A document by Trijn Israels. Click on the document to view its contents.

Nuclear receptor subfamily 5 group A member 2 (NR5A2) is known to be a key regulator in the development of a variety of tumor types. However, it is still uncertain how NR5A2 affects cutaneous squamous cell carcinoma (cSCC). The aim of this work, therefore, was to determine the function of NR5A2 in cSCC proliferation, cell cycling, cell migration, and invasion. In this study, based on a systematic study of previous data, we conducted a preliminary exploration of NR5A2 expression in cSCC using bioinformatics databases. Immunohistochemical staining for NR5A2 expression was then performed in cSCC tissues and healthy tissues from 7 patients. NR5A2 expression was also examined in human keratin-forming cells (HaCaT) and human cSCC cell lines (A431, Colo-16, SCL-1, and SCL-2). A stable A431 cell line consisting of sh-RNA-NR5A2 was created to detect changes in cell proliferation, cell cycle, clonogenic ability, and the key proteins about the Wnt/β-catenin pathway. The results illustrated that NR5A2 showed enhanced expressed in cSCC tissues than in healthy adjacent tissues and was more robustly expression in Colo-16, A431, SCL-1, and SCL-2 cells versus HaCaT cells. Downregulation of NR5A2 expression in cSCC cells led to a less malignant phenotype. NR5A2 knockdown decreased the expression of proteins in the Wnt/β-catenin, and this inhibition could be reversed by the Wnt signaling pathway agonist LiCl. In conclusion, NR5A2 appears to encourage the development and metastasis of cSCC by Wnt/β-catenin pathway.

Background Atrial fibrillation (AF) is associated with impaired quality of life, anxiety and depression. Compared with the use of antiarrhythmic drugs, the quality of life of patients with AF after catheter ablation (CA) has significantly improved, but the research on the role of family function, anxiety and depression is relatively limited. This study aims to determine how different treatment strategies lead to changes in the quality of life, family function, anxiety and depression of patients with symptomatic paroxysmal AF, and to explore the influencing factors of clinically significant changes in the quality of life of patients with symptomatic paroxysmal AF. Methods The patients with AF diagnosed and treated in the Department of Cardiology of the Second Hospital of Lanzhou University from January 1, 2021 to May 1, 2022 were selected as the research objects in strict accordance with the inclusive criteria. Questionnaires were designed to collect general information about the patients; the Atrial Fibrillation Effect on Quality-of-life (AFEQT), the Family Adaptation, Partnership, Growth, Affection, Resolve (APGAR), the Generalized Anxiety Disorder 7 (GAD-7) and the Patient Health Questionnaire 9 (PHQ-9) were used to assess the patients’ quality of life, family function, anxiety and depression levels at baseline and after 6 months of clinical follow-up, respectively.Construction of a logistic regression model to analyze the factors influencing clinically meaningful changes in overall quality of life in patients with symptomatic paroxysmal AF. Results 188 patients with AF were included in this study, including 87 cases in the CA group and 101 cases in the antiarrhythmic drug (AAD) group. Compared with the AAD group, patients in the CA group had significantly better quality of life (60.81±6.63 vs 76.30±6.86), family function (5.67±2.38 vs 8.01±2.13), anxiety (6.36±2.62 vs 4.98±2.58) and depression levels (5.39±2.89 vs 4.45±3.52) significantly improved (all P < 0.05). Analysis of factors influencing clinically meaningful changes in overall quality of life in patients with symptomatic paroxysmal AF revealed, a clinically meaningful increase in overall quality of life in patients who underwent CA (OR=233.20, 95% CI: 58.51-929.43, P=0.001), and a clinically meaningful decrease in overall quality of life in patients with AF of more than 5 years duration (OR=3.32, 95% CI: 1.13-9.74, P = 0.029) had a clinically meaningful decrease in overall quality of life. Conclusions CA is effective in improving quality of life, family function, anxiety, and depressive symptoms in patients with symptomatic paroxysmal AF compared with AAD, and patients undergoing CA are more likely to experience clinically meaningful increases in overall quality of life, primarily due to relief of AF symptoms and reduced disease burden.

