bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Parameters of Silent Corticotroph Adenomas With Positive and Negative Adrenocorticotropic Hormone Immunostaining: A Large Retrospective Single-Center Study of 105 Cases
Authors: Zhang Keyi , Shou Xuefei , Chen Hong , Qiao Nidan , He Wenqiang , Chen Zhengyuan , Shen Ming , Li Shiqi , Zhao Yao , Zhang Zhaoyun , Li Yiming , Ye Hongying , Wang Yongfei 
Published: January 2021

PurposeTo investigate the different clinical characteristics of silent corticotroph adenomas (SCAs) with positive and negative adrenocorticotropic hormone (ACTH) immunostaining, and to explore the value of pituitary-restricted transcription factor (Tpit) immunostaining for diagnosing SCAs.MethodsThe clinical materials of patients with SCAs who had a typical pathological feature with positive Tpit immunostaining and positive/negative ACTH immunostaining, and without clinical features and biochemical evidence for Cushing’s Syndrome in our center from April 2018 to March 2019 were analyzed retrospectively. The differences in clinical characteristics and surgical results between ACTH-positive and -negative SCAs were explored.ResultsA total of one hundred and five patients (94.3% female) with SCAs were included. There were 66 SCAs with ACTH-negative (66/105, 62.9%), and 39 SCAs with ACTH-positive (39/105, 37.1%). Cases with ACTH-negative SCAs were more likely to have lower ACTH levels (27.5 ± 24.0 vs. 54.4 ± 58.6, P = 0.011), more multiple microcysts (81.8% vs. 61.5%, P = 0.022) and lower levels of Ki-67 expression (low expression rate 90.9% vs. 74.4%, P = 0.023). No statistical significant differences were observed between patients with ACTH-positive and -negative SCAs regarding gender (97.0% vs. 89.7%, P = 0.192), age (50.3 ± 10.3 vs. 49.0 ± 11.2, P = 0.543), surgical history (16.7% vs. 23.1%, P = 0.419), suprasellar extension (66.7% vs. 74.4%, P = 0.408), sphenoid sinus extension (51.5% vs. 56.4%, P = 0.627), cavernous sinus invasion (75.8% vs. 66.7%, P = 0.314), large cyst on Magnetic Resonance Imaging (MRI) (47.0% vs. 61.5%, P = 0.149), or gross total resection rate (42.4% vs. 51.3%, P = 0.379).ConclusionsACTH-negative SCAs were observed to be more clinically silent and more likely to demonstrate multiple microcysts on MRI. The prevalence of SCAs, especially ACTH-negative SCAs, proved to be substantially underestimated and thus they should be given enough attention in consideration of the high aggressiveness of this subtype of refractory pituitary adenoma (PA).
VLA-1 Binding to Collagen IV Controls Effector T Cell Suppression by Myeloid-Derived Suppressor Cells in the Splenic Red Pulp
Authors: Eckert Ina N. , Ribechini Eliana , Jarick Katja J. , Strozniak Sandra , Potter Sarah J. , Beilhack Andreas , Lutz Manfred B. 
Published: January 2021

Myeloid-derived suppressor cells (MDSCs) represent a major population controlling T cell immune responses. However, little is known about their molecular requirements for homing and T cell interaction to mediate suppression. Here, we investigated the functional role of the homing and collagen IV receptor VLA-1 (α1β1-integrin) onin vitroGM-CSF generated murine MDSCs from wild-type (WT) and CD49a/α1-integrin (Itga1−/−) gene-deficient mice. Here, we found that effector (Teff) but not naive (Tn) CD4+T cells express VLA-1 and monocytes further up-regulated their expression after culture in GM-CSF when they differentiated into the monocytic subset of resting MDSCs (R-MDSCs). Subsequent activation of R-MDSCs by LPS+IFN-γ (A-MDSCs) showed increasedin vitrosuppressor potential, which was independent of VLA-1. Surprisingly, VLA-1 deficiency did not influence A-MDSC motility or migration on collagen IVin vitro. However, interaction times ofItga1−/−A-MDSCs with Teff were shorter than with WT A-MDSCs on collagen IV but not on fibronectin substratein vitro. After injection, A-MDSCs homed to the splenic red pulp where they co-localized with Teff and showed immediate suppression already after 6 h as shown by inhibition of T cell proliferation and induction of apoptosis. Injection of A-MDSCs fromItga1−/−mice showed equivalent homing into the spleen but a reduced suppressive effect. Interaction studies of A-MDSCs with Teff in the subcapsular red pulp with intravital two-photon microscopy revealed also here that MDSC motility and migration parameters were not altered by VLA-1 deficiency, but the interaction times with Teff were reduced. Together, our data point to a new role of VLA-1 adhesion to collagen IV as a prerequisite for extended contact times with Teff required for suppression.
Steroid Hormone Sensitivity in Reproductive Mood Disorders: On the Role of the GABAA Receptor Complex and Stress During Hormonal Transitions
Authors: Schweizer-Schubert Sophie , Gordon Jennifer L. , Eisenlohr-Moul Tory A. , Meltzer-Brody Samantha , Schmalenberger Katja M. , Slopien Radoslaw , Zietlow Anna-Lena , Ehlert Ulrike , Ditzen Beate 
Published: January 2021

