Adult granulosa cell tumors (AGCTs) of the ovary are characterized by their propensity for late recurrences and are primarily managed surgically due to the limited efficacy of systemic treatment. The FOXL2 p.C134W somatic mutation has been identified in ∼95% of AGCT cases, and TERT promoter alterations have been linked to worse overall survival. This study highlights the potential prognostic significance of FOXO1 mutations, suggesting that they may be associated with poorer overall survival and shorter time to recurrence. A total of 183 primary AGCTs and 44 recurrences without corresponding primary tumors were analyzed. The primary AGCTs were categorized into 3 groups: 77 nonrecurrent tumors, 18 tumors that later recurred (including 9 cases with matched primary-recurrence pairs), and 88 tumors with unknown recurrence status. Targeted next-generation sequencing was conducted on 786 cancer-related genes to investigate their genetic profile. The study aimed to identify the molecular alterations associated with AGCT pathogenesis and recurrence rate, comparing primary versus recurrent tumors, and primary recurrent versus primary nonrecurrent cases. Our findings confirmed the high prevalence (99%) of the FOXL2 p.C134W mutation in AGCTs. Secondary truncating FOXL2 mutations were observed in 5% of cases. Two cases with typical AGCT morphology were FOXL2 wild-type, harboring mutations in KRAS or KMT2D instead, suggesting alternative genetic pathways. TERT promoter mutations were found in 43% of cases, more frequently in recurrences. Other recurrent mutations detected in the cohort included KMT2D (10%), FOXO1 (7%), CHEK2 (5%), TP53 (3.5%), PIK3CA (3.5%), and AKT1 (3%). Two recurrent, FOXL2-mutated cases also carried DICER1 mutations. One tumor exhibited MSI-high status and a tumor mutation burden of 19 mut/Mb.Our results indicate the need for further investigation into the role of FOXO1 as a potential prognostic marker in AGCTs.

• MeSH
• Adult MeSH
• Forkhead Box Protein O1 * genetics   metabolism   MeSH
• Middle Aged MeSH
• Humans MeSH
• Neoplasm Recurrence, Local * genetics   MeSH
• Mutation * MeSH
• Granulosa Cell Tumor * genetics   pathology   MeSH
• Ovarian Neoplasms * genetics   pathology   MeSH
• Prognosis MeSH
• Disease Progression MeSH
• Forkhead Box Protein L2 genetics   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Telomerase genetics   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

PURPOSE: High-dose intravenous glucocorticoids are the standard first-line treatment in active, moderate to severe and severe thyroid eye disease (TED). We evaluate the usefulness of clinical activity score (CAS) and thyroid-stimulating immunoglobulin (TSI) as predictors and/or post-treatment markers of corticoresistance in patients with TED and the effect of rituximab in second-line treatment. METHODS: We enrolled 236 patients with an active TED into this retrospective single-tertiary-center cohort study. All patients were initially treated with high-dose systemic glucocorticoids. Rituximab was later administered to 29 of 42 corticoresistant patients. RESULTS: The CAS of the corticoresistant patients was significantly higher both before (p = 0.0001) and after (p = <0.0001) first-line treatment compared to the corticosensitive group. ROC analysis established the cut-point value as CAS ≥ 2.5 with a sensitivity of 96.3%, specificity of 57.5% and area under the curve of 82.8%. In 22 patients treated with rituximab, CAS gradually decreased to zero values without reactivation during extended follow-up. There was no difference in the TSI of corticosensitive and corticoresistant patients before or after first-line therapy. CONCLUSION: CAS ≥ 2, after first-line treatment, could be used as a corticoresistance marker. Corticoresistant patients should be subject to long-term follow-up for early detection of reactivation to reduce the delay to second-line treatment. Rituximab is a well-tolerated choice of second-line treatment and has a long-lasting effect on disease activity. Although TSI is a valuable biomarker of Graves' disease and TED activity, according to our results, TSI cannot be used as a marker of corticoresistance.

