bluuebunny/crossref_metadata_2025_split huggingface dataset:
IFN-γ/Doxorubicin Complex Nanoparticles for Enhancing Therapy in the Context of Human Ovarian Carcinoma
Authors: Yi Rongyuan , Lv Wanwan , Zheng Shan , Zhang Ningyu , Zhang Yuheng , Yang Kai , Huang Tuo , Yang Yanning , Chu Hui , Chen Jian 
Published: July 2022

The cytokine interferon gamma (IFN-γ) and doxorubicin mono-therapy has been approved by the Food and Drug Administration (FDA) for the treatment of tumors. The importance of IFN-γ in the immune system lies in its immunomodulatory effects, and the importance of doxorubicin in antitumor therapy lies in inhibiting RNA and DNA synthesis. In this work, the role of IFN-γ in the antitumor activity in combination with doxorubicin was investigated. Meanwhile, IFN-γ was used as a vehicle to load doxorubicin over immunotherapy and chemotherapy for synergistic therapy. IFN-γ/doxorubicin complex nanoparticles were prepared by a fusion method with a size of approximately 13 nm and a low polydispersity index. The doxorubicin release profile was analyzed with different pH ranges, and it showed an enhanced release in acidic pH. The ability of IFN-γ/doxorubicin complex nanoparticles to induce human ovarian carcinoma cell (Skov 3) apoptosis was evaluated by the cytotoxicity test. The cellular uptake of IFN-γ/doxorubicin complex nanoparticles was time-dependent, and the IFN-γ/doxorubicin complex nanoparticles showed a higher apoptosis efficiency than free doxorubicin by flow cytometry analysis and fluorescence imaging. This work bridged IFN-γ with doxorubicin to utilize their potential for antitumor activities, opening new avenues for their use in clinical settings.
Clinical, epidemiological, and laboratory prognostic factors in patients with leprosy reactions: A 10-year retrospective cohort study
Authors: Antunes Douglas Eulálio , Santos Diogo Fernandes , Lima Mayara Ingrid Sousa , Caixeta Larissa Pereira , Correa Meydson Benjamin Carvalho , Moraes Emilly Caroline dos Santos , Conceição Natalia Carine Almeida , Goulart Luiz Ricardo , Goulart Isabela Maria Bernardes 
Published: July 2022

IntroductionLeprosy reactions, the main cause of neural damage, can occur up to 7 years after starting multidrug therapy. We aimed to approach the prognostic factors that may influence the leprosy reactions over the follow-up time.MethodsRetrospective cohort study, encompassing 10 years of data collection, composed of 390 patients, divided into 201 affected by reactions and 189 reaction-free individuals. Epidemiological, clinical, and laboratory variables were approached as prognostic factors associated with leprosy reactions. The association among variables was analyzed by a binomial test and survival curves were compared by the Kaplan-Meier and Cox proportional-hazards regression.Results51.5% (201/390) of patients were affected by leprosy reactions. These immunological events were associated with lepromatous leprosy (16.2%; 63/390; p &lt; 0.0001) and multibacillary group (43%; 169/390; p &lt; 0.0001). This study showed that survival curves for the prognostic factor anti-PGL-I, comparing positive and negative cases at diagnosis, differed in relation to the follow-up time (Log Rank: p = 0.0760; Breslow: p = 0.0090; Tarone-Ware: p = 0.0110). The median survival times (time at which 50% of patients were affected by leprosy reactions) were 5 and 9 months for those reactional cases with negative (26/51) and positive serology (75/150), respectively. The time-dependent covariates in the cox proportional-hazards regression showed anti-PGL-I as the main prognostic factor to predict leprosy reactions (hazard ratio=1.91; p = 0.0110) throughout the follow-up time.ConclusionsFinally, these findings demonstrated that anti-PGL-I serology at diagnosis is the most important prognostic factor for leprosy reactions after starting multidrug therapy, thus enabling prediction of this immunological event.
The Potential Role of Vitamin D in the Development of Tuberculosis in Chinese Han Population: One Case-Control Study
Authors: Cai Li , Hou Shuangyi , Huang Yadong , Liu Shuang , Huang Xibao , Yin Xiaoxv , Jiang Nan , Tong Yeqing 
Published: July 2022

