bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of small extracellular vesicle protein biomarkers for pediatric Ewing Sarcoma
Authors: Turaga Soumya M. , Sardiu Mihaela E. , Vishwakarma Vikalp , Mitra Amrita , Bantis Leonidas E. , Madan Rashna , Merchant Michael L. , Klein Jon B. , Samuel Glenson , Godwin Andrew K.
Published: April 2023

Ewing Sarcoma (EWS) is the second most common osseous malignancy in children and young adults after osteosarcoma, while it is the fifth common osseous malignancy within adult age population. The clinical presentation of EWS is quite often non-specific, with the most common symptoms at presentation consisting of pain, swelling or general discomfort. The dearth of clinically relevant diagnostic or predictive biomarkers continues to remain a pressing clinical challenge. Identification of tumor specific biomarkers can lend towards an early diagnosis, expedited initiation of therapy, monitoring of therapeutic response, and early detection of recurrence of disease. We carried-out a complex analysis of cell lines and cell line derived small extracellular vesicles (sEVs) using label-free-based Quantitative Proteomic Profiling with an intent to determine shared and distinct features of these tumor cells and their respective sEVs. We analyzed EWS cells with different EWS-ETS fusions (EWS-FLI1 type I, II, and III and EWS-ERG) and their corresponding sEVs. Non-EWS controls included osteosarcoma, rhabdomyosarcoma, and benign cells, i.e., osteoid osteoma and mesenchymal stem cells. Proteomic profiling identified new shared markers between cells and their corresponding cell-derived sEVs and markers which were exclusively enriched in EWS-derived sEVs. These exo-biomarkers identified were validated by in silico approaches of publicly available protein databases and by capillary electrophoresis based western analysis (Wes). Here, we identified a protein biomarker named UGT3A2 and found its expression highly specific to EWS cells and their sEVs compared to control samples. Clinical validation of UGT3A2 expression in patient tumor tissues and plasma derived sEV samples demonstrated its specificity to EWS, indicating its potential as a EWS biomarker.
Case Report: Clinical delineation of CACNA1D mutation: New cases and literature review
Authors: Alzahrani Alshaimaa , Alshalan Maha , Alfurayh Mohammed , Bin Akrish Abdulaziz , Alsubeeh Najlaa A. , Al Mutairi Fuad
Published: April 2023

Background

Calcium ions are involved in several human cellular processes; nevertheless, the relationship between calcium channelopathies (CCs) and autism spectrum disorder (ASD) or intellectual disability (ID) has been previously investigated. We delineate the spectrum of clinical phenotypes and the symptoms associated with a syndrome caused by an inherited gain-of-function mutation in CACNA1D in a family with a history of neuropsychiatric disorders. We also review the clinical and molecular phenotype of previously reported variants of CACNA1D.

Case presentation

We report the case of a 9-year-old female patient, diagnosed with ASD, severe ID, hyperactivity, and aggressive impulsive behaviors. The father, who was a 65-year-old at the time of his death, had ID and developed major depressive disorder with catatonic features and nihilistic delusion, followed by rapidly progressive dementia. He died after experiencing prolonged seizures followed by post-cardiac arrest. The patient’s sister was a 30-year-old woman, known to have a severe ID with aggressive behaviors and sleep disorders. The sister has been diagnosed with bipolar disorder and psychosis. Through whole exome sequencing, a heterozygous previously identified and functionally characterized missense likely pathogenic variant was identified in the CACNA1D gene NM_001128840.3: c.2015C > T (p.Ser672Leu). These findings are consistent with the genetic diagnosis of autosomal dominant primary aldosteronism, seizures, and neurological abnormalities. This variant was found in the heterozygous status in the patient, her father, and her affected sister.

Conclusion

This case report will help to determine the key clinical features of this syndrome, which exhibits variable clinical presentations.
Anti-mGluR1 encephalitis: Case illustration and systematic review
Authors: Khojah Osama , Makkawi Seraj , Alghamdi Saeed
Published: April 2023

Background

The literature for immune-mediated neurological disorders is evolving like no other field of neurological illnesses. Many new antibodies or disorders have been described in the last decade. The cerebellum is a brain structure susceptible to these immune-mediated pathologies, and anti-metabotropic glutamate receptor 1 (mGluR1) antibody has a predilection to the cerebellar tissue. Anti-mGluR1 encephalitis is a rare autoimmune disease affecting the central and peripheral nervous systems, triggering an acute or subacute cerebellar syndrome with varying degrees of severity. Anti-mGluR1 encephalitis is a rare autoimmune disease affecting the central nervous system. We aimed to systematically review reported cases of anti-mGluR1 encephalitis and summarize their clinical presentation, management, outcomes, and case reports.

Methods

A search of the PubMed and Google Scholar databases was conducted and included all cases of anti-mGluR1 encephalitis published in English before October 1, 2022. A comprehensive systematic review was conducted using “metabotropic glutamate receptor type 1,” “mGluR1,” autoantibodies,” “autoantibodies,” “autoimmunity,” and “antibody” as keywords. The risk of bias assessment of the evidence was performed using appropriate tools. The qualitative variables were presented as frequency and percentage.