Women worldwide are two to three times more likely to suffer from depression in their lifetime than are men. Female risk for depressive symptoms is particularly high during the reproductive years between menarche and menopause. The term “Reproductive Mood Disorders” refers to depressive disorders triggered by hormonal fluctuations during reproductive transitions including the perimenarchal phase, the pre-menstrual phase, pregnancy, the peripartum period and the perimenopausal transition.Here we focus on reproductive mood disorders manifesting in adult life. We propose a research agenda that draws together several reproductive mood disorders and investigates which genetic, endocrinological, neural, and psychosocial factors can explain depressive symptoms during phases of hormonal transitions in women. Based on current research it is assumed that some women experience an increased sensitivity to not only fluctuations in reproductive steroids (estrogen and progesterone), but also stress-related steroids. We integrate both dynamics into the concept of “steroid hormone sensitivity,” expanding on the concept of “reproductive hormone sensitivity.” We suggest that a differential response of the stress steroid system including corticosteroids, neurosteroids, like allopregnanolone and the GABA-A Receptor complex, as well as a differential (epi)genetic risk in serotonergic and GABAergic signaling, are moderators or mediators between changes in the reproductive steroid system and the physiological, affective, and cognitive outcomes manifesting in reproductive mood disorders. We point to the lack of research on the role of psychosocial factors in increasing a woman's stress level and at some point also the sensitivity of her stress steroid system within the etiology of Reproductive Mood Disorders.Drawing together the evidence on various reproductive mood disorders we seek to present a basis for the development of more effective pharmacological, social, and psychological treatment interventions and prevention strategies for women susceptible to these disorders. This could pave the way for new research as well as medical and psychological teaching and practice- such as a new type of Practice for Gynecological Psychoneuroendocrinology- with the aim of working on and ultimately offering more integrative forms of support not yet available to women suffering from depression during hormonal transitions. In medical history women have been left alone with this integrative challenge.
Triglyceride/HDL-Cholesterol Ratio as an Index of Intracranial Atherosclerosis in Nonstroke Individuals
Authors: Woo Min-Hee , Lee Kee Ook , Chung Darda , Choi Jung-Won , Kim Sang-Heum , Oh Seung-Hun 
Published: January 2021

Background: Triglyceride (TG)/high-density lipoprotein cholesterol ratio (THR) is a marker of dyslipidemia, and high THR is associated with an increase in cardiovascular events. In the present study, whether THR was associated with various markers of cerebral vascular pathologies, atherosclerosis of major cerebral arteries, including large artery atherosclerosis (LAA) and cerebral small vessel disease (SVD), in neurologically healthy individuals was investigated.Methods: Vascular risk factors, brain magnetic resonance imaging (MRI) scans, and MR angiograms of 851 study subjects were evaluated. Findings of extracranial atherosclerosis (ECAS) and intracranial atherosclerosis (ICAS) were considered indices of LAA based on brain MR angiograms. The presence of silent lacunar infarct (SLI) and white matter hyperintensities (WMHs) were evaluated as indices of SVD based on brain MRIs.Results: Subjects with ICAS (odds ratio, 1.83; 95% confidence interval, 1.06–3.16; P = 0.03) were significantly more likely to have high THR tertile (THR &gt; 2.06) than low THR tertile (THR &lt; 1.37) after adjusting for cardiovascular risk factors. THR was higher in subjects with multiple ICAS lesions than in those with single ECAS or without ICAS lesions. Associations among THR tertiles in ECAS, SLI, and WMHs were not significant.Conclusion: In the present study, a positive association between high THR and the development of ICAS was observed in neurologically healthy participants.
Role of Preoperative Chemoradiotherapy in Clinical Stage II/III Rectal Cancer Patients Undergoing Total Mesorectal Excision: A Retrospective Propensity Score Analysis
Authors: Lee Jii Bum , Kim Han Sang , Ham Ahrong , Chang Jee Suk , Shin Sang Jun , Beom Seung-Hoon , Koom Woong Sub , Kim Taeil , Han Yoon Dae , Han Dai Hoon , Hur Hyuk , Min Byung Soh , Lee Kang Young , Kim Nam Kyu , Park Yu Rang , Lim Joon Seok , Ahn Joong Bae 
Published: January 2021

