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AbstractObjectives This cross-sectional study aimed to compare the sexual function (SF) and pelvic floor function of men with systemic sclerosis (SSc) with age-matched healthy controls (HC) and to identify the implications of clinical features on SF.Material and method Twenty SSc males and 20 HC aged 18–70 years completed eleven questionnaires assessing SF [International Index of Erectile Function (IIEF), Male Sexual Health Questionnaire (MSHQ)]; sexual quality of life: Sexual Quality of Life Questionnaire-Male (SQoL-M); pelvic floor function: Pelvic Floor Impact Questionnaire-Short Form 7 (PFIQ-7), fatigue, depression, physical fitness, functional disability, and quality of life. Clinical data were collected.Results Significantly worse SF was observed in patients (median IIEF erectile function 12 in SSc versus 29 in HC, p

Background. Complex networks of chemokines are part of the immune reaction targeted against tumor cells. Chemokines influence cancer growth. It is unclear whether the concentrations of chemokines at the time of NSCLC (non-small cell lung cancer) diagnosis differ from healthy controls and reflect the extent of NSCLC. Aims. To compare chemokine concentrations (CCL2, CCL8, CXCL12) in the plasma of patients with resectable NSCLC to those without cancer. To determine whether the chemokine concentrations differ relative to the stage of disease. Methods. Sixty-nine patients undergoing surgery for proven/suspected NSCLC were enrolled. They underwent standard diagnostic and staging procedures to determine resectability, surgery was performed. Forty-two patients were diagnosed with NSCLC, while 27patients had benign lung lesions and functioned as the control group. Chemokine concentrations in peripheral blood were assessed using ELISA. Parametric statistics were used for the analysis of results. Results. There were no differences in plasma chemokine concentrations in NSCLC patients compared to controls. CXCL12 concentrations correlated positively with tumor extent expressed as clinical stage, (mean values: stage I 5.08 ng/mL, SEM 0.59; stage II and IIIA 7.82 ng/mL; SEM 1.06; P=0.022). Patients with NSCLC stages II+IIIA had significantly higher CXCL12 concentrations than controls (mean values: stage II+IIIA 7.82 ng/mL; SEM 1.06; controls 5.3 ng/mL; SEM 0.46; P=0.017). Conclusion. CXCL12 was related to tumor growth and could potentially be used as a biomarker of advanced disease.

Renal cell carcinoma (RCC) is a common malignancy frequently diagnosed at the metastatic stage. We performed a comprehensive analysis of the tumor immune microenvironment (TIME) in RCC patients, including the peritumoral tissue microenvironment, to characterize the phenotypic patterns and functional characteristics of infiltrating immune cells. T cells from various compartments (peripheral blood, tumor, peritumoral area, and adjacent healthy renal tissue) were assessed using flow cytometry and Luminex analyses, both before and after T cell-specific stimulation, to evaluate activation status and migratory potential. Our findings demonstrated that tumor-infiltrating lymphocytes (TILs) exhibited heightened cytokine production compared to peritumoral T cells (pTILs), acting as the primary source of cytotoxic markers (IFN-γ, granzyme B, and FasL). CD8+ T cells primarily employed Fas Ligand for cytotoxicity, while CD4+ T cells relied on CD107a. In addition, a statistically significant negative correlation between patient mortality and the presence of CD4+CD107+ pTILs was demonstrated. The engagement with the PD-1/PD-L1 pathway was also more evident in CD4+ and CD8+ pTILs as opposed to TILs. PD-L1 expression in the non-leukocyte fraction of the tumor tissue was relatively lower than in their leukocytic counterparts and upon stimulation, peripheral blood T cells displayed much stronger responses to stimulation than TILs and pTILs. Our results suggest that tumor and peritumoral T cells exhibit limited responsiveness to additional activation signals, while peripheral T cells retain their capacity to respond to stimulatory signals

