bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcomes in Patients With Lung Adenocarcinoma With Transformation to Small Cell Lung Cancer After EGFR Tyrosine Kinase Inhibitors Resistance: A Systematic Review and Pooled Analysis
Authors: Xu Jinhe , Xu Lihuan , Wang Baoshan , Kong Wencui , Chen Ying , Yu Zongyang 
Published: January 2022

BackgroundLung adenocarcinoma can transform into small-cell lung cancer (SCLC) when resistance to tyrosine kinase inhibitors (TKIs) develops. Approximately 3% to 10% of epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) could transform to SCLC. This phenomenon has been described in several case reports and small patient series. However, the characteristics and treatment outcomes of this population have not been comprehensively reported, and their clinical course is poorly characterized.MethodsWe performed a systematic review of the published literature to summarize the clinical and pathological features and prognosis of the reported cases and analyzed the demographics, disease features, and outcomes.ResultsA total of 72 patients (50 females and 22 males) initially diagnosed with lung adenocarcinoma were included. EGFR mutations included 19-deletion (75%), L858R (22%), and G719X (3%). All patients received EGFR-TKIs before SCLC transformation. The median time from diagnosis to transformation was 20.5 months (95% CI, 15.45 to 26.55 months). Of the 67 patients with post-translational gene test results, 58 maintained their EGFR mutation, and only 1 of 18 with prior T790M positivity retained T790M mutation. After the pathological transformation, both conventional chemotherapy regimen and chemotherapy combined targeted therapy yielded high response rates. The disease control rate of first-line therapy after transformation was 76%, while the objective response rate was 48%. The median overall survival (OS) since diagnosis was 27 months (95% CI, 22.90 to 31.10 months), whereas median OS since SCLC transformation was 8.5 months (95% CI, 5.50 to 11.60 months).ConclusionThe prognosis of transformed SCLC is worse than primary SCLC. The response rate to conventional chemotherapy was high. However, the progression-free survival and OS after transformation were short and the prognosis was poor with first-line therapies. New therapies are needed in the management of transformed SCLC.
PET/MR Imaging of Somatostatin Receptor Expression and Tumor Vascularity in Meningioma: Implications for Pathophysiology and Tumor Outcomes
Authors: Roytman Michelle , Kim Sean , Glynn Shannon , Thomas Charlene , Lin Eaton , Feltus Whitney , Magge Rajiv S. , Liechty Benjamin , Schwartz Theodore H. , Ramakrishna Rohan , Karakatsanis Nicolas A. , Pannullo Susan C. , Osborne Joseph R. , Knisely Jonathan P. S. , Ivanidze Jana 
Published: January 2022

Background and PurposeMeningiomas, the most common primary intracranial tumor, are vascular neoplasms that express somatostatin receptor-2 (SSTR2). The purpose of this investigation was to evaluate if a relationship exists between tumor vascularity and SSTR2 expression, which may play a role in meningioma prognostication and clinical management.Materials and MethodsGallium-68-DOTATATE PET/MRI with dynamic contrast-enhanced (DCE) perfusion was prospectively performed. Clinical and demographic patient characteristics were recorded. Tumor volumes were segmented and superimposed onto parametric DCE maps including flux rate constant (Kep), transfer constant (Ktrans), extravascular volume fraction (Ve), and plasma volume fraction (Vp). Meningioma PET standardized uptake value (SUV) and SUV ratio to superior sagittal sinus (SUVRSSS) were recorded. Pearson correlation analyses were performed. In a random subset, analysis was repeated by a second investigator, and intraclass correlation coefficients (ICCs) were determined.ResultsThirty-six patients with 60 meningiomas (20 WHO-1, 27 WHO-2, and 13 WHO-3) were included. Mean Kep demonstrated a strong significant positive correlation with SUV (r = 0.84, p &lt; 0.0001) and SUVRSSS (r = 0.81, p &lt; 0.0001). When stratifying by WHO grade, this correlation persisted in WHO-2 (r = 0.91, p &lt; 0.0001) and WHO-3 (r = 0.92, p = 0.0029) but not WHO-1 (r = 0.26, p = 0.4, SUVRSSS). ICC was excellent (0.97–0.99).ConclusionDOTATATE PET/MRI demonstrated a strong significant correlation between tumor vascularity and SSTR2 expression in WHO-2 and WHO-3, but not WHO-1 meningiomas, suggesting biological differences in the relationship between tumor vascularity and SSTR2 expression in higher-grade meningiomas, the predictive value of which will be tested in future work.
Progression-Free Survival and Time to Progression as Potential Surrogate Endpoints for Overall Survival in Chemoradiotherapy Trials in Limited-Stage Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis
Authors: Yang Yin , Wang Jianyang , Wang Wenqing , Zhang Tao , Zhao Jingjing , Wang Yu , Li Yexiong , Wang Luhua , Bi Nan 
Published: January 2022