Results

Including our case, 36 cases of anti-mGluR1 encephalitis (19 males, median age 52.5 years, 11.1% pediatric cases) have been reported. The most common clinical manifestations are ataxia, dysarthria, and nystagmus. Initial imaging was normal in 44.4% of patients; however, 75% of patients showed abnormality later in the disease course. The first-line therapy options include glucocorticoids, intravenous immunoglobulin, and plasma exchange. Rituximab is the most commonly used second-line treatment. Complete remission was achieved in only 22.2% of patients, and 61.8% were disabled by the end of their course.

Conclusion

Anti-mGluR1 encephalitis manifests as symptoms of cerebellar pathology. Although the natural history has not been completely elucidated, early diagnosis with prompt initiation of immunotherapy could be imperative. Any patient suspected to have autoimmune cerebellitis should be tested for the presence of anti-mGluR1 antibody in the serum and cerebrospinal fluid. Escalation to an aggressive therapy approach should be applied in cases that do not respond to first-line therapies, and extended follow-up durations are required in all cases.
SCN1A channelopathies: Navigating from genotype to neural circuit dysfunction
Authors: Bryson Alexander , Petrou Steven
Published: April 2023

The SCN1A gene is strongly associated with epilepsy and plays a central role for supporting cortical excitation-inhibition balance through the expression of NaV1.1 within inhibitory interneurons. The phenotype of SCN1A disorders has been conceptualized as driven primarily by impaired interneuron function that predisposes to disinhibition and cortical hyperexcitability. However, recent studies have identified SCN1A gain-of-function variants associated with epilepsy, and the presence of cellular and synaptic changes in mouse models that point toward homeostatic adaptations and complex network remodeling. These findings highlight the need to understand microcircuit-scale dysfunction in SCN1A disorders to contextualize genetic and cellular disease mechanisms. Targeting the restoration of microcircuit properties may be a fruitful strategy for the development of novel therapies.
Accelerated hypometabolism with disease progression associated with faster cognitive decline among amyloid positive patients
Authors: Yang Zhengshi , Cummings Jeffrey L. , Kinney Jefferson W. , Cordes Dietmar ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: April 2023

Objective

To evaluate the progression of brain glucose metabolism among participants with biological signature of Alzheimer’s disease (AD) and its relevance to cognitive decline.

Method

We studied 602 amyloid positive individuals who underwent 18F-fluorodeoxyglucose PET (FDG-PET) scan, 18F-AV-45 amyloid PET (AV45-PET) scan, structural MRI scan and neuropsychological examination, including 116 cognitively normal (CN) participants, 314 participants diagnosed as mild cognitive impairment (MCI), and 172 participants diagnosed as AD dementia. The first FDG-PET scan satisfying the inclusion criteria was considered as the baseline scan. Cross-sectional analysis were conducted with the baseline FDG-PET data to compare the regional differences between diagnostic groups after adjusting confounding factors. Among these participants, 229 participants (55 CN, 139 MCI, and 35 AD dementia) had two-year follow-up FDG-PET data available. Regional glucose metabolism was computed and the progression rates of regional glucose metabolism were derived from longitudinal FDG-PET scans. Then the group differences of regional progression rates were examined to assess whether glucose metabolism deficit accelerates or becomes stable with disease progression. The association of cognitive decline rate with baseline regional glucose metabolism, and progression rate in longitudinal data, were evaluated.

Results

Participants with AD dementia showed substantial glucose metabolism deficit than CN and MCI at left hippocampus, in addition to the traditionally reported frontal and parietal–temporal lobe. More substantial metabolic change was observed with the contrast AD – MCI than the contrast MCI – CN, even after adjusting time duration since cognitive symptom onset. With the longitudinal data, glucose metabolism was observed to decline the most rapidly in the AD dementia group and at a slower rate in MCI. Lower regional glucose metabolism was correlated to faster cognitive decline rate with mild–moderate correlations, and the progression rate was correlated to cognitive decline rate with moderate-large correlations.

Discussion and conclusion

Hippocampus was identified to experience hypometabolism in AD pathology. Hypometabolism accelerates with disease progression toward AD dementia. FDG-PET, particularly longitudinal scans, could potentially help predict how fast cognition declines and assess the impact of treatment in interventional trials.
Acupuncture and other traditional Chinese medicine therapies in the treatment of children’s tic syndrome: A network meta-analysis
Authors: Pu Tong , Liu Yu , Wang Junxia , Zhang Jieying , Zhang Jinhao , Ran Zhiling , Sheng Qiaoni , Yi Zhiqiang , Ye Jiansong , Li Yanling , Wang Xijun , Chi Hao , Luo Wei
Published: April 2023

Background

Tic disorders (TD) are a kind of neuropsychiatric disease that frequently occur among preschool and school-age children, mainly characterized by motor tics or sometimes accompanied by vocal tics, and its pathogenesis is still unclear. The clinical manifestations are mainly characterized by chronic multiple movements, rapid muscle twitching, involuntary occurrence, and language disorder. Acupuncture, tuina, traditional Chinese medicine, and other methods are commonly used in clinical treatments, which have unique therapeutic advantages but have not been recognized and accepted by the international community. This study conducted a quality evaluation and meta-analysis of the currently published randomized controlled trials (RCTs) of acupuncture for TD in children in order to provide reliable evidence-based medical evidence for acupuncture for TD.