BackgroundArtificial intelligence (AI) has advanced substantially in recent years, transforming many industries and improving the way people live and work. In scientific research, AI can enhance the quality and efficiency of data analysis and publication. However, AI has also opened up the possibility of generating high-quality fraudulent papers that are difficult to detect, raising important questions about the integrity of scientific research and the trustworthiness of published papers. ObjectiveThe aim of this study was to investigate the capabilities of current AI language models in generating high-quality fraudulent medical articles. We hypothesized that modern AI models can create highly convincing fraudulent papers that can easily deceive readers and even experienced researchers. MethodsThis proof-of-concept study used ChatGPT (Chat Generative Pre-trained Transformer) powered by the GPT-3 (Generative Pre-trained Transformer 3) language model to generate a fraudulent scientific article related to neurosurgery. GPT-3 is a large language model developed by OpenAI that uses deep learning algorithms to generate human-like text in response to prompts given by users. The model was trained on a massive corpus of text from the internet and is capable of generating high-quality text in a variety of languages and on various topics. The authors posed questions and prompts to the model and refined them iteratively as the model generated the responses. The goal was to create a completely fabricated article including the abstract, introduction, material and methods, discussion, references, charts, etc. Once the article was generated, it was reviewed for accuracy and coherence by experts in the fields of neurosurgery, psychiatry, and statistics and compared to existing similar articles. ResultsThe study found that the AI language model can create a highly convincing fraudulent article that resembled a genuine scientific paper in terms of word usage, sentence structure, and overall composition. The AI-generated article included standard sections such as introduction, material and methods, results, and discussion, as well a data sheet. It consisted of 1992 words and 17 citations, and the whole process of article creation took approximately 1 hour without any special training of the human user. However, there were some concerns and specific mistakes identified in the generated article, specifically in the references. ConclusionsThe study demonstrates the potential of current AI language models to generate completely fabricated scientific articles. Although the papers look sophisticated and seemingly flawless, expert readers may identify semantic inaccuracies and errors upon closer inspection. We highlight the need for increased vigilance and better detection methods to combat the potential misuse of AI in scientific research. At the same time, it is important to recognize the potential benefits of using AI language models in genuine scientific writing and research, such as manuscript preparation and language editing.

Abstract Hormone-secreting adenomas are treated in many neurosurgical centers within Europe. The goal of the survey is to understand variance in practice management of pituitary tumors amongst neurosurgical centers. A list of departments performing pituitary surgery was created. The survey consisted of 58 questions. This study focuses on neurosurgical care of hormone-secreting adenomas. For analysis, the departments were divided into four subgroups: academic/non-academic, high-volume/low-volume, “mainly endoscopic/mainly microscopic practice” and geographical regions. Data from 254 departments from 34 countries were obtained. Most centers surgically treat 1–5 hormone-secreting adenomas per year. In prolactinomas this is the case in 194 centers, (76.4%), in GH-secreting adenomas: 133 centers, (52.4%), ACTH-secreting adenomas: 172 centers, (69.8%). Surgery as a primary treatment of prolactinomas is considered in 64 centers (25.2%). In 47 centers (18.8%), GH-secreting microadenomas are often treated pharmacologically first. Debulking surgery for an invasive GH-secreting adenoma in which hormonal remission is not a realistic goal of the surgery and the patient has no visual deficit surgery is always or mostly indicated in 156 centers (62.9%). Routine postoperative hydrocortisone replacement therapy is administered in 147 centers (58.6%). Our survey shows that in most centers, few hormone-secreting adenomas are treated per year. In about 25% of the centers, prolactinoma surgery may be regarded as first-line treatment; in about 20% of the centers, medical treatment is the first-line treatment for GH-secreting adenomas. Pretreatment for ACTH-secreting adenomas is routinely used in 21% of centers. This survey may serve as plea for neurosurgical care centralization of hormone-secreting adenomas.

