bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cerebral Energy Status and Altered Metabolism in Early Brain Injury After Aneurysmal Subarachnoid Hemorrhage: A Prospective 31P-MRS Pilot Study
Authors: Treichl Stephanie Alice , Ho Wing Mann , Steiger Ruth , Grams Astrid Ellen , Rietzler Andreas , Luger Markus , Gizewski Elke Ruth , Thomé Claudius , Petr Ondra 
Published: February 2022

BackgroundAcute changes of cerebral energy metabolism in early brain injury (EBI) after aneurysmal subarachnoid hemorrhage (aSAH) may play a crucial role for overall neurological outcome. However, direct detection of these alterations is limited. Phosphorous magnetic resonance spectroscopy (31P-MRS) is a molecular-based advanced neuroimaging technique allowing measurements of pathophysiological processes and tissue metabolism based on various phosphorous compound metabolites. This method may provide objective assessment of both primary and secondary changes.ObjectiveThe aim of this pilot study was to evaluate the feasibility and the diagnostic potential of early 31P-MRS in aSAH.MethodsPatients with aSAH treated for ruptured aneurysms between July 2016 and October 2017 were prospectively included in the study. 3-Tesla-MRI including 31P-MRS was performed within the first 72 h after hemorrhage. Data of the vascular territories of the anterior, middle, and posterior cerebral arteries (ACA, MCA, PCA) and the basal ganglia were separately analyzed and compared with data of a healthy age- and sex-matched control group. Phosphorous compound metabolites were quantified, and ratios of these metabolites were further evaluated. Influence of treatment modality, clinical conditions, and analgosedation were analyzed.ResultsData of 13 patients were analyzed. 31P-MRS showed significant changes in cerebral energy metabolism after aSAH in all cerebrovascular territories. Both PCr/ATP and PCr/Pi ratio were notably increased (P &lt; 0.001). Also, Pi/ATP was significantly decreased in all cerebrovascular territories (P = 0.014). PME/PDE ratio was overall significant decreased (P &lt; 0.001).Conclusion31P-MRS is a promising non-invasive imaging tool for the assessment of changes in energy metabolism after aSAH. It allows a detailed insight into EBI and seems to harbor a high potential for clinical practice.
Motor Conduction Studies and Handgrip in Hereditary TTR Amyloidosis: Simple Tools to Evaluate the Upper Limbs
Authors: Di Stefano Vincenzo , Thomas Ewan , Giustino Valerio , Iacono Salvatore , Torrente Angelo , Pillitteri Guglielmo , Gagliardo Andrea , Lupica Antonino , Palma Antonio , Battaglia Giuseppe , Brighina Filippo 
Published: February 2022

PurposeHereditary transthyretin amyloidosis with polyneuropathy (ATTRv) is caused by mutations in theTTRgene, leading to misfolded monomers that aggregate generating amyloid fibrils. The clinical phenotype is heterogeneous, and characterized by a multisystemic disease affecting the sensorimotor and autonomic functions along with other organs.Materials and MethodsAll the patients were assessed by complete neurological assessment, neurophysiological evaluation, of the median nerve, and handgrip analysis. The data are presented as means and standard deviations. Parametric and non-parametric assessments have been performed to identify differences between groups. Pearson's correlation has been carried out when appropriate.ResultsTwenty patients with ATTRv (66.1 ± 8.4 years; eight females) and 30 controls (61.1 ± 11.6 years; 16 females) were enrolled. Handgrip strength was reduced in patients with ATTR in both right and left hands compared to the controls. Significant differences were found between patients and controls in the right (handgrip right, HGSRTTR 21.1 ± 13 kg vs. HGSRControl 29.4 ± 11.3 kg,p= 0.017) and left (handgrip left, HGSLTTR 22.2 ± 10.7 kg. vs. HGSLControl 31 ± 11.3 kg,p= 0.007). NIS and CMAP amplitude of the median nerve were related to HGS measures for both hands in patients with ATTRv.ConclusionsThe progression of bilateral carpal tunnel syndrome is related to neurophysiological data in the median nerve in ATTRv. Also, handgrip measures might represent an important tool for the assessment of disease progression in ATTRv. We propose using a combination of CMAP amplitude and HGS for the assessment of hand motor strength in ATTRv.
Tryptophan Metabolites as Biomarkers for Esophageal Cancer Susceptibility, Metastasis, and Prognosis
Authors: Chen Yun , Chen Jianliang , Guo Dainian , Yang Peixuan , Chen Shuang , Zhao Chengkuan , Xu Chengcheng , Zhang Qiuzhen , Lin Chaoxian , Zhong Shilong , Zhang Shuyao 
Published: February 2022