Methods

All the randomized controlled trials (RCTs) using the intervention methods acupuncture + traditional Chinese medical herbs, acupuncture + tuina, and acupuncture, and the control group using Western medicine were included in the analysis. The main outcomes were obtained by using the Yale Global Tic Severity Scale (YGTSS), the Traditional Chinese medicine (TCM) syndrome score scale, and clinical treatment efficiency. Secondary outcomes included adverse events. The risk of bias in the included studies was assessed according to the tool recommended by Cochrane 5.3. The risk of bias assessment chart, risk of bias summary chart, and evidence chart in this study will be produced using R and Stata software.

Results

There were 39 studies that met the inclusion criteria, including 3,038 patients. In terms of YGTSS, the TCM syndrome score scale changes and shows a clinically effective rate, and we found that acupuncture combined with Chinese medicine is the best treatment.

Conclusion

Acupuncture + traditional Chinese medical herbs may be the best therapy to improve TD in children. At the same time, compared with Western medicine commonly used in clinical practice, acupuncture and acupuncture combined with tuina therapy have better effects on improving TD in children.
Cell therapy for neurological disorders: Progress towards an embryonic medial ganglionic eminence progenitor-based treatment
Authors: Righes Marafiga Joseane , Baraban Scott C.
Published: April 2023

Impairment of development, migration, or function of inhibitory interneurons are key features of numerous circuit-based neurological disorders, such as epilepsy. From a therapeutic perspective, symptomatic treatment of these disorders often relies upon drugs or deep brain stimulation approaches to provide a general enhancement of GABA-mediated inhibition. A more effective strategy to target these pathological circuits and potentially provide true disease-modifying therapy, would be to selectively add new inhibitory interneurons into these circuits. One such strategy, using embryonic medial ganglionic (MGE) progenitor cells as a source of a unique sub-population of interneurons, has already proven effective as a cell transplantation therapy in a variety of preclinical models of neurological disorders, especially in mouse models of acquired epilepsy. Here we will discuss the evolution of this interneuron-based transplantation therapy in acquired epilepsy models, with an emphasis on the recent adaptation of MGE progenitor cells for xenotransplantation into larger mammals.
The solubility of oxygen in water and saline solutions
Authors: Bok F. , Moog H. C. , Brendler V.
Published: April 2023

Oxygen is one of the key reaction partners for many redox reactions also in the context of nuclear waste disposal. Its solubility influences radionuclides’ behavior, corrosion processes and even microbial activity. Therefore, a reliable calculation of the solubility of molecular oxygen in aqueous solutions is relevant for any safety assessment. Available geochemical speciation and reactive transport programs handle these data very differently. In some codes, the hypothetical equilibrium between dissolved oxygen and water is used to balance redox reactions. Equilibrium constants are given in “temperature grids” for up to 573.15 K. In other cases, temperature functions for the solubility of gaseous oxygen in water are given, without any reference to a valid temperature range. These settings become even more complicated when used in the context of modeling equilibria in high-saline solutions applying the Pitzer formalism. This raised the question about the experimental foundation of equilibrium constants given in such data files and their validity for the solubility of molecular oxygen in saline solutions. For this article, a thorough literature review was conducted with respect to the solubility of molecular oxygen in pure water and saline solutions. From these primary experimental O2 solubility data a temperature-dependent Henry’s law function as well as temperature-dependent binary and ternary Pitzer ion-interaction coefficients were derived. An internally consistent set of thermodynamic data for dissolved oxygen is presented, along with statements about its validity in terms of temperature and, as far as Pitzer interaction coefficients are concerned, of solution composition. This self-consistent activity-fugacity model containing thermodynamic data, Henry’s law temperature equation, and Pitzer interaction coefficients is capable of providing a more accurate description of redox transformations, allowing a reduction of conservatism in safety assessment calculations, not only in the context of a nuclear repository. The model reproduces well the reliable experimental data available, and is capable to predict the oxygen solubility in complex solution media. The temperature functions used to describe Henry’s constant and the Pitzer interaction coefficients are consistent with the implementation in commonly used geochemical computational programs, allowing direct use without further modification.
The phenolics, antioxidant activity and in vitro digestion of pomegranate (Punica granatum L.) peels: an investigation of steam explosion pre-treatment
Authors: Wang Qi , Yuan Tinglan , Zhu Xiaohuan , Song Gongshuai , Wang Danli , Li Ling , Huang Mingquan , Gong Jinyan
Published: April 2023