Abstract Background The structural and functional changes of the skeletal muscles in idiopathic inflammatory myopathies (IIM) caused by inflammation and immune changes can be severely disabling. The objective of this study was to assess the effect of a 24-week program combining a supervised training of activities of daily living (ADL), resistance, and stability with home exercise for improving muscle function, compared to a daily home-based exercise representing the regular outpatient care. Methods Fifty-seven patients with IIM were consecutively and non-selectively enrolled in an intervention (IG, n = 30) or control (CG, n = 27) group. Both groups were provided a standard-of-care pharmacological treatment and follow-up. Only the IG underwent the supervised intervention twice a week for 1 h per session. At baseline, 12, 24, and 48 weeks, all patients were assessed by an assessor blinded to the intervention for primary outcomes: muscle strength (Manual Muscle Testing of eight muscle groups [MMT-8]) and endurance (Functional Index-2 [FI-2]), and secondary outcomes: stability and body composition. Secondary outcomes also included questionnaires evaluating disability (Health Assessment Questionnaire [HAQ]), quality of life (Short Form 36 [SF-36]), depression (Beck’s Depression Inventory-II [BDI-II]), and fatigue (Fatigue Impact Scale [FIS]), and analysis of the systemic and local inflammatory response and perceived exertion to assess the safety of the intervention. Results Twenty-seven patients in the IG and 23 in the CG completed the entire program and follow-up. At week 24, compared to deterioration in the CG, we found a significant improvement in the IG in muscle strength (mean % improvement compared to baseline by 26%), endurance (135%), disability (39%), depression (26%), stability (11%), and basal metabolism (2%) and a stabilization of fitness for physical exercise. The improvement was clinically meaningful (a 24-week change by >20%) in most outcomes in a substantial proportion of patients. Although the improvement was still present at 48 weeks, the effect was not sustained during follow-up. No significant increase in the systemic or local expression of inflammatory markers was found throughout the intervention. Conclusions This 24-week supervised intervention focused on ADL training proved to be safe and effective. It not only prevented the progressive deterioration, but also resulted in a significant improvement in muscle strength, endurance, stability, and disability, which was clinically meaningful in a substantial proportion of patients. Trial registration ISRCTN35925199 (retrospectively registered on 22 May 2020).

Manufacturers recommend that linear position transducers (LPTs) should be placed on the side of a barbell (or wooden dowel) to measure countermovement jump (CMJ) height, but the validity and reliability of this placement have not been compared to other attachment sites. Since this recommended attachment site is far from the centre of mass, a belt attachment where the LPT is placed between the feet may increase the validity and reliability of CMJ data. Thirty-six physical education students participated in the study (24.6 ± 4.3 years; 177.0 ± 7.7 cm; 77.2 ± 9.0 kg). Parameters from the two LPT attachments (barbell and belt) were simultaneously validated to force plate data, where the nature of bias was analysed (systematic vs random). The within-session and between-session reliability of both attachment sites were compared to force plate data using a test-retest protocol of two sets of 5 CMJs separated by 7 days. The LPT provided highly reliable and valid measures of peak force, mean force, mean power, and jump height, where the bias was mostly systematic (r2 > 0.7; ICC > 0.9). Peak velocity, mean velocity, and peak power were in very good agreement with the force plate and were highly reliable (r2 > 0.5; ICC > 0.7). Therefore, both attachment sites produced similar results with a systematic bias compared to force plate data. Thus, both attachment sites seem to be valid for assessing CMJs when the measuring tool and site remain consistent across measurements. However, if LPT data are to be compared to force plate data, recalculation equations should be used.

Abstract Our previous study demonstrated increased expression of Heat shock protein (Hsp) 90 in the skin of patients with systemic sclerosis (SSc). We aimed to evaluate plasma Hsp90 in SSc and characterize its association with SSc-related features. Ninety-two SSc patients and 92 age-/sex-matched healthy controls were recruited for the cross-sectional analysis. The longitudinal analysis comprised 30 patients with SSc associated interstitial lung disease (ILD) routinely treated with cyclophosphamide. Hsp90 was increased in SSc compared to healthy controls. Hsp90 correlated positively with C-reactive protein and negatively with pulmonary function tests: forced vital capacity and diffusing capacity for carbon monoxide (DLCO). In patients with diffuse cutaneous (dc) SSc, Hsp90 positively correlated with the modified Rodnan skin score. In SSc-ILD patients treated with cyclophosphamide, no differences in Hsp90 were found between baseline and after 1, 6, or 12 months of therapy. However, baseline Hsp90 predicts the 12-month change in DLCO. This study shows that Hsp90 plasma levels are increased in SSc patients compared to age-/sex-matched healthy controls. Elevated Hsp90 in SSc is associated with increased inflammatory activity, worse lung functions, and in dcSSc, with the extent of skin involvement. Baseline plasma Hsp90 predicts the 12-month change in DLCO in SSc-ILD patients treated with cyclophosphamide.

