bluuebunny/crossref_metadata_2025_split huggingface dataset:
Performance of Intraoperative Assessment of Resection Margins in Oral Cancer Surgery: A Review of Literature
Authors: Barroso Elisa M. , Aaboubout Yassine , van der Sar Lisette C. , Mast Hetty , Sewnaik Aniel , Hardillo Jose A. , ten Hove Ivo , Nunes Soares Maria R. , Ottevanger Lars , Bakker Schut Tom C. , Puppels Gerwin J. , Koljenović Senada 
Published: March 2021

IntroductionAchieving adequate resection margins during oral cancer surgery is important to improve patient prognosis. Surgeons have the delicate task of achieving an adequate resection and safeguarding satisfactory remaining function and acceptable physical appearance, while relying on visual inspection, palpation, and preoperative imaging. Intraoperative assessment of resection margins (IOARM) is a multidisciplinary effort, which can guide towards adequate resections. Different forms of IOARM are currently used, but it is unknown how accurate these methods are in predicting margin status. Therefore, this review aims to investigate: 1) the IOARM methods currently used during oral cancer surgery, 2) their performance, and 3) their clinical relevance.MethodsA literature search was performed in the following databases: Embase, Medline, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, and Google Scholar (from inception to January 23, 2020). IOARM performance was assessed in terms of accuracy, sensitivity, and specificity in predicting margin status, and the reduction of inadequate margins. Clinical relevance (i.e., overall survival, local recurrence, regional recurrence, local recurrence-free survival, disease-specific survival, adjuvant therapy) was recorded if available.ResultsEighteen studies were included in the review, of which 10 for soft tissue and 8 for bone. For soft tissue, defect-driven IOARM-studies showed the average accuracy, sensitivity, and specificity of 90.9%, 47.6%, and 84.4%, and specimen-driven IOARM-studies showed, 91.5%, 68.4%, and 96.7%, respectively. For bone, specimen-driven IOARM-studies performed better than defect-driven, with an average accuracy, sensitivity, and specificity of 96.6%, 81.8%, and 98%, respectively. For both, soft tissue and bone, IOARM positively impacts patient outcome.ConclusionIOARM improves margin-status, especially the specimen-driven IOARM has higher performance compared to defect-driven IOARM. However, this conclusion is limited by the low number of studies reporting performance results for defect-driven IOARM. The current methods suffer from inherent disadvantages, namely their subjective character and the fact that only a small part of the resection surface can be assessed in a short time span, causing sampling errors. Therefore, a solution should be sought in the field of objective techniques that can rapidly assess the whole resection surface.
PSMA Expression in Glioblastoma as a Basis for Theranostic Approaches: A Retrospective, Correlational Panel Study Including Immunohistochemistry, Clinical Parameters and PET Imaging
Authors: Holzgreve Adrien , Biczok Annamaria , Ruf Viktoria C. , Liesche-Starnecker Friederike , Steiger Katja , Kirchner Maximilian A. , Unterrainer Marcus , Mittlmeier Lena , Herms Jochen , Schlegel Jürgen , Bartenstein Peter , Tonn Jörg-Christian , Albert Nathalie L. , Suchorska Bogdana 
Published: March 2021