BackgroundPerturbation of tryptophan (TRP) metabolism contributes to the immune escape of cancer; however, the explored TRP metabolites are limited, and their efficacy in clarifying the susceptibility and progression of esophageal cancer (EC) remains ambiguous. Our study sought to evaluate the effects of the TRP metabolic profile on the clinical outcomes of EC using a Chinese population cohort; and to develop a risk prediction model targeting TRP metabolism.MethodA total of 456 healthy individuals as control subjects and 393 patients with EC who were followed up for one year as case subjects were enrolled. Quantification of the plasma concentrations of TRP and its metabolites was performed using HPLC-MS/MS. The logistic regression model was applied to evaluate the effects of the clinical characteristics and plasma metabolites of the subjects on susceptibility and tumor metastasis events, whereas Cox regression analysis was performed to assess the overall survival (OS) of the patients.ResultsLevels of creatinine and liver enzymes were substantially correlated with multiple metabolites/metabolite ratios in TRP metabolism, suggesting that hepatic and renal function would exert effects on TRP metabolism. Age- and sex-matched case–control subjects were selected using propensity score matching. Plasma exposure to 5-HT was found to be elevated 3.94-fold in case subjects (N = 166) compared to control subjects (N = 203), achieving an AUC of 0.811 for predicting susceptibility event. Subsequent correlation analysis indicated that a higher plasma exposure to 5-HIAA significantly increased the risk of lymph node metastasis (OR: 2.16, p = 0.0114). Furthermore, it was figured out that OS was significantly shorter for patients with elevated XA/KYN ratio (HR: 1.99, p = 0.0016), in which medium and high levels of XA/KYN versus low level had a significantly lower OS (HR: 0.48, p = 0.0080 and HR: 0.42, p = 0.0031, respectively).ConclusionThis study provides a pivotal basis for targeting endogenous TRP metabolism as a potential therapeutic intervention.
Case Report: Opportunities and Challenges of Immunotherapy in Heavily-Treated EGFR-Mutant Advanced Squamous Cell Lung Carcinoma After Progression on EGFR-TKIs and Chemotherapy
Authors: Jin Wei , Wang Xin , Wang Jie , Lin Lin 
Published: February 2022

BackgroundEpidermal growth factor receptor (EGFR) mutations have a low incidence in squamous cell lung cancer (SqCLC), and the clinical efficacy of EGFR tyrosine kinase inhibitors (TKIs) in EGFR-mutated SqCLC is far less than that in EGFR-mutated lung adenocarcinoma. The treatment strategy for patients with EGFR-mutated non-small cell lung cancer who are refractory to EGFR TKIs has become a current dilemma and challenge.Case PresentationA case of a 69-year-old male patient suffering from intermittent cough and hemoptysis was diagnosed with EGFR-mutated advanced SqCLC (stage cT2bN2M1). The patient was treated with camrelizumab alone after five courses of different systemic therapies and achieved a partial response, with an eminent progression-free survival of more than 24 months. Grade 1 to 2 reactive cutaneous capillary endothelial proliferation and mild pruritus were observed during the treatment. No other immune-related adverse events were observed.ConclusionMonotherapy of immune-checkpoint inhibitors may be considered as a later-line option for EGFR-mutated advanced SqCLC patients with PD-L1 expression.
Impact of an Embedded Palliative Care Clinic on Healthcare Utilization for Patients With a New Thoracic Malignancy
Authors: Gast Kelly C. , Benedict Jason A. , Grogan Madison , Janse Sarah , Saphire Maureen , Kumar Pooja , Bertino Erin M. , Agne Julia L. , Presley Carolyn J. 
Published: February 2022

