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Scientific Reports Jan 2021Angiomatoid fibrous histiocytoma (AFH) is a rare tumor of intermediate malignancy. Treatment options for unresectable and/or metastatic tumors are very limited....
Angiomatoid fibrous histiocytoma (AFH) is a rare tumor of intermediate malignancy. Treatment options for unresectable and/or metastatic tumors are very limited. Immunotherapy with PD-1/PD-L1 inhibitors may be worth exploring. The aim of this study was to evaluate the expression of PD-L1 in AFHs. PD-L1 expression was assessed on 36 AFHs from 36 pediatric patients by immunohistochemical staining of PD-L1 (clone 22C3). Positivity was defined as membranous expression in ≥ 1% of either tumor or immune cells. The correlations between PD-L1 expression and clinicopathologic features were assessed. Two patients had lymph node metastasis. All patients underwent surgical resection; three of them also had systemic chemotherapy. Three patients had recurrence after initial resection; all patients were alive with a median follow-up of 2.5 years. Overall, twenty-two (61%) tumors were positively stained for PD-L1 and positivity was seen on both tumor and immune cells in eighteen of the 22 tumors. A positive correlation was found between tumor cell PD-L1 expression and CD8+ T-cell infiltration. There were no statistically significant differences between the status of PD-L1 expression and the clinicopathological features assessed. PD-L1 expression was identified in 61% of AFHs with a predominantly adaptive pattern. Our findings provide a rationale for future studies evaluating the potential of checkpoint immunotherapy for patients with unresectable and/or metastatic tumor.
Topics: Adolescent; B7-H1 Antigen; CD8-Positive T-Lymphocytes; Child; Child, Preschool; Female; Histiocytoma, Malignant Fibrous; Humans; Leukocytes; Lymphocytes, Tumor-Infiltrating; Male
PubMed: 33500467
DOI: 10.1038/s41598-021-81746-y -
Critical Care (London, England) Jul 2022Ventilator-associated pneumonia (VAP) is associated with high morbidity and health care costs, yet diagnosis remains a challenge. Analysis of airway microbiota by...
BACKGROUND
Ventilator-associated pneumonia (VAP) is associated with high morbidity and health care costs, yet diagnosis remains a challenge. Analysis of airway microbiota by amplicon sequencing provides a possible solution, as pneumonia is characterised by a disruption of the microbiome. However, studies evaluating the diagnostic capabilities of microbiome analysis are limited, with a lack of alignment on possible biomarkers. Using bronchoalveolar lavage fluid (BALF) from ventilated adult patients suspected of VAP, we aimed to explore how key characteristics of the microbiome differ between patients with positive and negative BALF cultures and whether any differences could have a clinically relevant role.
METHODS
BALF from patients suspected of VAP was analysed using 16s rRNA sequencing in order to: (1) differentiate between patients with and without a positive culture; (2) determine if there was any association between microbiome diversity and local inflammatory response; and (3) correctly identify pathogens detected by conventional culture.
RESULTS
Thirty-seven of 90 ICU patients with suspected VAP had positive cultures. Patients with a positive culture had significant microbiome dysbiosis with reduced alpha diversity. However, gross compositional variance was not strongly associated with culture positivity (AUROCC range 0.66-0.71). Patients with a positive culture had a significantly higher relative abundance of pathogenic bacteria compared to those without [0.45 (IQR 0.10-0.84), 0.02 (IQR 0.004-0.09), respectively], and an increased interleukin (IL)-1β was associated with reduced species evenness (r = - 0.33, p < 0.01) and increased pathogenic bacteria presence (r = 0.28, p = 0.013). Untargeted 16s rRNA pathogen detection was limited by false positives, while the use of pathogen-specific relative abundance thresholds showed better diagnostic accuracy (AUROCC range 0.89-0.998).
CONCLUSION
Patients with positive BALF culture had increased dysbiosis and genus dominance. An increased caspase-1-dependent IL-1b expression was associated with a reduced species evenness and increased pathogenic bacterial presence, providing a possible causal link between microbiome dysbiosis and lung injury development in VAP. However, measures of diversity were an unreliable predictor of culture positivity and 16s sequencing used agnostically could not usefully identify pathogens; this could be overcome if pathogen-specific relative abundance thresholds are used.
Topics: Adult; Bacteria; Dysbiosis; Humans; Lung; Microbiota; Pneumonia, Ventilator-Associated; RNA, Ribosomal, 16S
PubMed: 35794610
DOI: 10.1186/s13054-022-04068-z -
Polish Journal of Pathology : Official... 2022This study aimed to evaluate CD73 and PD-L1 and determine their relationship with each other and with overall survival (OS) in sarcoma patients. The paraffin blocks...
