bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Simple prEservatioN of Single cElls method for cryopreservation enables the generation of single-cell immune profiles from whole blood
Authors: Satpathy Sarthak , Thomas Beena E. , Pilcher William J. , Bakhtiari Mojtaba , Ponder Lori A. , Pacholczyk Rafal , Prahalad Sampath , Bhasin Swati S. , Munn David H. , Bhasin Manoj K. 
Published: November 2023

IntroductionCurrent multistep methods utilized for preparing and cryopreserving single-cell suspensions from blood samples for single-cell RNA sequencing (scRNA-seq) are time-consuming, requiring trained personnel and special equipment, so limiting their clinical adoption. We developed a method, Simple prEservatioN of Single cElls (SENSE), for single-step cryopreservation of whole blood (WB) along with granulocyte depletion during single-cell assay, to generate high quality single-cell profiles (SCP).MethodsWB was cryopreserved using the SENSE method and peripheral blood mononuclear cells (PBMCs) were isolated and cryopreserved using the traditional density-gradient method (PBMC method) from the same blood sample (n=6). The SCPs obtained from both methods were processed using a similar pipeline and quality control parameters. Further, entropy calculation, differential gene expression, and cellular communication analysis were performed to compare cell types and subtypes from both methods.ResultsHighly viable (86.3 ± 1.51%) single-cell suspensions (22,353 cells) were obtained from the six WB samples cryopreserved using the SENSE method. In-depth characterization of the scRNA-seq datasets from the samples processed with the SENSE method yielded high-quality profiles of lymphoid and myeloid cell types which were in concordance with the profiles obtained with classical multistep PBMC method processed samples. Additionally, the SENSE method cryopreserved samples exhibited significantly higher T-cell enrichment, enabling deeper characterization of T-cell subtypes. Overall, the SENSE and PBMC methods processed samples exhibited transcriptional, and cellular communication network level similarities across cell types with no batch effect except in myeloid lineage cells.DiscussionComparative analysis of scRNA-seq datasets obtained with the two cryopreservation methods i.e., SENSE and PBMC methods, yielded similar cellular and molecular profiles, confirming the suitability of the former method’s incorporation in clinics/labs for cryopreserving and obtaining high-quality single-cells for conducting critical translational research.
The autoinflammation-associated NLRC4V341A mutation increases microbiota-independent IL-18 production but does not recapitulate human autoinflammatory symptoms in mice
Authors: Eeckhout Elien , Asaoka Tomoko , Van Gorp Hanne , Demon Dieter , Girard-Guyonvarc’h Charlotte , Andries Vanessa , Vereecke Lars , Gabay Cem , Lamkanfi Mohamed , van Loo Geert , Wullaert Andy 
Published: November 2023

BackgroundAutoinflammation with infantile enterocolitis (AIFEC) is an often fatal disease caused by gain-of-function mutations in the NLRC4 inflammasome. This inflammasomopathy is characterized by macrophage activation syndrome (MAS)-like episodes as well as neonatal-onset enterocolitis. Although elevated IL-18 levels were suggested to take part in driving AIFEC pathology, the triggers for IL-18 production and its ensuing pathogenic effects in these patients are incompletely understood.MethodsHere, we developed and characterized a novel genetic mouse model expressing a murine version of the AIFEC-associated NLRC4V341A mutation from its endogenous Nlrc4 genomic locus.ResultsNLRC4V341A expression in mice recapitulated increased circulating IL-18 levels as observed in AIFEC patients. Housing NLRC4V341A-expressing mice in germfree (GF) conditions showed that these systemic IL-18 levels were independent of the microbiota, and unmasked an additional IL-18-inducing effect of NLRC4V341A expression in the intestines. Remarkably, elevated IL-18 levels did not provoke detectable intestinal pathologies in NLRC4V341A-expressing mice, even not upon genetically ablating IL-18 binding protein (IL-18BP), which is an endogenous IL-18 inhibitor that has been used therapeutically in AIFEC. In addition, NLRC4V341A expression did not alter susceptibility to the NLRC4-activating gastrointestinal pathogens Salmonella Typhimurium and Citrobacter rodentium.ConclusionAs observed in AIFEC patients, mice expressing a murine NLRC4V341A mutant show elevated systemic IL-18 levels, suggesting that the molecular mechanisms by which this NLRC4V341A mutant induces excessive IL-18 production are conserved between humans and mice. However, while our GF and infection experiments argue against a role for commensal or pathogenic bacteria, identifying the triggers and mechanisms that synergize with IL-18 to drive NLRC4V341A-associated pathologies will require further research in this NLRC4V341A mouse model.
Colorimetric sensing of uric acid based on sawdust-deposited silver nanoparticles via an eco-friendly and cost-effective approach
Authors: Nishan Umar , Khan Noaman , Muhammad Nawshad , Afridi Saifullah , Badshah Amir , Shah Mohibullah , Asad Muhammad , Ullah Raheed , Niamat Haris , Ullah Riaz , A. Ali Essam , Ojha Suvash Chandra 
Published: November 2023

