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A Comprehensive Literature Review of Fournier's Gangrene in Females.

Fournier gangrene (FG) is a rare but rapidly progressing disease with a higher mortality rate in women as compared to men. This study aims to perform a literature review about FG in females and associated mortality and morbidity. We searched databases including MEDLINE (Ovid), the National Library of Medicine (Medical Subject Headings (MeSH)), the Cochrane Database of Systematic Reviews (Wiley), as well as Embase (Ovid), Scopus, and Global Index Medicus (WHO), and reviewed literature from 2002 to 2022 and selected 22 studies that met our study's inclusion criteria, which included 134 female patients with a mean age of 55±6 years. The perineal abscess was a more common nidus (n=41, 35%; 95%CI 23-39%) than vulvar pathology (n=29, 22%; 95%CI 15-30%). The most common initial presentation was cellulitis (n=62, 46%; 95%CI 38-55%), followed by perineal pain (n=54, 40%; 95%CI 32-50%), fever (n=47, 35%; 95%CI 27-43%), and septic shock (n=38, 28%; 95%CI 21-37%).

Risk of Gastrointestinal Bleeding in Patients with End-Stage Renal Disease: The Link between Gut, Heart, and Kidneys.

Patients with end-stage renal disease (ESRD) have a five times higher risk of gastrointestinal bleed (GIB) and mortality than the general population. Aortic stenosis (AS) has been associated with GIB from intestinal angiodysplasia. In this retrospective analysis, we obtained data from the 2012 and 2019 National Inpatient Sample. The primary outcome of interest was all-cause in-hospital mortality and risk factors of mortality in patients with ESRD with GIB with aortic valve disorders especially AS. We identified all patients (≥18 years of age) with ESRD (

A Bayesian decision-theoretic design for simultaneous biomarker-based subgroup selection and efficacy evaluation.

The success of drug development of targeted therapy often hinges on an appropriate selection of the sensitive patient population, mostly based on patients' biomarker levels. At the planning stage of a phase II study, although a potential biomarker may have been identified, a threshold value for defining sensitive patient population is often unavailable for adopting many existing biomarker-guided designs. To address this issue, we propose a two-stage design that allows for simultaneous biomarker threshold selection and efficacy evaluation while accommodating situations where the drug is efficacious in the entire patient population. The design uses a Bayesian decision-theoretic approach and incorporates the benefit and cost considerations of the study into a utility function. The operating characteristics of the proposed design under different scenarios are investigated via simulations. We also provide a discussion on the choice of the benefit and cost parameters in practice.

Relationships between Obesity and Incidence of Fractures in a Middle-Aged Population: A Study from the CARTaGENE Cohort.

The association between obesity and fracture risk is complex and may vary by definition of obesity, skeletal site, and sex. We aimed to evaluate the relationships between obesity, defined using body mass index (BMI) or waist circumference (WC), and fracture incidence at any site and by skeletal site (i.e., major osteoporotic fractures [MOFs], distal lower limb fractures [tibia, ankle, feet], and distal upper limb fractures [forearm/elbow, wrist]). The secondary aim was to assess the aforementioned relationships by sex. We used CARTaGENE, a large population-based cohort of individuals aged 40-70 years from Quebec, Canada, who were assessed in 2009-2010. Incident fractures were identified via linkage with healthcare administrative databases over a 7-year period. Cox proportional hazard models adjusted for several potential confounders were used to estimate the relationships, with exposures treated as continuous variables. Results are reported as adjusted hazard ratios (aHRs) and 95% confidence intervals. We identified 19 357 individuals (mean ± standard deviation: age 54 ± 8 years, BMI 27 ± 5 kg/m

Denosumab Treatment Does Not Halt Progression of Bone Lesions in Multicentric Carpotarsal Osteolysis Syndrome.

Here we report the use of denosumab, a monoclonal antibody against receptor activator of nuclear factor κB ligand (RANKL), as monotherapy for multicentric carpotarsal osteolysis syndrome (MCTO) in an 11.5-year-old male with a heterozygous missense mutation in

Serum laser Raman spectroscopy as a potential diagnostic tool to discriminate the benignancy or malignancy of pulmonary nodules.

It has been proved that Raman spectral intensities could be used to diagnose lung cancer patients. However, the application of Raman spectroscopy in identifying the patients with pulmonary nodules was barely studied. In this study, we revealed that Raman spectra of serum samples from healthy participants and patients with benign and malignant pulmonary nodules were significantly different. A support vector machine (SVM) model was developed for the classification of Raman spectra with wave points, according to ANOVA test results. It got a good performance with a median area under the curve (AUC) of 0.89, when the SVM model was applied in discriminating benign from malignant individuals. Compared with three common clinical models, the SVM model showed a better discriminative ability and added more net benefits to participants, which were also excellent in the small-size nodules. Thus, the Raman spectroscopy could be a less-invasive and low-costly liquid biopsy.

Clinical Features, Brain-Structure Changes, and Cognitive Impairment in Basal Ganglia Infarcts: A Pilot Study.

Stroke has been considered to raise the risk of dementia in several studies, but the relationship between brain structural changes and poststroke cognitive impairment (PSCI) is unclear.

Prevalence of symptoms of burnout syndrome in primary health care professionals.

Burnout syndrome results from a response to chronic work stress and is responsible for causing symptoms related to three dimensions: emotional exhaustion, reflecting work overload; depersonalization, characterized by professional detachment and cynicism; and reduced professional accomplishment, related to low productivity at work. Burnout is often associated with jobs that require professionals to have direct contact with users, such as health professionals. Primary Health Care is the assistance level that greatest contact with the community and requires teamwork, thus exposing workers to potential psychosocial stressors.

Exposure of children to smoke in clay figures craft in Caruaru, state of Pernambuco, Brazil.

Alto do Moura, a neighborhood located in the city of Caruaru, state of Pernambuco, Brazil, is known by the production of figurative art in clay, which uses wood as the main fuel in its finishing process. Chronic exposure to toxic gases released in combustion can trigger respiratory atopies.

Sanitary and environmental conditions related to food poisoning among informal street vendors in downtown Medellín, Colombia, 2016.

Although studies with informal workers have been conducted in Latin America and the Caribbean, there is still scarce evidence on the prevalence of food poisoning among workers with subsistence jobs on the streets and sidewalks of cities and on the factors that influence its presentation.

Effect of miR-499-5p/SOX6 axis on atrial fibrosis in rats with atrial fibrillation.

Atrial fibrosis is involved in the progression of atrial fibrillation (AF). miR-499-5p is the most downregulated microRNA in arrhythmogenic cardiomyopathy hearts. Sry-related high-mobility-group box 6 (SOX6) is associated with apoptosis, inflammatory responses, and fibrosis. This study investigated the mechanism of miR-499-5p in ameliorating AF rats by regulating SOX6. AF rat models were established by injecting Ach-CaCl

Two case reports of maturity-onset diabetes of the young type 3 caused by the hepatocyte nuclear factor 1α gene mutation.

Maturity-onset diabetes of the young type 3 (MODY3) is a specific type of diabetes mellitus with inherited impairment of the islet β cell function due to the mutation in the hepatocyte nuclear factor 1α (HNF1α) gene. It is a rare condition and easily misdiagnosed as T1DM or T2DM. In this study, the clinical features of two unrelated Chinese MODY3 probands were described and analyzed. Next-generation sequencing was performed to identify the mutated genes, and Sanger sequencing was employed to verify the location of the pathogenic variant in the related family members. It was found that proband 1 inherited a start codon mutation c.2T>C (p.Met1?) in exon 1 of the HNF1α gene from his affected mother, and proband 2 inherited a frameshift mutation c.1136_1137del (p.Pro379fs) in exon 6 of the HNF1α gene also from her affected mother. Proband 1 and proband 2 differed in islet dysfunction, complications, and treatments due to their different disease durations and levels of hemoglobin A

A Survey on the Integration of Blockchains and Databases.

The success of blockchain technology in cryptocurrencies reveals its potential in the data management field. Recently, there is a trend in the database community to integrate blockchains and traditional databases to obtain security, efficiency, and privacy from the two distinctive but related systems. In this survey, we discuss the use of blockchain technology in the data management field and focus on the fusion system of blockchains and databases. We first classify existing blockchain-related data management technologies by their locations on the blockchain-database spectrum. Based on the taxonomy, we discuss three types of fusion systems and analyze their design spaces and trade-offs. Then, by further investigating the typical systems and techniques of each type of fusion system and comparing the solutions, we provide insights of each fusion model. Finally, we outline the unsolved challenges and promising directions in this field and believe that fusion systems will take a more important role in data management tasks. We hope this survey can help both academia and industry to better understand the advantages and limitations of blockchain-related data management systems and develop fusion systems that meet various requirements in practice.