Introduction:CNS embryonal tumors are highly malignant undifferentiated or poorly differentiated tumors of neuroepithelial origin, they take origin from embryonic cells that remain in the brain after birth, These tumors tend to spread through the cerebrospinal fluid (CSF) to other parts of the brain and spinal cord.Central nervous system embryonal tumor, not otherwise specified (NOS) was previously called primitive neuroectodermal tumors (PNET), these are rare tumors that form in the brain and spinal cord. (1)We describe CNS (NOS) that arose in the occipital lobe of a 27 year old patient.

IntroductionEctopic pancreas tissue (EPT) or pancreatic heterotopia is a rarely observed congenital abnormality defined as the presence of pancreatic tissue in another organ without any anatomical or vascular connection to the pancreas. The term consists of the two Greek words ”hetero-” which means ”other” and ”-topia” which means ”site”, pointing out the unique location of pancreatic cells. EPT’s favored sites are the stomach, duodenum, colon, jejunum, and Meckel’s diverticula (1). The gallbladder is a highly infrequent location for EPT (2). Almost all cases are detected incidentally during the histopathological examination after cholecystectomy for other pathologies. The prevalence of EPT in the gastrointestinal tract varies from 0.6% to 13.7% in autopsy series and 0.2% in laparotomies (3, 4). Although the malignant transformation of this tissue is not frequently expected, pathologists must be aware of it to ensure no malignant pathology is present and prevent further misdiagnosis. In this study, we present a case of EPT that we found incidentally during the histopathological examination of the specimen from the gallbladder in a patient who underwent cholecystectomy due to acute cholecystitis.Case HistoryA 40-year-old male was referred to the emergency department for acute pain in the right upper quadrant of the abdomen. The pain was constant and initiated hours before and intensified when he had dinner. He also reported fever, anorexia, nausea, and one involuntary vomiting episode containing only stomach contents. Besides intellectual disability and epilepsy, patient’s medical history was unremarkable otherwise. He was on Valproate(200mg/D), Risperidone(1mg/BD) and Clonazepam(1mg/HS). He denied smoking and any recreational drug use. No allergies were reported. During the clinical examination, his vitals were slightly above normal ranges (Blood pressure: 115/70mmHg; Heart rate: 108bpm; Respiratory rate: 19 breaths/min; Temperature: 37.9°C; Oxygen saturation: 99% without supplemental oxygen). The palpation of the abdomen revealed tenderness in the right upper quadrant and a positive Murphy sign with no rebound tenderness or guarding. The laboratory evaluation was within normal range except for a WBC count of 10300, ESR of 32, and a 2+ CRP. Additionally, he underwent an ultrasonographic evaluation of the upper abdomen, reporting a thickened wall gallbladder containing multiple stones (measuring up to 8x10mm). The patient was scheduled for emergency laparoscopic cholecystectomy under the diagnosis of acute calculous cholecystitis. During surgery, the gallbladder was found to be gangrenous. The patient had a complicated postoperative period due to surgical wound infections and was hospitalized for a week to receive intravenous antibiotics; however, he did not report any delayed complications or symptoms after discharge.

The Practical Byzantine Fault Tolerance protocol (PBFT) has been widely deployed in the blockchain network. However, two main issues, the communication complexity and the inability of nodes to join/exit the network without restarting the system, significantly degrade consensus efficiency. To solve these problems, we propose a novel dynamic practical byzantine fault tolerance protocol based on node grouping (NG-PBFT), which is realized by grouping nodes into consensus and observation groups. The nodes in observation group preprocess nodes’ joining/exiting requests, while the nodes in consensus group reach con sensus about the preprocessed results. Furthermore, an adaptive three phases or two phases consensus mechanism that can effectively improve consensus efficiency is proposed. We provide theoretical complexity to show that our protocol reduces the communication complexity of con sensus and improves consensus efficiency significantly.