Uric acid is directly linked to gout, arthritis, neurological, cardiovascular, and kidney-related disorders. It is a byproduct obtained from the breakdown of purines and a significant indicator of hyperuricemia observed in both urine and blood. In the absence of any enzyme, it's quite difficult to develop a novel, cost-effective, and clinical method for uric acid detection. Herein, we report a very simple, low-cost, and non-enzymatic method for the selective identification and quantification of uric acid using green synthesized silver nanoparticles (Ag NPs). The desired Ag NPs were synthesized by the hydrothermal method using Erythrina suberosa sawdust as a deagglomeration agent and Psidium guajava extract as a reductant. The synthesis of the sensing platform, i.e., sawdust-deposited Ag NPs, was confirmed through different techniques such as UV-Vis spectrophotometer, FTIR, XRD, EDX, and scanning electron microscopy (SEM). Sawdust can offer a good, environmentally friendly, and cost-effective strategy to overcome the problem of agglomeration in nanoparticles. The enzyme mimic, with the help of H2O2, oxidizes the colorless 3,3′,5,5′-tetramethylbenzidine (TMB) to oxidized TMB with a blue-green color. The addition of uric acid reduces the oxidized TMB to a colorless product, resulting in a colorimetric change. For quality improvement, different reaction parameters, including pH, time, TMB, and NPs concentration, were optimized. Our proposed sensor responds in linear ranges of 0.04–0.360 μM, with a limit of quantification of 0.01 μM and a limit of detection of 0.004 μM. The suggested enzyme mimic detected uric acid in blood samples, with particular specificity in the presence of competitive analytes.
Neuropathic post-COVID pain symptomatology is not associated with serological biomarkers at hospital admission and hospitalization treatment in COVID-19 survivors
Authors: Fernández-de-las-Peñas César , Guijarro Carlos , Velasco-Arribas María , Torres-Macho Juan , Franco-Moreno Ana , Truini Andrea , Pellicer-Valero Oscar , Arendt-Nielsen Lars 
Published: November 2023

ObjectiveEvidence suggests that individuals who had survived to coronavirus disease, 2019 (COVID-19) could develop neuropathic post-COVID pain. This study investigated the association of serological biomarkers and treatments received during hospitalization with development of neuropathic-associated symptoms.MethodsOne hundred and eighty-three (n = 183) previously hospitalized COVID-19 survivors during the first wave of the pandemic were assessed in a face-to-face interview 9.4 months after hospitalization. Nineteen serological biomarkers, hospitalization data, and treatment during hospitalization were obtained from medical records. Neuropathic pain symptoms (Self-Report Leeds Assessment of Neuropathic Scale), sleep quality (Pittsburgh Sleep Quality Index), pain catastrophizing (Pain Catastrophizing Scale) and anxiety/depressive levels (Hospital Anxiety and Depression Scale) were assessed.ResultsThe prevalence of post-COVID pain was 40.9% (n = 75). Fifteen (20%) patients reported neuropathic symptoms. Overall, no differences in hospitalization data and serological biomarkers were identified according to the presence or not of neuropathic-associated symptoms. Patients with post-COVID pain had the highest neutrophil count, and post hoc analysis revealed that patients with neuropathic post-COVID associated symptoms had lower neutrophil count (p = 0.04) compared with those without neuropathic pain, but differences were small and possible not clinically relevant. No differences in fatigue, dyspnea, brain fog, anxiety or depressive levels, poor sleep, or pain catastrophism between patients with and without neuropathic symptoms were found.ConclusionIt seems that neuropathic-like post-COVID pain symptoms are not associated with neither of assessed serological biomarkers at hospital admission nor hospitalization treatments received in this cohort of hospitalized COVID-19 survivors.
Symptoms in unilateral vestibular hypofunction are associated with number of catch-up saccades and retinal error: results from the population-based KORA FF4 study
Authors: Aubele Maria , Grill Eva , Eggert Thomas , Schneider Erich , Strobl Ralf , Jahn Klaus , Müller Martin , Holle Rolf , Linkohr Birgit , Heier Margit , Ladwig Karl-Heinz , Lehnen Nadine 
Published: November 2023