BackgroundAlthough the current standard preoperative chemoradiotherapy (PCRT) for stage II/III rectal cancer decreases the risk of local recurrence, it does not improve survival and increases the likelihood of preoperative overtreatment, especially in patients without circumferential resection margin (CRM) involvement.MethodsStage II/III rectal cancer without CRM involvement and lateral lymph node metastasis was radiologically defined by preoperative magnetic resonance imaging (MRI). Patients who received PCRT followed by total mesorectal excision (TME) (PCRT group) and upfront surgery (US) with TME (US group) between 2010 and 2016 were analyzed. We derived cohorts of PCRT group versus US group using propensity-score matching for stage, age, and distance from the anal verge. Three-year relapse-free survival rate, disease-free survival (DFS), and overall survival (OS) were compared between the two groups.ResultsA total of 202 patients were analyzed after propensity score matching. There were no differences in baseline characteristics. The median follow-up duration was 62 months (interquartile range, 46–87). There was no difference in the 3-year disease-free survival rate between the PCRT and US groups (83 vs. 88%, respectively; p=0.326). Likewise, there was no significant difference in the 3-year OS (89 vs. 91%, respectively; p=0.466). The 3-year locoregional recurrence rates (3 vs. 2% with US, p=0.667) and distant metastasis rates (16 vs. 11%, p=0.428) were not significantly different between the two groups. Time to completion of curative treatment was significantly shorter in the US group (132 days) than in the PCRT group (225 days) (p&lt;0.001).ConclusionUsing MRI-guided selection for better risk stratification, US without neoadjuvant therapy can be considered in early stage patients with good prognosis. PCRT may not be required for all stage II/III rectal cancer patients, especially for the MRI-proven intermediate-risk group (cT1-2/N1, cT3N0) without CRM involvement and lateral lymph node metastasis. Further prospective studies are warranted.
Premature Birth Infants Present Elevated Inflammatory Markers in the Meconium
Authors: Rodríguez-Benítez María Victoria , Gámez-Belmonte Reyes , Gil-Campos Mercedes , Hernández-Chirlaque Cristina , Bouzas Paula R. , Sánchez de Medina Fermín , Martínez-Augustin Olga 
Published: January 2021

Introduction: Prematurity, a well-established risk factor for various intestinal diseases in newborns, results in increased morbidity and mortality. However, the intestinal inflammatory status of preterm (PT) infants has been poorly characterized. Here we have broadly described the intestinal and systemic inflammatory status of PT children.Materials and Methods: Meconium and plasma from 39 PT and 32 full term (T) newborns were studied. Fecal calprotectin, polymorphonuclear leukocyte elastase (PMN-E), TNF, IL-17A, IL-8, IP-10, MCP-1, MIP-1, IL-1β, IL-1α, and E-selectin and the enzymatic activities of myeloperoxidase (MPO) and alkaline phosphatase (AP) in meconium were measured. Plasma levels of AP, hepatocyte growth factor, nerve growth factor (NGF), proinflammatory cytokines, leptin, adiponectin, PAI-1, and resistin were also determined. Correlations with gestational age (GA) and birth weight (BW) were studied.Results: Neutrophil derived PMN-E, MPO and calprotectin were increased in the meconium of PT compared to T newborns, while AP was decreased. No significant differences were found in other inflammatory parameters. Considering data from all children, GA and BW showed inverse correlation with neutrophil markers, while AP directly correlated with BW. Plasma levels of IL-1β and NGF were enhanced in PT infants, and were also negatively correlated with BW. PT children additionally showed neutropenia and decreased adiponectin, leptin, haematocrit, and haemoglobin. These parameters (neutrophils, adiponectin, and so forth) were positively correlated with GA and BW, while IL-8, MCP-1, PAI-1, and plasma AP were negatively correlated. PT children showing postnatal morbidity exhibited increased meconium MPO and MIP-1α.Conclusion: PT neonates present a significant elevation of intestinal inflammatory parameters, characterized by the presence of neutrophil markers, associated with mild systemic inflammation.
Population Pharmacokinetics and Dose Optimization of Ganciclovir in Critically Ill Children
Authors: Li SiChan , Shu Chang , Wu SanLan , Xu Hua , Wang Yang 
Published: January 2021

