bluuebunny/crossref_metadata_2025_split huggingface dataset:
Case Report: Significant Response to the Combination of Lenvatinib and Immune Checkpoint Inhibitor in a Patient With Heavily Pretreated Metastatic Triple Negative Breast Cancer
Authors: Lee Jin Sun , Yost Susan E. , Yuan Yuan 
Published: January 2021

BackgroundTriple negative breast cancer (TNBC) has poor prognosis without targetable mutations. The combination of lenvatinib and pembrolizumab has shown clinical activity in different types of solid tumors.Case PresentationWe report a case of one patient with metastatic TNBC who has been heavily pretreated. The patient had been treated with multiple lines (≥ 8 lines) of chemotherapy without durable clinical responses. Her tumor regressed significantly under the combination of lenvatinib and immune checkpoint inhibitor, and remains stable for 10 months.ConclusionsThe combination of lenvatinib and immune checkpoint inhibitor may have significant clinical activity in selective patients with heavily pretreated metastatic TNBC.
Dosimetry of Submandibular Glands on Xerostomia for Nasopharyngeal Carcinoma
Authors: Pan Xin-Bin , Liu Yang , Huang Shi-Ting , Pei Su , Chen Kai-Hua , Qu Song , Li Ling , Zhu Xiao-Dong 
Published: January 2021

PurposeTo investigate dosimetry of submandibular glands on xerostomia after intensity-modulated radiotherapy for nasopharyngeal carcinoma (NPC).MethodsFrom September 2015 to March 2016, 195 NPC patients were investigated. Xerostomia was evaluated at 12 months after treatment via the RTOG/EORTC system. The least absolute shrinkage and selection operator regression model was used to optimize feature selection for grades 2–3 xerostomia. Multivariable logistic regression analysis was applied to build a predicting model incorporating the feature selected in the least absolute shrinkage and selection operator regression model. Discrimination, calibration, and clinical usefulness of the predicting model were assessed using the C-index, calibration plot, and decision curve analysis.ResultsThe V30 of the parotid glands was selected based on the least absolute shrinkage and selection operator regression. The nomogram displayed good discrimination with a C-index of 0.698 (95% confidence interval [CI]: 0.626–0.771) and good calibration (model 1). Addition of the dosimetric parameters including the mean dose to the submandibular glands, V50 of the submandibular glands, and volume of the submandibular glands to the model 1 failed to show incremental prognostic value (model 2). The model 2 showed a C-index of 0.704 (95% CI: 0.632–0.776). Decision curve analysis demonstrated that the model 1 was clinically useful when intervention was decided at the possibility threshold of &gt; 20%. Within this range, net benefit was comparable between the model 1 and model 2.ConclusionPGv30 was a major predictive factor of grades 2–3 xerostomia for NPC. In contrast, the mean dose to the submandibular glands, V50 of the submandibular glands, and volume of the submandibular glands were not independent predictive factors.
NRF2 -617 C/A Polymorphism Impacts Proinflammatory Cytokine Levels, Survival, and Transplant-Related Mortality After Hematopoietic Stem Cell Transplantation in Adult Patients Receiving Busulfan-Based Conditioning Regimens
Authors: Huang Jingjing , Hao Chenxia , Li Ziwei , Wang Ling , Jiang Jieling , Tang Wei , Wang Lining , Zhang Weixia , Hu Jiong , Yang Wanhua 
Published: January 2021