ObjectiveThe presence and intensity of symptoms vary in patients with unilateral vestibular hypofunction. We aimed to determine which saccadic and vestibulo-ocular reflex parameters best predict the presence of symptoms in unilateral vestibular hypofunction in order to better understand vestibular compensation and its implications for rehabilitation therapy.MethodsVideo head impulse test data were analyzed from a subpopulation of 23 symptomatic and 10 currently symptom-free participants with unilateral vestibular hypofunction, embedded in the KORA (Cooperative Health Research in the Region of Augsburg) FF4 study, the second follow-up of the KORA S4 population-based health survey (2,279 participants).ResultsA higher number of catch-up saccades, a higher percentage of covert saccades, and a larger retinal error at 200 ms after the onset of the head impulse were associated with relevant symptoms in participants with unilateral vestibular hypofunction (p = 0.028, p = 0.046, and p = 0.038, respectively). After stepwise selection, the number of catch-up saccades and retinal error at 200 ms remained in the final logistic regression model, which was significantly better than a null model (p = 0.014). Age, gender, saccade amplitude, saccade latency, and VOR gain were not predictive of the presence of symptoms.ConclusionThe accuracy of saccadic compensation seems to be crucial for the presence of symptoms in unilateral vestibular hypofunction, highlighting the role of specific gaze stabilization exercises in rehabilitation. Early saccades, mainly triggered by the vestibular system, do not seem to compensate accurately enough, resulting in a relevant retinal error and the need for more as well as more accurate catch-up saccades, probably triggered by the visual system.
Efficacy and toxicities of doxorubicin plus ifosfamide in the second-line treatment of uterine leiomyosarcoma
Authors: Niu Szu-Yun , Sun Lou , Hsu Shih-Tien , Hwang Sheau-Feng , Liu Chih-Ku , Shih Yu-Hsiang , Lu Ting-Fang , Chen Yen-Fu , Lai Li-Ching , Chang Pei-Lun , Lu Chien-Hsing 
Published: November 2023

PurposeUterine leiomyosarcoma is a rare and aggressive tumor known for its drug resistance and metastatic potential. The standard first-line treatment typically involves anthracycline-based chemotherapy or a combination of gemcitabine and docetaxel; however, there is currently no established second-line treatment. Therefore, the aim of this study was to evaluate the efficacy and toxicity of doxorubicin plus ifosfamide as a potential second-line treatment for uterine leiomyosarcoma.Materials and methodsThis is a retrospective, single-center, single-arm study. We reviewed the tumor registry data from January 2010 to December 2022 and identified patients with uterine leiomyosarcoma who had previously received first-line salvage or adjuvant treatment involving gemcitabine and taxotere, and later experienced tumor recurrence. Patients who met these criteria were included in the study. The primary endpoint was the efficacy of doxorubicin and ifosfamide as a second-line treatment for uterine leiomyosarcoma, as measured by progression-free survival, 1-year overall survival, and response rate. The secondary endpoint was the adverse events associated with this regimen.ResultsFifty-two patients were diagnosed with uterine leiomyosarcoma during the study period, nine of whom were included in the data analysis. All patients had previously received gemcitabine-docetaxel as first-line adjuvant therapy, with a median progression-free survival period of 8.4 months. Doxorubicin-ifosfamide was administered as second-line treatment, with a median progression-free survival of 6.0 months (range: 2.7-79.9 months). The clinical benefit rate of the second-line treatment was 66.7%, with a median overall survival of 33.0 months, and a 1-year overall survival rate of 83.3%. Previous reports have shown that the median progression-free survival for second-line treatments using other regimens ranged from 1.4-5.6 months. The most common adverse event was myelosuppression, with five patients requiring granulocyte colony-stimulating factor and one patient requiring a blood transfusion. No patient discontinued treatment due to unmanageable adverse events.ConclusionUse of doxorubicin with ifosfamide may be a promising and reasonable second-line treatment with manageable adverse events for patients with uterine leiomyosarcoma.
Are there clinical and subclinical/pathological forms of Paget’s disease of the breast?
Authors: Pelorca Rafael José Fábio , de Oliveira-Junior Idam , Vieira René Aloisio da Costa 
Published: November 2023