This paper proposed an improved toughness exhaustion model on the basis of the toughness exhaustion model. Specifically, in this model, a new logarithmic function of the stress amplitude is adopted into the damage equivalence equation, which can reflect the influence of load interaction. In addition, the fatigue state function using the improved model is constructed and analyzed by the probability density evolution method. Then, experimental data of four materials are used to verify the proposed model, and results show that the residual life fraction predicted by this model is accurate. Furthermore, the time-varying fatigue reliability of the proposed model is validated using experimental data of two materials. The results show that the improved model has better applicability and higher accuracy.

Due to the additional local stress concentration caused by undercut and misaligned defects, welded joints own less fatigue strength. This work uses probabilistic technique and fracture mechanics theory to quantitatively investigate the impacts of undercuts and misalignments on fatigue performance and reliability of Load-carrying Cruciform Welded Joint (LCWJ). Firstly, the geometrical characteristics summary of the size and type of undercuts and misalignments are provided from researches and experiments. Subsequently. Evaluations of the stress levels are combined with the nominal loadings in LCWJs, probabilistic distributions of material fracture properties, and various configurations of geometries and flaws. Meanwhile, the estimations of fatigue strengths are conducted by the probabilistic reliability theory by taking into account the distributions of the actual fatigue data. The findings reveal a clear disparity between the base metal and weldment test results. Different reliability levels for various defect types and sizes and in LCWJs are caused by the tolerance limits.

Topical probiotic L. lactis treatment in atopic dermatitis - A double-blinded, placebo-controlled pilot studyTo the Editor,Changes in the skin microbiome have been identified as major pathogenetic components in atopic dermatitis (AD). Probiotics have been studied as potential therapeutic agents to maintain normal cutaneous microbiome and prevent colonization with pathogens.1We aimed to compare the efficacy of probiotic Lactococcus lactislysate cream in different concentrations in AD.We conducted a prospective, double-blinded, randomized, placebo-controlled, split-body clinical interventional study. 13 patients were enrolled and randomly assigned to one of four groups with different concentrations of probiotic lysate cream including placebo (Supplement Table S1).Patient’s skin was investigated 3 times, at baseline, after 4 weeks of treatment and after 4 weeks of follow-up. During each visit, the skin was evaluated, and AD severity was characterized with investigator-dependent methods and patient-reported questionnaires. Online Supplement presents detailed information about the study setting and patient characteristics.There were no clear differences between the treatment groups regarding disease severity (EASI, IGA), TEWL or parameters associated with QoL (pruritus and sleep disturbance VAS, DLQI, POEM, ADCT). Mean changes in disease severity (EASI local and total), TEWL and QoL indicators (DLQI and POEM) are shown in Fig. 1.Mean local EASI (eczema site) baseline values were 3.00, 1.47 and 1.05 in the 3%, 10% and 30% probiotic lysate groups respectively, and 4.93 in the placebo group. After 4 weeks of treatment, local EASI values were 3.20, 1.20 and 0.80 in the probiotic lysate groups and 4.53 in the placebo group, with no significant decrease compared to baseline (p=0.76). Total EASI values showed similar results (p=0.31) and there were also no differences between local EASI and total EASI. IGA values were similar (p=0.61) (Table 1).QoL associated parameters did not change significantly during the study and were similar in all patient groups (Supplement Table S2). Mean DLQI was 9.33, 7.00 and 8.00 in the probiotic lysate groups and 10.67 in the placebo group. At 4 weeks the values were comparable, 9.00, 8.00 and 10.33 in the probiotic lysate groups and 7.67 in the placebo group, with no significant differences (p=0.76). POEM and ADCT showed no significant differences (p=0.76 and p=0.72, respectively). Complete study results, clinical data, eosinophil counts, total serum IgEs and specific IgEs to aeroallergens at baseline are presented in the Supplement (Table S3).While enteral probiotics have been studied in detail, the role of topical probiotics in AD remains uncertain. Several studies have investigated the use of probiotics in creams with living or dead bacteria or bacterial lysates with inconsistent results.2,3 Further evidence is needed to determine efficacy, dosing, and specific bacterial strains. Most of the previous studies observed positive effects, which is contrary to our findings.4In addition to ameliorating disease severity, in vitro studies have shown that probiotics suppress cutaneous inflammation and Th2-responses through immunomodulatory mechanisms.5 We did not measure inflammatory parameters in our patients. However, to our knowledge, our study is the first in vivo study in humans investigating Lactococci in the treatment of AD.Most probiotic preparations are considered relatively safe and are classified as commercial food supplements. We did not observe relevant adverse effects and the used probiotic L. lactis lysate cream was well tolerated.Important study limitations were small and heterogenous patient groups, relatively short follow-up time and no long-term evaluation.We observed no clear differences between the treatment groups of probiotic L. lactis lysate cream and placebo. Further research is needed to investigate the role of topical probiotics in AD. It would be interesting to investigate anti-inflammatory effects in larger patient cohorts.6Table 1: Severity of atopic dermatitis and TEWL values, results of follow-up and comparisons