Busulfan (BU) is widely used in conditioning regimens prior to hematopoietic stem cell transplantation (HSCT). The exposure-escalated BU directed by therapeutic drug monitoring (TDM) is extremely necessary for the patients with high-risk hematologic malignancies in order to diminish relapse, but it increases the risk of drug-induced toxicity. BU exposure, involved in the glutathione- (GSH-) glutathione S-transferases (GSTs) pathway and proinflammatory response, is associated with clinical outcomes after HSCT. However, the expression of genes in the GSH-GSTs pathway is regulated by NF-E2-related factor 2 (Nrf2) that can also alleviate inflammation. In this study, we evaluated the influence of NRF2 polymorphisms on BU exposure, proinflammatory cytokine levels, and clinical outcomes in HSCT patients. A total of 87 Chinese adult patients receiving twice-daily intravenous BU were enrolled. Compared with the patients carrying wild genotypes, those with NRF2 -617 CA/AA genotypes showed higher plasma interleukin (IL)-6, IL-8 and tumor necrosis factor (TNF)-α levels, poorer overall survival (OS; RR = 3.91), and increased transplant-related mortality (TRM; HR = 4.17). High BU exposure [area under the concentration-time curve (AUC) &gt; 9.27 mg/L × h)] was related to BU toxicities. Furthermore, NRF2 -617 CA/AA genotypes could significantly impact TRM (HR = 4.04; p = 0.0142) and OS (HR = 3.69; p = 0.0272) in the patients with high BU AUC. In vitro, we found that high exposure of endothelial cell (EC) to BU, in the absence of Nrf2, elicited the hyperstimulation of NF-κB-p65, accompanied with the elevated secretion of proinflammatory cytokines, and led to EC death. These results showed that NRF2 -617 CA/AA genotypes, correlated with high proinflammatory cytokine levels, could predict inferior outcomes in HSCT patients with high BU AUC. Thus, NRF2 -617 CA/AA genotyping combined with TDM would further optimize personalized BU dosing for sufficient efficacy and safety endpoint.
Salvianolic Acid B Protects Against Fatty Acid-Induced Renal Tubular Injury via Inhibition of Endoplasmic Reticulum Stress
Authors: Mai Xiaoyi , Yin Xin , Chen Peipei , Zhang Minzhou 
Published: January 2021

Background/Aims: Obesity-related kidney disease is associated with elevated levels of saturated free fatty acids (SFA). SFA lipotoxicity in tubular cells contributes to significant cellular apoptosis and injury. Salvianolic acid B (SalB) is the most abundant bioactive molecule from Radix Salviae Miltiorrhizae. In this study, we investigated the effect of SalB on SFA-induced renal tubular injury and endoplasmic reticulum (ER) stress, in vivo and in vitro.Methods: C57BL/6 mice were assigned to five groups: a control group with normal diet (Nor), high-fat diet group (HFD), and HFD with three different SalB treatment doses, low (SalBL; 3 mg/kg), medium (SalBM; 6.25 mg/kg), and high (SalBH; 12.5 mg/kg) doses. SalB was intraperitoneally injected daily for 4 weeks after 8 weeks of HFD. After 12 weeks, mice were sacrificed and kidneys and sera were collected. Apoptosis and ER stress were induced in human proximal tubule epitelial (HK2) cells by palmitic acid (PA, 0.6 mM), tunicamycin (TM, 1 μg/ml), or thapsigargin (TG, 200 nM) in vitro.Results: C57BL/6 mice fed a high-fat diet (HFD) for 12 weeks exhibited increased apoptosis (Bax and cleaved caspase-3) and ER stress (BIP, P-eIF2α, ATF4, CHOP, ATF6, IRE1α, and XBP1s) markers expression in the kidney, compared with control mice, which were remarkably suppressed by SalB treatment. In vitro studies showed that PA (0.6 mM) induced apoptosis and ER stress in cultured HK2 cells. SalB treatment attenuated all the adverse effects of PA. However, SalB failed to inhibit TM or TG-induced ER stress in HK2 cells.Conclusion: The study indicated that SalB may play an important role in obesity-related kidney injury via mediating SFA-induced ER stress.
A New Framework to Implement Model-Informed Dosing in Clinical Guidelines: Piperacillin and Amikacin as Proof of Concept
Authors: Hartman Stan J. F. , Swaving Joost G. E. , van Beek Stijn W. , van Groen Bianca D. , de Hoop Marika , van der Zanden Tjitske M. , ter Heine Rob , de Wildt Saskia N. 
Published: January 2021

