bluuebunny/crossref_metadata_2025_split huggingface dataset:
Galectin-3 and Estrogen Receptor Alpha as Prognostic Markers in Prolactinoma: Preliminary Results From a Pilot Study
Authors: Bima Chiara , Chiloiro Sabrina , Giampietro Antonella , Gessi Marco , Mattogno Pier Paolo , Lauretti Liverana , Anile Carmelo , Rindi Guido , Pontecorvi Alfredo , De Marinis Laura , Bianchi Antonio 
Published: July 2021

IntroductionProlactin-secreting pituitary tumors (PRL-omas) are generally benign neoplasia. However, a percentage of cases show aggressive behavior. Prognostic markers may allow for the identification of aggressive cases. In this study, we investigated the prognostic role of galectin-3 and the estrogen receptor alpha (ERα), as predictive biomarkers of aggressiveness and poor prognosis.Patients and MethodsA mono-centric and retrospective study was conducted on consecutive cases of PRL-omas that underwent first line treatment with surgery and were followed-up for at least five years. The immunohistochemical expression of ERα and galectin-3 was investigated in each case.Results36 patients were enrolled. Galectin-3 resulted positive in 11 patients (30.6%). The median expression of ERα was 85% (IQR: 37). Among the group of 21 patients who underwent radical surgery (58.3%), recurrence occurred in 12 cases (33.3%). 27 patients were treated post-surgery with a dopamine agonist (DA) (12 for recurrence and 22 for a history of partial surgery). 13 patients (48.1%) were responsive to DA. Six of 11 cases positive for galactin-3 underwent partial surgery (54.5%, p&lt;0.001). Recurrence occurred in all five cases that underwent radical surgery, which were also positive for galectin-3 (p=0.03). Galectin-3 resulted positive in 9 patients resistant to DA treatment (81.1%, p=0.01). ERα expression was lower in tumors positive for galectin-3 (p&lt;0.001), with mitotic activity (p=0.012), with higher Ki67 Li (p&lt;0.001), and in males with post-surgical recurrence (p&lt;0.001).ConclusionGalectin-3 and ERα play as markers of aggressiveness and prognosis in PRL-omas and may be tested to identify the aggressive forms of the disease.
Inflammatory Stratification in Primary Sjögren’s Syndrome Reveals Novel Immune Cell Alterations in Patients’ Minor Salivary Glands
Authors: Bharaj Tamandeep K. , Aqrawi Lara A. , Fromreide Siren , Jonsson Roland , Brun Johan G. , Appel Silke , Skarstein Kathrine 
Published: July 2021

There is a critical need to deconvolute the heterogeneity displayed by the minor salivary glands of primary Sjögren’s syndrome (pSS) patients. This is challenging primarily because the disease etiology remains unknown. The hypothesis includes that initial events in the disease pathogenesis target the salivary glands, thereby triggering the development of focal infiltrates (≥50 mononuclear cells) and finally germinal center-like structures. However, the proportion of key mononuclear immune cells residing at these sites, in combination with the overall ratio of morphometric tissue atrophy and adipose infiltration within the minor salivary glands (MSG) parenchyma at distinct phases of inflammatory disease establishment and progression have not been quantified in detail. In this cross-sectional study, we intended to address this problem by stratifying 85 patients into mild (S1), moderate (S2), and severe (S3) stages using the Inflammatory severity index. We found that mild (&lt;3%) and marked (≥3%) levels of atrophy were accompanied by the respective levels of adipose infiltration in the non-SS sicca controls (p &lt;0.01), but not in pSS patients. The percentage of adipose infiltration significantly correlated with the age of patients (r = 0.458, p &lt;0.0001) and controls (r = 0.515, p &lt;0.0001). The CD4+ T helper cell incidence was reduced in the focal infiltrates of the MSG of S2 patients compared to S1 (p &lt;0.01), and in S2 compared to S1 and S3 combined (p &lt;0.05). CD20+ B cells increased from S1 to S3 (p &lt;0.01) and S2 to S3 (p &lt;0.01), meanwhile CD138+ plasma cells diminished in S3 patients compared to both S1 and S2 groups combined (p &lt;0.01). The proportion of patients with anti-Ro/SSA+, anti-La/SSB+, and RF+ increased over the course of inflammatory disease progression and they were significantly more common in the S3 group relative to S1 (p &lt;0.05). On the other hand, S2 patients measured a higher mean salivary flow relative to S1 and S3 patients combined (p &lt;0.05). Our results demonstrate how the proposed Inflammatory severity index stratification revealed pathological cell and tissue-associated aberrations in the salivary component over the course of inflammatory progression, and their correlations to clinical outcomes. This could be directly transferred to the optimization of available diagnostic strategies applied for pSS patients.
Cognitive and Motor Cortical Activity During Cognitively Demanding Stepping Tasks in Older People at Low and High Risk of Falling
Authors: Pelicioni Paulo H. S. , Lord Stephen R. , Sturnieks Daina L. , Halmy Bethany , Menant Jasmine C. 
Published: July 2021

