bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of the Lung Immune Prognostic Index in Non-Small Cell Lung Cancer Patients Treated With Systemic Therapy: A Retrospective Study and Meta-Analysis
Authors: Huang Litang , Han Hedong , Zhou Li , Chen Xi , Xu Qiuli , Xie Jingyuan , Zhan Ping , Chen Si , Lv Tangfeng , Song Yong 
Published: June 2021

The lung immune prognostic index (LIPI) has been shown to be an important prognostic marker for various tumors. However, the prognostic value of LIPI among non-small cell lung cancer (NSCLC) patients treated with systemic therapy remains controversial. We aimed to evaluate survival status according to LIPI among NSCLC patients receiving different forms of systemic therapy at our institution. We also performed a meta-analysis of articles from PubMed and Embase to illustrate this question. For our cohort, we found that good LIPI was associated with better overall survival (OS) among 91 patients on immunotherapy, 329 patients on targeted therapy, and 570 patients on chemotherapy. For the meta-analysis, a total of eight studies with 8,721 patients were included. Pooled results showed that a higher LIPI (those with 1 or 2 factors) was associated with poor overall progression-free survival (PFS) (hazard ratio [HR], 1.57; 95% confidence interval [CI], 1.45−1.71) and OS (HR, 2.01; 95% CI, 1.75−2.31). Subgroup analyses showed that a higher LIPI was related to poor survival among patients prescribed different systemic therapies: immunotherapy (OS HR, 2.50; 95% CI, 1.99–3.13; PFS HR, 1.77; 95% CI, 1.56–2.01), chemotherapy (OS HR, 1.58; 95% CI, 1.34–1.86; PFS HR, 1.38; 95% CI, 1.23–1.55), and targeted therapy (OS HR; 2.15, 95% CI, 1.57–2.96; PFS HR, 1.60; 95% CI, 1.25–2.06). The study shows that the LIPI is a clinically significant prognostic factor for NSCLC patients receiving systemic therapy.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD420209009.
Predicting Severe Radiation Esophagitis in Patients With Locally Advanced Esophageal Squamous Cell Carcinoma Receiving Definitive Chemoradiotherapy: Construction and Validation of a Model Based in the Clinical and Dosimetric Parameters as Well as Inflammatory Indexes
Authors: Yu Yilin , Zheng Hongying , Liu Lingyun , Li Hui , Zheng Qunhao , Wang Zhiping , Wu Yahua , Li Jiancheng 
Published: June 2021

ObjectiveRadiation esophagitis (RE) is common in patients treated with radiotherapy (RT) for locally advanced esophageal squamous cell carcinoma (ESCC). We aim to construct a nomogram predicting the severe RE (grade ≥2) in patients with ESCC receiving definitive chemoradiotherapy (dCRT).Materials and MethodsLogistic regression was performed to evaluate the risk factors in predicting RE. Nomogram was built based on the multivariate analysis result. The model was validated using the area under the receiver operating curve (ROC) curve (AUC), calibration curves, and decision curve analyses (DCA). Spearman correlation analysis was used to evaluate the correlation between inflammation indexes.ResultsA total of 547 patients with stage II–IVA ESCC treated with dCRT from the retrospective study were included. Two hundred and thirty-two of 547 patients (42.4%) developed grade ≥2 RE. Univariate analysis indicated that gender (p = 0.090), RT dose (p &lt; 0.001), targeted therapy (p = 0.047), tumor thickness (p = 0.013), lymphocyte-monocyte ratio (LMR, p = 0.016), neutrophil-lymphocyte ratio (NLR, p &lt; 0.001), and platelet-lymphocyte ratio (PLR, p &lt; 0.001) were the significant factors for a higher incidence of RE. In multivariate analysis, RT dose [p &lt; 0.001; odds ratio (OR), 4.680; 95% confidence interval (CI), 2.841–6.709], NLR (p &lt; 0.001; OR, 0.384; 95% CI, 0.239–0.619), and PLR (p &lt; 0.001; OR, 3.539; 95% CI: 2.226–5.626) were independently associated grade ≥2 RE and were involved in the nomogram. ROC curves showed the AUC of the nomogram was 0.714 (95% CI, 0.670–0.757), which was greater than each factor alone (RT dose: 0.615; NLR: 0.596; PLR: 0.590). Calibration curves showed good consistency between the actual observation and the predicted RE. DCA showed satisfactory positive net benefits of the nomogram among most threshold probabilities.ConclusionsThe study demonstrated that RT dose, NLR, and PLR were independent risk factors for grade ≥2 RE in patients with locally advanced ESCC receiving dCRT. A predictive model including all these factors was built and performed better than it based on each separately. Further validation in large patient populations is still warranted.
HER2 Positivity in Histological Subtypes of Salivary Gland Carcinoma: A Systematic Review and Meta-Analysis
Authors: Egebjerg Kristian , Harwood Cecilie Dupont , Woller Nina Claire , Kristensen Claus Andrup , Mau-Sørensen Morten 
Published: June 2021