Background: Modeling and simulation is increasingly used to study pediatric pharmacokinetics, but clinical implementation of age-appropriate doses lags behind. Therefore, we aimed to develop model-informed doses using published pharmacokinetic data and a decision framework to adjust dosing guidelines based on these doses, using piperacillin and amikacin in critically ill children as proof of concept.Methods: Piperacillin and amikacin pharmacokinetic models in critically ill children were extracted from literature. Concentration-time profiles were simulated for various dosing regimens for a virtual PICU patient dataset, including the current DPF dose and doses proposed in the studied publications. Probability of target attainment (PTA) was compared between the different dosing regimens. Next, updated dosing recommendations for the DPF were proposed, and evaluated using a new framework based on PK study quality and benefit-risk analysis of clinical implementation.Results: Three studies for piperacillin (critically ill children) and one for amikacin (critically ill pediatric burn patients) were included. Simulated concentration-time profiles were performed for a virtual dataset of 307 critically ill pediatric patients, age range 0.1–17.9 y. PTA for unbound piperacillin trough concentrations &gt;16 mg/L was &gt;90% only for continuous infusion regimens of 400 mg/kg/day vs. 9.7% for the current DPF dose (80 mg/kg/6 h, 30 min infusion). Amikacin PTA was &gt;90% with 20 mg/kg/d, higher than the PTA of the DPF dose of 15 mg/kg/d (63.5%). Using our new decision framework, altered DPF doses were proposed for piperacillin (better PTA with loading dose plus continuous infusion), but not for amikacin (studied and target population were not comparable and risk for toxicity with higher dose).Conclusions: We show the feasibility to develop model-informed dosing guidelines for clinical implementation using existing pharmacokinetic data. This approach could complement literature and consensus-based dosing guidelines for off-label drugs in the absence of stronger evidence to support pediatricians in daily practice.
Violence Exposure Is Associated With Atypical Appraisal of Threat Among Women: An EEG Study
Authors: Perizzolo Pointet Virginie Chloé , Moser Dominik Andrea , Vital Marylène , Rusconi Serpa Sandra , Todorov Alexander , Schechter Daniel Scott 
Published: January 2021

IntroductionThe present study investigates the association of lifetime interpersonal violence (IPV) exposure, related posttraumatic stress disorder (IPV-PTSD), and appraisal of the degree of threat posed by facial avatars.MethodsWe recorded self-rated responses and high-density electroencephalography (HD-EEG) among women, 16 of whom with lifetime IPV-PTSD and 14 with no PTSD, during a face-evaluation task that displayed male face avatars varying in their degree of threat as rated along dimensions of dominance and trustworthiness.ResultsThe study found a significant association between lifetime IPV exposure, under-estimation of dominance, and over-estimation of trustworthiness. Characterization of EEG microstates supported that lifetime IPV-PTSD modulates emotional appraisal, specifically in encoding and decoding processing associated with N170 and LPP evoked potentials. EEG source localization demonstrated an overactivation of the limbic system, in particular the parahippocampal gyrus, in response to non-threatening avatars. Additionally, dysfunctional involvement of attention-related processing anterior prefrontal cortex (aPFC) was found in response to relatively trustworthy avatars in IPV-PTSD individuals compared with non-PTSD controls.DiscussionThis study showed that IPV exposure and related PTSD modulate individuals’ evaluation of facial characteristics suggesting threat. Atypical processing of these avatar characteristics was marked by group differences in brain regions linked to facial processing, emotion regulation, and memory.
Early Life Stress Predicts Depressive Symptoms in Adolescents During the COVID-19 Pandemic: The Mediating Role of Perceived Stress
Authors: Gotlib Ian H. , Borchers Lauren R. , Chahal Rajpreet , Gifuni Anthony J. , Teresi Giana I. , Ho Tiffany C. 
Published: January 2021

BackgroundExposure to early life stress (ELS) is alarmingly prevalent and has been linked to the high rates of depression documented in adolescence. Researchers have theorized that ELS may increase adolescents’ vulnerability or reactivity to the effects of subsequent stressors, placing them at higher risk for developing symptoms of depression.MethodsWe tested this formulation in a longitudinal study by assessing levels of stress and depression during the COVID-19 pandemic in a sample of adolescents from the San Francisco Bay Area (N = 109; 43 male; ages 13–20 years) who had been characterized 3–7 years earlier (M = 5.06, SD = 0.86 years) with respect to exposure to ELS and symptoms of depression.ResultsAs expected, severity of ELS predicted levels of depressive symptoms during the pandemic [r(107) = 0.26, p = 0.006], which were higher in females than in males [t(107) = −3.56, p &lt; 0.001]. Importantly, the association between ELS and depression was mediated by adolescents’ reported levels of stress, even after controlling for demographic variables.ConclusionsThese findings underscore the importance of monitoring the mental health of vulnerable children and adolescents during this pandemic and targeting perceived stress in high-risk youth.
Parents' Experiences and Perspectives Toward Tuberculosis Treatment Success Among Children in Malaysia: A Qualitative Study
Authors: Awaluddin S. Maria , Ismail Nurhuda , Yasin Siti Munira , Zakaria Yuslina , Mohamed Zainudin Norzila , Kusnin Faridah , Mohd Yusoff Mas Ahmad Sherzkawee , Razali Asmah 
Published: January 2021