The somatic parameters and body composition are important indicators of physical fitness and general health not only non-athletes, but of athletes. The aim of this study was to determine the somatic characteristics and body composition in 15 Czech sub-elite female handball players (age 21.5 ± 1.8 years, body height 170.5 ± 6.6 cm, body weight 64.7 ± 10.2 kg, BMI 22.2 ± 2.9 kg m−2). Body composition was measured by a multifrequency bioimpedance method Tanita MC-980 (Tanita Europe BV). The monitored parameters were the following: fat mass (FM), fat free mass (FFM), muscle mass (MM), bone mass (BM), total body water (TBW), intracellular water (ICW), extracellular water (ECW) and segmental analysis of muscle distribution. In our female group, we recorded the mean value of FM = 21.5 ± 5.4% (14.3 ± 5.7 kg), FFM = 50.4 ± 5.9 kg, muscle mass = 47.9 ± 5.6 kg, bone mass = 2.6 ± 0.3 kg, TBW = 56.2 ± 3.2% (36.2 ± 4.8 kg), ICW = 22.6 ± 3.5 kg, ECW = 13.6 ± 1.3 kg. Monitoring of muscle distribution in the extremities showed a significant difference in upper extremities (p < 0.05, ES < 0.2) and in lower extremities (p < 0.05, ES < 0.2). Our results confirm on previous data about the presence of anthropometric differences and body composition differences between individual players in handball team.

Aims: Preoperative chemical vestibular ablation can reduce vestibular symptoms in patients who have gone through vestibular schwannoma resection. The goal of this study was to determine whether chemical vestibular prehabituation influences the patients' post-operative perception of visual stimulation, mental status and quality of life. We also tried to find out whether increases of optokinetic nystagmus, measured by routine electronystagmography, correlate with subjective symptoms. Methods: We preoperatively administered (2 months prior to surgery) 0.5 - 1.0 mL of 40 mg/mL nonbuffered gentamicin in three intratympanic instillations in 11 patients. Head impulse and caloric tests confirmed reduction of vestibular function in all patients. The control group consisted of 21 patients. Quality of life in both groups was evaluated using the Glasgow Benefit Inventory, the Glasgow Health Status Inventory and the Dizziness Handicap Inventory questionnaires. Visual symptoms and optokinetic sensation were evaluated using a specific questionnaire developed by our team and by measuring gains preoperatively and postoperatively in both groups using routine electronystagmography. The psychological profile was evaluated using the Zung Self-Rating Depression Scale and the Generalised Anxiety Disorder Assessment questionnaires. Results: There were no statistically significant differences between both groups with regards to the results of the questionnaires. Patients who received preoperative gentamicin were less sensitive to visual stimulation (P

Objective. Pituitary adenoma surgery has evolved rapidly in recent decades. This study aims to determine current practice across a wide range of European neurosurgical centers. Methods. A list of eligible departments performing pituitary adenoma surgery was created. The survey consisted of 58 questions. For analysis, the departments were divided into four subgroups: academic/nonacademic, high-volume/low-volume, “mainly endoscopic/mainly microscopic practice,” and geographical regions. Results. Data from 254 departments from 34 countries were obtained. In 108 centers (42.5%), 100 adenoma surgeries per year. Number of neurosurgeons performing endonasal surgeries are as follows: 1 in 24.9% of centers and 2 in 49.8% of centers. All residents assisted endonasal surgeries in 126 centers (49.8%). In 28 centers (21.1%), all residents performed endonasal surgery under supervision during residency. In 141 centers (56.8%), the endoscopic approach was used in >90% of the surgeries. Regular pituitary board (either weekly or once a month) meetings were held in 147 centers (56.3%). Nonfunctioning adenomas represent >70% of pituitary caseload in 149 centers (58.7%). Conclusions. In our survey, most centers perform less than 100 surgeries for pituitary adenomas. In most centers, pituitary surgeries are performed by one or two neurosurgeons. Residents have a limited exposure to this type of surgery, and the formal pituitary board is not a standard. Nonfunctioning adenomas make up most of surgically treated adenomas. This study can serve as a benchmark for further analyses of pituitary adenoma centers in Europe.