IntroductionPalliative care is beneficial for patients with advanced lung cancer, but the optimal model of palliative care delivery is unknown. We investigated healthcare utilization before and after embedding a palliative care physician within a thoracic medical oncology “onco-pall” clinic.MethodsThis is a retrospective cross-sectional cohort study comparing healthcare outcomes in two cohorts: “pre-cohort” 12 months prior to and “post-cohort” 12-months after the onco-pall clinic start date. Patients were included if they had a new diagnosis of lung cancer and received care at The Ohio State University Thoracic Oncology Center, and resided in Franklin County or 6 adjacent counties. During the pre-cohort time period, access to palliative care was available at a stand-alone palliative care clinic. Palliative care intervention in both cohorts included symptom assessment and management, advance care planning, and goals of care discussion as appropriate. Outcomes evaluated included rates of emergency department (ED) visits, hospital admissions, 30-day readmissions, and intensive care unit (ICU) admissions. Estimates were calculated in rates per-person-years and with Poisson regression models.ResultsIn total, 474 patients met criteria for analysis (214 patients included in the pre-cohort and 260 patients in the post-cohort). Among all patients, 52% were male and 48% were female with a median age of 65 years (range 31-92). Most patients had non-small cell lung cancer (NSCLC - 17% stage 1-2, 20% stage 3, 47% stage 4) and 16% had small cell lung cancer. The post-cohort was older [median age 66 years vs 63 years in the pre-cohort (p-value: &lt; 0.01)]. The post-cohort had a 26% reduction in ED visits compared to the pre-cohort, controlling for age, race, marital status, sex, county, Charlson score at baseline, cancer type and stage (adjusted relative risk: aRR: 0.74, 95% CI: 0.58-0.94, p-value = 0.01). Although not statistically significant, there was a 29% decrease in ICU admissions (aRR: 0.71, 95% CI: 0.41-1.21, p-value = 0.21) and a 15% decrease in hospital admissions (aRR: 0.85, 95% CI: 0.70-1.03, p-value = 0.10). There was no difference in 30-day readmissions (aRR: 1.03, 95% CI: 0.73-1.45, p-value = 0.85).ConclusionsEmbedding palliative care clinics within medical oncology clinics may decrease healthcare utilization for patients with thoracic malignancies. Further evaluation of this model is warranted.
How Best to Play the Role of Tumor Deposits in Stage III Colon Cancer?
Authors: Liu Yunxiao , Zhang Hao , Wang Yuliuming , Wang Chunlin , Xiong Huan , Wang Yang , Jing Haoyu , Jiang Xia , Hu Hanqing , Tang Qingchao , Wang Guiyu 
Published: February 2022

BackgroundThe purpose of this study is to comprehensively evaluate the prognostic role of tumor deposits (TD) in stage III colon cancer.Methods24,600 CC patients with III stage colon cancer were collected from the Surveillance, Epidemiology, and End Result (SEER) database and 618 CC patients from the Second Affiliated Hospital of Harbin Medical University. All patients were divided into development, internal, and external validation cohorts. The combination of positive lymph nodes (PLN) and the status or number of TD was defined as modified pN (mpN) and novel pN (npN). The Cox proportional hazard regression model was used to analyze the relationship between cancer-specific survival (CSS) and mpN or npN. CSS stratified by pN, mpN, and npN was analyzed by the Kaplan–Meier curves. The area under the receiver operating characteristic curve (AUC) was used to demonstrate the predictive abilities of the pN, mpN, and npN stages. The validation cohorts were used to validate the results.ResultsThe Cox proportional hazard regression model showed that mpN and npN were an independent prognostic factor for CSS. AUC showed that the predictive accuracy of mpN was better than that of the pN stage for 5-year CSS in the development (0.621 vs. 0.609, p &lt; 0.001) and internal validation cohorts (0.618 vs. 0.612, p = 0.016) and the npN was also better than the pN stage for 5-year CSS in the development (0.623 vs. 0.609, p &lt; 0.001) and internal validation cohorts (0.620 vs. 0.612, p = 0.001). However, there was no significant difference between the AUCs of mpN and npN. Moreover, the pN stage for 5-year CSS in the external validation cohort is 0.606 vs. 0.563, p = 0.045.ConclusionsIn stage III CC, mpN and npN may be superior to the pN stage in assessing prognosis, suggesting that the TD information should be included in the pN stage.
Breathing Patterns and Oxygenation Saturation During Sleep in Children Habitually Living at High Altitude in the Andes: A Systematic Review
Authors: Ucrós Santiago , Castro-Guevara Javier A. , Hill Catherine M. , Castro-Rodriguez Jose A. 
Published: February 2022