• MeSH
• Adult MeSH
• Glucocorticoids therapeutic use   MeSH
• Graves Ophthalmopathy * drug therapy   blood   MeSH
• Immunoglobulins, Thyroid-Stimulating blood   MeSH
• Immunologic Factors therapeutic use   MeSH
• Drug Resistance * MeSH
• Middle Aged MeSH
• Humans MeSH
• Retrospective Studies MeSH
• Rituximab * therapeutic use   MeSH
• Aged MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

The sacroiliac joint (SIJ) exhibits significant variation in auricular surface morphology. This variation influences the mechanics of the SIJ, a central node for transmitting mechanical energy from upper body to lower limbs and vice versa. The impact of the auricular surface morphology on stress and deformation in the SIJ remains poorly understood to date. Computed tomography scans obtained from 281 individuals were included to extract the geometry of the pelvic ring. Then, the auricular surface area, SIJ cartilage thickness, and total SIJ cartilage volume were identified. Based on these reconstructions, 281 finite element models were created to simulate SIJ mechanical loading. It was found that SIJ cartilage thickness only weakly depended on age or laterality, while being strongly sex sensitive. Auricular surface area and SIJ cartilage volume depended weakly and non-linearly on age, peaking around menopause in females, but without significant laterality effect. Larger SIJs, characterized by greater auricular area and cartilage volume, exhibited reduced stress and deformation under loading. These findings highlight the significant role of SIJ morphology in its biomechanical response, suggesting a potential link between morphological variations and the risk of SIJ dysfunction. Understanding this relationship could improve diagnosis and targeted treatment strategies for SIJ-related conditions.

• MeSH
• Finite Element Analysis MeSH
• Biomechanical Phenomena physiology   MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Stress, Mechanical MeSH
• Adolescent MeSH
• Young Adult MeSH
• Tomography, X-Ray Computed * MeSH
• Sacroiliac Joint * anatomy & histology   physiology   diagnostic imaging   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: Head tremor poses diagnostic problems, especially when present as an isolated or predominant symptom. OBJECTIVES: To assess how maneuvers activating upper limb postural tremor can help differentiate head tremor in essential tremor (ET) from dystonic tremor (DT) in cervical dystonia. METHODS: 48 patients with head tremor (25 ET, 23 DT), underwent clinical examination and accelerometric evaluation of head and upper limb tremor during routine tremor-inducing tasks. RESULTS: While accelerometric power and clinical scores of head tremor did not significantly differ between patient groups, task-induced variations revealed distinctions. ET patients exhibited increased head tremor power and clinical scores during forward outstretched and lateral wing-beating arm positions, unlike DT patients. Coherence between head and upper limb tremor remained consistent. Tremor stability index showed no significant differences. CONCLUSIONS: Task-induced changes in head tremor could aid in distinguishing between ET and DT. Further research is needed to refine diagnostic approaches for head tremor.

• MeSH
• Accelerometry instrumentation   methods   MeSH
• Diagnosis, Differential MeSH
• Adult MeSH
• Dystonia diagnosis   physiopathology   MeSH
• Essential Tremor * diagnosis   physiopathology   MeSH
• Head * physiopathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Arm * physiopathology   MeSH
• Posture physiology   MeSH
• Aged MeSH
• Torticollis diagnosis   physiopathology   MeSH
• Tremor * diagnosis   physiopathology   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

In the present work, we addressed the relationship between parental leave policies and social norms. Using a pre-registered, cross-national approach, we examined the relationship between parental leave policies and the perception of social norms for the gender division of childcare. In this study, 19,259 students (11,924 women) from 48 countries indicated the degree to which they believe childcare is (descriptive norm) and should be (prescriptive norm) equally divided among mothers and fathers. Policies were primarily operationalized as the existence of parental leave options in the respective country. The descriptive and prescriptive norms of equal division of childcare were stronger when parental leave was available in a country - also when controlling for potential confounding variables. Moreover, analyses of time since policy change suggested that policy change may initially affect prescriptive norms and then descriptive norms at a later point. However, due to the cross-sectional nature of the data, drawing causal inferences is difficult.