Background and aims:Spinal serum 25-hydroxyvitamin D [25[OH]D] status plays an important role in mediating innate immune responses by acting as a cofactor for induction of antimycobacterial activity and is thus involved in the development of Tuberculosis (TB). Results reported regarding the association of vitamin D with TB remained controversial. We aimed to identify any common association between 25[OH]D status and TB in the Chinese Han population.Methods280 subjects (70 TB patients and 210 matched controls) were recruited. TB cases were diagnosed based on the presence of acid-fast bacilli on smears from sputum and MTB isolation. Healthy controls were randomly selected from four local community-based populations. 25[OH]D was detected by electrochemiluminescence immunoassay (ECLIA) on Roche Elecsys before the initial treatment. Multivariable logistic regression analysis was used to examine the association of Vitamin D with TB.ResultsThere was no significant difference in the serum vitamin D level between total cases and controls, but we found a strong tendency toward a higher serum vitamin D level in male population (P &lt; 0.05) with TB but not in females. High serum vitamin D increased the risk of TB in the Chinese Han population (OR = 1.035, 95%CI: 1.001–1.070, P &lt; 0.05). The serum vitamin D level was significantly decreased with age increasing in cases and controls (all P &lt; 0.001).ConclusionsHigh serum vitamin D may be an independent risk factor for TB in the Chinese Han population.
Mild reinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant: First case report from Indonesia
Authors: Isnaini Naniek , Mardian Yan , Lokida Dewi , Budiono Fajar , Butar-butar Deni P. , Arlinda Dona , Salim Gustiani , Kosasih Herman , Wulan Wahyu Nawang , Perodin Jacqueline , Neal Aaron , Lane H. Clifford , Karyana Muhammad 
Published: July 2022

BackgroundReinfection with SARS-CoV-2 has been well documented, yet little is known about the degree of protection a previous infection provides against reinfection, especially against Variants of Concern (VOC).Case presentationHere we describe a case of an unvaccinated 49-year-old man who experienced two sequential SARS-CoV-2 infections with two different variants, as evidenced by genomic sequencing. The first episode was caused by the Pango lineage B.1.466.2 and resulted in severe COVID-19 with 5 days in an intensive care unit (ICU). The second episode occurred approximately 6 months later, during the Delta surge in Indonesia. Genomic analysis showed that the second infection was caused by the Delta variant (Pango lineage B.1.617.2) and resulted in mild disease that did not require hospitalization. No SARS-CoV-2 nucleic acid was detected between the two episodes, but both binding and neutralizing antibodies to SARS-CoV-2 were detected prior to the reinfection, with the second infection leading to an increase in the levels of antibody.ConclusionWe confirmed that the patient experienced a reinfection instead of persistent viral shedding from the first infection based on epidemiological, clinical, serological, and genomic analyses. Our case supports the hypothesis that SARS-CoV-2 reinfection may occur once antibody titers decrease or following the emergence of a new variant. The milder presentation in the patient’s second infection deserves further investigation to provide a clear picture of the role of post-infection immunity in altering the course of subsequent disease.
Aversive Pavlovian inhibition in adult attention-deficit/hyperactivity disorder and its restoration by mindfulness-based cognitive therapy
Authors: Geurts Dirk E. M. , den Ouden Hanneke E. M. , Janssen Lotte , Swart Jennifer C. , Froböse Monja I. , Cools Roshan , Speckens Anne E. M. 
Published: July 2022

BackgroundControl over the tendency to make or withhold responses guided by contextual Pavlovian information plays a key role in understanding impulsivity and hyperactivity. Here we set out to assess (1) the understudied relation between contextual Pavlovian inhibitory control and hyperactivity/impulsivity in adults with ADHD and (2) whether this inhibition can be enhanced by mindfulness based cognitive therapy (MBCT).MethodsWithin the framework of a randomized controlled trial 50 Adult ADHD patients were assessed before and after 8 weeks of treatment as usual (TAU) with (n = 24) or without (n = 26) MBCT. We employed a well-established behavioral Pavlovian-to-instrumental transfer task that quantifies Pavlovian inhibitory control over instrumental behavior.ResultsTask results revealed (1) less aversive Pavlovian inhibition in ADHD patients with clinically relevant hyperactivity/impulsivity than in those without; and (2) enhanced Pavlovian inhibition across all ADHD patients after TAU+MBCT compared with TAU.ConclusionThese findings offer new insights in the neurocognitive mechanisms of hyperactivity/impulsivity in ADHD and its treatment: We reveal a role for Pavlovian inhibitory mechanisms in understanding hyperactive/impulsive behaviors in ADHD and point toward MBCT as an intervention that might influence these mechanisms.
A modified mouse model for observational fear learning and the influence of social hierarchy
Authors: Shi Tianyao , Feng Shufang , Shi Wenlong , Fu Yuan , Zhou Wenxia 
Published: July 2022