IntroductionBreast disease management has changed over recent decades, related to molecular subtype, oncoplastic surgery and targeted therapies. Nevertheless, literature on Paget’s disease of the breast (PDB), initially described as a clinical entity and now considered a multifocal/multicentric disease.MethodsPDB was classified as clinical in the presence of areolar abnormalities and as subclinical/pathological in all other cases. Clinical and prognostic data were evaluated and compared between the different presentation forms. Statistics comprised descriptive analysis, inter-group comparison (chi-square and Mann-Whitney tests) and overall and cancer-specific survival rates (Kaplan-Meier method and the log-rank test).ResultsOf 85 patients included in this series, PDB was clinical in 58.8%. Overall, 27.1% had stage 0 and 92.9% had multifocal/multicentric disease. Most patients (83.5%) had the HER2 or luminal HER2 molecular subtype. Patients with clinical PDB had a higher rate of in situ disease (p=0.028) and were more likely to undergo breast-conserving surgery (p&lt;0.001). Most of the 43 patients with HER2 invasive disease received anti-HER therapy. Mean follow-up time was 71.2 ± 43.3 months. Cancer-specific actuarial survival at 60 and 120 months was 92.3% and 83.1%, respectively. Survival was unaffected by the clinical form of PDB (p=0.275), anti-HER therapy (p=0.509) or oncoplastic surgery (p=0.821). Conversely, clinical stage affected survival significantly (p ≤ 0.001).ConclusionPDB is a rare condition associated with multifocality/multicentricity and HER2 overexpression. Cases of clinical disease and those of subclinical/pathological disease differ significantly. Further studies are required to evaluate the clinical/areolar disease and the impact of advances in breast disease management on PDB.
Psoas muscle mass index and peak expiratory flow as measures of sarcopenia: relation to outcomes of elderly patients with resectable esophageal cancer
Authors: Zhang Mingzhi , Xiong Yaqiong , Chen Mengzhou , Xu Dafu , Xu Keping , Tian Wenze 
Published: November 2023

ObjectivesThe objective of this study is to investigate whether the evaluation of postoperative outcomes or overall survival in patients who undergo surgery for esophageal cancer can be achieved by assessing sarcopenia using psoas muscle mass index and peak expiratory flow.MethodsThis retrospective study analyzed the clinical data of 356 elderly patients (≥ 65 years) who had undergone radical surgery for esophageal cancer. Muscle mass and muscle strength were assessed by psoas muscle mass index (bilateral psoas area/height2) and peak expiratory flow, using preoperative computed tomography and spirometry, respectively. Sarcopenia is defined as a condition where both the psoas muscle mass index and peak expiratory flow fall below their gender-specific cutoff values. Survival and postoperative complications were compared between patients with and without sarcopenia.ResultsOut of the 356 elderly individuals diagnosed with esophageal cancer, 84 patients (23.6%) were found to have sarcopenia. The group with sarcopenia showed a notably higher occurrence of postoperative pneumonia (29.8% vs 16.9%, P &lt; 0.001) and anastomotic leak (9.5% vs 3.7%, P &lt; 0.05) compared to those without sarcopenia. Additionally, a multivariate analysis concluded that sarcopenia independently acted as a risk factor for postoperative pneumonia, possessing an odds ratio of 1.90 (P &lt; 0.05). The survival rate after 3 years for individuals with sarcopenia was considerably lower than those without sarcopenia (57.8% vs 70.2%, P &lt; 0.05). Sarcopenia was identified as an unfavorable prognostic factor for overall survival, with a hazard ratio of 1.51 (P &lt; 0.05).ConclusionsPreoperative sarcopenia diagnosed by psoas muscle mass index and peak expiratory flow is associated with reduced overall survival and adverse postoperative outcomes among elderly individuals suffering from esophageal cancer.
miR-6805-5p as a biomarker of cisplatin-induced nephrotoxicity in patients with head and neck cancer
Authors: Torso Nadine De Godoy , Quintanilha Julia Coelho França , Cursino Maria Aparecida , Pincinato Eder De Carvalho , Loren Pía , Salazar Luis A. , Lima Carmen Silvia Passos , Moriel Patricia 
Published: November 2023