Currently, in Republic of Korea, most of the research that requires huge computational resources utilizes the supercomputer resources of the National Supercomputing Center. However, the average utilization rate of the resources for the past three years has reached 80%. In order to secure the stability of the national infrastructure, the establishment of specialized supercomputing center infrastructure is being promoted to distribute computational demand by field. Therefore, it is necessary to accurately predict the computational demand distributed to the specialized centers in order to build an appropriate scale of infrastructure for the specialized centers in the future. In this paper, a preference survey was conducted for national center and specialized centers by using the results of individual behavior surveys through logit model analysis applying probability utility theory. Through the computational demand share of the national center and the specialized center derived through the analysis results, it will be used as the highest level of evidence when calculating the infrastructure size of the specialized center for each field in the future.

Alloy-type antimony (Sb) is considered as an attractive candidate anode for high-energy lithium-ion batteries (LIBs) because of its high theoretical specific capacity and volumetric capacity. However, Sb suffers from enormous volume variation during cycling, which causes electrode cracking and pulverization, and hence the fast capacity decay and poor cyclability, limiting its practical applications as a LIB anode. Herein, we report a facile, scalable, low-cost and efficient route to successfully fabricate BiSb/C composites via a two-step high-energy mechanical milling (HEMM) process. The as-prepared BiSb/C composites consist of nanosized BiSb totally embedded in a conductive carbon matrix. As LIB anodes, BiSb/C-73 (with 30 wt % carbon) electrodes exhibit excellent Li storage properties in terms of stable high reversible capacities, long-cycle life, and high-rate performance. Reversible capacities of ∼583, ∼466, ∼433 and ∼425 mAh g–1 at a current density of 500 mA g–1 after 100, 300, 500 and 1000 cycles, respectively, were achieved. In addition, a high capacity of ∼380 mAh g−1 can still be retained at a high rate of 5 A g−1. Such outstanding cycling stability and rate capability could be mainly attributed to the synergistic effects between the ability of nanosized BiSb particles to withstand electrode fracture during Li insertion/extraction and the buffering effect of the carbon matrix. The as-prepared BiSb/C composites are based on commercially available and low-cost Bi, Sb and graphite materials. Interestingly, HEMM is more convenient, efficient, scalable, green and mass-production route, making as-prepared materials attractive for high-energy LIBs.

Objective To evaluate the feasibility and safety of laparoendoscopic single-site (LESS) vaginal hysterectomy compared to conventional three-port laparoscopic-assisted vaginal hysterectomy (LAVH) for benign and pre-invasive uterine disease. Design Randomised controlled trial. Setting South Korea. Population Patients who were scheduled to undergo laparoscopic hysterectomy for the benign and pre-invasive uterine diseases Methods Patients were randomised to LESS LAVH group and conventional three-port LAVH group. Main outcome Measures To compare the average length of postoperative hospital stay and the proportion of patients discharged within two days after surgery between the LESS and three-port groups. Results A total of 428 patients were randomised to the LESS group (n=216) and the conventional group (n=212). The two groups did not show significant differences in the average length of postoperative hospital stay (LESS vs. three-port, 2.17 days vs. 2.15 days, P = 0.757) and the proportion of patients discharged within two days after surgery (LESS vs. three-port, 93% vs. 90%, P = 0.277). There were also no significant differences in operating time, hemoglobin change, and perioperative complications. While the visual analogue score (VAS) pain score during hospital stay was similar between the two groups, the pain score at the first outpatient visit was significantly lower in the LESS group (LESS vs. three-port, 3.29 vs. 3.93, P = 0.012). Conclusions Although LESS LAVH was not superior to conventional multiport surgery, it is a feasible, safe procedure for managing benign and pre-invasive uterine diseases.