This study aimed to evaluate CD73 and PD-L1 and determine their relationship with each other and with overall survival (OS) in sarcoma patients. The paraffin blocks of 101 patients were analysed. 56.4% were female, and the mean age was 51.39 years. The mean OS was 20.73 months, and the Ki-67 proliferative index was 41.45. A positive correlation was found between CD73 tumour and CD73 tumour-infiltrating lymphocyte (TIL) findings. CD73 tumour and TIL findings were also positively correlated with PD-L1 percentages and PD-L1 intensity. An inverse correlation was detected between OS and CD73 tumour and TIL groups of 5-25%, 25-50%, 50-75%, 75-90%, and > 90%, but no such correlation was found for the ≤ 5% group. There was an inverse correlation between OS and the PD-L1 percentages of 50% and the PD-L1 intensity of weak-moderate and strong, but no correlation was found for the negative values. Lastly, an inverse correlation was found between OS and the Ki-67 proliferative index. We found CD73 and PD-L1 positivity to be associated with decreased OS in sarcoma patients and determined a significant correlation between these parameters. This result is promising in terms of achieving better survival and disease control with anti-CD73 and anti-PD-L1 therapy in selected patients.
Topics: Humans; Female; Middle Aged; Male; Ki-67 Antigen; Prognosis; Sarcoma; Lymphocytes, Tumor-Infiltrating
PubMed: 36946270
DOI: 10.5114/pjp.2022.125537 -
Psychology Research and Behavior... 2023Attention deficit hyperactivity disorder (ADHD) among the youth and university students differs internationally. This study aims to assess the prevalence of ADHD...
BACKGROUND
Attention deficit hyperactivity disorder (ADHD) among the youth and university students differs internationally. This study aims to assess the prevalence of ADHD positivity from a validated screening test among medical students across the Kingdom of Saudi Arabia (KSA) and its associated sociodemographic and family-related factors and the impact of ADHD on students' academic performance. Also, to highlight the implications of the current findings on epidemiologists and family physicians in the region.
METHODS
This cross-sectional study utilised the Adult ADHD Self-Report Scale (ASRS) symptom checklist along with several questions on sociodemographic, siblings and personal academic achievement. Multivariable logistic regression models were performed to obtain the Odds Ratios (ORs) of risk of ADHD screening positivity and their 95% confidence intervals (CIs) against potential predictors.
RESULTS
The overall prevalence of positively screened medical students was 38.86%. After adjustment, a statistically significant increased risk of ADHD positivity was observed for students who had one sibling (OR = 1.70, 95% CI = 1.09-2.64). Also, upon examination of birth order, a significant increased risk was observed for students who were firstborn (OR = 1.22, 95% CI = 1.02-1.47). With regard to academic achievement, both before and after adjustment, students who screened positive had a 14% increased risk of obtaining an F GPA (OR = 1.14, 95% CI = 0.99-1.30).
CONCLUSION
A considerable number of medical students are potentially positive for ADHD. Albeit not diagnostically confirmed - this indicates that a substantial number of people have displayed symptoms akin to ADHD, but were not clinically diagnosed. Research into ADHD in the region is still in its infancy, and epidemiologists would benefit from high-quality databases to address this condition. Also, primary care physicians should develop skills in detecting and managing ADHD in children at an earlier age to improve symptoms in adulthood.
PubMed: 37817910
DOI: 10.2147/PRBM.S426715 -
Social Cognitive and Affective... May 2021People often engage in impression management by presenting themselves and others as socially desirable. However, specific behavioral manifestations and underlying neural...
People often engage in impression management by presenting themselves and others as socially desirable. However, specific behavioral manifestations and underlying neural mechanisms of impression management remain unknown. In this study, we investigated the neural mechanism of impression management during self- and friend-evaluation. Only participants assigned to the observation (OBS) group, not the control (CON) group, were informed that their responses would be monitored. They answered how well positive and negative trait adjectives described themselves or their friends. The behavioral results showed that the OBS group was more likely to reject negative traits for self-evaluation and to accept positive traits for friend-evaluation. An independent study revealed that demoting negative traits for oneself and promoting positive traits for a friend helps manage one's impression. In parallel with the behavioral results, in the OBS vs the CON group, the rostromedial prefrontal cortex (rmPFC) and anterior insula (AI) activity showed a greater increase as the negativity of negatively valenced adjectives increased during self-evaluation and also showed a greater increase as the positivity of positively valenced adjectives increased during friend-evaluation. The present study suggests that rmPFC and AI are critically involved in impression management, promoting socially desirable target evaluations under social observation.