BackgroundHER2 aberrations in salivary gland carcinomas (SGC) as well as benefit of HER2 directed therapy have been reported in small studies. However, reliable estimates of the prevalence of HER2 positivity in SGC and its various histological subtypes are lacking.ObjectiveTo assess the prevalence of HER2 positivity in histological subtypes of salivary gland carcinomas (SGC).MethodsStudies were identified by a systematic review of the literature. Data on in situ hybridization (ISH) and immunohistochemistry (IHC) were extracted to derive pooled prevalence estimates calculated by a random effects model. Characteristics of the studies were extracted for subgroup analysis.ResultsFifty studies including 3372 patients were identified, providing data on sixteen histological subtypes. Based on the meta-analysis, the estimated prevalence of HER2 positivity were 43% (95% CI: 36% – 51%) in salivary duct carcinoma (SDC), 39% (95% CI: 32% – 45%) in carcinoma ex pleomorphic adenoma (CEP), 17% (95% CI: 7.5% – 33%) in squamous cell carcinoma (SCC), 13% (95% CI: 7.6% – 21%) in adenocarcinoma NOS (ADC), 6.7% (95% CI: 0.17%-32%) in poorly differentiated carcinoma, 5.5% (95% CI: 2.9% – 9.6%) in mucoepidermoid carcinoma, 4.3% (95% CI: 1.4% – 13%) in myoepithelial carcinoma, 1.8% (95% CI: 0.04%-9.6%) in epithelial-myoepithelial carcinoma, 0.45% (95% CI: 0.0097% – 18%) in acinic cell carcinoma and 0.15% (0.037% – 5.4%) in adenoid cystic carcinoma. Estimates for five additional subtypes were assessed.ConclusionPrevalence of HER 2 positivity in SGC varies greatly based on histological subtype, with SDC, CEP, SCC, and ADC displaying the highest rates.
Clinical Implementation of Automated Treatment Planning for Rectum Intensity-Modulated Radiotherapy Using Voxel-Based Dose Prediction and Post-Optimization Strategies
Authors: Zhong Yang , Yu Lei , Zhao Jun , Fang Yingtao , Yang Yanju , Wu Zhiqiang , Wang Jiazhou , Hu Weigang 
Published: June 2021

PurposeThis study aims to demonstrate the feasibility of clinical implementation of automated treatment planning (ATP) using voxel-based dose prediction and post-optimization strategies for rectal cancer on uRT (United Imaging Healthcare, Shanghai, China) treatment planning system.MethodsA total of 180 previously treated rectal cancer cases were enrolled in this study, including 160 cases for training, 10 for validation and 10 for testing. Using CT image data, planning target volumes (PTVs) and contour delineation of the organs at risk (OARs) as input and three-dimensional (3D) dose distribution as output, a 3D-Uet DL model was developed. Based on the voxel-wise prediction dose distribution, intensity-modulated radiation therapy (IMRT) plans were then generated automatedly using post-optimization strategies, including a complex clinical dose target metrics homogeneity index (HI) and conformation index (CI). To evaluate the performance of the proposed ATP approach, the dose-volume histogram (DVH) parameters of OARs and PTV and the 3D dose distributions of the plan were compared with those of manual plans.ResultsBy combining clinical post-optimization strategies, the automatically generated treatment plan can achieve better homogeneous PTV coverage and dose sparing for OARs except the mean dose for femoral-head compared with the use of the mean square error objective function alone. Compared with the manual plan, no statistically significant differences in HI, CI or global maximum dose were found. The manual plans perform slightly better than plans with post-optimization strategies in other dosimetric indexes, but these plans are still within clinical requirements.ConclusionsWith the help of clinical post-optimization strategies, the proposed new ATP solution can generate IMRT plans that are within clinically acceptable levels and comparable to plans manually generated by dosimetrists.
Influenza vs. COVID-19: Comparison of Clinical Characteristics and Outcomes in Pediatric Patients in Mexico City
Authors: Laris-González Almudena , Avilés-Robles Martha , Domínguez-Barrera Clemen , Parra-Ortega Israel , Sánchez-Huerta José Luis , Ojeda-Diezbarroso Karla , Bonilla-Pellegrini Sergio , Olivar-López Víctor , Chávez-López Adrián , Jiménez-Juárez Rodolfo 
Published: June 2021