Cinchonine, a Potential Oral Small-Molecule Glucagon-Like Peptide-1 Receptor Agonist, Lowers Blood Glucose and Ameliorates Non-Alcoholic Steatohepatitis.

The glucagon-like peptide-1 receptor (GLP-1R) is an effective therapeutic target for type 2 diabetes mellitus (T2DM) and non-alcoholic steatohepatitis (NASH). Research has focused on small-molecule GLP-1R agonists because of their ease of use in oral formulations and improved patient compliance. However, no small-molecule GLP-1R agonists are currently available in the market. We aimed to screen for a potential oral small-molecule GLP-1R agonist and evaluated its effect on blood glucose and NASH.

Intrathecal Dexamethasone in Febrile Infection-Related Epilepsy Syndrome: A Case Report.

Febrile infection-related epilepsy syndrome (FIRES) is characterized by explosive onset refractory status epilepticus (RSE) in healthy individuals that is refractory to antiseizure medication (ASM), continuous anesthetic infusions (CIs), and immunomodulators. Recently, a case series of patients receiving intrathecal dexamethasone (IT-DEX) was reported with improved RSE control.

Treatment of axial spondyloarthritis with biologic and targeted synthetic DMARDs: British Society for Rheumatology guideline scope.

Pharmacological management has advanced considerably since the 2015 British Society for Rheumatology axial spondyloarthritis (axSpA) guideline to incorporate new classes of biologic DMARDs (bDMARDs, including biosimilars), targeted synthetic DMARDs (tsDMARDs) and treatment strategies such as drug tapering. The aim of this guideline is to provide an evidence-based update on pharmacological management of adults with axSpA (including AS and non-radiographic axSpA) using b/tsDMARDs. This guideline is aimed at health-care professionals in the UK who care directly for people with axSpA, including rheumatologists, rheumatology specialist nurses, allied health professionals, rheumatology specialty trainees and pharmacists; people living with axSpA; and other stakeholders, such as patient organizations and charities.

A Large Dentigerous Cyst in a Child as a Complication of Deciduous Molar Endodontic Treatment: An Interesting Case Report with Short Literature Review.

This study presents a case report of an inflammatory dentigerous cyst of tooth #35, associated with its previously endodontically treated deciduous predecessor. Cystic lesion growth caused impaction of the second premolar, displacing it closer to the lower border of the mandible. The lesion represents a typical dentigerous cyst that possibly arises in association with periapical inflammation of a deciduous molar involving the follicle of the premolars. This report highlights the inflammatory etiology of dentigerous cysts, which mainly occur in mixed dentition. A 12-year-old patient was referred to Oral Surgery Department regarding a sizeable radiolucent lesion in the unerupted mandibular second premolar region, detected on an Orthopantomagram (OPG) X-ray. A non-vital primary predecessor had been endodontically treated at least one year before an examination, with a control OPG X-ray showing no signs of pathology at the time. The patient did not report any symptoms. Clinical examination revealed an egg-like tumefaction of the alveolar bone in the left premolar region of the mandible. Cone-beam computed tomography analysis showed a sizeable translucent lesion surrounding the crown of the impacted tooth. The lesion was enucleated in its entirety, along with the impacted premolar, under local anesthesia. Clinical findings combined with radiographic and microscopic examinations confirmed the diagnosis of an inflammatory dentigerous cyst. The seventeen month follow-up revealed good bone healing. This case presented a rare complication of endodontic treatment of deciduous teeth and informed on possible complications of endodontic therapy in deciduous teeth, emphasizing the importance of early diagnosis of cysts in preventing extraction of permanent teeth.

Conformational, Host, and Vibrational Effects Giving Rise to Dynamic TADF Behavior in the Through-Space Charge Transfer, Triptycene Bridged Acridine-Triazine Donor Acceptor TADF Molecule

We present a joint experimental and theoretical study of the through-space charge transfer (CT) TADF molecule

Feasibility and Acceptability of the Pain Profile, a Clinical Questionnaire Aimed at Improving Pain Care.

Despite being one of the most common medical complaints, chronic pain is difficult to manage due to ineffective communication between providers and patients and time restraints during appointments. Patient-centered questionnaires have the potential to optimize communication by assessing a patient's pain history, prior treatments, and associated comorbidities to develop an effective treatment plan. This study aimed to analyze the feasibility and acceptability of a pre-visit clinical questionnaire aimed at improving communication and pain care.

Chronic ethanol alters adrenergic receptor gene expression and produces cognitive deficits in male mice.

Hyperkateifia and stress-induced alcohol cravings drive relapse in individuals with alcohol use disorder (AUD). The brain stress signal norepinephrine (also known as noradrenaline) tightly controls cognitive and affective behavior and was thought to be broadly dysregulated with AUD. The locus coeruleus (LC) is a major source of forebrain norepinephrine, and it was recently discovered that the LC sends distinct projections to addiction-associated regions suggesting that alcohol-induced noradrenergic changes may be more brain region-specific than originally thought. Here we investigated whether ethanol dependence alters adrenergic receptor gene expression in the medial prefrontal cortex (mPFC) and central amgydala (CeA), as these regions mediate the cognitive impairment and negative affective state of ethanol withdrawal. We exposed male C57BL/6J mice to the chronic intermittent ethanol vapor-2 bottle choice paradigm (CIE-2BC) to induce ethanol dependence, and assessed reference memory, anxiety-like behavior and adrenergic receptor transcript levels during 3-6 days of withdrawal. Dependence bidirectionally altered mouse brain α1 and β receptor mRNA levels, potentially leading to reduced mPFC adrenergic signaling and enhanced noradrenergic influence over the CeA. These brain region-specific gene expression changes were accompanied by long-term retention deficits and a shift in search strategy in a modified Barnes maze task, as well as greater spontaneous digging behavior and hyponeophagia. Current clinical studies are evaluating adrenergic compounds as a treatment for AUD-associated hyperkatefia, and our findings can contribute to the refinement of these therapies by increasing understanding of the specific neural systems and symptoms that may be targeted.

Role of Cardiopulmonary Exercise Testing in Predicting Perioperative Outcomes in Cancer Patients Undergoing Thoracoabdominal Surgeries; An Observational Cohort Study.

The cancer patients are at a high risk of developing perioperative complications. Cardiopulmonary exercise testing (CPET) is a non-invasive, perioperative risk stratification tool that predicts perioperative morbidity and mortality. Prior literature has concluded that CPET has a valuable role in predicting post-operative complications in major surgical procedures. However, the data on the effectiveness of CPET in evaluating the perioperative risk in cancer-specific populations are limited. This study assessed the usefulness of CPET in perioperative risk stratification of patients with thoracoabdominal cancer who underwent elective major thoracoabdominal surgeries.

Talking about inequities: A comparative analysis of COVID-19 narratives in the UK, US, and Brazil.

Disproportionate mortality and morbidity burdens of the COVID-19 pandemic and coinciding media coverage of public acts of violence perpetrated against people of color in 2020 precipitated reckonings with structural inequities in global, national, and local contexts. This cross-country comparative analysis aims to describe how people voice and make sense race, racism, and privilege in their experiences with COVID-19 infection in the United States, United Kingdom, and Brazil. Anchored by continuous reflection on our individual and collective positionality, we conducted an inductive comparative analysis conceptually situated in intersectionality and critical race theory. Countries used a shared qualitative methodology to collect and analyze 166 narratives of people with experience of COVID-19 infection from 2020 to 2023. We selected 19 cases that illustrate cross-national differences in peoples' acknowledgment and narration of structural privilege and disadvantage in their observations of COVID-19 in their countries and in their personal experiences. People in the US had the most fluency with voicing race directly. In Brazil, while some respondents (especially younger people) demonstrated high racial consciousness, others struggled to identify and talk about racial relationships. In the UK, people voiced racial identifications, though often within white norms of politeness and an accompanying sense of discomfort. The findings overall illustrate moments the interview becomes or does not become a space for voicing social categories and systemic underpinnings of difference in COVID-19 infections and healthcare experiences. We reflect on cross-country differences in historical and contemporary racialized discourse and elaborate on implications of focusing on voicing in qualitative research.

Pre- and Post-Sexual Maturity Liver-specific ERα Knockout Does Not Impact Hepatic Mitochondrial Function.