Objective To explore and characterise maternity healthcare professionals’ (MHCPs) experience and practice of informed decision-making (IDM), to inform policy, research and practice development. Design Qualitative focus group study. Setting Online with MHCPs from a single maternity unit in the Southwest of England. Population MHCPs who give information relating to clinical procedures and pregnancy care and are directly involved in decision-making conversations purposively sampled from a single National Health Service (NHS) Trust. Data collection: A semi-structured topic guide was used. Data Analysis: Reflexive thematic analysis . Results Twenty-four participants attended seven focus groups. Two themes were developed: contextualising decision-making and controversies in current decision-making. Contextual factors that influenced decision-making practices included lack of time, and challenges faced in intrapartum care. MHCPs reported variation in how they approach decision-making conversations and asked for more training on how to consistently achieve IDM. There were communication challenges with women/birthing people who do not speak English. Three controversies were explored in the controversies theme: the role of prior clinical experience, the validity of informed consent when women/birthing people were in pain and during emergencies, and instances where women/birthing people declined medical advice. Conclusions We found that MHCPs are committed to IDM but need better support to deliver it consistently. Structured processes including core information sets, communication skills training and the decision support aids may help to standardise the information and better support IDM.

A document by Francesco Comandatore. Click on the document to view its contents.

Background and Purpose: Hypertension is a chronic medical condition that increases the risk of cardiovascular diseases. Recently, HDAC inhibitors were shown to lower blood pressure through endothelium-dependent mechanisms. However, the antihypertensive potential and precise mechanisms of most HDAC inhibitors remain unexplored. Experimental Approach: We first examined YPX-C-05(a novel hydroxamic acid-based HDAC inhibitor) effects on phenylephrine-induced hypertension in mice. We also determined the vasodilatory effects of YPX-C-05 ex vivo using isolated aortic rings precontracted with phenylephrine. We performed Network pharmacology analysis to predict the putative targets of YPX-C-05. We then validated the involvement of the PI3K/Akt/eNOS pathway using pharmacological inhibitors and Western blotting. Levels of phosphorylated and total Akt and eNOS were measured in Human umbilical vein endothelial cell lysates after YPX-C-05 treatment. In vivo, we examined the chronic antihypertensive effects of YPX-C-05 in N-omega-nitro-L-arginine-induced hypertensive mice. Vascular remodeling was assessed by histological analysis. Key Results: YPX-C-05 could attenuate the hypertensive effects of phenylephrine and reduced blood pressure, increase NO levels, improve endothelium-dependent relaxation and decrease vascular damage in chronic hypertensive mice. Network pharmacology analysis predicted YPX-C-05 might activate endothelial eNOS via PI3K/Akt signaling pathway. Western blotting confirmed that YPX-C-05 increased phosphorylated Akt and eNOS levels and eNOS expression and activity. Conclusion and Implications: This study demonstrates for the first time that the novel hydroxamic acid-based HDAC inhibitor YPX-C-05 exerts significant antihypertensive and vasodilatory effects. Our findings support the developing prospect of YPX-C-05 as a novel antihypertensive drug. Keywords: Hydroxamic acid derivative YPX-C-05; vasodilation; hypertension; vascular function; Akt/eNOS/NO pathway.