• MeSH
• Child MeSH
• Adult MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Child Care * MeSH
• Cross-Sectional Studies MeSH
• Parental Leave * MeSH
• Social Norms * MeSH
• Cross-Cultural Comparison MeSH
• Public Policy MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

BACKGROUND & AIMS: Homozygous Pi∗Z mutation in alpha-1 antitrypsin (Pi∗ZZ genotype) predisposes to pulmonary loss-of-function and hepatic gain-of-function injury. To facilitate selection into clinical trials typically targeting only 1 organ, we systematically evaluated an international, multicenter, longitudinal, Pi∗ZZ cohort to uncover natural disease course and surrogates for future liver- and lung-related endpoints. METHODS: Cohort 1 recruited 737 Pi∗ZZ individuals from 25 different centers without known liver comorbidities who received a baseline clinical and laboratory assessment as well as liver stiffness measurement (LSM). A follow-up interview was performed after at least 6 months. Cohort 2 consisted of 135 Pi∗ZZ subjects without significant liver fibrosis, who received a standardized baseline and follow-up examination at least 2 years later, both including LSM. RESULTS: During 2634 patient-years of follow-up, 39 individuals died, with liver and lung being responsible for 46% and 36% of deaths, respectively. Forty-one Pi∗ZZ subjects who developed a hepatic endpoint presented with significantly higher baseline liver fibrosis surrogates, that is, LSM (24 vs 5 kPa, P < .001) and aspartate aminotransferase-to-platelet ratio index (1.1 vs 0.3 units, P < .001). Liver-related endpoints within 5 years were most accurately predicted by LSM (area under the curve 0.95) followed by aspartate aminotransferase-to-platelet ratio index (0.92). Baseline lung parameters displayed only a moderate predictive utility for lung-related endpoints within 5 years (forced expiratory volume in the first second area under the curve 0.76). Fibrosis progression in those with no/mild fibrosis at baseline was rare and primarily seen in those with preexisting risk factors. CONCLUSIONS: Noninvasive liver fibrosis surrogates accurately stratify liver-related risks in Pi∗ZZ individuals. Our findings have direct implications for routine care and future clinical trials of Pi∗ZZ patients.

• MeSH
• alpha 1-Antitrypsin * genetics   blood   MeSH
• Biomarkers blood   MeSH
• Time Factors MeSH
• alpha 1-Antitrypsin Deficiency * genetics   diagnosis   complications   MeSH
• Adult MeSH
• Elasticity Imaging Techniques MeSH
• Genotype MeSH
• Homozygote MeSH
• Liver Cirrhosis * genetics   diagnosis   MeSH
• Middle Aged MeSH
• Humans MeSH
• Longitudinal Studies MeSH
• Mutation MeSH
• Lung physiopathology   pathology   diagnostic imaging   MeSH
• Lung Diseases genetics   etiology   diagnosis   MeSH
• Disease Progression * MeSH
• Risk Factors MeSH
• Severity of Illness Index MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH

AIM: Despite the high sensitivity of neonatal screening in detecting the classical form of congenital adrenal hyperplasia due to 21-hydroxylase deficiency, one of the unclear issues is identifying asymptomatic children with late onset forms. The aim of this nationwide study was to analyse the association between genotype and screened level of 17-hydroxyprogesterone in patients with the late onset form of 21-hydroxylase deficiency and to quantify false negativity. METHODS: In the Czech Republic, 1,866,129 neonates were screened (2006-2022). Among this cohort, 159 patients were confirmed to suffer from 21-hydroxylase deficiency, employing the 17-hydroxyprogesterone birthweight/gestational age-adjusted cut-off limits, and followed by the genetic confirmation. The screening prevalence was 1:11,737. Another 57 patients who were false negative in neonatal screening were added to this cohort based on later diagnosis by clinical suspicion. To our knowledge, such a huge nationwide cohort of false negative patients has not been documented before. RESULTS: Overall, 57 patients escaped from neonatal screening in the monitored period. All false negative patients had milder forms. Only one patient had simple virilising form and 56 patients had the late onset form. The probability of false negativity in the late onset form was 76.7%. The difference in 17-hydroxyprogesterone screening values was statistically significant (p<0.001) between severe forms (median 478.8 nmol/L) and milder (36.2 nmol/L) forms. Interestingly, the higher proportion of females with milder forms was statistically significant compared with the general population. CONCLUSIONS: A negative neonatal screening result does not exclude milder forms of 21-hydroxylase deficiency during the differential diagnostic procedure of children with precocious pseudopuberty.