Background: Choice stepping reaction time tasks are underpinned by neuropsychological, sensorimotor, and balance systems and therefore offer good indices of fall risk and physical and cognitive frailty. However, little is known of the neural mechanisms for impaired stepping and associated fall risk in older people. We investigated cognitive and motor cortical activity during cognitively demanding stepping reaction time tasks using functional near-infrared spectroscopy (fNIRS) in older people at low and high fall risk.Methods: Ninety-five older adults [mean (SD) 71.4 (4.9) years, 23 men] were categorized as low or high fall risk [based on 12-month fall history (≥2 falls) and/or Physiological Profile Assessment fall risk score ≥1]. Participants performed a choice stepping reaction time test and a more cognitively demanding Stroop stepping task on a computerized step mat. Cortical activity in cognitive [dorsolateral prefrontal cortex (DLPFC)] and motor (supplementary motor area and premotor cortex) regions was recorded using fNIRS. Stepping performance and cortical activity were contrasted between the groups and between the choice and Stroop stepping conditions.Results: Compared with the low fall risk group (n = 71), the high fall risk group (n = 24) exhibited significantly greater DLPFC activity and increased intra-individual variability in stepping response time during the Stroop stepping task. The high fall risk group DLPFC activity was greater during the performance of Stroop stepping task in comparison with choice stepping reaction time. Regardless of group, the Stroop stepping task elicited increased cortical activity in the supplementary motor area and premotor cortex together with increased mean and intra-individual variability of stepping response times.Conclusions: Older people at high fall risk exhibited increased DLPFC activity and stepping response time variability when completing a cognitively demanding stepping test compared with those at low fall risk and to a simpler choice-stepping reaction time test. This increased hemodynamic response might comprise a compensatory process for postural control deficits and/or reflect a degree of DLPFC neural inefficiency in people with increased fall risk.
Correlation Analysis Between Serum Uric Acid, Prealbumin Level, Lactate Dehydrogenase, and Severity of COVID-19
Authors: Jin Zhenmu , Zheng Mo , Shi Jichan , Ye Xinchun , Cheng Fang , Chen Que-Lu , Huang Jianping , Jiang Xian-Gao 
Published: July 2021

Objective: To analyze the correlation between serum uric acid, prealbumin levels, lactate dehydrogenase (LDH), and the severity of COVID-19.Methods: The data from 135 patients with COVID-19 was collected, and the patients were divided into a non-severe group (110 cases) and a severe group (25 cases), according to the severity of illness. Sixty cases with normal physical examinations over the same period and 17 cases diagnosed with other viral pneumonia in the past five years were selected as the control group to analyze the correlation between the detection index and the severity of COVID-19.Results: Serum albumin and prealbumin in the severe group were significantly lower than those in the non-severe group (p &lt; 0.01); serum uric acid in the severe group was lower than that in the non-severe group (p &lt; 0.05). LDH and C-reaction protein (CRP) in the severe group were higher than those in non-severe group (p &lt; 0.01); the levels of albumin, prealbumin, serum uric acid, and LDH in the severe group were significantly different from those in healthy control group (p &lt; 0.01) and the levels of prealbumin, serum uric acid, LDH, and CRP in the severe group were significantly different from those in the other viral pneumonia group (p &lt; 0.01). Serum albumin and prealbumin were positively correlated with the oxygenation index (p &lt; 0.001), while LDH was negatively correlated with oxygenation index (p &lt; 0.001).Conclusion: Serum albumin, prealbumin, the oxygenation index, and LDH are risk factors of COVID-19.
Resting-State Functional Connectivity of the Ageing Female Brain—Differences Between Young and Elderly Female Adults on Multislice Short TR rs-fMRI
Authors: Podgórski Przemysław , Waliszewska-Prosół Marta , Zimny Anna , Sąsiadek Marek , Bladowska Joanna 
Published: July 2021