BackgroundHuman respiratory physiology changes significantly in high altitude settings and these changes are particularly marked during sleep. It is estimated that 170 million people live above 2,500 m in environments where normal sleep parameters differ from those established at sea level or low altitude.MethodsWe conducted a systematic review of publications reporting sleep studies in healthy children living at high altitude. For this purpose, data from PubMed, EMBASE, SciELO and Epistemomikos bases were retrieved up to August 2021.ResultsSix articles met specified inclusion criteria; all reporting data were from South America involving 245 children (404 sleep studies) in children aged 0.6 months to 18 years, at altitudes between 2,560 to 3,775 m. The main results were: (1) Central apnea index decreased as the age increased. (2) The obstructive apnea/hypopnea index showed a bimodal profile with an increase in young infants up to age of 4 months, decreasing to 15 months of age, and then a second peak in children aged 4 to 9 years of age, dropping in older schoolchildren and adolescents. (3) Periodic breathing in the first months of life is more marked with increasing altitude and decreases with age.ConclusionsThere are few studies of sleep physiology in children living at high altitude. The international parameters defining normal apnea indices currently used at low altitude cannot be applied to high altitude settings. The interpretation of sleep studies in children living at high altitude is complex because there are important developmental changes across childhood and a wide range of altitude locations. More normative data are required to determine thresholds for respiratory pathology at a variety of high altitude settings.
Implementation and Evaluation of Resuscitation Training for Childcare Workers
Authors: Michel Jörg , Ilg Tim , Neunhoeffer Felix , Hofbeck Michael , Heimberg Ellen 
Published: February 2022

Background and ObjectiveChildren spend a large amount of time in daycare centers or schools. Therefore, it makes sense to train caregivers well in first-aid measures in children. The aim of this study is to evaluate whether a multimodal resuscitation training for childcare workers can teach adherence to resuscitation guidelines in a sustainable way.Materials and MethodsCaregivers at a daycare center who had previously completed a first-aid course received a newly developed multimodal resuscitation training in small groups of 7–8 participants by 3 AHA certified PALS instructors and providers. The 4-h focused retraining consisted of a theoretical component, expert modeling, resuscitation exercises on pediatric manikins (Laerdal Resusci Baby QCPR), and simulated emergency scenarios. Adherence to resuscitation guidelines was compared before retraining, immediately after training, and after 6 months. This included evaluation of chest compressions per round, chest compression rate, compression depth, full chest recoil, no-flow time, and success of rescue breaths. For better comparability and interpretation of the results, the parameters were evaluated both separately and summarized in a resuscitation score reflecting the overall adherence to the guidelines.ResultsA total of 101 simulated cardiopulmonary resuscitations were evaluated in 39 participants. In comparison to pre-retraining, chest compressions per round (15.0 [10.0–29.0] vs. 30.0 [30.0–30.0], p &lt; 0.001), chest compression rate (100.0 [75.0–120.0] vs. 112.5 [105–120.0], p &lt; 0.001), correct compression depth (6.7% [0.0–100.0] vs. 100.0% [100.0–100.0], p &lt; 0.001), no-flow time (7.0 s. [5.0–9.0] vs. 4.0 s. [3.0–5.0], p &lt; 0.001), success of rescue breaths (0.0% [0.0–0.0] vs. 100.0% [100.0–100.0], p &lt; 0.001), and resuscitation score were significantly improved immediately after training (3.9 [3.2–4.9] vs. 6.3 [5.6–6.7], p &lt; 0.001). At follow-up, there was no significant change in chest compression rate and success of rescue breaths. Chest compressions per round (30.0 [15.0–30.0], p &lt; 0.001), no-flow time (5.0 s. [4.0–8.0], p &lt; 0.001), compression depths (100.0% [96.7–100.0], p &lt; 0.001), and resuscitation score worsened again after 6 months (5.7 [4.7–6.4], p = 0.03). However, the results were still significantly better compared to pre-retraining.ConclusionOur multimodal cardiopulmonary resuscitation training program for caregivers is effective to increase the resuscitation performance immediately after training. Although the effect diminishes after 6 months, adherence to resuscitation guidelines was significantly better than before retraining.
Direct Thrombin Inhibitor Dabigatran Compromises Pulmonary Endothelial Integrity in a Murine Model of Breast Cancer Metastasis to the Lungs; the Role of Platelets and Inflammation-Associated Haemostasis
Authors: Smeda Marta , Stojak Marta , Przyborowski Kamil , Sternak Magdalena , Suraj-Prazmowska Joanna , Kus Kamil , Derszniak Katarzyna , Jasztal Agnieszka , Kij Agnieszka , Kurpinska Anna , Kieronska-Rudek Anna , Wojnar-Lason Kamila , Buczek Elzbieta , Mohaissen Tasnim , Chlopicki Stefan 
Published: February 2022