BackgroundHeat shock proteins (Hsp) are chaperones playing essential roles in skeletal muscle physiology, adaptation to exercise or stress, and activation of inflammatory cells. We aimed to assess Hsp90 in patients with idiopathic inflammatory myopathies (IIM) and its association with IIM-related features.MethodsHsp90 plasma levels were analyzed in a cross-sectional cohort (277 IIM patients and 157 healthy controls [HC]) and two longitudinal cohorts to assess the effect of standard-of-care pharmacotherapy (n=39 in early disease and n=23 in established disease). Hsp90 and selected cytokines/chemokines were measured by commercially available ELISA and human Cytokine 27-plex Assay.ResultsHsp90 plasma levels were increased in IIM patients compared to HC (median [IQR]: 20.2 [14.3–40.1] vs 9.8 [7.5–13.8] ng/mL, p

BackgroundInterleukin 40 (IL-40) is a newly identified B cell-associated cytokine implicated in humoral immune responses and B cell homeostasis. As B cells play a pivotal role in autoimmunity, we investigated the function of IL-40 in rheumatoid arthritis (RA).MethodsIL-40 expression was determined in the synovial tissue from RA and osteoarthritis (OA) patients. IL-40 was analysed in the serum/synovial fluid of patients with RA (n=50), systemic lupus erythematosus (SLE, n=69), OA (n=44), and healthy controls (HC, n=50). We assessed the changes of IL-40 levels in RA patients following the B cell depletion by rituximab (n=29) or after the TNF inhibition by adalimumab (n=25). We examined the relationship between IL-40, disease activity, autoantibodies, cytokines, and NETosis markers. Effect of IL-40 on synovial fibroblasts was determined.ResultsIL-40 was overexpressed in RA synovial tissue, particularly by synovial lining and infiltrating immune cells. The levels of IL-40 were up-regulated in the synovial fluid of RA versus OA patients (p

Purpose. To evaluate a 12-year follow-up of myopic patients after iris-fixated phakic intraocular lenses (IF pIOLs) implantation. Setting. Ophthalmology Department, Military University Hospital in Prague (Czech Republic). Design. Single-center retrospective cohort study. Methods. We describe the results of a cohort study that included 85 eyes of 46 myopic patients who underwent implantation of Verisyse myopia, Veriflex, and Verisyse myopia toric (all Abbott Medical Optics, Inc.) intraocular lenses. Refractive functions and adverse events were assessed preoperatively, at 6 months, and 1, 2, 5, and 12 years after IF pIOL implantation. Results. Mean spherical equivalent was measured as −9.37 ± 2.87 D, 0.14 ± 0.61 D, and −0.42 ± 1.08 D, preoperatively, at 6 months and 12 years postoperatively, respectively. There was a significant reduction in the cylinder after surgery. At 12 years postoperatively, 90% of eyes had uncorrected distance visual acuity (UDVA) of 20/40 and 64% of 20/20. The safety index was 1.10 for the whole postoperative follow-up period. We found cataract formation in 3 eyes (3.5%). The endothelial cells loss (EC loss) directly caused by IF pIOL implantation was 6.0%, 8.10%, 12.8%, and 11.9%, at 1, 2, 5, and 12 years, respectively. In our cohort, 95% of eyes lost a higher percentage of EC than would be expected from a physiological loss at 12 years postoperatively. We found a significant negative interaction between preoperative pachymetry and EC loss, indicating that the lower pachymetry leads to a faster decline in endothelial cells density (ECD). IF pIOL re-enclavation was found in 28% of eyes. 7% of subluxations were caused by trauma. The mean time of nontraumatic re-enclavation was 6 years postoperatively. Conclusions. The study confirmed the advantages of IF pIOL implantation due to rapid visual recovery and stable visual function over the 12-year follow-up and also showed the influence of lower corneal pachymetry regarding EC loss.

The Sport Motivation Scale (SMS) is a widely used instrument that assesses motivational processes within sport and exercise environments. The scale has demonstrated validity and reliability in multiple cultures, however, there is yet no empirical evidence regarding its psychometric properties in the Czech population. In this study we therefore set out to examine the reliability and construct validity of the SMS in a sample of Czech university-aged athletes. We first examined the SMS factor structure using a nonparametric item response theory model (Mokken monotone homogeneity model) and identified six items violating the unidimensionality of the particular subscales. Remaining items were then subjected to test of hypothesized seven-factor structure and several different forms of measurement invariance examined based on gender, competition level and type of sport (individual vs team sports). The hypothesized seven-factor fit well and there was sufficient evidence supporting full invariance across the examined groups. All SMS subscales had adequate internal consistencies ranging from 0.66 to 0.89. Results of correlational analysis among the SMS subscales and between the SMS and two outcomes of interest further supported validity of the scale. Observed differences in SMS subscales between males and females, recreational and competitive athletes, as well as between individual and team-based sport activities, comported with prior empirical studies using a self-determination theory framework. In conclusion, results reinforce the utility and performance of the SMS in a sample of Czech university athletes. The SMS may therefore be recommended for measurement of the multidimensional motivational processes taking place in the exercise and sport domain.