Pomegranate peels, the main byproduct of pomegranate production, are rich in phenolic compounds that are known for their effective antioxidant properties and have vast application prospects. In this study, steam explosion, an environmentally friendly technique, was applied to pretreat pomegranate peels for phenol extraction. We investigated the effects of explosion pressure, duration, and particle size on the content of total and individual phenolics, and antioxidant activity of pomegranate peels before and afterin vitrodigestion. The optimal conditions for a steam explosion for pomegranate peels in terms of total phenol content were a pressure of 1.5 MPa, a maintenance time of 90 s, and a particle size of 40 mesh. Under these conditions, pomegranate peel extract presented a higher yield of total phenols, gallic acid, and ellagic acid. However, it also had a lower content of punicalin and punicalagin, compared to the unexploded peels. There was no improvement in the antioxidant activity of pomegranate peels after the steam explosion. Moreover, the content of total phenol, gallic acid, ellagic acid, punicalin, and punicalagin, as well as the antioxidant activity of pomegranate peels, all increased after gastric digestion. Nevertheless, there was a large variation in the pomegranate peel processed by different pressure, duration, and sieve fractions. Overall, this study demonstrated that steam explosion pre-treatment could be an efficient method for improving the release of phenolics, especially gallic acid, and ellagic acid, from pomegranate peels.
Potential prebiotic effect of two Atlantic whole brown seaweeds, Saccharina japonica and Undaria pinnatifida, using in vitro simulation of distal colonic fermentation
Authors: Lopez-Santamarina Aroa , Sinisterra-Loaiza Laura , Mondragón-Portocarrero Alicia , Ortiz-Viedma Jaime , Cardelle-Cobas Alejandra , Abuín Carlos Manuel Franco , Cepeda Alberto
Published: April 2023

Two brown seaweeds (Saccharina japonica and Undaria pinnatifida) were characterized in terms of their nutritional and mineral composition, as well as their potential to modify the human gut microbiota. Nutritional analysis of these seaweeds showed that they comply with the criteria set out in European legislation to be labeled “low fat,” “low sugar,” and “high fiber.” Mineral content analysis showed that 100 g of seaweed provided more than 100% of the daily Ca requirements, as well as 33–42% of Fe, 10–17% of Cu, and 14–17% of Zn requirements. An in vitro human digest simulator system was used to analyze the effect of each seaweed on the human colonic microbiota. The gut microbiota was characterized by 16S rRNA amplicon sequencing and short-chain fatty-acid analysis. Seaweed digestion and fermentation showed beneficial effects, such as a decrease in the phylum Firmicutes and an increase in the phyla Bacteroidetes and Actinobacteria. At the species level, seaweed fermentation increased the proportion of beneficial bacteria such as Parabacteroides distasonis and Bifidobacterium. Regarding of metabolic pathways, no significant differences were found between the two seaweeds, but there were significant differences concerning to the baseline. An increase in short-chain fatty-acid content was observed for both seaweeds with respect to the negative control, especially for acetic acid. Given of the obtained results, S. japonica and U. pinnatifida intake are promising and could open new opportunities for research and application in the fields of nutrition and human health.
Effect of physiological pH on the molecular characteristics, rheological behavior, and molecular dynamics of κ-carrageenan/casein
Authors: Guo Juanjuan , Zhu Siliang , Chen Peilin , Liu Zhiyu , Lin Luan , Zhang Jie
Published: April 2023

Introduction

During gastrointestinal digestion, κ-carrageenan (κ-CGN) undergoes physicochemical changes, which associated with the risk of colitis.

Methods

To understand the effect of physiological pH on the conformational transition and binding stability of κ-CGN and κ-carrageenan/casein (κ-CC), we conducted experiments at pH 3.0 (gastric environment) and pH 7.0 (intestinal environment). We evaluated zeta potential, free sulfate group content, Fourier transform infrared spectroscopy, thermodynamic properties, microstructure, and molecular mechanism.

Results and Discussion

Our results revealed that the helical conformation of κ-CGN and κ-CC were more ordered and stable, and sulfate group exposure both lower in the intestinal environment (pH 7.0). However, in gastric environment (pH 3.0), the charge density of κ-CGN decreased, accompanied by random curling conformation and free sulfate group content increased. In contrast, the intermolecular interactions between κ-CGN and casein increased in gastric acid environments due to casein flocculation and secondary structure folding, and significantly reduced the exposure of free sulfate groups of κ-CGN. Our research results provide an important theoretical basis for elucidating the molecular mechanism and structure-activity relationship of κ-CGN under casein matrix to protect the mucosal barrier and inhibit colitis, and are of great significance for guiding and expanding the safe application of κ-CGN, thus assisting food nutrition to be absorbed.
Nutritional deficiencies in low-sociodemographic-index countries: a population-based study
Authors: Li Huansong , Ren Huiming , Guo Xu , Chen Zhu
Published: April 2023

Background

We aimed to estimate the burden of nutritional deficiency according to sex and age in countries with a low sociodemographic index (SDI).

Methods

Following the methods of the Global Burden of Diseases, Injuries, and Risk Factors Study 2019, estimated annual percentage changes (EAPCs) were calculated to determine trends in the age-standardized rates of incidence and disability-adjusted life-years (DALYs) of nutritional deficiency and its main subcategories from 1990 to 2019 in low-SDI countries.

Findings

From 1990 to 2019, the age-standardized incidence and DALY rates of nutritional deficiency showed decreasing trends, with EAPCs of −0.90 [95% confidence interval (CI), 1.06 to −0.75] and −3.20 (95% CI, −3.29 to −3.10), respectively, in low-SDI countries. In 2019, of the subcategories analyzed, vitamin A deficiency had the highest age-standardized incidence rate and protein–energy malnutrition had the highest age-standardized DALY rate. From 1990 to 2019, the greatest decrease in the age-standardized incidence rate was observed for vitamin A deficiency and the greatest decrease in the age-standardized DALY rate was observed for protein–energy malnutrition. At the national level, from 1990 to 2019, the greatest increase in the age-standardized incidence rate of overall nutritional deficiency was observed in males in Afghanistan (EAPC: 0.28; 95% CI, 0.07 to 0.49). Of the age groups analyzed, the highest incidence and DALY rates of overall nutritional deficiency and dietary iron deficiency were observed in children aged 1–4 years.