Topics: Adult; Brain Mapping; Cerebral Cortex; Friends; Humans; Magnetic Resonance Imaging; Male; Prefrontal Cortex; Reaction Time; Self Concept; Self-Assessment; Social Desirability; Young Adult
PubMed: 33449108
DOI: 10.1093/scan/nsab008 -
PloS One 2021In Western societies, the stereotype prevails that pink is for girls and blue is for boys. A third possible gendered colour is red. While liked by women, it represents...
In Western societies, the stereotype prevails that pink is for girls and blue is for boys. A third possible gendered colour is red. While liked by women, it represents power, stereotypically a masculine characteristic. Empirical studies confirmed such gendered connotations when testing colour-emotion associations or colour preferences in males and females. Furthermore, empirical studies demonstrated that pink is a positive colour, blue is mainly a positive colour, and red is both a positive and a negative colour. Here, we assessed if the same valence and gender connotations appear in widely available written texts (Wikipedia and newswire articles). Using a word embedding method (GloVe), we extracted gender and valence biases for blue, pink, and red, as well as for the remaining basic colour terms from a large English-language corpus containing six billion words. We found and confirmed that pink was biased towards femininity and positivity, and blue was biased towards positivity. We found no strong gender bias for blue, and no strong gender or valence biases for red. For the remaining colour terms, we only found that green, white, and brown were positively biased. Our finding on pink shows that writers of widely available English texts use this colour term to convey femininity. This gendered communication reinforces the notion that results from research studies find their analogue in real word phenomena. Other findings were either consistent or inconsistent with results from research studies. We argue that widely available written texts have biases on their own, because they have been filtered according to context, time, and what is appropriate to be reported.
Topics: Color; Female; Humans; Language; Male; Sexism; Young Adult
PubMed: 34061875
DOI: 10.1371/journal.pone.0251559 -
International Journal of Colorectal... Sep 2022HER2-positive colorectal cancer was drawn increasing attention in recent years. Accumulating evidence showed HER2-positive metastatic colorectal cancer could benefit...
PURPOSE
HER2-positive colorectal cancer was drawn increasing attention in recent years. Accumulating evidence showed HER2-positive metastatic colorectal cancer could benefit from HER2-targeted therapy. While HER2 expression and the relationship between HER2 status and clinicopathological characteristics of overall colorectal cancer remains largely unknown. The aim of this study was to evaluate HER2 expression in colorectal cancer and compare the clinicopathological features between HER2-positive and HER2-negative colorectal cancer.
METHODS
We retrospectively analyzed 3910 primary colorectal cancer patients treated in our institution from January 2016 to December 2019. Medical records and pathology reports after surgery were collected to provide information about HER2 status and other clinicopathological characteristics.
RESULTS
We identified 3347 HER2-negative and 79 HER2-positive colorectal cancer patients in our cohort. The chi-square test showed that vessel invasion was significantly more common in HER2-positive colorectal cancer patients. Crude analysis showed HER2 positive was associated with vessel invasion in colorectal cancer [OR and 95% CI 0.534 (0.341, 0.835), p = 0.006]. After adjusting for N stage, a significant association was still observed between HER2 status and vessel invasion in colorectal cancer [OR and 95% CI 0.550 (0.322, 0.941), p = 0.029]. Survival analysis showed that there was no significant difference in 3-year overall survival rate between HER2 positive and HER2 negative group (p = 0.603).
CONCLUSION
Our findings indicate that the rate of HER2 positivity in colorectal cancer was relatively low, and HER2 status was strongly associated with vessel invasion while having no significant influence on the 3-year overall survival rate in colorectal cancer patients.
Topics: Cohort Studies; Colorectal Neoplasms; Humans; Prognosis; Receptor, ErbB-2; Retrospective Studies; Survival Rate
PubMed: 36006442
DOI: 10.1007/s00384-022-04243-2 -
Bone Reports Jun 2020We assessed the validity of self-reported fractures, over a median follow-up period of 6.2 years, in a well characterized population-based cohort of 3560 postmenopausal...