1. The severe decline of hazel dormice (Muscardinus avellanarius) is well documented and has led to increased legislative protection both in the UK and across Europe. Conservation measures for this species often include provision of nestboxes as a mitigation or enhancement technique after development projects. Previous research has offered some insights into how to select suitable general locations for nestboxes, but where to best place individual boxes to promote occupancy is less well understood. We hypothesised microhabitat variables related to proximity to food sources and nest building material will affect nestbox occupancy by dormice and should be considered when placing individual boxes within a selected site. 2. To assess individual nestbox occupancy by hazel dormice, 76 microhabitat variables were collected from 45 occupied and unused nestboxes in a deciduous woodland in Berkshire,UK. Variables were then used to predict probability of nestbox occupancy (observed from 2017 to 2021) using Random Regression models. 3. Results reveal nestboxes were more likely to be occupied by hazel dormice in sites with higher local cover and abundance of hazel trees (Corylus avellana), greater overall tree abundance but not fully closed canopies (best around 80-85%), more hawthorn (Crataegus monogyna) and honeysuckle (Lolium periclymenum), and when located further from footpaths. 4. Our results build on previous literature on habitat preferences of hazel dormice and importantly provide insight into relevant microhabitat variables that offer recommendations for where to place individual nestboxes to promote occupancy and facilitate recovery of hazel dormice.

Drought-induced leaf senescence is related to high sugar levels in leaves, photosynthesis inhibition, and ultimate yield loss. This physiological phenomenon in leaves bears resemblance to the symptom of diabetes in human disease. However, the underlying mechanisms of plant diabetes on carbon imbalance in maize leaf and corresponding detoxification strategy have not been well understood. In this study, we demonstrated that foliar application of exogenous methylglyoxal (MG) delayed leaf senescence and promoted photoassimilation, retrieved 14% yield loss induced by drought stress during grain filling stage. Transcriptome and metabolite analysis revealed that drought increased sugar accumulation in leaf with inhibition of sugar transporters facilitating phloem loading. This further lead to disequilibrium of glycolysis and over-accumulation of endogenous MG. Contrarily, exogenous MG significantly upregulated glycolytic flux and glyoxalase system catabolizing endogenous MG and advanced glycation end products toxicity, ultimately alleviating plant diabetes. Besides, the genes facilitating anabolism and catabolism of trehalose-6-phosphate were promoted and suppressed by drought, respectively, whereas exogenous MG reversed the effect, revealing that trehalose-6-phosphate metabolism or signaling may contribute to MG-delayed leaf senescence under drought. Moreover, exogenous MG increased the activation of phenylpropanoid biosynthetic pathways, likely promoting cell structural integrity. Collectively, these results suggest that exogenous MG alleviates the toxic effect from drought-induced excessive sugar accumulation and activates the defense-related pathway, thereby maintaining leaf function and yield production.

Introduction: Primary osteoporotic pain (POPP) seriously affects the life of patients. Although chronic pain is associated with altered central nervous activity, the central pathological mechanism of POPP is still unclear. This study aimed to explore the differences of brain activity between POPP patients and healthy controls (HCs), as well as the correlations between altered brain regions and pain. Method: Magnetic resonance imaging data (MRI) and visual analogue scale (VAS) scores of subjects were collected. MRI data were preprocessed and then regional homogeneity (ReHo) and amplitude of low-frequency fluctuation (ALFF) values of brain regions were calculated. ReHo and ALFF values were compared between groups. Result: (1) Compared with HCs, reduced ReHo values were found in the left medial superior frontal gyrus, middle frontal gyrus, opercular part of inferior frontal gyrus and right dorsolateral superior frontal gyrus of POPP patients. (2) Reduced ALFF values were identified in the left dorsolateral superior frontal gyrus, medial superior frontal gyrus, orbital part of middle frontal gyrus, opercular part of inferior frontal gyrus and right dorsolateral superior frontal gyrus. (3) Negative correlations were identified between ReHo values of the left middle frontal gyrus and VAS scores in the patient group. Conclusion：The prefrontal dysfunction may be related to the occurrence of POPP. In addition, the left middle frontal gyrus can be used as an indicator to evaluate the severity of pain in patients with POPP. These findings help us to further understand the pathogenesis of POPP from the perspective of neuroimaging.