Introduction:Age-related brain changes are one of the most important world health problems due to the rising lifespan and size of the elderly populations. The aim of the study was to assess the effect of ageing in women on coordinated brain activity between eight resting-state networks.Material and Methods:The study group comprised 60 healthy female volunteers who were divided into two age groups: younger women (aged 20–30n= 30) and older women (aged 55–80n= 30). Resting-state data were collected during a 15 min scan in the eyes-closed condition using a 3T MR scanner. Data were preprocessed and analysed using the CONN toolbox version 19.c. The large-scale network analysis includeda prioriselected regions of interest of the default mode, the sensorimotor, the visual, the salience, the dorsal attention, the fronto-parietal, the language, and the cerebellar network.Results:Within the visual, the default mode, the salience, and the sensorimotor network, the intra-network resting-state functional connectivity (RSFC) was significantly higher with increasing age. There was also a significant increase in the inter-network RSFC in older females compared to young females found in the following networks: sensorimotor lateral and salience, salience and language, salience and fronto-parietal, cerebellar anterior and default mode, cerebellar posterior and default mode, visual and sensorimotor lateral, visual and sensorimotor, visual lateral and default mode, language and cerebellar anterior, language and cerebellar posterior, fronto-parietal and cerebellar anterior, dorsal attention and sensorimotor, dorsal attention and default mode, sensorimotor superior, and salience. Compared to young females, elderly women presented bilaterally significantly lower inter-network RSFC of the salience supramarginal gyrus and cerebellar posterior, sensorimotor lateral, and cerebellar anterior network, and sensorimotor lateral and cerebellar posterior as well as sensorimotor superior and cerebellar posterior network.Conclusion:Increased RSFC between some brain networks including the visual, the default mode, the salience, the sensorimotor, the language, the fronto-parietal, the dorsal attention, and the cerebellar networks in elderly females may function as a compensation mechanism during the ageing process of the brain. To the best of our knowledge, this study is the first to report the importance of increase of cerebellar networks RSFC during healthy female ageing.
The Evoked Compound Action Potential as a Predictor for Perception in Chronic Pain Patients: Tools for Automatic Spinal Cord Stimulator Programming and Control
Authors: Pilitsis Julie G. , Chakravarthy Krishnan V. , Will Andrew J. , Trutnau Karen C. , Hageman Kristin N. , Dinsmoor David A. , Litvak Leonid M. 
Published: July 2021

ObjectivesSpinal cord stimulation (SCS) is a drug free treatment for chronic pain. Recent technological advances have enabled sensing of the evoked compound action potential (ECAP), a biopotential that represents neural activity elicited from SCS. The amplitudes of many SCS paradigms – both sub- and supra-threshold – are programmed relative to the patient’s perception of SCS. The objective of this study, then, is to elucidate relationships between the ECAP and perception thresholds across posture and SCS pulse width. These relationships may be used for the automatic control and perceptually referenced programming of SCS systems.MethodsECAPs were acquired from 14 subjects across a range of postures and pulse widths with swept amplitude stimulation. Perception (PT) and discomfort (DT) thresholds were recorded. A stimulation artifact reduction scheme was employed, and growth curves were constructed from the sweeps. An estimate of the ECAP threshold (ET), was calculated from the growth curves using a novel approach. Relationships between ET, PT, and DT were assessed.ResultsETs were estimated from 112 separate growth curves. For the postures and pulse widths assessed, the ET tightly correlated with both PT (r = 0.93; p &lt; 0.0001) and DT (r = 0.93; p &lt; 0.0001). The median accuracy of ET as a predictor for PT across both posture and pulse width was 0.5 dB. Intra-subject, ECAP amplitudes at DT varied up to threefold across posture.ConclusionWe provide evidence that the ET varies across both different positions and varying pulse widths and suggest that this variance may be the result of postural dependence of the recording electrode-tissue spacing. ET-informed SCS holds promise as a tool for SCS parameter configuration and may offer more accuracy over alternative approaches for neural and perceptual control in closed loop SCS systems.
Fatty Acid Esters of Hydroxy Fatty Acids (FAHFAs) Are Associated With Diet, BMI, and Age
Authors: Kellerer Teresa , Kleigrewe Karin , Brandl Beate , Hofmann Thomas , Hauner Hans , Skurk Thomas 
Published: July 2021

