven leaf phenology and growth to improve predictions of gross primary productivity in North American forests

Forest ecosystems are an important sink for terrestrial carbon sequestration. Hence, accurate modeling of the intra‐ and interannual variability of forest photosynthetic productivity remains a key objective in global biology. Applying climate‐driven leaf phenology and growth in models may improve predictions of the forest gross primary productivity (GPP). We used a dynamic non‐structural carbohydrates (NSC) model (FORCCHN2) that couples leaf development and phenology to investigate the relationships among photosynthesis and environmental factors. FORCCHN2 simulates spring and autumn phenological events from heat and chilling, respectively. Leaf area index data from satellites along with climate data estimated localized phenological parameters. NSC limitation, immediate temperature, accumulated heat, and growth potential comprised a daily leaf‐growth model. Functionally, leaf growth was decoupled from photosynthesis. Leaf biomass determined overall photosynthetic production. We compared this model with outputs of the other six terrestrial biospheric models and with observations from the North American Carbon Program Site Interim Synthesis in 18 forest sites. This model improved the predicted performance of yearly GPP with a 57%–210% increase in correlation (median) and up to a 102% reduction in biases (median), compared to three prognostic models and three prescribed models. At the North America continental scale, the model predicted the average annual GPP of 7.38 Pg C/year from forest ecosystems during 1985–2016. The results showed an increasing trend of GPP in North America (1.0 Pg C/decade). The inclusion of climate‐driven phenology and growth has a significant potential for improving dynamic vegetation models, and promotes a further understanding of the complex relationship between environment and photosynthesis.
The Updated Role of the Blood Brain Barrier in Subarachnoid Hemorrhage: From Basic and Clinical Studies

Subarachnoid hemorrhage (SAH) is a type of hemorrhagic stroke associated with high mortality and morbidity. The blood-brain-barrier (BBB) is a structure consisting primarily of cerebral microvascular endothelial cells, end feet of astrocytes, extracellular matrix, and pericytes. Post-SAH pathophysiology included early brain injury and delayed cerebral ischemia. BBB disruption was a critical mechanism of early brain injury and was associated with other pathophysiological events. These pathophysiological events may propel the development of secondary brain injury, known as delayed cerebral ischemia. Imaging advancements to measure BBB after SAH primarily focused on exploring innovative methods to predict clinical outcome, delayed cerebral ischemia, and delayed infarction related to delayed cerebral ischemia in acute periods. These predictions are based on detecting abnormal changes in BBB permeability. The parameters of BBB permeability are described by changes in computed tomography (CT) perfusion and magnetic resonance imaging (MRI). Kep seems to be a stable and sensitive indicator in CT perfusion, whereas Ktrans is a reliable parameter for dynamic contrast-enhanced MRI. Future prediction models that utilize both the volume of BBB disruption and stable parameters of BBB may be a promising direction to develop practical clinical tools. These tools could provide greater accuracy in predicting clinical outcome and risk of deterioration. Therapeutic interventional exploration targeting BBB disruption is also promising, considering the extended duration of post-SAH BBB disruption.
Custom-made 3D-printed cup-cage implants for complex acetabular revisions: evaluation of pre-planned versus achieved positioning and 1-year migration data in 10 patients