Interpretation

The age-standardized incidence and DALY rates of nutritional deficiency decreased significantly from 1990 to 2019, especially for vitamin A deficiency and protein–energy malnutrition. Overall nutritional deficiency and dietary iron deficiency occurred primarily in children aged 1–4 years.
Spatial transcriptomics reveals the heterogeneity and FGG+CRP+ inflammatory cancer-associated fibroblasts replace islets in pancreatic ductal adenocarcinoma
Authors: Ren Zhangyong , Pan Bing , Wang Fangfei , Lyu Shaocheng , Zhai Jialei , Hu Xiumei , Liu Zhe , Li Lixin , Lang Ren , He Qiang , Zhao Xin
Published: April 2023

Background

Understanding the spatial heterogeneity of the tumor microenvironment (TME) in pancreatic cancer (PC) remains challenging.

Methods

In this study, we performed spatial transcriptomics (ST) to investigate the gene expression features across one normal pancreatic tissue, PC tissue, adjacent tumor tissue, and tumor stroma. We divided 18,075 spatial spots into 22 clusters with t-distributed stochastic neighbor embedding based on gene expression profiles. The biological functions and signaling pathways involved in each cluster were analyzed with gene set enrichment analysis.

Results

The results revealed that KRT13+FABP5+ malignant cell subpopulation had keratinization characteristics in the tumor tissue. Fibroblasts from adjacent tumor tissue exhibited a tumor-inhibiting role such as “B-cell activation” and “positive regulation of leukocyte activation.” The FGG+CRP+ inflammatory cancer-associated fibroblasts replaced the islets in tumor stroma. During PC progression, the damage to pancreatic structure and function was heavier in the pancreatic exocrine (AMYA2+PRSS1+) than in the endocrine (INS+GCG+).

Conclusion

Our results revealed the spatial heterogeneity of dynamic changes and highlighted the significance of impaired exocrine function in PC.
Body mass index and baseline platelet count as predictive factors in Merkel cell carcinoma patients treated with avelumab
Authors: Incorvaia Lorena , Dimino Alessandra , Algeri Laura , Brando Chiara , Magrin Luigi , De Luca Ida , Pedone Erika , Perez Alessandro , Sciacchitano Roberta , Bonasera Annalisa , Bazan Russo Tancredi Didier , Li Pomi Federica , Peri Marta , Gristina Valerio , Galvano Antonio , Giuffrida Dario , Fazio Ivan , Toia Francesca , Cordova Adriana , Florena Ada Maria , Giordano Antonio , Bazan Viviana , Russo Antonio , Badalamenti Giuseppe
Published: April 2023

Background

Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer, associated with a worse prognosis. The Immune Checkpoint Inhibitors (ICIs) avelumab and pembrolizumab have been recently approved as first-line treatment in metastatic MCC (mMCC). The clinical observation of improved outcomes in obese patients following treatment with ICIs, known as the “obesity paradox”, has been studied across many types of tumors. Probably due to the rarity of this tumor, data on mMMC patients are lacking.

Patients and methods

This is an observational, hospital-based, study to investigate the role of Body Mass Index (BMI) as predictive biomarker of ICI response in mMCC patients treated with avelumab as first-line treatment. The study population included the patients treated from February 2019 to October 2022 in an Italian referral center for rare tumors. Clinico-pathological characteristics, BMI, laboratory parameters (NLR and platelet count), and response to avelumab were analyzed from a MCC System database prospectively collected.

Results

Thirty-two (32) patients were included. Notably, the presence of pre-treatment BMI ≥ 30 was significantly associated with longer PFS [BMI < 30 Group: median PFS, 4 months (95% CI: 2.5-5.4); BMI ≥ 30 Group: median PFS, not reached; p<0.001)[. Additionally, the median PFS was significantly higher in patients with higher PLT (median PFS: 10 months in the “low PLT” Group (95% CI: 4.9, 16.1) vs 33 months (95% CI: 24.3, 43.2) in the “high PLT” Group (p=0.006). The multivariable Cox regression model confirmed these results.

Conclusion

To our knowledge, this is the first study that investigates the predictive role of BMI in MCC patients. Our data were consistent with the clinical observation of improved outcomes in obese patients across other tumor types. Thus, advanced age, a weakened immune system, and the obesity-associated “inflammaging”, are key factors that could impact the cancer immune responses of mMCC patients.
Clinical features and molecular genetics associated with brain metastasis in suspected early-stage non-small cell lung cancer
Authors: Kim Kangjoon , Lee Jibeom , Lee Jeong-Yun , Yong Seung Hyun , Kim Eun Young , Jung Ji Ye , Kang Young Ae , Park Moo Suk , Kim Young Sam , Oh Chang-Myung , Lee Sang Hoon
Published: April 2023

Introduction

Regarding whether brain magnetic resonance imaging (MRI) should be routine in patients with suspected early-stage lung cancer, guideline recommendations are inconsistent. Therefore, we performed this study to evaluate the incidence of and risk factors for brain metastasis (BM) in patients with suspected early-stage non-small-cell lung cancer (NSCLC).