Introduction: Respiratory viruses are among the leading causes of disease and death among children. Co-circulation of influenza and SARS-CoV2 can lead to diagnostic and management difficulties given the similarities in the clinical picture.Methods: This is a cohort of all children hospitalized with SARS-CoV2 infection from March to September 3rd 2020, and all children admitted with influenza throughout five flu-seasons (2013–2018) at a pediatric referral hospital. Patients with influenza were identified from the clinical laboratory database. All hospitalized patients with confirmed SARS-CoV2 infection were followed-up prospectively.Results: A total of 295 patients with influenza and 133 with SARS-CoV2 infection were included. The median age was 3.7 years for influenza and 5.3 years for SARS-CoV2. Comorbidities were frequent in both groups, but they were more common in patients with influenza (96.6 vs. 82.7%, p &lt; 0.001). Fever and cough were the most common clinical manifestations in both groups. Rhinorrhea was present in more than half of children with influenza but was infrequent in those with COVID-19 (53.6 vs. 5.8%, p &lt; 0.001). Overall, 6.4% percent of patients with influenza and 7.5% percent of patients with SARS-CoV2 infection died. In-hospital mortality and the need for mechanical ventilation among symptomatic patients were similar between groups in the multivariate analysis.Conclusions: Influenza and COVID-19 have a similar picture in pediatric patients, which makes diagnostic testing necessary for adequate diagnosis and management. Even though most cases of COVID-19 in children are asymptomatic or mild, the risk of death among hospitalized patients with comorbidities may be substantial, especially among infants.
Concentration-dependent alpha1-Adrenoceptor Antagonism and Inhibition of Neurogenic Smooth Muscle Contraction by Mirabegron in the Human Prostate
Authors: Huang Ru , Liu Yuhan , Ciotkowska Anna , Tamalunas Alexander , Waidelich Raphaela , Strittmatter Frank , Stief Christian G. , Hennenberg Martin 
Published: June 2021

Introduction: Mirabegron is available for treatment of storage symptoms in overactive bladder, which may be improved by β3-adrenoceptor-induced bladder smooth muscle relaxation. In addition to storage symptoms, lower urinary tract symptoms in men include obstructive symptoms attributed to benign prostatic hyperplasia, caused by increased prostate smooth muscle tone and prostate enlargement. In contrast to the bladder and storage symptoms, effects of mirabegron on prostate smooth muscle contraction and obstructive symptoms are poorly understood. Evidence from non-human smooth muscle suggested antagonism of α1-adrenoceptors as an important off-target effect of mirabegron. As α1-adrenergic contraction is crucial in pathophysiology and medical treatment of obstructive symptoms, we here examined effects of mirabegron on contractions of human prostate tissues and on proliferation of prostate stromal cells.Methods: Contractions were induced in an organ bath. Effects of mirabegron on proliferation, viability, and cAMP levels in cultured stromal cells were examined by EdU assays, CCK-8 assays and enzyme-linked immunosorbent assay.Results: Mirabegron in concentrations of 5 and 10 μM, but not 1 µM inhibited electric field stimulation-induced contractions of human prostate tissues. Mirabegron in concentrations of 5 and 10 µM shifted concentration response curves for noradrenaline-, methoxamine- and phenylephrine-induced contractions to the right, including recovery of contractions at high concentrations of α1-adrenergic agonists, increased EC50 values, but unchanged Emax values. Rightshifts of noradrenaline concentration response curves and inhibition of EFS-induced contractions were resistant to L-748,337, l-NAME, and BPIPP. 1 µM mirabegron was without effect on α1-adrenergic contractions. Endothelin-1- and U46619-induced contractions were not affected or only inhibited to neglectable extent. Effects of mirabegron (0.5–10 µM) on proliferation and viability of stromal cells were neglectable or small, reaching maximum decreases of 8% in proliferation assays and 17% in viability assays. Mirabegron did not induce detectable increases of cAMP levels in cultured stromal cells.Conclusion: Mirabegron inhibits neurogenic and α1-adrenergic human prostate smooth muscle contractions. This inhibition may be based on antagonism of α1-adrenoceptors by mirabegron, and does not include activation of β3-adrenoceptors and requires concentrations ranging 50-100fold higher than plasma concentrations reported from normal dosing. Non-adrenergic contractions and proliferation of prostate stromal cells are not inhibited by mirabegron.
The Effect of a Novel Serine Protease Inhibitor on Inflammation and Intestinal Permeability in a Murine Colitis Transfer Model
Authors: Van Spaendonk Hanne , Ceuleers Hannah , Smet Annemieke , Berg Maya , Joossens Jurgen , Van der Veken Pieter , Francque Sven M. , Lambeir Anne-Marie , De Man Joris G. , De Meester Ingrid , Augustyns Koen , De Winter Benedicte Y. 
Published: June 2021