Background and purpose — The use of custom-made 3D-printed titanium implants for the reconstruction of large acetabular defects has been successively introduced in the last decade. In an observational cohort study we evaluated the agreement between preoperatively planned and actually achieved cup-cage position as well as 1-year follow-up migration of the cup-cage component. Patients and methods — 10 patients with Paprosky III defects underwent revision surgery using a custom-made 3D-printed cup-cage. The position of the implant on postoperative CT scan was compared with the preoperative plan and the postoperative CT scan was compared with the 1-year follow-up CT scan. Results — There was a median deviation in postoperative position versus planned in inclination of 3.6° (IQR 1.0–5.4), in anteversion of –2.8° (IQR –7.5 to 1.2), and in rotation of –1.2° (IQR –3.3 to 0.0). The median deviation in position of the center of rotation (COR) was –0.5 mm (IQR 2.9 to 0.7) in the anteroposterior (AP) plane, –0.6 mm (IQR –1.8 to –0.1) in the mediolateral (ML) plane, and 1.1 mm (IQR –1.6 to 2.8) in the superoinferior (SI) plane. The migration between postoperative and 1-year follow-up caused a mean change in inclination of 0.04° (IQR –0.06 to 0.09), in anteversion of –0.13° (IQR –0.23 to –0.06), and in rotation of 0.05° (IQR –0.46 to 1.4). The migration of COR was –0.08 mm (IQR –0.18 to –0.04) in the AP plane, 0.14 mm (IQR –0.08 to 0.22) in the ML plane, and 0.06 mm (IQR –0.02 to 0.35) in the SI plane. There was no re-revision. Interpretation — The early results show good agreement between planned and achieved cup-cage position and small measured migration values of the cup-cage component at the 1-year follow-up.
Effect of isgin (Rheum ribes L.) on biochemical parameters, antioxidant activity and DNA damage in rats with obesity induced with high-calorie diet

Abstract The present study was designed to investigate the effects of Rheum ribes L. plant root extracts on DNA damage, biochemical and antioxidant parameters in rats with experimental obesity induced with a high-calorie diet. The study groups were divided as “normal control(NC)”, “obese control(OC)”, “obese + Rheum ribes(OR1)(200 mg/kg)” and “obese + Rheum ribes (OR2)(400 mg/kg)”. At the end of the application, rats were sacrificed and blood and tissue samples were obtained. According to the results obtained, the marker of DNA damage in tissues of 8-OHdG was determined to be significantly reduced in brain tissue of the OR1 and OR2 groups compared to the NC group. However, fluctuations were identified in the MDA activity, antioxidant defense system elements and serum biomarkers in tissues. In conclusion, Rheum ribes plant root extract ensured improvements in DNA damage in brain tissues and MDA levels and showed positive effects on antioxidant parameter activities in different tissues.
Awareness of the risk of developing medication-related osteonecrosis of the jaw among bisphosphonate users

Objective In this retrospective observational study, we evaluated awareness among patients using bisphosphonates (BPs) regarding the risk of developing medication-related osteonecrosis of the jaw (MRONJ) and whether they received appropriate dental screening and treatment prior to commencing medication. Methods Patients using BPs who attended the endodontics clinic at Jordan University Hospital in 2019 were interviewed using a pre-designed questionnaire. Data were analysed using descriptive statistics and chi-squared tests. Results In total, 110 patients were interviewed (84 women, 26 men; age 40–78 years). A total of 94 patients were using oral BP and 16 received intravenous (IV) BP. We found that only 12.4% of participants were aware about the risk of MRONJ following BP use, and only one third of them has received information from their prescribing physicians. In total, 5% of participants were referred to a dentist for screening prior to initiating BP treatment. Patients receiving IV BP and those with a university-level education had better awareness about the risk of MRONJ than oral BP users and those with a high school education level. Conclusion Patients’ awareness about MRONJ risk was low in our population. Better patient education and collaboration among physicians and dentists are needed prior to starting BP treatment.
Influence of Target Location, Size, and Patient Age on Normal Tissue Sparing- Proton and Photon Therapy in Paediatric Brain Tumour Patient-Specific Approach