Purpose: The aim of this study was to explore the correlation between brain functional network alterations and cerebrospinal fluid (CSF) pathological biomarkers in Alzheimer’s disease (AD)-spectrum patients. Method: A total of 39 individuals were recruited, including 23 AD patients and 16 control subjects. All subjects underwent a battery of neuropsychological examinations, CSF measurement and multimodal magnetic resonance imaging scans. Independent component analysis was used to investigate the differences of functional connectivity（FC）among the two groups based on the resting-sate functional MRI (fMRI) data. Then correlation analyses were used to estimate the potential relationship between functional network alterations and cerebral amyloid and tau burden. Result: Multiple inter- and intra-network functional connections were altered in AD patients compared to the Non ADCI group. Alterations in FC between VN and PCC, as well as the functional connections of SMN were found to be associated with the dynamic changes of CSF Tau. Compared the AD group with the non-AD CI group, the aforementioned altered functional brain connectivity, with the exception of FC in the PCC and VN, was significantly associated with a decrease in CSF Aβ Conclusion: This study provides provisional evidence that the brain functional network alterations was closely associated with CSF pathological characteristics, and these exploratory results support new research ideas for the early diagnosis of AD.

Anju Murayama1,2*

LETTER TO THE EDITORTITLE: Sarcoid-like reaction in a child following prolonged therapeutic exposure to dabrafenib and trametinib for BRAF V600E mutated hypothalamic/ chiasmatic gliomaAuthors : Mari Wilhelmsson MD, PhD1,2; Foo Jen Chun MD1; Rae S M Yeung MD, PhD3; Fiona Krtizinger MBChB, MMed4; Tata McKeown, MSc1; Ailish Coblentz, MD5; Birgit Ertl-Wagner, MD5; Uri Tabori MD, PhD1, Ute Bartels MD, PhD 1; Anirban Das MBBS, MD, DM 1AFFILIATIONS: 1. Division of Haematology Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada; 2. Department of Women´s and Children´s Health, Karolinska Institutet, Stockholm, Sweden. 3. Division of Rheumatology, The Hospital for Sick Children, Toronto, Ontario, Canada. 4. Division of Respiratory Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada. 5. Department of Diagnostic Imaging, The Hospital for Sick Children, Toronto, Ontario, Canada.WORD COUNT:   853FIGURES:  1RUNNING TITLE: Sarcoid-like reaction with BRAF/MEK-inhibitionKEYWORDS : MEK-inhibitor, BRAF inhibitor, sarcoidosis/sarcoid‑like reaction (S/SLR), Low-grade glioma, pediatric

A document by Somee Rauniyar. Click on the document to view its contents.

Metastatic Prostatic Adenocarcinoma Presenting as Generalized Lymphadenopathy Unmasked by a COVID Booster Vaccine

Introduction: Cervical cancer, predominantly caused by human papillomavirus (HPV), is a common malignancy in women. Distinct histological subtypes, such as squamous cell carcinomas (SCC) and adenocarcinomas (AC), exhibit different characteristics and treatment responses. Immune checkpoint molecules, including programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1), contribute to immune evasion. This study aims to investigate PD-L1 expression in SCC and AC of cervix and explore its association with clinical features. Methods: This cross-sectional study was conducted on samples from 2016 to 2022 in Shahid Beheshti University of Medical Sciences-affiliated hospitals, Tehran, Iran. Paraffin-embedded samples of histologically confirmed cervical cancers (48 SCC - 16 AC) were analyzed, and clinical data were extracted from medical records. PD-L1 expression was assessed using immunohistochemistry, and the combined positive score was utilized. Statistical analyses included T-tests, Chi-Square tests, and non-parametric equivalents. Results: PD-L1 expression tended to be higher in SCC cases, although the difference was not statistically significant. Positive PD-L1 expression was more common in SCC cases. However, no significant correlation was observed between PD-L1 expression and clinical features in either subgroup. Mean age and clinical characteristics did not significantly differ between the SCC and AC groups. Conclusion: This study investigated PD-L1 expression in SCC and AC of the cervix and its relationship with clinical features. Although SCC cases tended to exhibit higher PD-L1 expression, the difference was not statistically significant. Further research is warranted to elucidate the role of PD-L1 in cervical cancer and its potential implications for immunotherapy.