Methods

A review of the medical charts of consecutive NSCLC patients diagnosed between January 2006 and May 2020 was performed. We identified 1,382 NSCLC patients with clinical staging of T1/2aN0M0 (excluding BM), and investigated the incidence, clinical predictors, and prognosis of BM in the cohort. We also performed RNA-sequencing differential expression analysis using transcriptome of 8 patients, using DESeq2 package (version 1.32.0) with R (version 4.1.0).

Results

Among 1,382 patients, nine hundred forty-nine patients (68.7%) underwent brain MRI during staging, and 34 patients (3.6%) were shown to have BM. Firth’s bias-reduced logistic regression showed that tumor size (OR 1.056; 95% CI 1.009-1.106, p=0.018) was the only predictor of BM, and pathologic type was not a predictor of BM in our cohort (p>0.05). The median overall survival for patients with brain metastasis was 5.5 years, which is better than previously reported in the literature. RNA-sequencing differential expression analysis revealed the top 10 significantly upregulated genes and top 10 significantly downregulated genes. Among the genes involved in BM, Unc-79 homolog, non-selective sodium leak channel (NALCN) channel complex subunit (UNC79) was the most highly expressed gene in the lung adenocarcinoma tissues from the BM group, and an in vitro assay using A549 cells revealed that the NALCN inhibitor suppressed lung cancer cell proliferation and migration.

Conclusions

Given the incidence and favorable outcome of BM in patients with suspected early-stage NSCLC, selective screening with brain MRI may be considered, especially in patients with high-risk features.
Climbing behavior by mice as an endpoint for preclinical assessment of drug effects in the absence and presence of pain
Authors: Santos Edna J. , Giddings Arianna N. , Kandil Farah A. , Negus S. Stevens
Published: April 2023

This study evaluated climbing in mice as a tool to assess the expression and treatment of pain-related behavioral depression in male and female ICR mice. Mice were videotaped during 10-min sessions in a vertical plexiglass cylinder with wire mesh walls, and “Time Climbing” was scored by observers blind to treatments. Initial validation studies demonstrated that baseline climbing was stable across repeated days of testing and depressed by intraperitoneal injection of dilute lactic acid (IP acid) as an acute pain stimulus. Additionally, IP acid-induced depression of climbing was blocked by the positive-control non-steroidal anti-inflammatory drug (NSAID) ketoprofen but not by the negative control kappa opioid receptor agonist U69593. Subsequent studies examined effects of single-molecule opioids (fentanyl, buprenorphine, naltrexone) and of fixed-proportion fentanyl/naltrexone mixtures (10:1, 3.2:1, and 1:1) that vary in their efficacy at the mu opioid receptor (MOR). Opioids administered alone produced a dose- and efficacy-dependent decrease in climbing, and fentanyl/naltrexone-mixture data indicated that climbing in mice is especially sensitive to disruption by even low-efficacy MOR activation. Opioids administered as a pretreatment to IP acid failed to block IP acid-induced depression of climbing. Taken together, these findings support the utility of climbing in mice as an endpoint to evaluate candidate-analgesic effectiveness both to (a) produce undesirable behavioral disruption when the test drug is administered alone, and (b) produce a therapeutic blockade of pain-related behavioral depression. The failure of MOR agonists to block IP acid-induced depression of climbing likely reflects the high sensitivity of climbing to disruption by MOR agonists.
Pediatricians’ experiences of managing outpatient care during the COVID-19 pandemic: A qualitative study in Germany
Authors: von Sommoggy Julia , Grepmeier Eva-Maria , Apfelbacher Christian , Brandstetter Susanne , Curbach Janina
Published: April 2023

Background

Pediatricians are important sources of information for parents regarding their children's health. During the COVID-19 pandemic, pediatricians faced a variety of challenges regarding information uptake and transfer to patients, practice organization and consultations for families. This qualitative study aimed at shedding light on German pediatricians’ experiences of providing outpatient care during the first year of the pandemic.

Methods

We conducted 19 semi-structured, in-depth interviews with pediatricians in Germany from July 2020 to February 2021. All interviews were audio recorded, transcribed, pseudonymized, coded, and subjected to content analysis.

Results

Pediatricians felt able to keep up to date regarding COVID-19 regulations. However, staying informed was time consuming and onerous. Informing the patients was perceived as strenuous, especially when political decisions had not been officially communicated to pediatricians or if the recommendations were not supported by the professional judgment of the interviewees. Some felt that they were not taken seriously or adequately involved in political decisions. Parents were reported to consider pediatric practices as sources of information also for non-medical inquiries. Answering these questions was time consuming for the practice personnel and involved non-billable hours. Practices had to adapt their set-up and organization immediately to the new circumstances of the pandemic, which proved costly and laborious as well. Some changes in the organization of routine care, such as the separation of appointments for patients with acute infection from preventive appointments, were perceived as positive and effective by some study participants. Telephone and online consultations were established at the beginning of the pandemic and considered helpful for some situations, whereas for others these methods were deemed insufficient (e.g. for examinations of sick children). All pediatricians reported reduced utilization mainly due to a decline in acute infections. However, preventive medical check-ups and immunization appointments were reported to be mostly attended.