Compared with males, premenopausal women and female rodents are protected against hepatic steatosis and present with higher functioning mitochondria (greater hepatic mitochondrial respiration and reduced H

The promise and challenge of spatial omics in dissecting tumour microenvironment and the role of AI.

Growing evidence supports the critical role of tumour microenvironment (TME) in tumour progression, metastases, and treatment response. However, the

The chromosomal instability 25 gene signature is identified in clear cell renal cell carcinoma and serves as a predictor for survival and Sunitinib response.

Chromosomal instability (CIN) is a cancer hallmark and it is difficult to directly measure its phenotype, while a CIN25 gene signature was established to do so in several cancer types. However, it is currently unclear whether there exists this signature in clear cell renal cell carcinoma (ccRCC), and if so, which biological and clinical implications it has.

A pan-cancer analysis of ABI3BP: a potential biomarker for prognosis and immunoinfiltration.

ABI Family Member 3 Binding Protein (ABI3BP) is an extracellular matrix protein that affects the carcinogenesis of lung and esophageal cancer. However, the relevance of ABI3BP in different forms of cancer is uncertain.

Quantitative proteomic studies addressing unmet clinical needs in sarcoma.

Sarcoma is a rare and complex disease comprising over 80 malignant subtypes that is frequently characterized by poor prognosis. Challenges in clinical management include uncertainties in diagnosis and disease classification, limited prognostic and predictive biomarkers, incompletely understood disease heterogeneity among and within subtypes, lack of effective treatment options, and limited progress in identifying new drug targets and novel therapeutics. Proteomics refers to the study of the entire complement of proteins expressed in specific cells or tissues. Advances in proteomics have included the development of quantitative mass spectrometry (MS)-based technologies which enable analysis of large numbers of proteins with relatively high throughput, enabling proteomics to be studied on a scale that has not previously been possible. Cellular function is determined by the levels of various proteins and their interactions, so proteomics offers the possibility of new insights into cancer biology. Sarcoma proteomics therefore has the potential to address some of the key current challenges described above, but it is still in its infancy. This review covers key quantitative proteomic sarcoma studies with findings that pertain to clinical utility. Proteomic methodologies that have been applied to human sarcoma research are briefly described, including recent advances in MS-based proteomic technology. We highlight studies that illustrate how proteomics may aid diagnosis and improve disease classification by distinguishing sarcoma histologies and identify distinct profiles within histological subtypes which may aid understanding of disease heterogeneity. We also review studies where proteomics has been applied to identify prognostic, predictive and therapeutic biomarkers. These studies traverse a range of histological subtypes including chordoma, Ewing sarcoma, gastrointestinal stromal tumors, leiomyosarcoma, liposarcoma, malignant peripheral nerve sheath tumors, myxofibrosarcoma, rhabdomyosarcoma, synovial sarcoma, osteosarcoma, and undifferentiated pleomorphic sarcoma. Critical questions and unmet needs in sarcoma which can potentially be addressed with proteomics are outlined.

B-cell lymphoblastic lymphoma following intravenous BNT162b2 mRNA booster in a BALB/c mouse: A case report.

Unprecedented immunization campaigns have been rolled out worldwide in an attempt to contain the ongoing COVID-19 pandemic. Multiple vaccines were brought to the market, among two utilizing novel messenger ribonucleic acid technology. Despite their undisputed success in decreasing COVID-19-associated hospitalizations and mortality, various adverse events have been reported. The emergence of malignant lymphoma is one of such rare adverse events that has raised concern, although an understanding of the mechanisms potentially involved remains lacking. Herein, we present the first case of B-cell lymphoblastic lymphoma following intravenous high-dose mRNA COVID-19 vaccination (BNT162b2) in a BALB/c mouse. Two days following booster vaccination (

Molecular mechanisms of osteosarcoma metastasis and possible treatment opportunities.

In osteosarcoma patients, metastasis of the primary cancer is the leading cause of death. At present, management options to prevent metastasis are limited and non-curative. In this study, we review the current state of knowledge on the molecular mechanisms of metastasis and discuss promising new therapies to combat osteosarcoma metastasis. Genomic and epigenomic changes, metabolic reprogramming, transcription factors, dysregulation of physiologic pathways, and alterations to the tumor microenvironment are some of the changes reportedly involved in the regulation of osteosarcoma metastasis. Key factors within the tumor microenvironment include infiltrating lymphocytes, macrophages, cancer-associated fibroblasts, platelets, and extracellular components such as vesicles, proteins, and other secreted molecules. We conclude by discussing potential osteosarcoma-limiting agents and their clinical studies.

Non-small cell lung cancer patients treated with Anti-PD1 immunotherapy show distinct microbial signatures and metabolic pathways according to progression-free survival and PD-L1 status.

Due to the high variance in response rates concerning anti-PD1 immunotherapy (IT), there is an unmet need to discover innovative biomarkers to predict immune checkpoint inhibitor (ICI)-efficacy. Our study included 62 Caucasian advanced-stage non-small cell lung cancer (NSCLC) patients treated with anti-PD1 ICI. Gut bacterial signatures were evaluated by metagenomic sequencing and correlated with progression-free survival (PFS), PD-L1 expression and other clinicopathological parameters. We confirmed the predictive role of PFS-related key bacteria with multivariate statistical models (Lasso- and Cox-regression) and validated on an additional patient cohort (

M2 macrophage-derived exosomes suppress tumor intrinsic immunogenicity to confer immunotherapy resistance.

T-cell-based immune checkpoint blockade therapy (ICB) can be undermined by local immunosuppressive M2-like tumor-associated macrophages (TAMs). However, modulating macrophages has proved difficult as the molecular and functional features of M2-TAMs on tumor growth are still uncertain. Here we reported that immunosuppressive M2 macrophages render cancer cells resistant to CD8

Effectiveness of COVID-19 Vaccination Against SARS-CoV-2 Omicron Variant Infection and Symptoms - China, December 2022-February 2023.

A considerable percentage of the population has received both primary and booster vaccinations, which could potentially provide protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron infections and related symptoms.

Discovery of a Novel Series of Potent SHP2 Allosteric Inhibitors.

Src homology 2-containing protein tyrosine phosphatase 2 (SHP2) is the first reported nonreceptor oncogenic tyrosine phosphatase connecting multiple signal transduction cascades and exerting immunoinhibitory function through the PD-1 checkpoint receptor. As part of a drug discovery program aimed at obtaining novel allosteric SHP2 inhibitors, a series of pyrazopyrazine derivatives bearing an original bicyclo[3.1.0]hexane basic moiety on the left-hand side region of the molecule were identified. We report herein the discovery process, the in vitro pharmacological profile, and the early developability features of compound

Synthesis of Artesunic Acid-Coumarin Hybrids as Potential Antimelanoma Agents.

Current therapy against melanoma relies on surgical treatment or, in alternative, on conventional drug therapy. Often these therapeutic agents are ineffective due to the development of resistance phenomena. For this purpose, chemical hybridization emerged as an effective strategy to overcome the development of drug resistance. In this study, a series of molecular hybrids were synthesized combining the sesquiterpene artesunic acid with a panel of phytochemical coumarins. Cytotoxicity, antimelanoma effect, and cancer selectivity of the novel compounds were evaluated by MTT assay on primary and metastatic cells and on healthy fibroblasts as a reference. The two most active compounds showed lower cytotoxicity and higher activity against metastatic melanoma than paclitaxel and artesunic acid. Further tests, including cellular proliferation, apoptosis, confocal microscopy, and MTT analyses in the presence of an iron chelating agent, were conducted with the aim of tentatively addressing the mode of action and the pharmacokinetic profile of selected compounds.

Novel Imidazotriazine Derivatives as IL-17 Modulators for Treating Inflammatory and Autoimmune Disorders.

Provided herein are novel imidazotriazine derivatives used as IL-17 modulators, their pharmaceutical compositions, the use of such compounds in treating inflammatory and autoimmune disorders, and processes for preparing such compounds.

Novel Serine-Arginine Protein Kinase Inhibitors for Treating Cancer.

Described herein are novel serine-arginine protein kinase (SRPK) inhibitors, their pharmaceutical compositions, the use of such compounds in treating cancer, and processes for preparing such compounds.

Novel Tricyclic Compounds as KRAS Inhibitors for Treating Cancer.

Provided herein are novel tricyclic compounds as KRAS inhibitors, pharmaceutical compositions, use of such compounds in treating cancer and processes for preparing such compounds.