Introduction: The trends of tuberculosis (TB) treatment success rate among children in Malaysia plateaued at 90% from 2014 to 2017. Malaysia sets a higher treatment success target of 95% to be achieved in line with an affordable, accessible, and holistic approach in managing TB among children.Objective: This study aims to explore the parents' experiences and perspectives toward achieving treatment success among children who were diagnosed with TB in two districts in Selangor state, Malaysia.Methods: The study was conducted using phenomenology study design via an in-depth interview of 15 mothers who were purposively sampled from the list of pediatric TB cases in the MyTB version 2.1 database in Klang and Petaling Districts of Selangor state. The R-based qualitative data analysis package of R version 0.2-8 was used to perform the thematic analysis.Results: Two main themes were identified from this study. The first theme was trust toward the healthcare services with the subthemes of acceptance, self-efficacy, holistic care, and perceived benefits. The second theme was the motivation to take or continue medication. The subthemes were support from family, healthcare workers' (HCWs') support, the convenience of healthcare services, community support, personal strength, and child's character.Conclusion: TB treatment success for children can be achieved when parents develop trust in healthcare services and have strong motivational factors to remain steadfast in achieving a successful treatment goal. Psychosocial support should be provided to the primary caregiver who faced any difficulty, while good relationships between parents and HCWs should be maintained. These results will inform the TB program managers to strengthen the holistic approach and identify the motivational factors among parents of children with TB disease.
Equity and Efficiency of Health Resource Allocation of Chinese Medicine in Mainland China: 2013–2017
Authors: Li Zhengjun , Yang Lili , Tang Shaoliang , Bian Yaoyao 
Published: January 2021

Background: In this study, we aimed to estimate the equity and efficiency of traditional Chinese medicine (TCM) health resource allocation, utilization, and trend in mainland China from 2013 to 2017.Methods: The data were downloaded from the China Health Statistical Yearbook (2014–2018) and the China Statistical Yearbook (2018). The equity of TCM health resource allocation was evaluated through the Lorenz curve, Gini coefficient (G), and Theil index (T) based on population size and geographical area. The efficiency and productivity of TCM health resource utilization were assessed using the data envelopment analysis-based Malmquist productivity index.Results: TCM health resource had an increasing trend every year. The equity allocated by population (G ranging from 0.1 to 0.3) was better than that by geographic region (G &gt; 0.5). T in the intra-groups was higher than those in the inter-groups. The equity of TCM resource allocation was the middle region &gt; eastern region &gt; western region. Most provinces (29 out of 31) had negative productivity changes, suggesting deterioration in productivity. Moreover, the middle region with higher scale sizes had more redundant inputs than the other two regions. However, the low technological development (all technical values &lt;1) might hinder productive progress.Conclusion: The equity of TCM health allocated by the population was better than that by the geographic region. The intra-regional difference was the main reason for inequity sources. Productivities in more than 97% of provinces are inefficient. The frequency distribution of scale efficiency (score &gt; 1) had increased since 2015. However, the frequency distribution of technical change (score &gt; 1) decreased every year. The slow technological progress and low scale size might be the main reasons for low productivity.
A Qualitative Assessment of Mothers' Experience With Pediatric Anemia Care in Arequipa, Peru
Authors: Louzado-Feliciano Paola , Vargas Brianna , Dandu Madhavi , Fuller Shannon , Santos Nicole , Quiñones Ángela , Martin Holly M. , Caban-Martinez Alberto J. 
Published: January 2021

Background: Despite national efforts to control pediatric anemia in Peru, each year, 67.4% of all newborns are diagnosed with anemia during their first year of life. The literature on Peruvian mothers' understanding and beliefs of pediatric anemia is limited. In the present study, we aimed to understand mother's perspective of pediatric anemia and explore their perceptions on how to prevent and treat anemia in Peru.Methods: During May–June 2018, we administered a short demographic questionnaire and conducted language-sensitive interviews with mothers of children clinically diagnosed with anemia in three different governmental health centers in Arequipa, Peru. Interviews were audio-recorded and transcribed verbatim. We used the Framework Analysis approach to analyze qualitative data.Results: A total of 14 Peruvian mothers were interviewed. Across interviews, three main themes emerged: (I) Mothers' Understanding of Pediatric Anemia; (II) Attitudes about Provider Recommendations for Pediatric Anemia Control; and (III) Barriers to Effective Pediatric Anemia Control. Peruvian mothers expressed skepticism toward national pediatric anemia guidelines as they believe recommendations received at health clinics jeopardized their children's overall health. Participants identified several barriers to effective anemia control: limited and confusing health information received during pediatric healthcare appointments, lack of systematic protocols in health clinics, and inconsistent referral processes.Conclusion: We identified factors that limit the acceptance of current pediatric anemia control guidelines followed at governmental health centers in Arequipa, Peru. Understanding maternal beliefs concerning pediatric anemia can guide future anemia control guidelines at the primary care level for pediatric patients in Peru.
Prophylactic Onlay Mesh Implantation During Definitive Fascial Closure After Open Abdomen Therapy (PROMOAT): Absorbable or Non-absorbable? Methodical Description and Results of a Feasibility Study
Authors: Schaaf Sebastian , Schwab Robert , Güsgen Christoph , Willms Arnulf 
Published: January 2021