Conclusion

Positive experiences of reorganizing pediatric practice should be disseminated as “best practices” in order to improve future pediatric health services. Further research could show how some of these positive experiences in reorganizing care during the pandemic are to be maintained by pediatricians in the future.
Research on infrared target detection based on neural network fusion
Authors: Fu Gui , Han Lixiang , Huang Shaohan , Liu Liwen , Wang You , Zhu Xinyu
Published: April 2023

Infrared technology can detect targets under special weather conditions, such as night, rain and fog. To improve the detection accuracy of vehicles, pedestrians and other targets in infrared images, an infrared target detection algorithm with fusion neural network is proposed. Firstly, we use Ghost convolution to replace the resunit unit of the convolution layer of the deep residual network layer in YOLOv5s, which can reduce the amount of parameters without losing accuracy. Then, the global channel attention (GCA) is added to the upper sampling layer, the detection accuracy of network is further improved by enhancing the characteristics of the overall goal. Also, the Channel Space Attention (CPA) space attention mechanism is added to the output end to obtain more accurate target location information. The infrared data set taken by the UAV is trained and tested. The accuracy rate of detection based on YOLOv5s and fusion neural network is 96.47%, the recall rate is 91.51%, and the F1 score is 94%, which is 7% higher than YOLOv5s. The results show that the target detection rate of infrared images is improved by proposed method, which has strong research value and broad application prospects.
Predicting respiratory decompensation in mechanically ventilated adult ICU patients
Authors: Tan Yvette , Young Michael , Girish Akanksha , Hu Beini , Kurian Zina , Greenstein Joseph L. , Kim Han , Winslow Raimond L , Fackler James , Bergmann Jules
Published: April 2023

Introduction: Mechanical ventilation is a life-saving treatment in the Intensive Care Unit (ICU), but often causes patients to be at risk of further respiratory complication. We created a statistical model utilizing electronic health record and physiologic vitals data to predict the Center for Disease Control and Prevention (CDC) defined Ventilator Associated Complications (VACs). Further, we evaluated the effect of data temporal resolution and feature generation method choice on the accuracy of such a constructed model.

Methods: We constructed a random forest model to predict occurrence of VACs using health records and chart events from adult patients in the Medical Information Mart for Intensive Care III (MIMIC-III) database. We trained the machine learning models on two patient populations of 1921 and 464 based on low and high frequency data availability. Model features were generated using both basic statistical summaries and tsfresh, a python library that generates a large number of derived time-series features. Classification to determine whether a patient will experience VAC one hour after 35 h of ventilation was performed using a random forest classifier. Two different sample spaces conditioned on five varying feature extraction techniques were evaluated to identify the most optimal selection of features resulting in the best VAC discrimination. Each dataset was assessed using K-folds cross-validation (k = 10), giving average area under the receiver operating characteristic curves (AUROCs) and accuracies.

Results: After feature selection, hyperparameter tuning, and feature extraction, the best performing model used automatically generated features on high frequency data and achieved an average AUROC of 0.83 ± 0.11 and an average accuracy of 0.69 ± 0.10.

Discussion: Results show the potential viability of predicting VACs using machine learning, and indicate that higher-resolution data and the larger feature set generated by tsfresh yield better AUROCs compared to lower-resolution data and manual statistical features.
Exogenous 24-epibrassinolide promoted growth and nitrogen absorption and assimilation efficiency of apple seedlings under salt stress
Authors: Yu Bo , Wang Laiping , Guan Qiuzhu , Xue Xiaomin , Gao Wensheng , Nie Peixian
Published: April 2023

Introduction

High salinity significantly hampers global agricultural productivity. Plants typically undergo lower nitrogen utilization efficiency (NUE) under salt stress. As an active byproduct from brassinolide biosynthesis, 24-epibrassinolide (EBR) is involved in regulating the stress-treated plant N absorption and assimilation. However, the exogenous EBR application effects’ on N absorption and assimilation in apple exposed to the salt-stressed condition remains unclear.

Methods

We sprayed exogenous EBR (0.2 mg L−1) on apple dwarf rootstock (M9T337) seedlings (growing hydroponically) under salt (NaCl) stress in a growth chamber. We analyzed the seedling development, photosynthesis and its-mediated C fixation, N (NO3−) absorption and assimilation in reponse to exogenous EBR application under salt stress.

Results

The findings demonstrated that NaCl stress greatly hampered seedlings’ root growth and that exogenous EBR application obviously alleviated this growth suppression. Exogenous EBR-treated plants under NaCl stress displayed the more ideal root morphology and root activity, stronger salt stress tolerance and photosynthetic capacity as well as higher C- and N-assimilation enzyme activities, NO3− ion flow rate and nitrate transporter gene expression level than did untreated plants. Furthermore, the results of isotope labeling noted that exogenous EBR application also enhanced 13C-photoassimilate transport from leaves to roots and 15NO3− transport from roots to leaves under NaCl stress.