AimThe aim of the current study was to enlighten the evolution of prostate-specific membrane antigen (PSMA) expression in glioblastoma between initial diagnosis and recurrence in order to provide preliminary insight for further clinical investigations into innovative PSMA-directed treatment concepts in neuro-oncology.MethodsPatients who underwent resection for de-novo glioblastoma (GBM) and had a re-resection in case of a recurrent tumor following radiochemotherapy and subsequent chemotherapy were included (n = 16). Histological and immunohistochemical stainings were performed at initial diagnosis and at recurrence (n = 96 tissue specimens). Levels of PSMA expression both in endothelial and non-endothelial cells as well as vascular density (CD34) were quantified via immunohistochemistry and changes between initial diagnosis and recurrence were determined. Immunohistochemical findings were correlated with survival and established clinical parameters.ResultsPSMA expression was found to be present in all GBM tissue samples at initial diagnosis as well as in all but one case of recurrent tumor samples. The level of PSMA expression in glioblastoma varied inter-individually both in endothelial and non-endothelial cells. Likewise, the temporal evolution of PSMA expression highly varied in between patients. The level of vascular PSMA expression at recurrence and its change between initial diagnosis and recurrence was associated with post recurrence survival time: Patients with high vascular PSMA expression at recurrence as well as patients with increasing PSMA expression throughout the disease course survived shorter than patients with low vascular PSMA expression or decreasing vascular PSMA expression. There was no significant correlation of PSMA expression with MGMT promoter methylation status or Ki-67 labelling index.ConclusionPSMA is expressed in glioblastoma both at initial diagnosis and at recurrence. High vascular PSMA expression at recurrence seems to be a negative prognostic marker. Thus, PSMA expression in GBM might present a promising target for theranostic approaches in recurrent glioblastoma. Especially PSMA PET imaging and PSMA-directed radioligand therapy warrant further studies in brain tumor patients.
Causes of Death After Colorectal Cancer Diagnosis: A Population-Based Study
Authors: Feng Yuqian , Jin Huimin , Guo Kaibo , Wasan Harpreet S. , Ruan Shanming , Chen Cihui 
Published: March 2021

Background: Non-cancer causes of death in patients with colorectal cancer (CRC) have not received much attention until now. The purpose of the current study is to investigate the non-cancer causes of death in patients with CRC at different periods of latency.Methods: Eligible patients with CRC were included from the Surveillance, Epidemiology, and End Results (SEER) database, and standardized mortality ratios (SMRs) were calculated using the SEER*Stat software 8.3.8.Results: A total of 475,771 patients with CRC were included, of whom 230,841 patients died during the follow-up period. Within 5 years, CRC was the leading cause of death. Over time, non-cancer causes of death account for an increasing proportion. When followed up for more than 10 years, non-cancer deaths accounted for 71.9% of all deaths worldwide. Cardiovascular diseases were the most common causes of non-cancer deaths, accounting for 15.4% of the total mortality. Patients had a significantly higher risk of death from septicemia within the first year after diagnosis compared with the general population (SMR, 3.39; 95% CI, 3.11–3.69). Within 5–10 years after CRC diagnosis, patients had a significantly higher risk of death from diabetes mellitus (SMR, 1.27; 95% CI, 1.19–1.36). During the course of more than 10 years, patients with CRC had a significantly higher risk of death from atherosclerosis (SMR 1.47; 95% CI, 1.11–1.9).Conclusions: Although CRC has always been the leading cause of death in patients with CRC, non-cancer causes of death should not be ignored. For patients with cancer, we should not only focus on anti-tumor therapies but also pay attention to the occurrence of other risks to prevent and manage them in advance.
Antihypertensive Effect of a Novel Angiotensin II Receptor Blocker Fluorophenyl Benzimidazole: Contribution of cGMP, Voltage-dependent Calcium Channels, and BKCa Channels to Vasorelaxant Mechanisms
Authors: Iqbal Hina , Verma Amit Kumar , Yadav Pankaj , Alam Sarfaraz , Shafiq Mohammad , Mishra Divya , Khan Feroz , Hanif Kashif , Negi Arvind Singh , Chanda Debabrata 
Published: March 2021

Background: The current study presents the novel angiotensin II receptor blocker fluorophenyl benzimidazole (FPD) as an antihypertensive agent in the SHR model of hypertension. We investigated the role of cGMP, voltage-dependent L-type calcium channels, and BKCa channels in the vasorelaxant mechanisms of FPD in the rat superior mesenteric artery.Methods: The antihypertensive effect of FPD was examined using an invasive technique measuring blood pressure in SHR animals. Using a myograph, tension measurement was completed in the superior mesenteric artery to elucidate the mechanisms of vasorelaxation involving AT1 receptors, the NO/cGMP pathway, L-type calcium channels, and BKCa channels. Ion flux (Ca2+, K+) studies were conducted in aortic smooth muscle cells. Putative targets proteins were determined by in silico docking studies. A safety evaluation of FPD was carried out using Swiss albino mice.Results: FPD significantly decreased blood pressure in SHR. It relaxed superior mesenteric arteries in a concentration-dependent manner and significantly inhibited angiotensin II-induced contraction. The relaxation response was also mediated by an increase in tissue cGMP levels, inhibition of L-type calcium channels, and the opening of BKCa channels. FPD further enhanced efflux of K+ and inhibited Bay K8644-stimulated Ca2+ influx in aortic smooth muscle cells and docked well in an in silico study with the targets. It was well tolerated in the toxicity study.Conclusion: The present study reports the antihypertensive activity of novel AT-1 receptor blocker FPD at 50 and 100 mg kg−1 with cGMP, L-type calcium channels, and BKCa channels as putative targets of vasorelaxation, and was found safe in oral toxicity.
Behavioral Consequences of a Combination of Gad1 Haplodeficiency and Adolescent Exposure to an NMDA Receptor Antagonist in Long-Evans Rats
Authors: Fujihara Kazuyuki , Sato Takumi , Higeta Kazuya , Miyasaka Yoshiki , Mashimo Tomoji , Yanagawa Yuchio 
Published: March 2021