Rational Design of Highly Potent and Selective Covalent MAP2K7 Inhibitors.

The mitogen-activated protein kinase signaling cascade is conserved across eukaryotes, where it plays a critical role in the regulation of activities including proliferation, differentiation, and stress responses. This pathway propagates external stimuli through a series of phosphorylation events, which allows external signals to influence metabolic and transcriptional activities. Within the cascade, MEK, or MAP2K, enzymes occupy a molecular crossroads immediately upstream to significant signal divergence and cross-talk. One such kinase, MAP2K7, also known as MEK7 and MKK7, is a protein of great interest in the molecular pathophysiology underlying pediatric T cell acute lymphoblastic leukemia (T-ALL). Herein, we describe the rational design, synthesis, evaluation, and optimization of a novel class of irreversible MAP2K7 inhibitors. With a streamlined one-pot synthesis, favorable

Anatomical spatial distribution of the bilateral coronary ostia and aortic valve commissures relative to the aortic arch.

Previous studies have shown the importance of achieving commissural alignment during transcatheter aortic valve replacement (TAVR). However, the anatomical spatial distribution of the bilateral coronary ostia and aortic valve commissures relative to the aortic arch is still unknown. This study aimed to evaluate this anatomical relationship.

Improved diagnostic yield of symptom association probability involving only cough for gastroesophageal reflux-induced chronic cough.

Use of symptom association probability (SAP) is recommended for identifying gastroesophageal reflux-induced chronic cough (GERC). This study aimed to compare the diagnostic yield of SAPs involving only cough (C-SAP) or total symptoms (T-SAP) for GERC identification.

Bufalin suppresses esophageal squamous cell carcinoma progression by activating the PIAS3/STAT3 signaling pathway.

Esophageal cancer, especially esophageal squamous cell carcinoma (ESCC), is a common malignant tumor of the digestive tract. Bufalin is an effective anti-tumor compound. However, little is known about the regulatory mechanisms of Bufalin in ESCC. To investigate the effect and molecular mechanism of Bufalin on the proliferation, migration and invasion of ESCC cells will provide a more reliable basis for the application of Bufalin in clinical tumor therapy.

miR-183-5p regulates ECM and EMT to promote non-small cell lung cancer progression by targeting LOXL4.

Non-small cell lung cancer (NSCLC) progression is mediated by changes in gene expression induced by microRNAs. However, the underlying mechanisms remain to be elucidated. In this study, we investigated the roles of miR-183-5p and its target gene in lung cancer development.

Establishment and validation of a long-term prognosis prediction model for patients with non-small cell lung cancer.

The incidence of non-small cell lung cancer ranks second among malignant tumors, while the mortality rate ranks first. We established a prediction model for the long-term prognosis of lung cancer patients to accurately identify patients with a high risk of postoperative death and provide a theoretical basis for improving the prognosis of patients with non-small cell lung cancer.

Sepsis-related immunosuppression: a bibliometric analysis.

Sepsis is one of the main causes of death in critically ill patients. Immunosuppression was involved deeply in the process of sepsis. The status of research on sepsis-related immunosuppression remains unclear. In this study, a bibliometric analysis was conducted to provide a preliminarily analysis of the current research status in sepsis-related immunosuppression.

Agitated saline with 10% blood increases number and stability of microbubbles in detection right-to-left shunt by contrast-enhanced transcranial Doppler: an

Agitated saline (AS) with blood has been shown to have good tolerance and increased efficacy when used in contrast-enhanced transcranial Doppler (c-TCD) to detect right-to-left shunt (RLS). However, little is known about the effects of blood volume on c-TCD results. Our study investigated the characterization of AS with different blood volumes

A bioinformatics analysis of the susceptibility genes in Stanford type A aortic dissection.

The expression levels of long noncoding RNAs (lncRNAs) and mRNAs in human acute Stanford type A aortic dissecting aneurysm and normal active vascular tissues were compared using the array lncRNA/mRNA expression profile chip technology.

Hypothyroidism induced by immune checkpoint inhibitors combined with antiangiogenic agents is associated with higher body mass index.

Recent studies have reported that the combination of immune checkpoint inhibitors (ICIs) and antiangiogenic agents could be a promising therapeutic strategy for advanced non-small cell lung cancer (NSCLC). However, both ICIs and antiangiogenic agents are associated with endocrine dysfunctions, mainly hypothyroidism. The risk of hypothyroidism is potentially increased with the combination of ICIs and antiangiogenic agents. This study aimed to investigate the incidence and risk factors of hypothyroidism in patients receiving combination therapy.

Developing & integrating a mobile application tool into a survivorship clinic for esophageal cancer patients.

Esophageal cancer (EC) patients are living longer due to enhanced screening and novel therapeutics, however, the post-esophagectomy long-term management remains challenging for patients, caregivers, and providers. Patients experience significant morbidity and have difficulty managing symptoms. Providers struggle to manage symptoms, affecting patients' quality of life and complicating care coordination between surgical teams and primary care providers. To address these patient unique needs and create a standardized method for evaluating patient reported long-term outcomes after esophagectomy for EC, our team developed the Upper Digestive Disease Assessment tool, which evolved to become a mobile application. This mobile application is designed to monitor symptom burden, direct assessment, and quantify data for patient outcome analysis after foregut (upper digestive) surgery, including esophagectomy. It is available to the public and enables virtual and remote access to survivorship care. Patients using the Upper Digestive Disease Application (UDD App) must consent to enroll, agree to terms of use, and acknowledge use of health-related information prior to gaining access to the UDD App. The results of patients scores can be utilized for triage and assessment. Care pathways can guide management of severe symptoms in a scalable and standardized method. Here we describe the history, process, and methodology for developing a patient-centric remote monitoring program to improve survivorship after EC. Programs like this that facilitate patient-centered survivorship should be an integral part of comprehensive cancer patient care.

A comprehensive clinical evaluation of first-line drugs for ALK-positive advanced non-small cell lung cancer.

Anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs) are mainly used in the treatment of ALK-positive advanced non-small cell lung cancer (NSCLC), but a comprehensive clinical evaluation of ALK-TKIs is lacking. Hence, a comparison of ALK-TKIs for first-line treatment of ALK-positive advanced NSCLC is essential to provide rational drug use and a basis for improving national policies and systems.

Dysregulated expression of microRNA involved in resistance to osimertinib in

An increasing amount of evidence has confirmed that the altered expression of microRNAs (miRNAs) is critical to the mechanism underlying primary and even acquired resistance to tyrosine kinase inhibitors (TKIs). However, studies on the linkage between the altered miRNAs expression and osimertinib resistance are few, and the effect of miRNAs in this context is still unclear. In the light of this, we hypothesized that the differential expression of multiple miRNAs is the driver in the osimertinib resistance process. Thus, the aim of our study was to find differentially expressed miRNAs in non-small cell lung cancer cells resistant to osimertinib.

Impact of delayed transition off intravenous vasoactive agents for aortic dissection on intensive care unit length of stay.

The initial management of acute aortic dissection centers around rapid control of blood pressure and heart rate, commonly requiring initiation of continuous intravenous (IV) antihypertensive agents and intensive care unit (ICU) admission. However, there is limited guidance for when and how to transition off IV infusions to enteral agents, potentially extending ICU length of stay (LOS) in stable patients who are otherwise ready for floor transfer. The objective of this study is to compare the impact of rapid

Store-operated calcium entry enhances the polarization and chemotaxis of neutrophils in the peripheral venous blood of patients with bronchial asthma by upregulating ERM protein.

Neutrophils can be rapidly recruited and are largely abundant in the airways of patients with asthma. However, whether the polarization and chemotaxis of neutrophils in patients with asthma are abnormal, and the underlying mechanisms, have not been clarified. Pseudopods formation is the initial step of neutrophils' polarization, ezrin, radixin and moesin (ERM) play an important role in the polarization of neutrophils. As an important signaling molecule in cell physiological processes, Ca2+ has been shown to be involved in the polarity changes of neutrophils. This study thus aimed to explore polarization and chemotaxis of neutrophils in patients with asthma and the underlying mechanism.

Establishment of an orthotopic model of lung cancer by transthoracic lung puncture using tumor fragments.

Orthotopic models of lung cancer have been widely utilized, and the purpose of this study was to demonstrate the viability of our proposed modified modeling approach.

Characterization of Parental Knowledge on Early Child Sleep and Association with Child Sleep Quality: A Cross-Sectional Pilot Study in Chongqing, China.