Introduction: Incisional hernia development after open abdomen therapy (OAT) remains a common complication in the long run. To demonstrate the feasibility, we describe our method of prophylactic onlay mesh implantation with definitive fascial closure after open abdomen therapy (PROMOAT). To display the feasibility of this concept, we evaluated the short-term outcome after absorbable and non-absorbable synthetic mesh implantation as prophylactic onlay.Material and Methods: Ten patients were prospectively enrolled, and prophylactic onlay mesh (long-term absorbable or non-absorbable) was implanted at the definitive fascial closure operation. The cohort was followed up with a special focus on incisional hernia development and complications.Results: OAT duration was 21.0 ± 12.6 days (95% CI: 16.9–25.1). Definitive fascial closure was achieved in all cases. No incisional hernias were present during a follow-up interval of 12.4 ± 10.8 months (range 1–30 months). Two seromas and one infected hematoma occurred. The outcome did not differ between mesh types.Conclusion: The prophylactic onlay mesh implantation of alloplastic, long-term absorbable, or non-absorbable meshes in OAT showed promising results and only a few complications that were of minor concern. Incisional hernias did not occur during follow-up. To validate the feasibility and safety of prophylactic onlay mesh implantation long-term data and large-scaled prospective trials are needed to give recommendations on prophylactic onlay mesh implantation after OAT.
Machine Learning for Prediction of Patients on Hemodialysis with an Undetected SARS-CoV-2 Infection
Authors: Monaghan Caitlin K. , Larkin John W. , Chaudhuri Sheetal , Han Hao , Jiao Yue , Bermudez Kristine M. , Weinhandl Eric D. , Dahne-Steuber Ines A. , Belmonte Kathleen , Neri Luca , Kotanko Peter , Kooman Jeroen P. , Hymes Jeffrey L. , Kossmann Robert J. , Usvyat Len A. , Maddux Franklin W. 
Published: January 2021

Background
We developed a machine learning (ML) model that predicts the risk of a patient on hemodialysis (HD) having an undetected SARS-CoV-2 infection that is identified after the following ≥3 days.

Methods
As part of a healthcare operations effort, we used patient data from a national network of dialysis clinics (February–September 2020) to develop an ML model (XGBoost) that uses 81 variables to predict the likelihood of an adult patient on HD having an undetected SARS-CoV-2 infection that is identified in the subsequent ≥3 days. We used a 60%:20%:20% randomized split of COVID-19–positive samples for the training, validation, and testing datasets.

Results
We used a select cohort of 40,490 patients on HD to build the ML model (11,166 patients who were COVID-19 positive and 29,324 patients who were unaffected controls). The prevalence of COVID-19 in the cohort (28% COVID-19 positive) was by design higher than the HD population. The prevalence of COVID-19 was set to 10% in the testing dataset to estimate the prevalence observed in the national HD population. The threshold for classifying observations as positive or negative was set at 0.80 to minimize false positives. Precision for the model was 0.52, the recall was 0.07, and the lift was 5.3 in the testing dataset. Area under the receiver operating characteristic curve (AUROC) and area under the precision-recall curve (AUPRC) for the model was 0.68 and 0.24 in the testing dataset, respectively. Top predictors of a patient on HD having a SARS-CoV-2 infection were the change in interdialytic weight gain from the previous month, mean pre-HD body temperature in the prior week, and the change in post-HD heart rate from the previous month.

Conclusions
The developed ML model appears suitable for predicting patients on HD at risk of having COVID-19 at least 3 days before there would be a clinical suspicion of the disease.