BackgroundIndirectly experiencing traumatic events either by witnessing or learning of a loved one’s suffering is associated with the highest prevalence rates of epidemiological features of PTSD. Social species can develop fear by observing conspecifics in distress. Observational fear learning (OFL) is one of the most widely used paradigms for studying fear contagion in mice. However, the impact of empathic fear behavior and social hierarchy on fear transfer in mice is not well understood.MethodsFear emotions are best characterized in mice by using complementary tests, rather than only freezing behavior, and simultaneously avoiding behavioral variability in different tests across time. In this study, we modified the OFL model by implementing freezing (FZ), open field (OF), and social interaction (SI) tests in a newly designed experimental facility and applied Z-normalization to assess emotionality changes across different behaviors.ResultsThe integrated emotionality scores revealed a robustly increased emotionality of observer mice and, more importantly, contributed to distinguishing susceptible individuals. Interestingly, fos-positive neurons were mainly found in the interoceptive network, and mice of a lower social rank showed more empathy-like behaviors.ConclusionOur findings highlight that combining this experimental model with the Z-scoring method yields robust emotionality measures of individual mice, thus making it easier to screen and differentiate between empathic fear-susceptible mice and resilient mice, and refining the translational applicability of these models.
Evidence of a Causal Relationship Between Vitamin D Status and Risk of Psoriasis From the UK Biobank Study
Authors: Zhang Yan , Jing Danrong , Zhou Guowei , Xiao Yi , Shen Minxue , Chen Xiang , Liu Hong 
Published: July 2022

BackgroundPlenty of observational studies suggested that vitamin D concentrations were associated with psoriasis, but the causality of this relationship was elusive.ObjectiveTo investigate the causal relationship between vitamin D and psoriasis.MethodsCox proportional hazard model was used to investigate the association between vitamin D status and psoriasis in a prospective cohort study from UK Biobank. Single nucleotide polymorphisms (SNPs) that are strongly associated with circulating 25OHD were constructed as instrumental variables in Mendelian randomization (MR) to determine the causality between vitamin D and psoriasis.ResultsDuring a median follow-up of 10.99 years, we identified 2,856 participants with incident psoriasis. The prospective cohort study demonstrated individuals with 25OHD deficiency (&lt; 25 nmol/L) at baseline were associated with approximately 20% increased risk of incident psoriasis in different categories of sex, age, and body mass index (BMI) after adjusting for covariates. The largest effect size was observed in the obese group (BMI &gt; 30 kg/m2), as 25OHD deficiency presented with 30% additional risk of incident psoriasis compared to those with 25OHD &gt; 50 nmol/L (HR = 0.701; 95% CI: 0.583–0.843; p &lt; 0.001). Additionally, 69 independent SNPs associated with circulating 25OHD level were selected for the MR analysis, and the result suggested that genetically predicted one standard deviation (SD) increment in log-transformed 25OHD was associated with 24% decreased risk of psoriasis (OR = 0.76; 95% CI: 0.60–0.98, p = 0.020).LimitationsThe association of 25OHD and severity of psoriasis could not be estimated in the current study.ConclusionThe combined prospective and MR analysis additionally provided evidence that the epidemiologically and genetically determined level of 25OHD conferred an increased risk of psoriasis.
Association of folate and vitamin B12 imbalance with adverse pregnancy outcomes among 11,549 pregnant women: An observational cohort study
Authors: Yuan Xiaosong , Han Xiaoya , Zhou Wenbo , Long Wei , Wang Huiyan , Yu Bin , Zhang Bin 
Published: July 2022