Abstract Background Intermittent hemodialysis (IHD) is the modality of choice in the extracorporeal treatment (ECTR) of acute methanol poisoning. However, the comparative clinical effectiveness of intermittent versus continuous modalities (CRRT) is unknown. During an outbreak of mass methanol poisoning, we therefore studied the effect of IHD versus CRRT on mortality and the prevalence of visual/central nervous system (CNS) sequelae in survivors. Methods The study was designed as prospective observational cohort study. Patients hospitalized with a diagnosis of acute methanol poisoning were identified for the study. Exploratory factor analysis and multivariate logistic regression were applied to determine the effect of ECTR modality on the outcome. Results Data were obtained from 41 patients treated with IHD and 40 patients with CRRT. The follow-up time in survivors was two years. Both groups of patients were comparable by age, time to presentation, laboratory data, clinical features, and other treatment applied. The CRRT group was more acidemic (arterial blood pH 6.96 ± 0.08 vs. 7.17 ± 0.07; p 0.05). Conclusions In spite of the faster correction of the acidosis and the quicker removal of the toxic metabolite in intermittent dialysis, we did not find significant differences in the treatment outcomes between the two groups after adjusting for the degree of acidemia and the severity of poisoning on admission. These findings support the strategy of “use what you have” in situations with large outbreaks and limited dialysis capacity.

The aim of this study was to analyse the dietary habits of subjects with spinal cord injury (SCI), especially to evaluate differences in the presence and distribution of various food groups among a group of males and females. Subjects (n = 50, n1 = 36 males, n2 = 14 females) completed a frequency questionnaire, which included questions focused on the detection of size of consumed foods and frequency of consumption of various food groups (cereals, potatoes, vegetables, fruits, dairy products, meat, meat products, fats, sweets). We noted significant differences in the composition of breakfast (meat intake), lunch (vegetable intake, dairy intake), dinner (dairy intake, sweet intake), snacks (fats intake) in males and females. Differences in dietary habits of males and females with SCI especially concerned sizes of consumed servings of food, but also the representation of individual food groups in the diet throughout the day. In this context, the adapted food pyramid can be used as a visual tool to facilitate understanding and the maintenance of a healthy diet.

A rise in sexually transmitted diseases and liberalization of sexual attitudes has encouraged several Islamic countries to actively pursue sexual education programs. Support for this effort requires psychometrically sound instruments that can be used to assess sexual attitudes and obtain a richer understanding of the relations between attitudes and behavior. To address this knowledge gap, we translated the Sexual Knowledge and Attitudes Test—Adolescents (SKAT-A) from English to Farsi. We then examined the instrument’s factorial structure and criterion validity using exploratory structural equation modeling (ESEM) with a sample of adolescent and young adult Iranians. A six-factor model fit well including constructs assessing premarital sexuality, masturbation, homosexuality, pornography, abortion, and sexual coercion. All scales had adequate internal consistencies ranging from .66 to .85. There was sufficient evidence supporting several different forms of measurement equivalence based on gender, age and religious participation. Associations between sexual attitudes and markers of sexual activity were moderate and in the expected directions. Total replication of the U.S. factor structure was not obtained, however, there is evidence that core constructs in the instrument assessing sexual attitudes are suitable for use in a wide range of cultures, even those predicated on a strong religious beliefs system.