Objective: The present study aims to establish a population pharmacokinetic model of ganciclovir and optimize the dosing regimen in critically ill children suffering from cytomegalovirus related disease.Methods: A total of 104 children were included in the study. The population pharmacokinetic model was developed using the Phoenix NLME program. The final model was validated by diagnostic plots, nonparametric bootstrap, visual predictive check, and normalized prediction distribution errors. To further evaluate and optimize the dosing regimens, Monte Carlo simulations were performed. Moreover, the possible association between systemic exposure and hematological toxicity were also monitored in the assessment of adverse events.Results: The ganciclovir pharmacokinetics could be adequately described by a one-compartment model with first-order elimination along with body weight and estimated glomerular filtration rate as significant covariates. As showed in this study, the typical population parameter estimates of apparent volume of distribution and apparent clearance were 11.35 L and 5.23 L/h, respectively. Simulations indicated that the current regimen at a dosage of 10 mg/kg/d would result in subtherapeutic exposure, and elevated doses might be required to reach the target ganciclovir level. No significant association between neutropenia, the most frequent toxicity reported in our study (19.23%), and ganciclovir exposure was observed.Conclusion: A population pharmacokinetic model of intravenous ganciclovir for critically ill children with cytomegalovirus infection was successfully developed. Results showed that underdosing of ganciclovir was relatively common in critically ill pediatric patients, and model-based approaches should be applied in the optimizing of empiric dosing regimens.
Validation of a German Version of the Grief Cognitions Questionnaire and Establishment of a Short Form
Authors: Doering Bettina K. , Boelen Paul A. , Eisma Maarten C. , Barke Antonia 
Published: January 2021

BackgroundWhereas the majority of bereaved persons recover from their grief without professional assistance, a minority develops pathological grief reactions. Etiological models postulate that dysfunctional cognitions may perpetuate such reactions. The Grief Cognitions Questionnaire (GCQ) assesses thoughts after bereavement in nine interrelated domains. A short form (GCQ-SF) with four domains is often used. However, an evaluation of the psychometric properties of the GCQ-SF and its utility compared to the GCQ is lacking and these instruments have not been validated in German.MethodGerman bereaved persons (time since loss 35.3 ± 34.6 months) responded to an online survey containing the GCQ, measures of grief severity, grief rumination, symptoms of depression and anxiety, and optimism and pessimism. 585 participants (18–78 years, 88% women) were included. Item analyses and confirmatory factor analyses were conducted. Correlations between the GCQ and GCQ-SF and grief rumination, optimism and pessimism assessed construct validity. Criterion-related validity was assessed by comparing whether the correlation of the GCQ (and the GCQ-SF) with grief severity was higher than with anxious and depressive symptoms. Logistic regression and receiver-operator characteristics (ROC) compared the questionnaires on their ability to predict probable prolonged grief ‘caseness’ (ICG ≥ 25, time since loss ≥6 months).ResultsInternal consistencies for both questionnaires were identical and excellent (α = 0.96). Confirmatory factor analyses obtained a satisfactory fit for models with nine and four correlated subscales and respective higher-order factor models. The GCQ and the GCQ-SF correlated higher with grief severity than with other measures of psychopathology. The logistic regression showed a significant association between the GCQ-SF and prolonged grief ‘caseness’. Of the remaining subscales of the GCQ, only one subscale (‘Others’) contributed to the prediction. The ROC analyses showed nearly identical areas under the curve.ConclusionThe translated GCQ and GCQ-SF demonstrated very good psychometric properties. The correlations with grief severity highlight the questionnaires’ clinical relevance. The questionnaires possessed identical diagnostic specificity and sensitivity. Whenever a timesaving assessment of the most typical grief-specific cognitions is important, the GCQ-SF represents an alternative to the GCQ. The original GCQ may still be superior when a more detailed description of a bereaved person’s cognitions is desirable.
Implementation of remote consulting in UK primary care following the COVID-19 pandemic: a mixed-methods longitudinal study
Authors: Murphy Mairead , Scott Lauren J , Salisbury Chris , Turner Andrew , Scott Anne , Denholm Rachel , Lewis Rhys , Iyer Geeta , Macleod John , Horwood Jeremy 
Published: January 2021