PurposeTo investigate whether progression-free survival (PFS) or time to progression (TTP) could be a valid surrogate endpoint for overall survival (OS) in patients with limited-stage small-cell lung cancer (LS-SCLC) receiving combined chemoradiotherapy.MethodsLiterature searching was performed in PubMed, Embase, and The Cochrane Library up to 2021. Prediction models were firstly established using data from phase III randomized controlled trials (RCTs) and then externally validated in phase II and retrospective studies. Correlation analysis was evaluated by a weighted linear regression model at both trial and arm levels. Cross-validation was performed to assess the consistency and robustness of the established models.Results37 studies, including 15 phase III RCTs, 12 phase II studies, and 10 retrospective studies, were selected in the final analysis. In trial-level surrogacy, a very good correlation was observed between hazard ratios (HRs) of PFS/TTP and OS (R2 = 0.783, 95% CI 0.771–0.794). In arm-level surrogacy, very good correlations were also observed between 2-year (R2 = 0.823, 95% CI 0.814–0.832), 3-year (R2 = 0.843, 95% CI 0.833–0.850), 5-year (R2 = 0.852, 95% CI 0.843–0.859) PFS/TTP, and 5-year OS. An excellent correlation was observed between 4-year PFS/TTP and 5-year OS (R2 = 0.906, 95% CI 0.901–0.910). Cross-validation demonstrated reasonable overall consistency. External validation in phase II and retrospective studies showed good agreement (R2, 0.728–0.824).ConclusionsPFS/TTP was a valid surrogate endpoint for OS in patients with LS-SCLC receiving combined chemoradiotherapy. The finding provides high-level evidence to support PFS/TTP as the primary endpoint in clinical trials so as to speed up introducing novel agents to the treatment of LS-SCLC.
Wave Reflection and Ventriculo-Arterial Coupling in Bicuspid Aortic Valve Patients With Repaired Aortic Coarctation
Authors: Milano Elena Giulia , Neumann Sandra , Sophocleous Froso , Pontecorboli Giulia , Curtis Stephanie L. , Bedair Radwa , Caputo Massimo , Luciani Giovanni Battista , Bucciarelli-Ducci Chiara , Biglino Giovanni 
Published: January 2022

BackgroundVentriculo-arterial (VA) coupling in bicuspid aortic valve (BAV) patients can be affected by the global aortopathy characterizing BAV disease and the presence of concomitant congenital lesions such as aortic coarctation (COA). This study aimed to isolate the COA variable and use cardiovascular magnetic resonance (CMR) imaging to perform wave intensity analysis non-invasively to shed light on VA coupling changes in BAV. The primary hypothesis was that BAV patients with COA exhibit unfavorable VA coupling, and the secondary hypothesis was that BAV patients with COA exhibit increased wave speed as a marker of reduced aortic distensibility despite successful surgical correction.MethodsPatients were retrospectively identified from a CMR database and divided into two groups: isolated BAV and BAV associated with repaired COA. Aortic and ventricular dimensions, global longitudinal strain (GLS), and ascending aortic flow data and area were collected and used to derive wave intensity from CMR data. The main variables for the analysis included all wave magnitudes (forward compression/expansion waves, FCW and FEW, respectively, and reflected backward compression wave, BCW) and wave speed.ResultsIn the comparison of patients with isolated BAV and those with BAV associated with repaired COA (n = 25 in each group), no differences were observed in left ventricular ejection fraction, GLS, or ventricular volumes, whilst significant increases in FCW and FEW magnitude were noted in the BAV and repaired COA group. The FCW inversely correlated with age and aortic size. Whilst the BCW was not significantly different compared with that in patients with/without COA, its magnitude tends to increase with a lower COA index. Patients with repaired COA exhibited higher wave speed velocity. Aortic wave speed (inversely related to distensibility) was not significantly different between the two groups.ConclusionIn the absence of a significant restenosis, VA coupling in patients with BAV and COA is not negatively affected compared to patients with isolated BAV. A reduction in the magnitude of the early systolic FCW was observed in patients who were older and with larger aortic diameters.
Non-invasively Measured Venous Oxygen Saturation as Early Marker of Impaired Oxygen Delivery in Preterm Neonates
Authors: Mileder Lukas P. , Buchmayer Julia , Baik-Schneditz Nariae , Schwaberger Bernhard , Höller Nina , Andersen Chad C. , Stark Michael J. , Pichler Gerhard , Urlesberger Berndt 
Published: January 2022