Activation of the coagulation cascade favours metastatic spread, but antithrombotic therapy might also have detrimental effects on cancer progression. In this study, we characterized the effects of dabigatran, a direct reversible thrombin inhibitor, on the pulmonary endothelial barrier and metastatic spread in a murine model of breast cancer metastasis. Dabigatran etexilate (100 mg kg−1) was administered to mice twice daily by oral gavage. Pulmonary metastasis, pulmonary endothelium permeability in vivo, and platelet reactivity were evaluated after intravenous injection of 4T1 breast cancer cells into BALB/c mice. The effect of dabigatran on platelet-dependent protection of pulmonary endothelial barrier in the presence of an inflammatory stimulus was also verified in vitro using human lung microvascular endothelial cell (HLMVEC) cultures. Dabigatran-treated mice harbored more metastases in their lungs and displayed increased pulmonary endothelium permeability after cancer cell injection. It was not associated with altered lung fibrin deposition, changes in INFγ, or complement activation. In the in vitro model of the pulmonary endothelial barrier, dabigatran inhibited platelet-mediated protection of pulmonary endothelium. In a murine model of breast cancer metastasis, dabigatran treatment promoted pulmonary metastasis by the inhibition of platelet-dependent protection of pulmonary endothelial barrier integrity.
Development and Validation of a Nomogram to Predict Cancer-Specific Survival for Middle-Aged Patients With Early-Stage Hepatocellular Carcinoma
Authors: Wen Chong , Tang Jie , Luo Hao 
Published: February 2022

BackgroundHepatocellular carcinoma is a common cause of death in middle-aged patients. We aimed to construct a new nomogram to predict cancer-specific survival (CSS) in middle-aged patients with hepatocellular carcinoma at an early stage.MethodWe collected clinicopathological information on early middle-aged patients with hepatocellular carcinoma from the SEER database. Univariate and multivariate Cox regression models were used to screen the independent risk factors for prognosis. These risk factors were used to construct predictions of CSS in patients with hepatocellular carcinoma. Consistency index (C- index), calibration curve, area under the receiver operating curve (AUC) were used. A decision analysis curve (DCA) was used to evaluate the clinical utility of the predictive model.ResultsA total of 6,286 patients with hepatocellular carcinoma in early middle age were enrolled. Univariate and multivariate Cox regression analysis showed that sex, marriage, race, histological tumor grade, T stage, surgery, chemotherapy, AFP, and tumor size were independent risk factors for prognosis. All independent risk factors were included in the nomogram to predict CSS at 1-, 3-, and 5-years in early middle age patients with hepatocellular carcinoma. In the training cohort and validation cohort, the C-index of the prediction model was 0.728 (95%CI: 0.716–0.740) and 0.733 (95%CI: 0.715–0.751), respectively. The calibration curve showed that the predicted value of the prediction model is highly consistent with the observed value. AUC also suggested that the model has good discrimination. DCA suggested that the nomogram had better predictive power than T staging.ConclusionWe constructed a new nomogram to predict CSS in middle-aged patients with early-stage hepatocellular carcinoma. This prediction model has good accuracy and reliability, which can help patients and doctors to judge prognosis and make clinical decisions.
Uncovering Historical Legacies to Contextualize Health Inequities in Puerto Rican Men: An Expansion of the Minority Stress Model
Authors: Valdez Luis A. , Mullany Anna , Barbieri Marielena , Gubrium Aline 
Published: February 2022

BackgroundLow/no-income Latino men are disproportionately burdened by chronic disease morbidity and mortality, which is often compounded by persistent exposure to stress. Chronic stress is a key mediating factor in pathways linking macro-level socio-structural forces to micro-level behavioral factors with negative health outcomes. Being that Latinxs continue to be one of the fastest growing populations in the U.S., it is imperative to better understand the roots of stress pathways and explore multi-level interventions.MethodsThis study presents qualitative findings from in-depth interviews with Puerto Rican men (95%) living in Springfield, Massachusetts. We utilized the Minority Stress Model (MSM) first posited by Ilan Meyers, as a framework to understand stress and stress processes amongst Puerto Rican men. We mapped our data onto Meyers' MSM, which allowed us to find diverging themes and identify areas for expansion.ResultsAs expected, participants reported stress rooted in experiences of racism and prejudice, expectations of rejection, English-language acquisition, family relationships, insecure housing, precarious employment, and lack of resources. Nevertheless, the MSM did not account for the historical contexts that, as our findings indicate, are used to filter and understand their experiences with everyday stressors. Participants described and linked histories of colonial violence and movement and migration to their stress and community wellbeing.DiscussionFindings suggest the need to expand the current MSM and our conceptualization of the stress process to include historical understandings when contextualizing present-day stress and future interventions. We propose an expanded heuristic model that delineates the impact of distinctive historical trajectories that aid in interpreting racial health disparities amongst minoritized populations. Future multi-level interventions should give weight to highlighting history and how this impacts the present, in this case including the culpability of U.S. policy regarding Puerto Rico and the adverse health effects for Puerto Rican men on the mainland.