Conclusion

Our findings imply that exogenous EBR application, through strengthening photosynthesis, C- and N-assimilation enzyme activities, nitrate absorption and transport as well as synchronized optimizing the distribution of seedlings’ C and N, has a fundamental role in improving NUE in apple rootstock seedlings under salt stress.
Older adults’ experiences with using information and communication technology and tech support services in New York City: findings and recommendations for post-pandemic digital pedagogy for older adults
Authors: Finkelstein Ruth , Wu Yiyi , Brennan-Ing Mark
Published: April 2023

Introduction

Although Information and Communication Technology (ICT) has great potential to help older adults cope with challenges associated with aging, the intended benefits of ICT are not always realized in this population due to access barriers and low digital literacy. During the COVID-19 pandemic, numerous tech support initiatives for older adults got underway. However, evaluation of the effectiveness of these initiatives is less common. This research partnered with a large, multi-service organization in New York City that gave some groups of their clients ICT devices, unlimited broadband, and access to technology training in response to COVID-19 lockdowns. This study investigates older adults’ experiences with ICT and ICT support services to better inform the existing and emerging tech support for older adults during and beyond the pandemic.

Methods

Data were obtained from interviewer-administered surveys of 35 older adult recipients of ICT devices, connectivity, and training in New York City. The average age was 74 years (range = 55–90 years). The group was diverse regarding race/ethnicity (Black 29%, Latino 19%, White 43%). All had low incomes. Surveys consisted of multiple-choice items and open-ended responses.

Results

The study found that one size does not fit all when it comes to ICT training and support for older adults. While connection to devices and services and tech support led to a degree of ICT adoption, the newly learned skills did not always lead to expanded device usage. The readily available tech support training and support do not guarantee service utilization, as success with tech services is related to one’s pre-existing ICT competence.

Discussion

The study concludes that customized training based on individuals’ skills rather than age is needed. Tech support training should start by understanding an individual’s interests and incorporate tech education to help users identify a wide range of existing and emerging online services that can meet their needs. Service organizations should consider including an assessment of ICT access, use, and skills into their standard intake protocols to ensure effective service delivery.
In the uncharted water: Meaning-making capacity and identity negotiation of Chinese lesbian and bisexual women
Authors: Hang Yang , Zhang Xiaojun
Published: April 2023

Chinese lesbian and bisexual women (LBW) often face difficulties and challenges on campus due to their multiple, socially-oppressed identities. These students have to navigate through uncharted environments to make meaning of their identities. In this qualitative study, by considering four environmental systems of student life, including the student club (microsystem), the university (mesosystem), families (exosystem), and society (macrosystem), we aim to explore what identity negotiation Chinese LBW students have in them and what their meaning-making capacity influence that identity negotiation. We find students experience identity security in the microsystem, identity differentiation-inclusion or inclusion in the mesosystem, and identity unpredictability-predictability or predictability in the exosystem and macrosystem. Moreover, they employ foundational, transitional (formulaic to foundational or symphonic), or symphonic meaning-making capacity to influence their identity negotiation. Suggestions are made for the university to create an inclusive climate accommodating students with different identities.
Impact of COVID-19 on the change in work conditions and career choices in general Vietnamese population
Authors: Doan Linh Phuong , Le Linh Khanh , Dam Vu Anh Trong , Vu Thuc Minh Thi , Boyer Laurent , Auquier Pascal , Fond Guillaume , Tran Bach , Latkin Carl A. , Ho Roger C. M. , Ho Cyrus S. H. , Zhang Melvyn W. B.
Published: April 2023

Objectives

The onset of COVID-19 has resulted in both morbidity and mortality. It also has a consequential impact on the Vietnamese economy. Prior studies have examined the impact of COVID-19 on healthcare professionals’ career decisions. However, no study remains to have examined the work conditions and career choices in a general Vietnamese population. Our study aims to identify factors associated with the change in work conditions and career choices in general Vietnamese population.

Methods

An online cross-sectional study between September 2021 through to November 2021 (during the Omicron COVID-19 pandemic). Snowball sampling method was utilized in recruiting the participants. The questionnaire used in this study included the following questions: (a) Socio-demographic information; (b) impact of COVID-19 on personal habits/daily expenses; (c) Current nature of work and impact of COVID-19 on work; (d) Impact of COVID-19 on career decisions. Data analysis was performed using STATA version 16. Descriptive analysis followed by Ordered logit regression was performed, to identify potential covariates.

Results

Six hundred and fifty participants were recruited, of which only 645 completed the survey. The completion rate was 99.2%. This study demonstrated the impact that COVID-19 has on finances, as only 32% of those sampled reported that they were able to pay in full. 46.6% of the respondents have had a decrease in their overall household income. With regards to their employment and work characteristics, 41.0% reported a decrease in their work satisfaction and 39.0% reported having reduced motivation for work. Females were less likely to consider transiting from their current job to another field than male participants. Respondents who were married, had a higher level of commitment to their current job, and lower inclination to transition to another field. Respondents experiencing financial difficulties were more likely to consider a transition to another field/work.

Conclusion

This is perhaps one of the first studies to have examined the impact of COVID-19 on work intentions regarding career choices and transitions in the general Vietnamese population. Future financial policies must take into consideration these factors.