ObjectiveThis study aimed to evaluate maternal serum levels of folate, vitamin B12, and their ratio on admission for labor and determine whether an imbalance between folate and vitamin B12, represented by a higher or lower serum folate to vitamin B12 ratio (SFVB12R), was associated with adverse pregnancy outcomes.MethodsA retrospective cohort study of 11,549 pregnant women attending a district specialized hospital and who had serum folate (SF) and serum vitamin B12 (SVB12) levels measured at delivery was performed. The levels of SF, SVB12, and SFVB12R were defined as high (&gt;95th percentile), normal (5–95th percentile), and low (&lt;5th percentile). Information on pregnancy outcomes was retrieved from medical records. Linear regression was performed to examine the association of abnormal SF, SVB12, and SFVB12R levels with fetal growth indicators. Logistic regression was applied to estimate the association between abnormal SF, SVB12, and SFVB12R levels and pregnancy outcomes.ResultsLower SF levels were associated with higher risks of intrahepatic cholestasis of pregnancy (ICP, OR 1.58; 95% CI 1.15–2.17), pre-eclampsia (PE, OR 1.89; 95% CI 1.28–2.81), and a lower risk of gestational diabetes mellitus (GDM, OR 0.40; 95% CI 0.23–0.70), whereas higher SVB12 levels were associated with a higher risk of ICP (OR 2.22; 95% CI 1.67–2.96), PE (OR 1.69; 95% CI 1.04-2.74), and GDM (OR 1.62; 95% CI 1.24–2.11). A higher SFVB12R increased birthweight (β 60.99; 95% CI 29.52–92.45) and was associated with a higher risk of large-for-gestational-age (LGA) newborns (OR 3.08; 95% CI 1.63–5.83); a lower SFVB12R decreased birthweight (β −43.81; 95% CI −75.62, −12.00) and was associated with a lower risk of LGA newborns (OR 0.75; 95% CI 0.56–1.00), and with higher risks of ICP (OR 2.03; 95% CI 1.54–2.67) and pregnancy-induced hypertension (PIH, OR 1.81; 95% CI 1.09–3.00).ConclusionAn imbalance between folate and vitamin B12, represented by a higher or lower SFVB12R before delivery, was significantly associated with adverse pregnancy outcomes (ICP/PIH/LGA).
Computational Analysis of Pathological Image Enables Interpretable Prediction for Microsatellite Instability
Authors: Zhu Jin , Wu Wangwei , Zhang Yuting , Lin Shiyun , Jiang Yukang , Liu Ruixian , Zhang Heping , Wang Xueqin 
Published: July 2022

BackgroundMicrosatellite instability (MSI) is associated with several tumor types and has become increasingly vital in guiding patient treatment decisions; however, reasonably distinguishing MSI from its counterpart is challenging in clinical practice.MethodsIn this study, interpretable pathological image analysis strategies are established to help medical experts to identify MSI. The strategies only require ubiquitous hematoxylin and eosin–stained whole-slide images and perform well in the three cohorts collected from The Cancer Genome Atlas. Equipped with machine learning and image processing technique, intelligent models are established to diagnose MSI based on pathological images, providing the rationale of the decision in both image level and pathological feature level.FindingsThe strategies achieve two levels of interpretability. First, the image-level interpretability is achieved by generating localization heat maps of important regions based on deep learning. Second, the feature-level interpretability is attained through feature importance and pathological feature interaction analysis. Interestingly, from both the image-level and feature-level interpretability, color and texture characteristics, as well as their interaction, are shown to be mostly contributed to the MSI prediction.InterpretationThe developed transparent machine learning pipeline is able to detect MSI efficiently and provide comprehensive clinical insights to pathologists. The comprehensible heat maps and features in the intelligent pipeline reflect extra- and intra-cellular acid–base balance shift in MSI tumor.
Low red blood cell predicts high risk of temporary postoperative complications after carotid body tumor surgical resection
Authors: Han Tonglei , Wang Shiying , Zhu Jiang , Sun Yudong , Xie Yongfu , Wei Xiaolong , Zhou Jian , Zhao Zhiqing 
Published: July 2022