IntroductionAdequate oxygen supply for preterm neonates may be defined through non-invasive measurement of venous oxygen saturation (SvO2) and fractional oxygen extraction using near-infrared spectroscopy (NIRS). We investigated whether there was a difference in peripheral muscle SvO2 (pSvO2) and peripheral fractional oxygen extraction (pFOE) in preterm neonates with early inflammation/infection compared to healthy subjects during the first 72 h after birth.Materials and MethodsWe retrospectively analyzed secondary outcome parameters of prospective observational studies, including preterm neonates at risk of infection in whom peripheral NIRS measurements were performed in combination with venous occlusions. Early neonatal inflammation/infection was diagnosed by clinical signs and laboratory parameters. Peripheral muscle tissue oxygenation index (pTOI) was measured using either NIRO 300 or NIRO 200-NX (both Hamamatsu Photonics, Japan) on the patients' lower legs. Using 20-s venous occlusions, pSvO2 and pFOE were calculated incorporating simultaneous measurements of arterial oxygen saturation (SpO2).ResultsWe analyzed measurements from 226 preterm neonates (median gestational age 33.9 weeks), 64 (28.3%) of whom were diagnosed with early neonatal inflammation/infection. During the first 24 h after birth, pSvO2 (66.9% [62.6–69.2] vs. 69.4% [64.6–72.0]; p = 0.04) and pTOI (68.6% [65.3–71.9] vs. 71.7% [67.3–75.1]; p = 0.02) were lower in those neonates with inflammation/infection, while there was no such difference for measurements between 24–48 and 48–72 h.DiscussionNIRS measurement of pSvO2 and pFOE is feasible and may be utilized for early detection of impaired peripheral oxygen delivery. As pTOI was also significantly lower, this parameter may serve as substitute for diminished regional oxygen supply.
Ketamine Induced Bladder Fibrosis Through MTDH/P38 MAPK/EMT Pathway
Authors: Zhu Quan , Li Kaixuan , Li Haozhen , Han Feng , Tang Zhengyan , Wang Zhao 
Published: January 2022

Purpose: Ketamine is an anesthetic in clinical, but it has also been used as an abusing drug due to its low price and hallucinogenic effects. It is proved that ketamine abusing would cause multiple system damage including the urinary system, which is called ketamine-induced cystitis (KIC). Bladder fibrosis is late stage in KIC and threaten abusers’ life. This study aimed to investigate the molecular mechanism of ketamine-induced bladder fibrosis.Methods: Female Sprague Dawley (SD) rats were randomly divided into 3 groups. 2 groups were treated with tail vein injection of ketamine (25 mg/kg/day, 50 mg/kg/day ketamine hydrochloride solution, respectively) for 12 weeks, whereas the control group was treated with normal saline solution. In each group, rat bladders were extracted and samples were examined for pathological and morphological alterations via hematoxylin and eosin (HE) staining, Masson’s trichrome staining and immunohistochemistry (IHC). SV-HUC-1 cells were treated with different concentrations of ketamine solution (0, 0.1, 0.5, 1 mmol/L). Rat bladder and SV-HUC-1 cells were extracted protein and RNA for Western blot and RT-PCR detection. Metadherin (MTDH) siRNAs and overexpression plasmids were used to knock down and overexpress the relative genes. P38 mitogen-activated protein kinase (MAPK) inhibitor was utilized to inhibit the MAPK pathway.Results: Rats in the ketamine group exhibited fibrosis compared to rats of the control group and fibrosis were also markedly upregulated in SV-HUC-1 cells after treated with ketamine, which were ketamine concentration-dependent. After treating with ketamine in SV-HUC-1 cells, there was an increase expression of MTDH, epithelial-mesenchymal transition (EMT) markers, P38 MAPK. MTDH knockdown would suppresses P38 MAPK/EMT pathway to inhibit fibrosis, however, MTDH overexpression could promote the pathway in SV-HUC-1 cells.Conclusion: In rats and SV-HUC-1 cells ketamine-treated models, MTDH can regulate EMT through the P38 MAPK pathway to regulate the process of bladder fibrosis.
Recombinant Human Nerve Growth Factor (Cenegermin)–Driven Corneal Wound Healing Process: An Evidence-Based Analysis
Authors: Bonzano Chiara , Olivari Sara , Cutolo Carlo Alberto , Macrì Angelo , Sindaco Daniele , Borroni Davide , Bonzano Elisabetta , Traverso Carlo Enrico 
Published: January 2022