Parental knowledge of child sleep is typically poor, and profiling of knowledge patterns has not been performed. In recent years, the Chinese government has issued a series of administrative and legal documents to promote guidance on family education and parenting knowledge. The purpose of this study was to characterize the pattern of parental sleep knowledge for 0~3-year-old children in Chongqing, China, and to examine the associations among the knowledge pattern, guidance channel, and sleep quality.

Endophytic fungi mediates production of bioactive secondary metabolites via modulation of genes involved in key metabolic pathways and their contribution in different biotechnological sector.

Endophytic fungi stimulate the production of an enormous number of bioactive metabolites in medicinal plants and affect the different steps of biosynthetic pathways of these secondary metabolites. Endophytic fungi possess a number of biosynthetic gene clusters that possess genes for various enzymes, transcription factors, etc., in their genome responsible for the production of secondary metabolites. Additionally, endophytic fungi also modulate the expression of various genes responsible for the synthesis of key enzymes involved in metabolic pathways of such as

Evaluation of Intralymphatic Immunotherapy in Allergic Rhinitis Patients: A Systematic Review and Meta-analysis.

Intralymphatic immunotherapy (ILIT) is short-course administration of allergen-specific immunotherapy (AIT). This study is aimed at assessing the clinical efficacy and safety of ILIT in patients with allergic rhinitis (AR).

Do Right, Be Bright: A Protocol on the Development of an Inter-Professional Health Intervention Model for Pre-School Children Through a Community-Based Service-Learning Initiative.

An inter-professional project with a collaborative endeavor between the programs of Dentistry, Nutrition and Medicine was carried out with the aim to emphasise oral health maintenance, making the right nutritional choices and effective hand washing among pre-school children. The purpose of this paper is to share a detailed description of the design, development process, implementation, and planned evaluation of an interprofessional school-based health promotion intervention model "Do Right, Be Bright". This model is part of a quasi-experimental study, targeting pre-school children as the "Targets of Change" through the empowerment of school teachers as the "Agents of Change". The program design was based on Bartholomew's Intervention Mapping Approach, which proposes a direction for developing a theory-based health promotion intervention and on the most extensively applied theories of health behavior, the Health Belief Model. Therefore, based on a thorough literature review and needs assessment, three key areas of needs were identified for the targeted preschool children: oral hygiene, hand hygiene and nutrition. The efficacy of this model will be pilot tested in a preschool in Kuala Lumpur Malaysia.

Psychological stress responses to a live performance by professional flamenco dancers.

Dance is a high demanding discipline that involves physiological and psychological pressures. The pressure increases when dancers perform in front of an audience that, on a physiological level, can generate hormonal responses similar to those of an athlete before a competition for social status. Low levels of testosterone (T) and high levels of cortisol (C) are related to a decrease in performance and an increase in the risk of injury. Therefore, this study sets out to analyse hormone response patterns in professional flamenco dance performances depending on whether the performances are completed successfully and whether there are differences by sex and professional category. Saliva specimens (2-5 ml) were taken from the participants before and after the performance. Samples were immunoassayed by duplicate to analyze momentary fluctuations in two hormones regularly used in studies with professional athletes. The results showed significant differences in solo dancers' T responses before and after the performance (

Lung Abscess and Pyothorax in Critically Ill COVID-19 Patients: A Single-Center Retrospective Study.

The mortality rate of patients with COVID-19 pneumonia requiring mechanical ventilation remains high. This study determined the percentage and characteristics of patients who developed lung abscesses or pyothorax and their mortality rates among adult patients with COVID-19 admitted to the ICU who required mechanical ventilation. Of the 64 patients with COVID-19 assessed, 30 (47%) developed ventilator-associated pneumonia (VAP), of whom 6 (20%) developed pyothorax or lung abscess. There were no statistically significant differences in patient characteristics, treatment after ICU admission, or outcomes between those with and without these complications, except for age. VAP complicated by Lung abscess or pyothorax was caused by a single organism, with

Diverged landscape of restaurant recovery from the COVID-19 pandemic in the United States.

The COVID-19 pandemic has imposed catastrophic impacts on the restaurant industry as a crucial socioeconomic sector that contributes to the global economy. However, the understanding of how the restaurant industry was recovered from COVID-19 remains underexplored. This study constructs a spatially explicit evaluation of the effect of COVID-19 on the restaurant industry in the US, drawing on the attributes of +200,000 restaurants from Yelp and +600 million individual-level restaurant visitations provided by SafeGraph from 1st January 2019 to 31st December 2021. We produce quantitative evidence of lost restaurant visitations and revenue amid the pandemic, the changes in the customers' origins, and the retained visitation law of human mobility-the number of restaurant visitations decreases as the inverse square of their travel distances-though such a distance-decay effect becomes marginal at the later pandemic. Our findings support policy makers to monitor economic relief and design place-based policies for economic recovery.

Mechanisms of Ganweikang Tablets against Chronic Hepatitis B: A Comprehensive Study of Network Analysis, Molecular Docking, and Chemical Profiling.

The hepatitis B virus (HBV) is one of the major viral infection problems worldwide in public health. The exclusive proprietary Chinese medicine Ganweikang (GWK) tablet has been marketed for years in the treatment of chronic hepatitis B (CHB). However, the pharmacodynamic material basis and underlying mechanism of GWK are not completely clear. This study is aimed at investigating the pharmacological mechanism of the GWK tablet in the treatment of CHB. The chemical ingredient information was obtained from the Traditional Chinese Medicine Database and Analysis Platform (TCMSP), Traditional Chinese Medicines Integrated Database (TCMID), and Shanghai Institute of Organic Chemistry of CAS. Ingredients and disease-related targets were defined by a combination of differentially expressed genes from CHB transcriptome data and open-source databases. Target-pathway-target (TPT) network analysis, molecular docking, and chemical composition analysis were adopted to further verify the key targets and corresponding active ingredients of GWK. Eight herbs of GWK were correlated to 330 compounds with positive oral bioavailability, and 199 correlated targets were identified. The TPT network was constructed based on the 146 enriched targets by KEGG pathway analysis, significantly associated with 95 pathways. Twenty-five nonvolatile components and 25 volatile components in GWK were identified in UPLC-QTOF/MS and GC-MS chromatograms. The key active ingredients of GWK include ferulic acid, oleanolic acid, ursolic acid, tormentic acid, 11-deoxyglycyrrhetic acid, dibenzoyl methane, anisaldehyde, wogonin, protocatechuic acid, psoralen, caffeate, dimethylcaffeic acid, vanillin,

NT-proBNP in Different Patient Groups of COPD: A Systematic Review and Meta-Analysis.

NT-proBNP, a peptide biomarker synthesized and secreted by cardiomyocytes in response to cardiac load, has gained attention in recent years for its potential role in respiratory diseases. Chronic Obstructive Pulmonary Disease (COPD), a chronic and progressive inflammatory condition affecting the respiratory system, is frequently associated with comorbidities involving the cardiovascular system. Consequently, the aim of this systematic review and meta-analysis was to evaluate the variations in NT-proBNP levels across distinct patient groups with COPD and establish a foundation for future investigations into the precise clinical significance of NT-proBNP in COPD.

Reasons for Admission and Outcome to an Acute Palliative Care Unit in Patients with Advanced Malignancy in a Cancer Hospital.

The alleviation of suffering is a primary goal of palliative care team for patients with terminal cancer. In some cases, patients experience symptoms requiring inpatient care. The purpose of this investigation was to assess the clinical presentation and outcomes of hospitalisation in patients that were admitted to the acute palliative care service.

Liver cystic echinococcosis: a parasitic review.

Liver cystic echinococcosis (CE), known as hydatid disease, is caused by the tapeworm

The genetics of specific cognitive abilities.

Most research on individual differences in performance on tests of cognitive ability focuses on general cognitive ability (g), the highest level in the three-level Cattell-Horn-Carroll (CHC) hierarchical model of intelligence. About 50% of the variance of g is due to inherited DNA differences (heritability) which increases across development. Much less is known about the genetics of the middle level of the CHC model, which includes 16 broad factors such as fluid reasoning, processing speed, and quantitative knowledge. We provide a meta-analytic review of 747,567 monozygotic-dizygotic twin comparisons from 77 publications for these middle-level factors, which we refer to as specific cognitive abilities (SCA), even though these factors are not independent of g. Twin comparisons were available for 11 of the 16 CHC domains. The average heritability across all SCA is 56%, similar to that of g. However, there is substantial differential heritability across SCA and SCA do not show the developmental increase in heritability seen for g. We also investigated SCA independent of g (SCA.g). A surprising finding is that SCA.g remain substantially heritable (53% on average), even though 25% of the variance of SCA that covaries with g has been removed. Our review highlights the need for more research on SCA and especially on SCA.g. Despite limitations of SCA research, our review frames expectations for genomic research that will use polygenic scores to predict SCA and SCA.g. Genome-wide association studies of SCA.g are needed to create polygenic scores that can predict SCA profiles of cognitive abilities and disabilities independent of g.