We assessed the validity of self-reported fractures, over a median follow-up period of 6.2 years, in a well characterized population-based cohort of 3560 postmenopausal women, aged 60-85 years, from the Fracture Risk Brussels Epidemiological Enquiry (FRISBEE) study. Incident low-traumatic (falls from a standing height or less) or non-traumatic fractures, including peripheral fractures, were registered during each annual follow-up telephone interview. A self-reported fracture was considered as a true positive if it was validated by written reliable medical reports (radiographs, CT scans or surgical report). False positives fractures were considered to be those for which the radiology report indicated that there was no fracture at the reported site. Among self-reported fractures, false positive rates were 14.4% for all fractures. The rate of false positives of 11.2% (n = 48/429) was not negligible for the four classical major osteoporotic fractures (MOFs: hip, clinical spine, forearm or shoulder fractures). In terms of fracture site, we found the lowest false positive rate (4.4%) at the hip, and the highest (16.8%) at the spine, with the proximal humerus and the wrist in between, at about 10% each. The global rates of false positives were 12.5% (n = 22/176) for other major fractures and 22.3% (n = 49/220) for minor fractures. Younger subjects, individuals with fractures at sites other than the hip, with a lower education level, or with a higher BMI were more likely to report false positive fractures. Our data indicate that the inaccuracy of self-reported fractures is clinically relevant for several major fractures, which could influence any fracture risk prediction model.
PubMed: 32382588
DOI: 10.1016/j.bonr.2020.100256 -
Metabolism Open Jun 2023In rodents, glomerular expression of insulin receptor substrate 1 (IRS1) is decreased in diabetic kidney disease (DKD) and reduced associated functioning is involved in...
BACKGROUND
In rodents, glomerular expression of insulin receptor substrate 1 (IRS1) is decreased in diabetic kidney disease (DKD) and reduced associated functioning is involved in the development and progression of DKD. This study aimed to evaluate the significance of glomerular IRS1 expression in DKD patients, and investigated whether glomerular IRS1 expression can reflect renal pathology and predict renal outcomes.
METHODS
This study included 10 patients who underwent renal biopsy and were diagnosed with DKD or minor glomerular abnormality (MGA). IRS1-positive cells were determined based on renal biopsy and immunostaining, and the associations of the number of these cells with baseline and prognostic parameters were analyzed.
RESULTS
IRS1-positive cells were significantly decreased in DKD than in MGA. IRS1 positivity tended to be negatively correlated with global glomerulosclerosis and tubulointerstitial fibrosis. The rate of change in estimated glomerular filtration rate before and 12 months after renal biopsy was positively correlated to the number of IRS1-positive cells. Furthermore, a tendency towards negative correlation was observed between the number of glomerular IRS1-positive cells and the proteinuria.
CONCLUSIONS
This study shows the glomerular IRS1-positive cell count was significantly decreased in DKD, and that the degree IRS1 positivity was partially correlated with renal pathology and function.
PubMed: 37025096
DOI: 10.1016/j.metop.2023.100240 -
Acta Psychologica May 2023The need to further our understanding of positive affect dysregulation in depression has been widely acknowledged. Two related relevant concepts in this realm, are...
The need to further our understanding of positive affect dysregulation in depression has been widely acknowledged. Two related relevant concepts in this realm, are Avoidance Of Positivity (AOP; referring to avoidance behaviour towards positivity) and Fear Of Positivity (FOP; referring to anxious or unpleasant feelings related to positivity). However, traditionally manifestations of AOP and FOP are considered in isolation, and self-report scales used to measure both concepts show considerable content overlap. Therefore, the first study aim was to examine how AOP and FOP relate to one another, depressive symptomatology and anhedonia, through new clearly delineated scales. For exploratory purposes, general and state-specific versions were developed. The second aim was to uncover beliefs that underlie the tendency towards AOP/FOP. An adult community sample (n = 197) completed online measures of AOP, FOP, depressive symptoms and anhedonia, and answered open-ended questions about reasons for AOP and FOP. Cross-sectionally, preliminary evidence was found for AOP and FOP being positively associated with one another, depressive symptomatology and anhedonia. Even after controlling for depressive symptomatology, anhedonia remained positively associated with AOP and FOP. So, AOP and FOP may be viable candidate mechanisms maintaining anhedonia that are worth further investigation and may be appropriate to target during treatment. Answers to the open-ended questions (n = 77) reflected various beliefs underlying AOP/FOP, which were broader than simply anticipating negative consequences of feeling positive and also touched on themes of unworthiness and social inappropriateness of feeling positive. Some theoretical and clinical implications of different beliefs underlying AOP/FOP are discussed.
Topics: Adult; Humans; Anhedonia; Emotions; Fear; Anxiety; Self Report
PubMed: 37018932
DOI: 10.1016/j.actpsy.2023.103901