Purpose: To evaluate anterior segment optical coherence tomography (AS-OCT) to detect the wound healing process as per monitoring the effectiveness of cenegermin to treat moderate to severe neurotrophic keratoplasty.Methods: A retrospective chart review was realized to identify patients treated with cenegermin at the Clinica Oculistica, University of Genoa, Italy. All patients underwent careful examinations at baseline and follow-up visits. AS-OCT scans centered on the minimum corneal thickness (CT) area were always performed. We compared findings of AS-OCT with the findings from the slit-lamp examination. A linear regression analysis was used to evaluate factors associated with corneal healing. A further analysis, including a control group treated with 50% autologous serum (AS), was done to investigate and compare the efficacy of cenegermin.Results: Data from 16 eyes were studied. The average patients' age was 60.9 ± 21.1 years; five (31.2%) eyes experienced persistent epithelial defect and 11 (68.8%) eyes had neurotrophic corneal ulcer. The average reepithelialization time was 3.9 ± 0.5 weeks in the cenegermin group versus 5.9 ± 1.9 weeks in the AS group (p &lt; 0.01). The AS‐OCT scans revealed an average CT at the thinnest point of 276.3 ± 74.1 μm before treatment with an average increase of 176.5 ± 60.3 μm at the end of the cenegermin treatment (B = −0.15; p = 0.035). The AS-OCT percentage increase in corneal thickness between the two groups was statistically significant (p &lt; 0.02).Conclusion: Understanding the cascade of events involved in the nerve growth factor–driven corneal wound healing process is clinically meaningful for the clinician. AS-OCT is an effective tool for systematic anterior segment imaging, allowing the detailed detection of the front-to-back layered corneal structure for quantitative analysis and monitoring of the healing process.
Potential Mechanisms of Quercetin Influence the ClfB Protein During Biofilm Formation of Staphylococcus aureus
Authors: Kang Xinyun , Ma Qiang , Wang Guilai , Li Na , Mao Yanni , Wang Xin , Wang Yuxia , Wang Guiqin 
Published: January 2022

This study aimed to establish the mode of binding between Quercetin (QEN) and an essential protein called ClfB in forming biofilm in Staphylococcus aureus (S. aureus). In this study, the raw data of GSE163153 were analyzed for quality control, alignment, and gene counts, and the differential analysis detected the key differentially expressed genes (DEGs) assisting in the formation of the S. aureus biofilm. Then, the protein-protein interaction (PPI) and gene function enrichment analyses of the target genes, identified a gene called clfB to be closely related to biofilm formation. ClfB was structurally characterized, molecularly docked, and kinetically simulated to unravel the mode of binding of QEN to ClfB. Meanwhile, the growth curve and transmission electron microscopy methods examined the effect of QEN on the S. aureus growth. Results indicated that the clfB gene was increasingly expressed during biofilm formation and was involved in cell adhesion, pathogenicity, and infection. We identified 5 amino acid sites of ClfB (D272, R331, I379, K391, E490) as potential sites for binding QEN, which would indirectly influence the changes in the functional sites N234, D270, Y273, F328, inhibiting the formation of biofilm. Meanwhile, 128 μg/ml of QEN could significantly inhibit the S. aureus biofilm formation. This manuscript serves as a molecular foundation for QEN as an antibacterial drug providing a new perspective for developing antibacterial drugs.
Changes in Loss Sensitivity During Treatment in Concurrent Disorders Inpatients: A Computational Model Approach to Assessing Risky Decision-Making
Authors: Todesco Stefanie , Chao Thomas , Schmid Laura , Thiessen Karina A. , Schütz Christian G. 
Published: January 2022