Safety and feasibility of carboplatin and paclitaxel in combination with nintedanib for non-small cell lung cancer patients with idiopathic pulmonary fibrosis: a prospective pilot study.

Idiopathic pulmonary fibrosis (IPF) is a risk factor for mortality in patients with lung cancer. Nintedanib has been known to slow down the decline of lung function and reduce IPF exacerbation. We aimed to explore the feasibility of adding nintedanib to chemotherapy for non-small cell lung cancer (NSCLC) patients with IPF.

Development of a cuproptosis-related signature for prognosis prediction in lung adenocarcinoma based on WGCNA.

Cuproptosis is a novel mitochondrial respiration-dependent cell death mechanism induced by copper that can kill cancer cells via copper carriers in cancer therapy. However, the clinical significance and prognostic value of cuproptosis in lung adenocarcinoma (LUAD) remains unclear.

False positivity in break apart fluorescence in-situ hybridization due to polyploidy.

In-situ hybridization (ISH) is a diagnostic tool in the detection of chromosomal anomalies, which has important implications for diagnosis, classification and prediction of cancer therapy in various diseases. Certain thresholds of number of cells showing an aberrant pattern are commonly used to declare a sample as positive for genomic rearrangements. The phenomenon of polyploidy can be misleading in the interpretation of break apart fluorescence in-situ hybridization (FISH). The aim of this study is to investigate the impact of cell size and ploidy on FISH results.

Circ_0087378 intensifies the malignant behavior of non-small cell lung cancer cells

Circular RNA hsa_circ_0087378 (circ_0087378) has been found to have different functions in different cancer types. However, its function in non-small cell lung cancer (NSCLC) remains unclear. This study revealed the effect of circ_0087378 on the malignant behavior of NSCLC cells

Cross-sectional Exploration of the Relationship Between Glutamate Abnormalities and Tic Disorder Severity Using Proton Magnetic Resonance Spectroscopy.

Glutamate (Glu) has been reported to be closely related to the pathophysiology of Tic Disorders (TD). By using proton magnetic resonance spectroscopy (

Current literature review on the tumor immune micro-environment, its heterogeneity and future perspectives in treatment of advanced non-small cell lung cancer.

Immune checkpoint inhibitors (ICI) were a major clinical advancement that provided an opportunity to improve the prognosis of patients with non-small cell lung cancer (NSCLC). However, programmed death-ligand-1 (PD-L1) expression does not sufficiently predict ICI efficacy in NSCLC patients. In recent studies, the tumor immune microenvironment (TIME) was shown to have a central role in lung cancer progression and to affect clinical outcome of patients diagnosed with lung cancer. As development of new therapeutic targets to overcome ICI resistance is a priority, understanding the TIME is important. Recently, a series of studies was conducted to target each component of TIME to improve efficacy of cancer treatment. In this review, important features related to TIME, its heterogeneity and current trends in treatment targeting the component of TIME are discussed.

Methylprednisolone alleviates cognitive functions through the regulation of neuroinflammation in Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease and linked to abnormal deposition of amyloid-β (Aβ), neurofibrillary tangles (NFTs), synaptic dysfunction, and neuroinflammation. Despite significant progress in unravelling the pathogenesis of AD, currently main therapeutic interventions is limited to symptomatic alleviation. Methylprednisolone (MP), a synthetic glucocorticoid, is recognized for its extensive anti-inflammatory properties. Our study assessed the neuroprotective effect of MP (25 mg/kg) administration to an Aβ

Identification of multiple novel susceptibility genes associated with autoimmune thyroid disease.

Autoimmune thyroid disease (AITD) is induced by various factors, including inheritability, which regulates gene expression. Multiple loci correlated with AITD have been discovered utilizing genome-wide association studies (GWASs). Nevertheless, demonstrating the biological relevance and function of these genetic loci is difficult.

TLR4 activation by lysozyme induces pain without inflammation.

Mostly, pain has been studied in association with inflammation, until recent studies which indicate that during bacterial infections, pain mechanisms could be independent of the inflammation. Chronic pain can sustain long after the healing from the injury, even in the absence of any visible inflammation. However, the mechanism behind this is not known. We tested inflammation in lysozyme-injected mice foot paw. Interestingly, we observed no inflammation in mice foot paw. Yet, lysozyme injections induced pain in these mice. Lysozyme induces pain in a TLR4-dependent manner and TLR4 activation by its ligands such as LPS leads to inflammatory response. We compared the intracellular signaling of MyD88 and TRIF pathways upon TLR4 activation by lysozyme and LPS to understand the underlying mechanism behind the absence of an inflammatory response upon lysozyme treatment. We observed a TLR4 induced selective TRIF and not MyD88 pathway activation upon lysozyme treatment. This is unlike any other previously known endogenous TLR4 activators. A selective activation of TRIF pathway by lysozyme induces weak inflammatory cytokine response devoid of inflammation. However, lysozyme activates glutamate oxaloacetate transaminase-2 (GOT2) in neurons in a TRIF-dependent manner, resulting in enhanced glutamate response. We propose that this enhanced glutaminergic response could lead to neuronal activation resulting in pain sensation upon lysozyme injections. Collectively we identify that TLR4 activation by lysozyme can induce pain in absence of a significant inflammation. Also, unlike other known TLR4 endogenous activators, lysozyme does not activate MyD88 signaling. These findings uncover a mechanism of selective activation of TRIF pathway by TLR4. This selective TRIF activation induces pain with negligible inflammation, constituting a chronic pain homeostatic mechanism.

Meniscal extrusion: risk factors and diagnostic tools to predict early osteoarthritis.

Meniscal extrusion (ME) is strongly correlated with cartilage wear and osteoarthritis (OA), be-cause of the altered kinematic and the decreased contact area between the tibia and femur. The aim of this narrative review is to analyze the process of ME, focusing on the possible causes, and to evaluate the correlation between ME and knee OA, in order to provide early diagnosis and treatments. Studies written in English that analyzed the causes of ME, provided indications re-garding diagnosis and treatment, and evaluated the relation between ME and early OA were in-cluded. Injuries, degeneration of the meniscal substance and meniscus root tears are associated with significantly increased ME. An extruded meniscus could be a manifestation of other pa-thologies such as disruption of coronary ligaments, cartilage loss, knee malalignment, ligament injuries, or OA. ME is strongly associated with osteoarthritis features, particularly with bone marrow lesion and cartilage damage. Magnetic resonance imaging represents the gold standard for the detection of ME. The severity of the medial meniscus extrusion may also affect healing af-ter repair, and meniscus extrusion is not completely reduced by meniscus posterior root tear re-pair. In this study, we proved that ME represents an important risk factor for early knee OA. We provided alternative theories of ME, such as meniscal fibers injury first and "dynamic extrusion of the menisci". The phenomenon of aging has been described as a new concept in the etiology of ME. Finally, we stated all the main techniques and characteristics of the diagnostic process, as well as the current knowledge in the therapeutic field.

Antioxidant activity of novel nitrogen scaffold with docking investigation and correlation of DFT stimulation.

Heterocyclic scaffolds are frequently employed in drug development to treat a variety of conditions, including cancers. These substances have the ability to engage covalently or non-covalently with particular residues in the target proteins, inhibiting them. In this study, the formation of N-, S-, and O-containing heterocycles by the interaction of chalcone with nitrogen-containing nucleophiles such as hydrazine, hydroxyl amine, guanidine, urea, and aminothiourea was explored. FT-IR, UV-visible, NMR, and mass spectrometric studies were used to confirm the heterocyclic compounds that were produced. These substances were tested for their antioxidant activity by their capacity to scavenge the artificial radicals 2,2-diphenyl-1-picrylhydrazyl (DPPH). The strongest antioxidant activity was demonstrated by compound 3 (IC

Integrated pipeline for ultrasensitive protein detection in cancer nanomedicine.

Although nanotechnologies have attractive attributes in cancer therapy, their full potential has yet to be realized due to challenges in their translation to clinical settings. The evaluation of cancer nanomedicine efficacy in preclinical

A new frontier for fat: dietary palmitic acid induces innate immune memory.