Salivary gland carcinomas (SGCs) are extremely morphologically heterogeneous, and treatment options for this disease are limited. Immunotherapy with immune checkpoint inhibitors (ICIs) represents a revolutionary treatment approach. However, SGCs remain largely resistant to this therapy. An increasing body of evidence suggests that resistance to ICI therapy is modulated by the Fas (CD95)–Fas ligand (FasL, CD178) interplay between tumor cells and immune cells. In this study, we examined the Fas–FasL interplay between tumor cells and tumor-infiltrating immune cells (TIICs) in the center and periphery of SGCs from 62 patients. We found that the Fas-expressing tumor cells accumulated in the center of SGC tumors with increasing tumor stage. Furthermore, this accumulation occurred regardless of the presence of TIICs expressing high levels of FasL. On the contrary, a loss of Fas-expressing TIICs with increasing tumor stage was found in the tumor periphery, whereas FasL expression in tumor cells in the tumor periphery correlated with tumor stage. These data suggest that SGC cells are resistant to FasL-induced apoptosis by TIICs but could utilize FasL to eliminate these cells in high-stage tumors to provide resistance to immunotherapy.

The treatment options for patients with advanced salivary gland cancers (SGCs) are limited. Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. However, the response to ICI immunotherapy is largely driven by the immune cell signatures within the tumor tissue and the para-tumoral tissue compartments. To date, there are no data on the expression of programed cell death protein-1/programed cell death protein-ligand 1 (PD-1/PD-L1) in SGC, which may enable the implementation of ICI immunotherapy for this disease. Thus, we performed an immunohistochemical analysis of PD-1 and PD-L1 expression in tumor cells and tumor-infiltrating immune cells (TIICs) in the tumor center and periphery of 62 SGC patients. The tumor periphery showed significantly higher expression of PD-L1 in tumor cells than in TIICs. Moreover, peripheral TIICs had significantly higher PD-1 expression than peripheral tumor cells. PD-1-positive tumor cells were detected exclusively in the tumor center of high-grade tumors, and most importantly, the presence of lymph node (LN) metastases and primary tumor stage significantly correlated with the presence of PD-L1-positive tumor cells in the tumor periphery. The PD-1/PD-L1 molecular signatures in SGC are clustered predominantly in the tumor periphery, reflect disease severity, and may predict the response to ICI immunotherapy in SGC patients.

Human data concerning exposure to nanoparticles are very limited, and biomarkers for monitoring exposure are urgently needed. In a follow-up of a 2016 study in a nanocomposites plant, in which only exhaled breath condensate (EBC) was examined, eight markers of oxidative stress were analyzed in three bodily fluids, i.e., EBC, plasma and urine, in both pre-shift and post-shift samples in 2017 and 2018. Aerosol exposures were monitored. Mass concentration in 2017 was 0.351 mg/m3 during machining, and 0.179 and 0.217 mg/m3 during machining and welding, respectively, in 2018. In number concentrations, nanoparticles formed 96%, 90% and 59%, respectively. In both years, pre-shift elevations of 50.0% in EBC, 37.5% in plasma and 6.25% in urine biomarkers were observed. Post-shift elevation reached 62.5% in EBC, 68.8% in plasma and 18.8% in urine samples. The same trend was observed in all biological fluids. Individual factors were responsible for the elevation of control subjects’ afternoon vs. morning markers in 2018; all were significantly lower compared to those of workers. Malondialdehyde levels were always acutely shifted, and 8-hydroxy-2-deoxyguanosine levels best showed chronic exposure effect. EBC and plasma analysis appear to be the ideal fluids for bio-monitoring of oxidative stress arising from engineered nanomaterials. Potential late effects need to be targeted and prevented, as there is a similarity of EBC findings in patients with silicosis and asbestosis.

Calprotectin may be a sensitive biomarker of rheumatoid arthritis (RA) disease activity.In the current study, we investigated whether calprotectin is a better biomarker than CRP for predicting clinical activity and ultrasound parameters in patients with RA.A total of 160 patients with RA underwent clinical (swollen joint count-SJC, tender joint count-TJC, Disease Activity Score-DAS28, Clinical Disease Activity Index-CDAI, and simplified Disease Activity Index-SDAI) and ultrasound (German US7) examination. Clinical and laboratory measures were correlated with ultrasound findings using Spearman´s correlation coefficient. Differences in serum calprotectin levels in patients with variable disease activity according to the DAS28-ESR and CDAI scores were assessed using ANOVA. Multivariate regression analysis was used to determine the predictive values of calprotectin, CRP and SJC for CDAI and PD US synovitis scores.Serum calprotectin was significantly associated with DAS28-ESR (r = 0.321, p