BackgroundRecent studies have employed computational modeling to characterize deficits in aspects of decision-making not otherwise detected using traditional behavioral task outcomes. While prospect utility-based modeling has shown to differentiate decision-making patterns between users of different drugs, its relevance in the context of treatment has yet to be examined. This study investigated model-based decision-making as it relates to treatment outcome in inpatients with co-occurring mental health and substance use disorders.Methods50 patients (Mage = 38.5, SD = 11.4; 16F) completed the Cambridge Gambling Task (CGT) within 2 weeks of admission (baseline) and 6 months into treatment (follow-up), and 50 controls (Mage = 31.9, SD = 10.0; 25F) completed CGT under a single outpatient session. We evaluated 4 traditional CGT outputs and 5 decisional processes derived from the Cumulative Model. Psychiatric diagnoses and discharge data were retrieved from patient health records.ResultsGroups were similar in age, sex, and premorbid IQ. Differences in years of education were included as covariates across all group comparisons. All patients had ≥1 mental health diagnosis, with 80% having &gt;1 substance use disorder. On the CGT, patients showed greater Deliberation Time and Delay Aversion than controls. Estimated model parameters revealed higher Delayed Reward Discounting, and lower Probability Distortion and Loss Sensitivity in patients relative to controls. From baseline to follow-up, patients (n = 24) showed a decrease in model-derived Loss Sensitivity and Color Choice Bias. Lastly, poorer Quality of Decision-Making and Choice Consistency, and greater Color Choice Bias independently predicted higher likelihood of treatment dropout, while none were significant in relation to treatment length of stay.ConclusionThis is the first study to assess a computational model of decision-making in the context of treatment for concurrent disorders. Patients were more impulsive and slower to deliberate choice than controls. While both traditional and computational outcomes predicted treatment adherence in patients, findings suggest computational methods are able to capture treatment-sensitive aspects of decision-making not accessible via traditional methods. Further research is needed to confirm findings as well as investigate the relationship between model-based decision-making and post-treatment outcomes.
Ideal Test Time for Coronavirus Disease 2019 Contact Tracing
Authors: Miyake Shigeta , Kato Hideaki , Tanaka Nobuko , Shimizu Kohei , Ozawa Hiroki , Kawakami Chiharu , Usuku Shuzo , Nakajima Hideaki , Yamamoto Tetsuya 
Published: January 2022

BackgroundEpidemiological contact tracing is a powerful tool to rapidly detect SARS-CoV-2 infection in persons with a close contact history with COVID-19-affected patients. However, it remains unclear whom and when should be PCR tested among the close contact subjects.MethodsWe retrospectively analyzed 817 close contact subjects, including 144 potentially SARS-CoV-2-infected persons. The patient characteristics and contact type, duration between the date of the close contact and specimen sampling, and PCR test results in PCR positive and negative persons were compared.ResultsWe found that male gender {adjusted odds ratio 1.747 [95% confidence interval (CI) 1.180–2.608]}, age ≥ 60 [1.749 (95% CI 1.07–2.812)], and household contact [2.14 (95% CI 1.388–3.371)] are independent risk factors for close contact SARS-CoV-2 infection. Symptomatic subjects were predicted 6.179 (95% CI 3.985–9.61) times more likely to be infected compared to asymptomatic ones. We could observe PCR test positivity between days 1 and 17 after close contact. However, no subject could be found with a Ct-value &lt;30, considered less infective, after day 14 of close contact.ConclusionsBased on our results, we suggest that contact tracing should be performed on the high-risk subjects between days 3 and 13 after close contacts.
What Prompted the Adoption of Self-Protective Behaviors in Response to COVID-19? Evidence From Women Living in the Rural Areas of Western China
Authors: Ye Ruixue , Wu Yuju , Sun Chang , Wang Qingzhi , Mao Yuping , Chang Wei , Zhou Huan 
Published: January 2022

BackgroundSelf-protective behaviors, such as handwashing and mask-wearing, are effective to reduce the spread of coronavirus disease (COVID-19), but few studies have focused on women living in rural areas who bear the brunt of the impacts of the pandemic due to their economic and social vulnerabilities. This study explores what prompted the adoption of self-protective behaviors in response to COVID-19 among women living in rural areas of western China.MethodsThe study sample consisted of 1,524 women from 116 townships across 10 counties in rural western China. We collected data in May and August 2020 on women's socioeconomic characteristics, exposure to COVID-19-related information, psychological response to COVID-19, and adoption of self-protective behaviors. Structural equation modeling (SEM) analyses were conducted to analyze the relations among the variables.ResultsDuring the lockdown, 1,221 (80.12%) of the 1,524 women in the study sample reported wearing a mask every time when they went outside and 1,021 (66.99%) reported handwashing with soap every time after they came home. Perceived efficacy had the strongest association with self-protective behaviors (β = 0.38; p &lt; 0.001). Receiving public health guidance (β = 0.18; p &lt; 0.001) was indirectly associated with more self-protective behaviors via greater perceived efficacy. Higher socioeconomic status was also directly associated with increased adoption of self-protective behaviors (β = 0.24; p &lt; 0.001). Other variables, such as receiving surveillance and risk information, communication channels, perceived risks, and fear, were indirectly associated with the adoption of self-protective behaviors with smaller effect sizes (all β were lower than 0.10).ConclusionsNot all women were able to adopt self-protective behaviors, such as mask-wearing and handwashing, during the COVID-19 pandemic in western China. To further encourage behavioral changes in response to public health crises, the government should develop clear and actionable guidelines and adopt targeted health communication strategies to reach the most disadvantaged groups of society. These findings may inform tailored responses to COVID-19 in other low- and middle-income countries.