Background: Fatty acid esters of hydroxy fatty acids (FAHFAs) are a group of fatty acids with potential anti-inflammatory and anti-diabetic effects. The blood levels of FAHFAs and their regulation in humans have hardly been studied.Objective: We aimed to investigate serum FAHFA levels in well-characterized human cohorts, to evaluate associations with age, sex, BMI, weight loss, diabetic status, and diet.Methods: We analyzed levels of stearic-acid-9-hydroxy-stearic-acid (9-SAHSA), oleic-acid-9-hydroxy-stearic-acid (9-OAHSA) and palmitic-acid-9-hydroxy-palmitic-acid (9-PAHPA) as well as different palmitic acid-hydroxy-stearic-acids (PAHSAs) by HPLC-MS/MS with the use of an internal standard in various cohorts: A cohort of different age groups (18–25y; 40–65y; 75–85y; Σn = 60); severely obese patients undergoing bariatric surgery and non-obese controls (Σn = 36); obese patients with and without diabetes (Σn = 20); vegetarians/vegans (n = 10) and omnivores (n = 9); and young men before and after acute overfeeding with saturated fatty acids (SFA) (n = 15).Results: Omnivores had substantially higher FAHFA levels than vegetarians/vegans [median (25th percentile; 75th percentile) tFAHFAs = 12.82 (7.57; 14.86) vs. 5.86 (5.10; 6.71) nmol/L; P &lt; 0.05]. Dietary overfeeding by supplementation of SFAs caused a significant increase within 1 week [median tFAHFAs = 4.31 (3.31; 5.27) vs. 6.96 (6.50; 7.76) nmol/L; P &lt; 0.001]. Moreover, obese patients had lower FAHFA levels than non-obese controls [median tFAHFAs = 3.24 (2.80; 4.30) vs. 5.22 (4.18; 7.46) nmol/L; P &lt; 0.01] and surgery-induced weight loss increased 9-OAHSA level while other FAHFAs were not affected. Furthermore, significant differences in some FAHFA levels were found between adolescents and adults or elderly, while no differences between sexes and between diabetic and non-diabetic individuals were detected.Conclusions: FAHFA serum levels are strongly affected by high SFA intake and reduced in severe obesity. Age also may influence FAHFA levels, whereas there was no detectable relation with sex and diabetic status. The physiological role of FAHFAs in humans remains to be better elucidated.Trial Registration: All studies referring to these analyses were registered in the German Clinical Trial Register (https://www.drks.de/drks_web/) with the numbers DRKS00009008, DRKS00010133, DRKS00006211, and DRKS00009797.
Identification of a Three-RNA Binding Proteins (RBPs) Signature Predicting Prognosis for Breast Cancer
Authors: Liu Yang , Sun Hefen , Li Xuan , Liu Qiqi , Zhao Yuanyuan , Li Liangdong , Xu Baojin , Hou Yifeng , Jin Wei 
Published: July 2021

BackgroundTo date, breast cancer remains the primary cause of tumor-related death among women, even though some leap-type developments of oncology have been done to slash the mortality. Considering the tumor heterogeneity and individual variation, the more reliable biomarkers are required to be identified for supporting the development of precision medicine in breast cancer.MethodsBased on the TCGA-BRCA and METABRIC databases, the differently expressed RNA binding proteins (RBPs) between tumor and normal tissues were investigated. In this study, we focused on the communal differently expressed RBPs in four subtypes of breast cancer. Lasso-penalized Cox analysis, Stepwise-multivariate Cox analysis and Kaplan–Meier survival curve were performed to identify the hub RBP-coding genes in predicting prognosis of breast cancer, and a prognostic model was established. The efficiency of this model was further validated in other independent GSE20685, GSE4922 and FUSCC-TNBC cohorts by calculating the risk score and performing survival analysis, ROC and nomogram. Moreover, pathologic functions of the candidate RBPs in breast cancer were explored using some routine experiments in vitro, and the potential compounds targeting these RBPs were predicted by reviewing the Comparative Toxicogenomics Database.ResultsHere, we identified 62 RBPs which were differently expressed between the tumor and normal tissues. Thereinto, three RBPs (MRPL12, MRPL13 and POP1) acted as independent risk factors, and their expression pattern also correlated with poor prognosis of patients. A prognostic model, built with these 3-RBPs, possessed statistical significance to predict the survival probability of patients with breast cancer. Furthermore, experimental validations showed that down-regulating the expression of endogenous MRPL12, MRPL13 or POP1 could dramatically suppress the cellular viability and migration of breast cancer cells in vitro. Besides, some compounds (such as the Acetaminophen, Urethane and Tunicamycin) were predicted for curing breast cancer via targeting MRPL12, MRPL13 and POP1 simultaneously.ConclusionThis study identified and established a 3-RBPs-based signature and nomogram for predicting the survival probability of patients with breast cancer. MRPL12, MRPL13 and POP1 might act as oncogenes in maintaining cellular viability and accelerating metastasis of breast cancer cells, implying the possibility of which to be designed as biomarkers and/or therapeutic targets for breast cancer.
The Risk of Immune-Related Thyroid Dysfunction Induced by PD-1/PD-L1 Inhibitors in Cancer Patients: An Updated Systematic Review and Meta-Analysis
Authors: Tian Yuan , Li Ran , Liu Yan , Li Meng , Song Yuxiao , Zheng Yan , Gao Aiqin , Wen Qing , Su Guohai , Sun Yuping 
Published: July 2021