Dietary saturated fats have recently been appreciated for their ability to modify innate immune cell function, including monocytes, macrophages, and neutrophils. Many dietary saturated fatty acids (SFAs) embark on a unique pathway through the lymphatics following digestion, and this makes them intriguing candidates for inflammatory regulation during homeostasis and disease. Specifically, palmitic acid (PA) and diets enriched in PA have recently been implicated in driving innate immune memory in mice. PA has been shown to induce long-lasting hyper-inflammatory capacity against secondary microbial stimuli in vitro and in vivo, and PA-enriched diets alter the developmental trajectory of stem cell progenitors in the bone marrow. Perhaps the most relevant finding is the ability of exogenous PA to enhance clearance of fungal and bacterial burdens in mice; however, the same PA treatment enhances endotoxemia severity and mortality. Westernized countries are becoming increasingly dependent on SFA-enriched diets, and a deeper understanding of SFA regulation of innate immune memory is imperative in this pandemic era.

Conceptualizing teachers' interactions with resources in crossing languages and cultures.

This paper introduces this special issue aiming to deepen and extend research on mathematics teachers' work, from a resource perspective, by taking language and culture into account, and exploring two questions: How are teachers' interactions with resources interpreted and modeled across contexts? And, What challenges and insights emerge through recent efforts to engage these models in cross-cultural (and linguistic) research? The fields of resources, language and culture in mathematics education are each extensive, and we do not attempt to survey comprehensively across them. We have chosen instead to propose three approaches on resources in mathematics teachers' work that developed somewhat contemporaneously from three different countries with differing linguistic, curricular, and social contexts, corresponding to the work of the three guest editors. The models developed through these approaches are driven by the educational, and so cultural and material conditions of the time and the location of each author, and allow us to propose preliminary answers to our two guiding questions. We then move to pull the threads from these models together, and discuss the contributions to this Special Issue. This results in more robust and nuanced responses to our questions, and in identifying two themes that emerge from research that sit at the convergence of studies of teachers' interactions with resources, languages, and cultures: an invisibility-visibility dialectic and a local-global tension. Finally, this study leads us to consider a new region of mathematics education research.

Bacteriological Quality and Antimicrobial Resistant Patterns of Foodborne Pathogens Isolated from Commonly Vended Street Foods in Arba Minch Town, Southern Ethiopia.

Ready-to-eat foods sold by street vendors act as potential sources for the spread of various foodborne infectious diseases. Thus, local determination of the level of foodborne bacterial pathogens and their antimicrobial resistance pattern is essential.

Association between HSP-Specific T-Cell Counts and Retinal Nerve Fiber Layer Thickness in Patients with Primary Open-Angle Glaucoma.

Previous laboratory reports implicate heat shock protein (HSP)-specific T-cell responses in glaucoma pathogenesis; here, we aimed to provide direct clinical evidence by correlating systemic HSP-specific T-cell levels with glaucoma severity in patients with primary open-angle glaucoma (POAG).

Contrast- and noise-dependent spatial resolution measurement for deep convolutional neural network-based noise reduction in CT using patient data.

Deep convolutional neural network (DCNN)-based noise reduction methods have been increasingly deployed in clinical CT. Accurate assessment of their spatial resolution properties is required. Spatial resolution is typically measured on physical phantoms, which may not represent the true performance of DCNN in patients as it is typically trained and tested with patient images and the generalizability of DNN to physical phantoms is questionable. In this work, we proposed a patient-data-based framework to measure the spatial resolution of DCNN methods, which involves lesion- and noise-insertion in projection domain, lesion ensemble averaging, and modulation transfer function measurement using an oversampled edge spread function from the cylindrical lesion signal. The impact of varying lesion contrast, dose levels, and CNN denoising strengths were investigated for a ResNet-based DCNN model trained using patient images. The spatial resolution degradation of DCNN reconstructions becomes more severe as the contrast or radiation dose decreased, or DCNN denoising strength increased. The measured 50%/10% MTF spatial frequencies of DCNN with highest denoising strength were (-500 HU:0.36/0.72 mm

Winner and losers: examining biotic interactions in forbs and grasses in response to changes in water and temperature in a semi-arid grassland.

Warming and changing water amount can alter the outcome of biotic interactions in native and exotic plants between facilitation and competition. Exotic plants may adapt better to changing environmental conditions, such that they may compete better than native plants. We conducted competition trials for four plant species, two exotic forbs (

Spatiotemporal variation of chasmogamy and cleistogamy in a native perennial grass: fecundity, reproductive allocation and allometry.

It is difficult to assess the relative variability or stability of chasmogamous (CH) and cleistogamous (CL) reproduction in perennial herbs with mixed mating because long-term data in natural populations are unavailable. Here, the aim was to quantify and compare spatial (between-habitat) and temporal (among-year) variation in CH and CL reproduction over 5 years in two subpopulations of the native perennial grass

JADPRO Live 2022: Reaching the Peak of Practice.

This special issue of JADPRO includes summaries of select educational sessions presented at JADPRO Live 2022.

Managing the Patient With Multiple Primary Tumors.

Multiple primaries are defined as more than one synchronous or metachronous cancer in the same individual. They can pose challenges to clinicians, as the goal is to find an anticancer therapy strategy that covers both cancer types without increased toxicity or drug interactions, and does not negatively impact a patient's overall outcome. At JADPRO Live 2022, presenters tackled this complicated topic by reviewing diagnostic criteria, epidemiology, and risk factors, demonstrating the prioritization of treatment, and discussing the role of the advanced practitioner in collaborative, interdisciplinary management of the patient with multiple primary tumors.

Medical Aid in Dying: Ethical and Practical Issues.

At JADPRO Live 2022, Jonathan Treem, MD, of the University of Colorado Palliative Care, explained medical aid in dying in order to prepare advanced practitioners to feel confident to counsel a patient who inquiries about aid in dying. He explained the law and protocol for participation, the history, ethics, and data behind the intervention, and steps for what is required. Finally, Dr. Treem discussed ethical considerations that may arise as patients and clinicians consider these types of interventions.

Uncovering and Addressing Implicit Bias in Oncology.

Implicit bias affects patient care every day, and not just in oncology. It impacts decision-making in already vulnerable populations such as the historically marginalized racial and ethnic groups, the LGBTQI+ population, patients with disabilities, and patients with low socioeconomic status or low health literacy. At JADPRO Live 2022 in Aurora, Colorado, panelists took a deep look at implicit bias and its impact on health inequities. They then discussed best practices for increasing equity and representation in clinical trials, ways to facilitate equitable communication and interactions with patients, and finally shared steps that advanced practitioners can take to minimize the impact of implicit bias.

Multi-stage optimal dynamic treatment regimes for survival outcomes with dependent censoring.

We propose a reinforcement learning method for estimating an optimal dynamic treatment regime for survival outcomes with dependent censoring. The estimator allows the failure time to be conditionally independent of censoring and dependent on the treatment decision times, supports a flexible number of treatment arms and treatment stages, and can maximize either the mean survival time or the survival probability at a certain time-point. The estimator is constructed using generalized random survival forests and can have polynomial rates of convergence. Simulations and analysis of the Atherosclerosis Risk in Communities study data suggest that the new estimator brings higher expected outcomes than existing methods in various settings.

Comparison of lesion detection and conspicuity between narrow-angle and wide-angle digital breast tomosynthesis for dense and non-dense breasts.

Digital breast tomosynthesis (DBT) has been shown to improve both sensitivity and specificity for breast cancer detection compared to full-field digital mammography. However, its performance could be limited for patients with dense breasts. Clinical DBT systems vary in their system designs, one of which is the acquisition angular range (AR), which leads to varied performance for different imaging tasks. In this study, we aim to compare DBT systems with different AR. We used a previously validated cascaded linear system model to investigate the dependence of in-plane breast structural noise (BSN) and detectability of masses on AR. We conducted a pilot clinical study to compare the lesion conspicuity between clinical DBT systems with the narrowest and the widest AR. Patients called back for diagnostic imaging on suspicious findings were imaged with both narrow-angle (NA) and wide-angle (WA) DBT. We analyzed the BSN for clinical images using noise power spectrum (NPS) analysis. A 5-point Likert scale was used in the reader study to compare the lesion conspicuity. Our theoretical calculation results show that increasing AR leads to reduced BSN and improved mass detectability. The NPS analysis on clinical images shows the lowest BSN for WA DBT. The WA DBT provides better lesion conspicuity for masses and asymmetries and shows a greater advantage for non-microcalcification lesions in dense breasts. The NA DBT provides better characterizations for microcalcifications. The WA DBT can downgrade false-positive findings seen on NA DBT. In conclusion, WA DBT could improve the detection of masses and asymmetries for patients with dense breasts.