Glutamate decarboxylase 67-kDa isoform (GAD67), which is encoded by the GAD1 gene, is one of the key enzymes that produce GABA. The reduced expression of GAD67 has been linked to the pathophysiology of schizophrenia. Additionally, the excitatory glutamatergic system plays an important role in the development of this disorder. Animal model studies have revealed that chronic blockade of NMDA-type glutamate receptors can cause GABAergic dysfunction and long-lasting behavioral abnormalities. Based on these findings, we speculated that Gad1 haplodeficiency combined with chronic NMDA receptor blockade would lead to larger behavioral consequences relevant to schizophrenia in a rat model. In this study, we administered an NMDAR antagonist, MK-801 (0.2 mg/kg), to CRISPR/Cas9-generated Gad1+/− rats during adolescence to test this hypothesis. The MK-801 treated Gad1+/− rats showed a shorter duration in each rearing episode in the open field test than the saline-treated Gad1+/+ rats. In contrast, immobility in the forced swim test was increased and fear extinction was impaired in Gad1+/− rats irrespective of MK-801 treatment. Interestingly, the time spent in the center region of the elevated plus-maze was significantly affected only in the saline-treated Gad1+/− rats. Additionally, the MK-801-induced impairment of the social novelty preference was not observed in Gad1+/− rats. These results suggest that the synergistic and additive effects of Gad1 haplodeficiency and NMDA receptor blockade during adolescence on the pathogenesis of schizophrenia may be more limited than expected. Findings from this study also imply that these two factors mainly affect negative or affective symptoms, rather than positive symptoms.
Role of Cigarette Smoke on Angiotensin-Converting Enzyme-2 Protein Membrane Expression in Bronchial Epithelial Cells Using an Air-Liquid Interface Model
Authors: Caruso Massimo , Distefano Alfio , Emma Rosalia , Di Rosa Michelino , Carota Giuseppe , Rust Sonja , Polosa Riccardo , Zuccarello Pietro , Ferrante Margherita , Raciti Giuseppina , Li Volti Giovanni 
Published: March 2021

Prevalence studies of current smoking, among hospitalized COVID-19 patients, demonstrated an unexpectedly low prevalence among patients with COVID-19. The aim of the present study was to evaluate the effect of smoke from cigarettes on ACE-2 in bronchial epithelial cells. Normal bronchial epithelial cells (H292) were exposed to smoke by an air-liquid-interface (ALI) system and ACE-2 membrane protein expression was evaluated after 24 h from exposure. Our transcriptomics data analysis showed a significant selective reduction of membrane ACE-2 expression (about 25%) following smoking exposure. Interestingly, we observed a positive direct correlation between ACE-2 reduction and nicotine delivery. Furthermore, by stratifying GSE52237 as a function of ACE-2 gene expression levels, we highlighted 1,012 genes related to ACE-2 in smokers and 855 in non-smokers. Furthermore, we showed that 161 genes involved in the endocytosis process were highlighted using the online pathway tool KEGG. Finally, 11 genes were in common between the ACE-2 pathway in smokers and the genes regulated during endocytosis, while 12 genes with non-smokers. Interestingly, six in non-smokers and four genes in smokers were closely involved during the viral internalization process. Our data may offer a pharmaceutical role of nicotine as potential treatment option in COVID-19.
Effects of a Short-Term Resistance-Training Program on Heart Rate Variability in Children With Cystic Fibrosis—A Randomized Controlled Trial
Authors: Estévez-González Agustín Jesús , Donadio Márcio Vinícius Fagundes , Cobo-Vicente Fernando , Fernández-Luna Álvaro , Sanz-Santiago Verónica , Villa Asensi José Ramón , Iturriaga Ramirez Tamara , Fernández-del-Valle Maria , Diez-Vega Ignacio , Larumbe-Zabala Eneko , Pérez-Ruiz Margarita 
Published: March 2021