BackgroundTo reduce contagion of COVID-19, in March 2020 UK general practices implemented predominantly remote consulting via telephone, video, or online consultation platforms.AimTo investigate the rapid implementation of remote consulting and explore impact over the initial months of the COVID-19 pandemic.Design and settingMixed-methods study in 21 general practices in Bristol, North Somerset and South Gloucestershire.MethodLongitudinal observational quantitative analysis compared volume and type of consultation in April to July 2020 with April to July 2019. Negative binomial models were used to identify if changes differed among different groups of patients. Qualitative data from 87 longitudinal interviews with practice staff in four rounds investigated practices’ experience of the move to remote consulting, challenges faced, and solutions. A thematic analysis utilised Normalisation Process Theory.ResultsThere was universal consensus that remote consulting was necessary. This drove a rapid change to 90% remote GP consulting (46% for nurses) by April 2020. Consultation rates reduced in April to July 2020 compared to 2019; GPs and nurses maintained a focus on older patients, shielding patients, and patients with poor mental health. Telephone consulting was sufficient for many patient problems, video consulting was used more rarely, and was less essential as lockdown eased. SMS-messaging increased more than three-fold. GPs were concerned about increased clinical risk and some had difficulties setting thresholds for seeing patients face-to-face as lockdown eased.ConclusionThe shift to remote consulting was successful and a focus maintained on vulnerable patients. It was driven by the imperative to reduce contagion and may have risks; post-pandemic, the model will need adjustment.
Single-trap phenomena stochastic switching for noise suppression in nanowire FET biosensors
Authors: Kutovyi Yurii , Madrid Ignacio , Boichuk Nazarii , Kim Soo Hyeon , Fujii Teruo , Jalabert Laurent , Offenhaeusser Andreas , Vitusevich Svetlana , Clément Nicolas 
Published: January 2021

Abstract
With the fast-shrinking of the transistor dimensions, the low-frequency noise level considerably increases emerging as an important parameter for the design of advanced devices for information technologies. Single-trap phenomena (STP) is a promising approach for the low-frequency noise suppression technique in nanotransistor biosensors by considering trapping/detrapping noise as a signal. We show a noise reduction mechanism offered by STP in nanoscale devices making the analogy with stochastic resonance effect found in biological systems by considering a single trap as a bistable stochastically driven nonlinear system which transmits and amplifies the weak signals. The STP noise suppression effect is experimentally demonstrated for the fabricated liquid-gated nanosensors exploiting STP. We found the optimal conditions and parameters including optimized gate voltages to implement a stochastic switching effect for the extraction of useful signals from the background noise level. These results should be considered for the development of reliable and highly sensitive nanoscale biosensors.
Importance of crystallinity improvement in MoS2 film by compound sputtering even followed by post sulfurization
Authors: Imai Shinya , Hamada Takuya , Hamada Masaya , Shirokura Takanori , Muneta Iriya , Kakushima Kuniyuki , Tatsumi Tetsuya , Tomiya Shigetaka , Tsutsui Kazuo , Wakabayashi Hitoshi 
Published: January 2021

Abstract
The MoS2 film for chip-size area was synthesized by two step processes consisting of MoS2-compound sputtering and post sulfurization. We intentionally revealed that the crystallinity of sulfurized MoS2 film depends on that of just-after-sputtered film. Therefore, a crystallinity improvement just-after sputtering is mandatory to achieve an excellent quality MoS2 film after sulfur-vapor annealing for thin film transistor, sensor and human interface device applications.
Separation of bias stress degradation between insulator and semiconductor carrier trapping in organic thin-film transistors
Authors: Oshima Kunihiro , Bian Song , Kuribara Kazunori , Sato Takashi 
Published: January 2021

Abstract
Organic thin-film transistors (OTFTs) are studied intensively for realizing practical applications of flexible or large-area circuits, but rapid degradation of OTFTs due to stress voltage or reaction with water vapor or oxygen in the air limits their lifetime. In order to analyze the cause of rapid bias-stress degradation, we propose a method that separates the cause of threshold voltage (V
th) shift into insulator carrier trapping (ICT) and semiconductor carrier trapping components. The experimental results show that the ICT components account for nearly 50% of the total V
th shift in n-type OTFTs, while the ICT-induced V
th shifts is about 20% of the total V
th shift in p-type OTFTs regardless of the insulator materials: SAM or parylene. The experimental results suggest that the short lifetime of the n-type OTFTs with SAM-based insulator is caused by the instability of the SAM-based insulator due to ICT. In addition, the instability of the p-type OTFTs with SAM-based insulator is discussed based on measurement, and as a result, capacitance shift due to ICT may also affect the degradation of highly biased p-type OTFTs.