Unusual Presentation of Treated Colon Cancer with Extramural Venous Invasion: A Case Report.

Colon cancer is one of the leading malignancies globally and continues to be one of the most typical causes of cancer-related mortality. The clinical outcome of the disease depends on the primary tumour stage, regional nodal involvement and distant disease dissemination. It often presents with haematogenous spread to the liver at the time of diagnosis. Another factor for increased mortality is the presence of extramural venous invasion. This is exceedingly important as it has significant prognostic significance and helps predict survival.

The Kendall interaction filter for variable interaction screening in high dimensional classification problems.

Accounting for important interaction effects can improve the prediction of many statistical learning models. Identification of relevant interactions, however, is a challenging issue owing to their ultrahigh-dimensional nature. Interaction screening strategies can alleviate such issues. However, due to heavier tail distribution and complex dependence structure of interaction effects, innovative robust and/or model-free methods for screening interactions are required to better scale analysis of complex and high-throughput data. In this work, we develop a new model-free interaction screening method, termed Kendall Interaction Filter (KIF), for the classification in high-dimensional settings. KIF method suggests a weighted-sum measure, which compares the overall to the within-cluster Kendall's

Sensitivity analysis of error-contaminated time series data under autoregressive models with the application of COVID-19 data.

Autoregressive (AR) models are useful in time series analysis. Inferences under such models are distorted in the presence of measurement error, a common feature in applications. In this article, we establish analytical results for quantifying the biases of the parameter estimation in AR models if the measurement error effects are neglected. We consider two measurement error models to describe different data contamination scenarios. We propose an estimating equation approach to estimate the AR model parameters with measurement error effects accounted for. We further discuss forecasting using the proposed method. Our work is inspired by COVID-19 data, which are error-contaminated due to multiple reasons including those related to asymptomatic cases and varying incubation periods. We implement the proposed method by conducting sensitivity analyses and forecasting the fatality rate of COVID-19 over time for the four most populated provinces in Canada. The results suggest that incorporating or not incorporating measurement error effects may yield rather different results for parameter estimation and forecasting.

A robust latent CUSUM chart for monitoring customer attrition.

In competitive business, such as insurance and telecommunications, customers can easily replace one provider for another, which leads to customer attrition. Keeping customer attrition rate low is crucial for companies, since retaining a customer is more profitable than recruiting a new one. As a main statistical process control (SPC) method, the CUSUM scheme is able to detect small and persistent shifts in customer attrition. However, customer attrition summaries are typically available on an uneven time scale (e.g. 4-week and 5-week 'business month'), which may not satisfy the assumptions of traditional CUSUM designs. This paper mainly develops a latent CUSUM chart based on an exponential model for monitoring 'monthly' customer attrition, under varying time scales. Both maximum likelihood and least squares methods are studied, where the former mostly performs better and the latter is advantageous for quite small shifts. We apply a Markov chain algorithm to obtain the average run length (ARL), make calibrations for different combinations of parameters, and present reference tables of cutoffs. Three more complicated models are considered to test the robustness of deviations from the initial model. Furthermore, a real example of monitoring monthly customer attrition from a Chinese insurance company is used to illustrate the scheme.

Early threat perception is independent of later cognitive and behavioral control. A virtual reality-EEG-ECG study.

Research on social threat has shown influences of various factors, such as agent characteristics, proximity, and social interaction on social threat perception. An important, yet understudied aspect of threat exposure concerns the ability to exert control over the threat and its implications for threat perception. In this study, we used a virtual reality (VR) environment showing an approaching avatar that was either angry (threatening body expression) or neutral (neutral body expression) and informed participants to stop avatars from coming closer under five levels of control success (0, 25, 50, 75, or 100%) when they felt uncomfortable. Behavioral results revealed that social threat triggered faster reactions at a greater virtual distance from the participant than the neutral avatar. Event-related potentials (ERPs) revealed that the angry avatar elicited a larger N170/vertex positive potential (VPP) and a smaller N3 than the neutral avatar. The 100% control condition elicited a larger late positive potential (LPP) than the 75% control condition. In addition, we observed enhanced theta power and accelerated heart rate for the angry avatar vs. neutral avatar, suggesting that these measures index threat perception. Our results indicate that perception of social threat takes place in early to middle cortical processing stages, and control ability is associated with cognitive evaluation in middle to late stages.

Phenotype overlap in the natural history of asthma.

The heterogeneity of asthma makes it challenging to unravel the pathophysiologic mechanisms of the disease. Despite the wealth of research identifying diverse phenotypes, many gaps still remain in our knowledge of the disease's complexity. A crucial aspect is the impact of airborne factors over a lifetime, which often results in a complex overlap of phenotypes associated with type 2 (T2), non-T2 and mixed inflammation. Evidence now shows overlaps between the phenotypes associated with T2, non-T2 and mixed T2/non-T2 inflammation. These interconnections could be induced by different determinants such as recurrent infections, environmental factors, T-helper plasticity and comorbidities, collectively resulting in a complex network of distinct pathways generally considered as mutually exclusive. In this scenario, we need to abandon the concept of asthma as a disease characterised by distinct traits grouped into static segregated categories. It is now evident that there are multiple interplays between the various physiologic, cellular and molecular features of asthma, and the overlap of phenotypes cannot be ignored.

A comprehensive evaluation of multicentric reliability of single-subject cortical morphological networks on traveling subjects.

Despite the prevalence of research on single-subject cerebral morphological networks in recent years, whether they can offer a reliable way for multicentric studies remains largely unknown. Using two multicentric datasets of traveling subjects, this work systematically examined the inter-site test-retest (TRT) reliabilities of single-subject cerebral morphological networks, and further evaluated the effects of several key factors. We found that most graph-based network measures exhibited fair to excellent reliabilities regardless of different analytical pipelines. Nevertheless, the reliabilities were affected by choices of morphological index (fractal dimension > sulcal depth > gyrification index > cortical thickness), brain parcellation (high-resolution > low-resolution), thresholding method (proportional > absolute), and network type (binarized > weighted). For the factor of similarity measure, its effects depended on the thresholding method used (absolute: Kullback-Leibler divergence > Jensen-Shannon divergence; proportional: Jensen-Shannon divergence > Kullback-Leibler divergence). Furthermore, longer data acquisition intervals and different scanner software versions significantly reduced the reliabilities. Finally, we showed that inter-site reliabilities were significantly lower than intra-site reliabilities for single-subject cerebral morphological networks. Altogether, our findings propose single-subject cerebral morphological networks as a promising approach for multicentric human connectome studies, and offer recommendations on how to determine analytical pipelines and scanning protocols for obtaining reliable results.

Prevalence and predictors of tuberculosis infection among people living with HIV in a high tuberculosis burden context.

Tuberculosis (TB) disease is the leading cause of mortality among people living with HIV (PLHIV). Interferon-gamma release assays (IGRAs) are approved for TB infection ascertainment. However, current IGRA data on the prevalence of TB infection in the context of near-universal access to antiretroviral therapy (ART) and TB preventive therapy (TPT) are lacking. We estimated the prevalence and determinants of TB infection among PLHIV within a high TB and HIV burden context.

Crossroads of methodological choices in research synthesis: insights from two network meta-analyses on preventing relapse in schizophrenia.

In recent years, network meta-analyses have been increasingly carried out to inform clinical guidelines and policy. This approach is under constant development, and a broad consensus on how to carry out several of its methodological and statistical steps is still lacking. Therefore, different working groups might often make different methodological choices based on their clinical and research experience, with possible advantages and shortcomings. In this contribution, we will critically assess two network meta-analyses on the topic of pharmacological prevention of relapse in schizophrenia, carried out by two different research groups. We will highlight the implications of different methodological choices on the analysis results and their clinical-epidemiological interpretation. Moreover, we will discuss some of the most relevant technical issues of network meta-analyses for which there is not a broad methodological agreement, including the assessment of transitivity.

Frequency of visual involvement in a 10-year interdisciplinary cohort of patients with giant cell arteritis.

We present the largest study of the frequency and nature of visual complications in a cohort of 350 patients consecutively diagnosed with giant cell arteritis (GCA).