Background: Cystic fibrosis (CF) affects the autonomic nervous system (ANS) and exercise in healthy children modulates the interaction between sympathetic and parasympathetic activity. This study aimed to evaluate the effects of a short-term resistance exercise program on heart rate variability (HRV) in children and adolescents with CF.Methods: A randomized controlled trial was carried out in children diagnosed with CF aged 6–18 years. Individuals were divided into two groups: control (CON) and resistance-training (EX). Individuals in the EX group completed an individualized guided resistance program (5-RM—60–80%) for 8 weeks (3 sessions of 60 min/week). Upper and lower limbs exercises (seated bench press, seated lateral row, and leg press) were used. HRV was measured using a Suunto watch with subjects in lying position.Results: Nineteen subjects (13 boys) were included (CON = 11; and EX = 8). Mean age was 12.2 ± 3.3, FEV1 (forced expiratory volume in the first second) z-score was 1.72 ± 1.54 and peak oxygen consumption (VO2peak) 42.7 ± 7.4 mL.Kg–1.min–1. Exercise induced significant changes in the frequency-domain variables, including a decrease in LF power (p = 0.001, d = 0.98) and LF/HF ratio (p = 0.020, d = 0.92), and an increase in HF power (p = 0.001, d = −0.97), compared to the CON group. No significant changes were found for time-domain variables, although increases with a moderate effect size were seen for SDNN (p = 0.152, d = −0.41) and RMSSD (p = 0.059, d = −0.49) compared to the CON group.Conclusion: A short-term resistance exercise-training program was able to modulate HRV in children and adolescents with CF presenting mild to moderate lung function impairment and good physical condition.Clinical Trial Registration:www.ClinicalTrials.gov, identifier NCT04293926.
Effects of Resting vs. Continuous Blood-Flow Restriction-Training on Strength, Fatigue Resistance, Muscle Thickness, and Perceived Discomfort
Authors: Schwiete Carsten , Franz Alexander , Roth Christian , Behringer Michael 
Published: March 2021

Introduction: The purpose of this study was to clarify whether blood-flow restriction during resting intervals [resting blood-flow restriction (rBFR)] is comparable to a continuous BFR (cBFR) training regarding its effects on maximum strength, hypertrophy, fatigue resistance, and perceived discomfort.Materials and Methods: Nineteen recreationally trained participants performed four sets (30-15-15-15 repetitions) with 20% 1RM on a 45° leg press twice a week for 6 weeks (cBFR, n = 10; rBFR, n = 9). Maximum strength, fatigue resistance, muscle thickness, and girth were assessed at three timepoints (pre, mid, and post). Subjective pain and perceived exertion were determined immediately after training at two timepoints (mid and post).Results: Maximum strength (p &lt; 0.001), fatigue resistance (p &lt; 0.001), muscle thickness (p &lt; 0.001), and girth (p = 0.008) increased in both groups over time with no differences between groups (p &gt; 0.05). During the intervention, the rBFR group exposed significantly lower perceived pain and exertion values compared to cBFR (p &lt; 0.05).Discussion: Resting blood-flow restriction training led to similar gains in strength, fatigue resistance, and muscle hypertrophy as cBFR training while provoking less discomfort and perceived exertion in participants. In summary, rBFR training could provide a meaningful alternative to cBFR as this study showed similar functional and structural changes as well as less discomfort.
The Role of Social Cognition Abilities in Parkinson's Disease in the Era of COVID-19 Emergency
Authors: Dodich Alessandra , Papagno Costanza , Turella Luca , Meli Claudia , Zappini Francesca , Narduzzi Pamela , Gober Alessandro , Pierotti Enrica , Falla Marika 
Published: March 2021