Simple Summary This manuscript investigates the latest proton and photon radiation delivery techniques and the delivered dose distribution dependence on age and brain tumour location for simulated paediatric patients. Brain tumors are the leading cause of cancer-related burden in childhood cancer survivors. Standard treatment regimens include radiotherapy, and whilst photon therapy is commonly prescribed, proton particles (where available) have been proven to reduce the risk of long-term illness and morbidities. Differences between the two modalities are not fully quantified in paediatric patients for various intracranial tumour sites or age. Ependymoma proton plans demonstrated greater dose reduction for the 9 vs. 13-year-old patients (pituitary gland p < 0.001). Whilst medulloblastoma proton plans achieved greater maximum dose sparing to optic structures (4.8–12.6 Gy optic chiasm), brainstem sparing was limited (~0.5 Gy). Understanding these differences may help clinicians estimate the benefit and improve referral across available centres. Abstract Background: Proton radiotherapy produces superior dose distributions compared to photon radiotherapy, reducing side effects. Differences between the two modalities are not fully quantified in paediatric patients for various intracranial tumour sites or age. Understanding these differences may help clinicians estimate the benefit and improve referral across available centres. Our aim was to compare intensity-modulated proton therapy (IMPT) and intensity-modulated photon radiotherapy (IMRT) radiation doses for select paediatric intracranial tumours. Methods: IMPT and IMRT dose distributions for gender-matched paediatric cranial CT-datasets (ages 5, 9 and 13 years) were retrospectively calculated to simulate irradiation of supratentorial (ependymoma) and infratentorial (medulloblastoma) target volumes diameters (1–3 cm) and position (central and 1–2 cm shifts). Results: Clinical dosimetric objectives were achieved for all 216 treatment plans. Whilst infratentorial IMPT plans achieved greater maximum dose sparing to optic structures (4.8–12.6 Gy optic chiasm), brainstem sparing was limited (~0.5 Gy). Mean dose difference for optic chiasm was associated with medulloblastoma target position (p < 0.0197). Supratentorial IMPT plans demonstrated greater dose reduction for the youngest patients (pituitary gland p < 0.001). Conclusions: Normal tissue sparing was achieved regardless of patient age for infratentorial tumours. However, for supratentorial tumours, there was a dosimetric advantage of IMPT across 9 vs. 13-year-old patients.
Adjuvantation of an Influenza Hemagglutinin Antigen with TLR4 and NOD2 Agonists Encapsulated in Poly(D,L-Lactide-Co-Glycolide) Nanoparticles Enhances Immunogenicity and Protection against Lethal Influenza Virus Infection in Mice

Along with their excellent safety profiles, subunit vaccines are typically characterized by much weaker immunogenicity and protection efficacy compared to whole-pathogen vaccines. Here, we present an approach aimed at bridging this disadvantage that is based on synergistic collaboration between pattern-recognition receptors (PRRs) belonging to different families. We prepared a model subunit vaccine formulation using an influenza hemagglutinin antigen incorporated into poly-(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles adjuvanted with monophosphoryl lipid A (TLR4 agonist) and muramyl dipeptide (NOD2 agonist). The efficacy studies were conducted in comparison to control vaccine formulations containing individual PRR agonists. We show that the complex adjuvant based on TLR4 and NOD2 agonists potentiates proinflammatory cell responses (measured by activity of transcription factors and cytokine production both in vitro and in vivo) and enhances the phagocytosis of vaccine particles up to comparable levels of influenza virus uptake. Finally, mice immunized with vaccine nanoparticles containing both PRR agonists exhibited enhanced humoral (IgG, hemagglutination-inhibition antibody titers) and cellular (percentage of proliferating CD4+ T-cells, production of IFNɣ) immunity, leading to increased resistance to lethal influenza challenge. These results support the idea that complex adjuvants stimulating different PRRs may present a better alternative to individual PAMP-based adjuvants and could further narrow the gap between the efficacy of subunit versus whole-pathogen vaccines.
Molecular Modeling of Pathogenic Mutations in the Keratin 1B Domain