BackgroundCarotid body tumor (CBT) is a rare paraganglioma located at the carotid bifurcation. The red blood cell count, hemoglobin, and hematocrit are indexes to be evaluated in blood routine tests. The purpose of this study was to clarify their predictive value for temporary postoperative complications in patients that had undergone CBT surgery.MethodsThis retrospective trial included data from 169 patients received surgical treatment for CBT from October 2008 to September 2018 in this retrospective study. Postoperative follow-up was conducted under the guidance of both vascular surgeon and neurologist. The symptoms existed less than 2 years postoperatively were regarded as temporary injuries. The red blood cell count, hemoglobin, and hematocrit were obtained from the complete blood count results of the participants. Analyses of multilevel multivariable regression and descriptive statistics were conducted.ResultsThe baseline data showed no significant difference. Patients were predominantly women (53.8%), with a mean age of 42.6 years. The total incidence of temporary postoperative complications was 22 (13.0%), including transient ischemic attack (8, 4.7%), tongue bias (7, 4.1%), dysphagia (2, 1.2%), hoarseness (4, 1.8%), and eyelid ptosis (1, 2.4%). The univariate and multivariate regression analysis results revealed that the occurrence of temporary postoperative complications was increased with age [odd ratio (OR, 0.09; 95% CI (CI), 0.9–1.0; P = 0.014], length of operation time (OR, 1.0; 95% CI, 1.0–1.0; P = 0.005), Shamblin type II vs. I (OR, 0.1; 95% CI, 0.0–0.5; P = 0.008), red blood cell count postoperative (OR, 0.2; 95% CI, 0.1–0.8; P = 0.026), hemoglobin (OR, 0.9; 95% CI, 0.9–1.0; P = 0.011), and hematocrit (OR, 0.8; 95% CI, 0.7–1.0; P = 0.025). The smooth curve fitting showed that the trend of complications occurrence rate was reduced with the increase of patients’ postoperative red blood cell count, hemoglobin, and hematocrit. Gender, weight, length of operation, Shamblin type, postoperative red blood cell count, hemoglobin, and hematocrit were included in the risk model with AUC = 0.86.ConclusionThese patients with CBT who received surgical resection with low postoperative red blood cell, hemoglobin, or hematocrit had a high risk of temporary postoperative complications. The risk prediction model established for predicting temporary postoperative complications showed satisfactory prediction effects.
Prematurity is a critical risk factor for respiratory failure after early inguinal hernia repair under general anesthesia
Authors: Schroepf Sebastian , Mayle Paulina M. , Kurz Matthias , Wermelt Julius Z. , Hubertus Jochen 
Published: July 2022

IntroductionThe purpose of this study was to determine the earliest timing of inguinal hernia repair under general anesthesia with minimized risk for respiratory complications during postoperative course.MethodsWe performed a monocentric analysis of patient records of premature and full-term infants undergoing inguinal hernia repair between 2009 and 2016. In addition to demographic and medical parameters, preexisting conditions and the perioperative course were recorded.ResultsThe study included 499 infants (preterm n = 285; full term n = 214). The number of subsequently ventilated patients was particularly high among preterm infants with bronchopulmonary dysplasia, up to 45.3% (p &lt; 0.001). Less than 10% of subsequent ventilation occurred in preterm infants after 45 weeks of postmenstrual age at the time of surgery or in patients with a body weight of more than 4,100 g. Preterm infants with a bronchopulmonary dysplasia had an increased risk of apneas (p &lt; 0.05). Only 10% of the preterm babies with postoperative apneas weighed more than 3,600 g at the time of surgery or were older than 44 weeks of postmenstrual age.ConclusionOur data indicate that after the 45th week of postmenstrual age and a weight above 4,100 g, the risk for respiratory failure after general anesthesia seems to be significantly decreased in preterm infants.
Prediction of adolescent suicidal ideation after the COVID-19 pandemic: A nationwide survey of a representative sample of Korea
Authors: Byeon Haewon 
Published: July 2022

ObjectiveThis study developed a model to predict groups vulnerable to suicidal ideation after the declaration of the COVID-19 pandemic based on nomogram techniques targeting 54,948 adolescents who participated in a national survey in South Korea.MethodsThis study developed a model to predict suicidal ideation by using logistic regression analysis. The model aimed to understand the relationship between predictors associated with the suicidal ideation of South Korean adolescents by using the top seven variables with the highest feature importance confirmed in XGBoost (extreme gradient boosting). The regression model was developed using a nomogram so that medical workers could easily interpret the probability of suicidal ideation and identify groups vulnerable to suicidal ideation.ResultsThis epidemiological study predicted that eighth graders who experienced depression in the past 12 months, had a lot of subjective stress, frequently felt lonely in the last 12 months, experienced much-worsened household economic status during the COVID-19 pandemic, and had poor academic performance were vulnerable to suicidal ideation. The results of 10-fold cross-validation revealed that the area under the curve (AUC) of the adolescent suicidal ideation prediction nomogram was 0.86, general accuracy was 0.89, precision was 0.87, recall was 0.89, and the F1-score was 0.88.ConclusionIt is required to recognize the seriousness of adolescent suicide and mental health after the onset of the COVID-19 pandemic and prepare a customized support system that considers the characteristics of persons at risk of suicide at the school or community level.