Background: A protease/antiprotease disbalance is observed in inflammatory bowel diseases (IBD). We therefore studied the effect of the novel serine protease inhibitor UAMC-00050 on intestinal inflammation and permeability in a chronic colitis T cell transfer mouse model to get further insight into the regulation of T cell-mediated immunopathology.Methods: Colitis was induced in severe combined immunodeficient (SCID) mice, by the adoptive transfer of CD4+CD25−CD62L+ T cells. Animals were treated intraperitoneally (i.p.) 2x/day with vehicle or UAMC-00050 (5 mg/kg) from week 2 onwards. Colonic inflammation was assessed by clinical parameters, colonoscopy, macroscopy, microscopy, myeloperoxidase activity and cytokine expression levels. At week 4, 4 kDa FITC-dextran intestinal permeability was evaluated and T helper transcription factors, protease-activated receptors and junctional proteins were quantified by RT-qPCR.Results: Adoptive transfer of CD4+CD25−CD62L+ T cells resulted in colonic inflammation and an altered intestinal permeability. The serine protease inhibitor UAMC-00050 ameliorated both the inflammatory parameters and the intestinal barrier function. Furthermore, a decrease in colonic mRNA expression of Tbet and PAR4 was observed in colitis mice after UAMC-00050 treatment.Conclusion: The beneficial effect of UAMC-00050 on inflammation was apparent via a reduction of Tbet, IFN-γ, TNF-α, IL-1β and IL-6. Based on these results, we hypothesize a pivotal effect of serine protease inhibition on the Th1 inflammatory profile potentially mediated via PAR4.
Patient and Payer Preferences for Additional Value Criteria
Authors: Jakab Ivett , Whittington Melanie D. , Franklin Elizabeth , Raiola Susan , Campbell Jonathan D. , Kaló Zoltán , McQueen R. Brett 
Published: June 2021

Background: Defining the value of healthcare is an elusive target, and depends heavily on the decision context and stakeholders involved. Cost-utility analysis and the quality-adjusted life year (QALY) have become the method and value definition of choice for traditional value judgements in coverage and pricing decisions. Other criteria that may influence value are often not measured and therefore omitted from value assessments, or are only used to qualitatively contextualize assessments. The objective of this study was to engage two key stakeholders; patients and payers to elicit and rank the importance of additional value criteria, potentially assessed in Multiple Criteria Decision Analysis (MCDA).Methods: This study consisted of a focus group with cancer patients (n = 7), including follow-up questions through an electronic survey, and in-depth phone interviews with payers (n = 5).Results: For payers, value equated either with criteria that provided tangible benefits (from their perspective) such as new treatment options that respond to serious unmet need. For patients, population-level value equated to options that would potentially benefit them in the future and the value of hope. However, these criteria were seen by payers as difficult to measure and incorporate into objective decision making.Limitations: The findings from this study are primarily limited due to generalizability. Due to the small sample size, it was outside the scope of this study to calculate a weight for each criterion that could be used as part of a quantitative MCDA.Conclusion: MCDA, with particular attention to qualitative aspects, is an avenue to incorporate these additional criteria into value assessments, as well as provide an opportunity for reflecting the patient’s preferences in assessing the value of a treatment.
How Should Athletes Coping With COVID-19: Focus on Severity and Psychological Support
Authors: Han Qi , Li Xueyang , Wang Zhenghanxiao 
Published: June 2021