Introduction: Parkinson's Disease (PD) is characterized by motor and non-motor symptoms, among which deficits in social cognition might affect ~20% of patients. This study aims to evaluate the role of social cognitive abilities in the perceived impact of COVID-19 emergency, and the effects of lockdown measures on patients' social network and caregivers' burden.Methods: Fourteen PD patients performed a neuropsychological battery including sociocognitive tasks before the introduction of COVID-19 restrictive measures (i.e., social distancing and isolation). A structured interview through an online platform was performed in the last 2 weeks of the first lockdown phase to assess patients' health status, perception of COVID-19 emergency, changes in caregivers' burden, and patients' social isolation. Non-parametric analyses were performed to evaluate the association between social skills and patients' COVID-19 perception, as well as the effects of restrictive measures.Results: At baseline evaluation, half of the PD patients showed sociocognitive dysfunctions, mainly on mentalizing abilities. Patients with impaired social cognition skills showed a significantly lower concern on the possible effects of COVID-19 on their health. Caregiver burden and patients' social network remained stable during the lockdown.Conclusion: These preliminary results underline that PD sociocognitive dysfunctions might affect patients' abilities to estimate the effects of COVID-19 infection. However, the lack of a significant increase in caregivers' burden and social isolation suggests, in our sample, a good coping to COVID-19 emergency. Since COVID-19 pandemic can have direct and indirect severe consequences in patients with PD, the development of educational and preventive programs is recommended.
The Onset of Falls Reduces Subjective Well-Being. Findings of a Nationally Representative Longitudinal Study
Authors: Hajek André , König Hans-Helmut 
Published: March 2021

Introduction: The prevalence of older individuals experiencing a fall is high. Moreover, falls can have deleterious effects on health status. Additionally, falls can affect the subjective well-being of individuals. However, there is a lack of studies examining the link between falls and subjective well-being. Therefore, the objective of this study was to investigate whether the onset of falling is associated with (intraindividual) decreases in subjective well-being in men and women.Materials and Methods: Longitudinal data (from wave 5 to wave 6) were taken from a population-based sample of individuals residing in private households in Germany [in our analytical sample: 3,906 observations (men), and 3,718 observations (women)]. Positive and negative affect were quantified using the Positive and Negative Affect Schedule (PANAS). Life satisfaction was assessed using the Satisfaction with Life Scale (SWLS).Results: Adjusting for various potential confounders, fixed effects regressions showed that the onset of falls was associated with a decrease in positive affect (β = 0.08, p &lt; 0.01), and an increase in negative affect (β = 0.07, p &lt; 0.01) among men. While the onset of falls was not associated with changes in positive affect in women, it was associated with a decrease in negative affect in women (β = 0.06, p &lt; 0.05). Sex differences were significant. The onset of falls was not associated with decreases in life satisfaction in men, nor in women.Discussion: The present study particularly highlights the link between the onset of falls and reduced affective well-being among men. Avoiding falls may contribute to maintaining affective well-being among middle-aged and older men.
The Value of Serum Cell-Free DNA Levels in Patients With Schizophrenia
Authors: Chen Ling-yun , Qi Jing , Xu Hong-lei , Lin Xiang-yun , Sun Ya-jun , Ju Shao-qing 
Published: March 2021

Background: Schizophrenia is a severe mental disorder, which has a major impact on the quality of life and imposes a huge burden on the family. However, the pathogenesis of schizophrenia remains unclear and there are no specific biomarkers. Therefore, we intend to explore whether cf-DNA levels are related to the occurrence and development of schizophrenia.Methods: We analyzed and compared the concentration of cf-DNA in 174 SZ patients and 100 matched healthy controls by using quantitative real-time PCR by amplifying the Alu repeats.Results: We found that cf-DNA levels in peripheral blood reliably distinguished SZ patients from healthy controls (P &lt; 0.05). The ROC analysis also supports the above conclusion. By tracking the absolute concentration of serum cf-DNA in primary cases, we found a distinct increase before treatment with antipsychotics, which decreased progressively after treatment.Conclusions: The present work indicates that cf-DNA may improve the efficiency of disease diagnosis, and the level of cf-DNA plays a predictive role in the development of schizophrenia. By evaluating the level of cf-DNA, we might play a certain role in a more reasonable and standardized clinical treatment of schizophrenia.