Keratin intermediate filaments constitute the primary cytoskeletal component of epithelial cells. Numerous human disease phenotypes related to keratin mutation remain mechanistically elusive. Our recent crystal structures of the helix 1B heterotetramer from keratin 1/10 enabled further investigation of the effect of pathologic 1B domain mutations on keratin structure. We used our highest resolution keratin 1B structure as a template for homology-modeling the 1B heterotetramers of keratin 5/14 (associated with blistering skin disorders), keratin 8/18 (associated with liver disease), and keratin 74/28 (associated with hair disorder). Each structure was examined for the molecular alterations caused by incorporating pathogenic 1B keratin mutations. Structural modeling indicated keratin 1B mutations can harm the heterodimer interface (R265PK5, L311RK5, R211PK14, I150VK18), the tetramer interface (F231LK1, F274SK74), or higher-order interactions needed for mature filament formation (S233LK1, L311RK5, Q169EK8, H128LK18). The biochemical changes included altered hydrophobic and electrostatic interactions, and altered surface charge, hydrophobicity or contour. Together, these findings advance the genotype-structurotype-phenotype correlation for keratin-based human diseases.
A review of thulium-fiber laser in stone lithotripsy and soft tissue surgery

Purpose of review To evaluate emerging evidence and practical applications of thulium-fiber laser (TFL) for genitourinary soft tissue disease and urinary stone disease treatment. Recent findings A systematic review was developed using the PubMed, ScienceDirect, Wiley, SpringerLink and Mary Ann Liebert Scopus databases between 2012 and 2020 years, using the PRISMA statement. We analyzed recent publications including in vitro and in humans outcomes of surgery using TFL. This new laser technology can be used in soft tissue diseases and stones present in the genitourinary system. Most of the comparisons are made with the Ho:YAG laser, using completely different settings. Nevertheless, TFL is safe, feasible and effective in the management of urologic diseases, showing superiority to Ho:YAG even in some studies. Summary The introduction of pulsed TFL technology has enabled the ablation of stones at rates comparable to or better than currently existing lasers in vitro, while also potentially reducing stone retropulsion. TFL is effective in treating genitourinary soft tissue diseases, including benign prostatic hyperplasia, and early data indicate that it may be effective in the treatment of urinary stone disease. More clinical studies are needed to better understand the indications for this novel technology and clarify its position in the urologic endoscopy armamentarium.
Impact of left ventricular ejection fraction on the effect of renin-angiotensin system blockers after an episode of acute heart failure: From the KCHF Registry

Objective This observational study aimed to examine the prognostic association of angiotensin-converting enzyme inhibitors (ACE-I)/angiotensin receptor blockers (ARB) in different left ventricular ejection fraction (LVEF) categories. Methods In 3717 patients enrolled in the KCHF Registry, a multicentre registry including consecutive patients hospitalized for acute heart failure (HF), we assessed patient characteristics and association between ACE-I/ARB and clinical outcomes according to LVEF. In the three LVEF categories (reduced LVEF [HFrEF], mid-range LVEF [HFmrEF] and preserved LVEF [HFpEF]), we compared the patients with ACE-I/ARB as discharge medication and those without, and assessed their 1-year clinical outcomes. We defined the primary outcome measure as a composite of all-cause death and HF hospitalization. Results The 1-year cumulative incidences of the primary outcome measure were 36.3% in HFrEF, 30.1% in HFmrEF and 33.8% in HFpEF (log-rank P = 0.07). The adjusted risks of the ACE-I/ARB group relative to the no ACE-I/ARB group for the primary outcome measure were significantly lower in HFrEF and HFmrEF (HR 0.66 [95%CI 0.54–0.79], P<0.001, and HR 0.61 [0.45–0.82], P = 0.001, respectively), but not in HFpEF (HR 0.95 [0.80–1.14], P = 0.61). There was a significant interaction between the LVEF category and the ACE-I/ARB use on the primary outcome measure (Pinteraction = 0.01). Conclusions ACE-I/ARB for patients who were hospitalized for acute HF was associated with significantly lower risk for a composite of all-cause death and HF hospitalization in HFrEF and HFmrEF, but not in HFpEF. ACE-I/ARB might be a potential treatment option in HFmrEF as in HFrEF.