Objective: Athletes are suffering from many uncertainties and hope to achieve the best possible position under the current circumstances of this global coronavirus disease (COVID-19) pandemic. In this study, we aimed to address the severity and psychological support for athletes with COVID-19.Methods: We extracted public data and news reports of the up-to-date first seven cases of elite athletes with COVID-19 confirmed in China and made psychological recommendations based on scientific evidence.Results: The severity and mortality in athletes who tested positive to COVID-19 are mild and extremely low. The included cases from different sports are two soccer players, two athletes from ice hockey, and three from fencing. In this study, we adapted well-recognized psychological questionnaires, improvised it for athletes to use under the COVID-19 pandemic, and also provided recommended psychological support.Conclusion: The severity and mortality in Chinese athletes contracted with COVID-19 are mild and low with zero death. Psychological support of any kind from nurses, team medical staff, psychologists, family, and friends through social media and telecommunication should be adopted and can be of great help.
Personal Agency in Borderline Personality Disorder: The Impact of Adult Attachment Style
Authors: Hashworth Talia , Reis Samantha , Grenyer Brin F. S. 
Published: June 2021

BackgroundPersonal agency- the degree to which one believes they have control over their life- is thought to influence how people understand their interpersonal relationships. Links between adult attachment and personal agency are theoretically relevant to the experience of borderline personality disorder (BPD) but this has yet to be empirically examined. The present research examines the impact of personal agency and adult attachment styles for individuals meeting criteria for BPD.MethodsParticipants consented to an online community study examining measures of locus of control (as an index of personal agency), BPD, and adult attachment. Participants meeting criteria for BPD (N = 96; mean age = 30.63; 70.5% female) were compared to age-matched healthy controls (N = 96; mean age = M = 31.99; 89.0% female).ResultsIndividuals who met criteria for BPD displayed lower personal agency and higher fearful and preoccupied attachment styles in their close relationships, compared to Controls. Controls reported greater personal agency and were more securely attached in their relationships. Using multiple mediation modeling, the indirect effect of personal agency on BPD was significant for preoccupied, fearful, and secure attachment, but was non-significant for dismissive attachment. Lower personal agency was associated with insecure adult attachment styles.ConclusionsFindings highlight the previously unexplored relationship between BPD and personal agency and indicate that adult attachment style plays a significant role. Low personal agency may increase challenges for individuals with symptoms of BPD by exacerbating relationship difficulties. People in treatment for BPD may benefit from focusing on both relationship insecurity and its impact on their perceived personal control.
Higher Levels of Psychological Burden and Alterations in Personality Functioning in Crohn’s Disease and Ulcerative Colitis
Authors: Engel Felicitas , Berens Sabrina , Gauss Annika , Schaefert Rainer , Eich Wolfgang , Tesarz Jonas 
Published: June 2021

Aims: Is there evidence for increased psychological distress and alterations in personality functioning in patients with Crohn’s disease (CD) and ulcerative colitis (UC) compared to healthy controls (HCs)?Background: In patients with CD and UC, perceived stress is closely associated with changes in disease activity. The stress response is influenced by psychological burden and personality functioning, but only little is known about these factors in inflammatory bowel diseases (IBD).Study: A total of 62 patients with an endoscopic ensured CD/UC without remission (n = 31 per group) and 31 HC were included. Patients with an active CD/UC and HC were individually matched (n = 93, 31 per group) for age, sex, education, and disease activity. Depression and anxiety were assessed to evaluate the effect of psychological burden (Patient Health Questionnaire-9/PHQ-9, Generalized Anxiety Disorder-7/GAD-7). Personality functioning was measured by validated questionnaires for psychodynamic structural characteristics, mentalization, and attachment (Operationalized Psychodynamic Diagnosis-Structure Questionnaire/OPD-SQ, Mentalization Questionnaire/MZQ, and Experiences in Close Relationships scale/ECR-RD 12).Results: Levels of depression and anxiety were higher in CD/UC patients than in HC with large effect sizes. Comparing personality functioning in CD/UC with HC, psychodynamic structural characteristics differed between CD/UC and HC with medium effect sizes, with structural differences occurring primarily in the domain of self-perception and regulation. Only minor differences were found regarding mentalization and attachment. CD and UC differed only with small effect sizes.Conclusion: Our data show that compared to HC, patients with CD/UC are characterized by a higher level of psychological burden and structural alterations in the domain of self.