Clinical remission in some patients with rheumatoid arthritis (RA) may be associated with ongoing synovial inflammation that is not always detectable on clinical examination or reflected by laboratory tests but can be visualized by musculoskeletal ultrasound. The goal of our study was to determine the levels of serum calprotectin, a major leukocyte protein, in patients with RA in clinical remission and to investigate the ability of serum calprotectin levels to distinguish patients in ultrasound-defined remission from those with residual ultrasound subclinical inflammation.Seventy RA patients in clinical remission underwent clinical and ultrasound examination. Ultrasound examination was performed according to the German US7 score. Ultrasound remission was defined as grey scale (GS) range 0-1 and power Doppler (PD) range 0. The levels of serum calprotectin and C-reactive protein (CRP) were determined. The discriminatory capacity of calprotectin and CRP in detecting residual ultrasound inflammation was assessed using ROC curves.The total number of patients fulfilling the DAS28-ESR, DAS28-CRP, SDAI and CDAI remission criteria was 58, 67, 32 and 31, respectively. Residual synovial inflammation was found in 58-67% of the patients who fulfilled at least one set of clinical remission criteria. Calprotectin levels were significantly higher in patients with residual synovial inflammation than in those with ultrasound-defined remission (mean 2.5±1.3 vs. 1.7±0.8 μg/mL, p

Thousands of researchers and workers worldwide are employed in nanocomposites manufacturing, yet little is known about their respiratory health. Aerosol exposures were characterized using real time and integrated instruments. Aerosol mass concentration ranged from 0.120 mg/m3 to 1.840 mg/m3 during nanocomposite machining processes; median particle number concentration ranged from 4.8 × 104 to 5.4 × 105 particles/cm3. The proportion of nanoparticles varied by process from 40 to 95%. Twenty employees, working in nanocomposite materials research were examined pre-shift and post-shift using spirometry and fractional exhaled nitric oxide (FeNO) in parallel with 21 controls. Pro-inflammatory leukotrienes (LT) type B4, C4, D4, and E4; tumor necrosis factor (TNF); interleukins; and anti-inflammatory lipoxins (LXA4 and LXB4) were analyzed in their exhaled breath condensate (EBC). Chronic bronchitis was present in 20% of researchers, but not in controls. A significant decrease in forced expiratory volume in 1 s (FEV1) and FEV1/forced vital capacity (FVC) was found in researchers post-shift (p ˂ 0.05). Post-shift EBC samples were higher for TNF (p ˂ 0.001), LTB4 (p ˂ 0.001), and LTE4 (p ˂ 0.01) compared with controls. Nanocomposites production was associated with LTB4 (p ˂ 0.001), LTE4 (p ˂ 0.05), and TNF (p ˂ 0.001), in addition to pre-shift LTD4 and LXB4 (both p ˂ 0.05). Spirometry documented minor, but significant, post-shift lung impairment. TNF and LTB4 were the most robust markers of biological effects. Proper ventilation and respiratory protection are required during nanocomposites processing.

Researchers in nanocomposite processing may inhale a variety of chemical agents, including nanoparticles. This study investigated airway oxidative stress status in the exhaled breath condensate (EBC). Nineteen employees (42.4 ± 11.4 y/o), working in nanocomposites research for 18.0 ± 10.3 years were examined pre-shift and post-shift on a random workday, together with nineteen controls (45.5 ± 11.7 y/o). Panels of oxidative stress biomarkers derived from lipids, nucleic acids, and proteins were analyzed in the EBC. Aerosol exposures were monitored during three major nanoparticle generation operations: smelting and welding (workshop 1) and nanocomposite machining (workshop 2) using a suite of real-time and integrated instruments. Mass concentrations during these operations were 0.120, 1.840, and 0.804 mg/m3, respectively. Median particle number concentrations were 4.8 × 104, 1.3 × 105, and 5.4 × 105 particles/cm3, respectively. Nanoparticles accounted for 95, 40, and 61%, respectively, with prevailing Fe and Mn. All markers of nucleic acid and protein oxidation, malondialdehyde, and aldehydes C6–C13 were elevated, already in the pre-shift samples relative to controls in both workshops. Significant post-shift elevations were documented in lipid oxidation markers. Significant associations were found between working in nanocomposite synthesis and EBC biomarkers. More research is needed to understand the contribution of nanoparticles from nanocomposite processing in inducing oxidative stress, relative to other co-exposures generated during welding, smelting, and secondary oxidation processes, in these workshops.