BackgroundThyroid dysfunction is common for cancer patients receiving PD-1/PD-L1 inhibitor therapies. To clarify the incidence risk of thyroid dysfunction would be important for guiding anti-PD-1 and anti-PD-L1 immunotherapy. Therefore, the updated meta-analysis was conducted to evaluate the incidence risk of thyroid dysfunction caused by PD-1/PD-L1 inhibitors.MethodsPD-1/PD-L1 inhibitor related clinical trials were collected by a systematic search of the PubMed. Some relevant studies were identified by a manual search. The incidence risk of all grades and grades 3-5 was analyzed and evaluated by random effect model. The Newcastle Ottawa Scale was used for the quality assessment of all clinical trials.ResultsForty-three clinical trials were collected. Compared with chemotherapy, the risk of hypothyroidism of all grades was significantly higher (OR=7.15, 95%CI:[4.85, 10.55], I2 = 40%, Z=9.91(P &lt;0.00001)) in PD-1/PD-L1 group. Similar results could also be noted, when the control group was placebo or CTLA-4. When PD-1/PD-L1 was combined with other treatments for cancer patients, the risk of hypothyroidism of all grades was also significantly increased. Similar to the analysis results of hypothyroidism, PD-1/PD-L1 inhibitors played the same role in increasing the risk of hyperthyroidism and thyroiditis. Few significant analysis results was noted, when the risk of thyroid dysfunction of grades 3-5 was assessed.ConclusionWhether used alone or in combination with other anti-tumor drugs, PD-1/PD-L1 inhibitors increased the risk of thyroid dysfunction, especially for hypothyroidism. Furthermore, PD-1/PD-L1 was better than chemotherapy and CTLA-4 in increasing the risk of thyroid dysfunction.
Prognostic Value of Perineural Invasion in Oral Tongue Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis
Authors: Li Jiajia , Liu Shan , Li Zhangao , Han Xinxin , Que Lin 
Published: July 2021

ObjectivesA significant number of recently published research has outlined the contribution of perineural invasion (PNI) to clinical outcomes in oral tongue squamous cell carcinoma (OTSCC), but some results remain conflicting. This study aimed to determine whether patients with OTSCC with PNI have a worse prognosis than those without PNI.Materials and MethodsPubMed, Embase, and the Cochrane Library were queried for potentially eligible articles published up to December 2020. The primary outcomes were the hazard ratio (HR) for locoregional recurrence, overall survival (OS), disease-free survival (DFS), and cancer-specific survival (CSS). The random-effect model was used in all analyses.ResultsSeventeen studies (4445 patients) were included. Using adjusted HRs, the presence of PNI was associated with a higher risk of locoregional recurrence (HR=1.73, 95%CI: 1.07-2.79, P=0.025, I2 = 33.1%, Pheterogeneity=0.224), worse OS (HR=1.94, 95%CI: 1.39-2.72, P&lt;0.001, I2 = 0.0%, Pheterogeneity=0.838), worse DFS (HR=2.13, 95%CI: 1.53-2.96, P&lt;0.001, I2 = 48.4%, Pheterogeneity=0.071), and worse CSS (HR=1.93, 95%CI: 1.40-2.65, P&lt;0.001, I2 = 25.5%, Pheterogeneity=0.251). PNI had an impact on locoregional recurrence in early-stage OTSCC but not in all stages, and on OS, DFS, and CSS in all-stage and early-stage OTSCC. The sensitivity analyses showed that the results were robust.ConclusionThe presence of PNI significantly affects the locoregional recurrence and survival outcomes among patients with OTSCC.