Introduction: The standard treatment for head and neck squamous cell carcinoma (HNSCC) is cisplatin chemoradiotherapy. One of the main treatment adverse reactions is nephrotoxicity, for which there is currently no adequate specific and sensitive biomarker. Thus, this study aimed to evaluate the use of microRNAs (miRNAs) as renal biomarker candidates.Methods: This was a retrospective cohort study. Nephrotoxicity was assessed through blood samples collected before and 5 days (D5) after chemotherapy. MiRNAs were extracted from urine samples collected at baseline and D5, and RNA sequencing identified miRNAs differentially expressed between participants with and without cisplatin-induced nephrotoxicity.Results: A total of 49 participants were included (n = 49). A significant difference was seen between the two groups for traditional renal markers (serum creatinine and creatinine clearance) and for the acute kidney injury (AKI) categories. Among the six miRNAs evaluated as biomarkers, four were upregulated (hsa-miR-6729-5p, hsa-miR-1238-5p, hsa-miR-4706, and hsa-miR-4322) and two were downregulated (hsa-miR-6805-5p and hsa-miR-21-5p), but only hsa-miR-6805-5p had a significant difference (p &lt; 0.0001). Its receiver operating characteristic curve revealed excellent specificity (0.920) for its expression fluctuation assessment, while its absolute expression in D5 showed greater sensitivity (0.792).Conclusion: So, the integrated use of these two parameters seems to be an interesting approach for AKI.
Prediction of pediatric dose of tirzepatide from the reference adult dose using physiologically based pharmacokinetic modelling
Authors: Guan Ruifang , Li Xuening , Ma Guo 
Published: November 2023

Tirzepatide is an emerging hypoglycemic agent that has been increasing used in adults, yet its pharmacokinetic (PK) behavior and dosing regimen in pediatric population remain unclear. This study aimed to employ the physiologically based pharmacokinetic (PBPK) model to predict changes of tirzepatide exposure in pediatric population and to provide recommendations for its dose adjustments. A PBPK model of tirzepatide in adults was developed and verified by comparing the simulated plasma exposure with the observed data using PK-Sim&amp;MoBi software. This model was then extrapolated to three specific age subgroups, i.e., children (10–12 years), early adolescents (12–15 years), and adolescents (15–18 years). Each subgroup included healthy and obese population, respectively. All known age-related physiological changes were incorporated into the pediatric model. To identify an appropriate dosing regimen that yielded PK parameters which were comparable to those in adults, the PK parameters for each aforementioned subgroup were predicted at pediatric doses corresponding to 87.5%, 75%, 62.5%, and 50% of the adult reference dose. According to the results of simulation, dose adjustments of tirzepatide are necessary for the individuals aged 10–12 years, as well as those aged 12–15 years with healthy body weights. In conclusion, the adult PBPK model of tirzepatide was successfully developed and validated for the first time, and the extrapolated pediatric model could be used to predict pediatric dosing regimen of tirzepatide, which will provide invaluable references for the design of future clinical trials and its rational use in the pediatric population.
Depression, anxiety, and stress in medical students in Peru: a cross-sectional study
Authors: Valladares-Garrido Danai , Quiroga-Castañeda Pedro P. , Berrios-Villegas Iván , Zila-Velasque J. Pierre , Anchay-Zuloeta Claudia , Chumán-Sánchez Marisella , Vera-Ponce Víctor J. , Pereira-Victorio César J. , Failoc-Rojas Virgilio E. , Díaz-Vélez Cristian , Valladares-Garrido Mario J. 
Published: November 2023

ObjectiveTo determine the prevalence and factors associated with depressive, anxious, and stress symptoms in medical students in Peru, during the second pandemic wave of COVID-19.MethodsWe conducted an analytical cross-sectional study in 405 medical students from a university in northern Peru. The DASS-21 instrument was used to evaluate mental health outcomes (depression, anxiety, and stress), and to investigate their association with socio-educational characteristics.ResultsWe found a prevalence of depressive, anxious, and stress symptoms of 71.6% (95% CI: 66.94–75.95), 71.9% (95% CI: 67.2–76.2), and 62.7% (95% CI: 57.8–67.4); respectively. Students with eating behavior disorders had a higher prevalence of depressive symptoms (PR: 1.35), anxious symptoms (PR: 1.27), and stress symptoms (PR: 1.31). The prevalence of depressive symptoms (PR: 1.57), anxious symptoms (PR: 1.27), and stress symptoms (PR: 1.24) increased in students who did not report regular physical activity. In addition, having almost always academic exhaustion increased the prevalence of depressive symptoms (PR: 1.46), stress symptoms (PR: 1.72). On the contrary, the prevalence of depressive symptoms (PR: 0.79), anxious symptoms (PR: 0.73) and stress symptoms (PR: 0.82) decreased in male students. Students who reported sleeping 8 or more hours daily had a lower prevalence of stress symptoms (PR: 0.82).ConclusionSymptoms of depression and anxiety occurred in 7 out of 10 students, and stress in 6 out of 10. Among the factors associated with the presence of anxiety, depression, and stress were eating behavior disorder and not regularly exercising. Periodic evaluations of mental symptomatology are required and counseling should be promoted in medical schools.