• MeSH
• 17-alpha-Hydroxyprogesterone * blood   MeSH
• False Negative Reactions MeSH
• Adrenal Hyperplasia, Congenital * diagnosis   blood   MeSH
• Humans MeSH
• Infant, Newborn MeSH
• Neonatal Screening * methods   MeSH
• Steroid 21-Hydroxylase genetics   MeSH
• Age of Onset MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Infant, Newborn MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic MeSH

The formation of memories is a complex, multi-scale phenomenon, especially when it involves integration of information from various brain systems. We have investigated the differences between a novel and consolidated association of spatial cues and amphetamine administration, using an in situ hybridisation method to track the short-term dynamics during the recall testing. We have found that remote recall group involves smaller, but more consolidated groups of neurons, which is consistent with their specialisation. By employing machine learning analysis, we have shown this pattern is especially pronounced in the VTA; furthermore, we also uncovered significant activity patterns in retrosplenial and prefrontal cortices, as well as in the DG and CA3 subfields of the hippocampus. The behavioural propensity towards the associated localisation appears to be driven by the nucleus accumbens, however, further modulated by a trio of the amygdala, VTA and hippocampus, as the trained association is confronted with test experience. Moreover, chemogenetic analysis revealed central amygdala as critical for linking appetitive emotional states with spatial contexts. These results show that memory mechanisms must be modelled considering individual differences in motivation, as well as covering dynamics of the process.

• MeSH
• Amphetamine pharmacology   MeSH
• Amygdala physiology   MeSH
• Hippocampus * physiology   MeSH
• Memory Consolidation * physiology   MeSH
• Rats MeSH
• Brain physiology   MeSH
• Neurons physiology   metabolism   MeSH
• Nucleus Accumbens * physiology   MeSH
• Reward * MeSH
• Memory physiology   MeSH
• Cues MeSH
• Prefrontal Cortex physiology   MeSH
• Mental Recall * physiology   MeSH
• Machine Learning MeSH
• Ventral Tegmental Area * physiology   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

AIMS: One treatment option for refractory ventricular arrythmias is stellate ganglion block (SGB). We examined differences in SGB success by patient and arrhythmia characteristics and predictors of successful SGB. METHODS AND RESULTS: This was a multicenter analysis of patients treated for refractory ventricular arrythmias in the Czech Republic and the United States. The primary outcome was absence of ventricular arrythmias at 24 h post SGB. SGB effectiveness was examined according to aetiology of cardiomyopathy, arrhythmia type, laterality of SGB, presence of inotropes, and presence of mechanical circulatory support. Binary logistic regression was used to examine variables associated with the primary outcome. In total there were 117 patients with refractory ventricular arrythmias treated with SGB. Overall, the mean age was 63.5 ± 11.0 years, majority of patients were male (94.0%), White (87.2%), and had an implantable cardioverter defibrillator in situ (70.1%). There were no differences in efficacy of SGB based on aetiology of cardiomyopathy (P = 0.623), arrhythmia type (0.852), laterality of block (P = 0.131), and presence of inotropes (P = 0.083). Multivariable analysis demonstrated that increased age was associated with decreased odds of SGB success (odds ratio: 0.96, confidence interval: 0.92-0.99, P = 0.039) whereas increased left ventricular ejection fraction trended towards increased odds of SGB success (odds ratio: 1.05, confidence interval: 0.995-1.11, P = 0.077). CONCLUSIONS: In this multicentre experience, SGB was similarly effective despite the aetiology of cardiomyopathy, type of arrhythmia, laterality, and inotropic or mechanical support. SGB was less effective for the suppression of ventricular arrythmias at 24 h for the elderly.

• MeSH
• Autonomic Nerve Block * methods   MeSH
• Stellate Ganglion * MeSH
• Tachycardia, Ventricular therapy   physiopathology   etiology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Follow-Up Studies MeSH
• Recurrence MeSH
• Retrospective Studies MeSH
• Aged MeSH
• Treatment Outcome MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Geographicals
• Czech Republic MeSH
• United States MeSH

Artists and laypeople differ in their ability to create drawings. Previous research has shown that artists have improved memory performance during drawing; however, it is unclear whether they have better visual memory after the drawing is finished. In this paper, we focused on the question of differences in visual memory between art students and the general population in two studies. In Study 1, both groups studied a set of images and later drew them in a surprise visual recall test. In Study 2, the drawings from Study 1 were evaluated by a different set of raters based on their drawing quality and similarity to the original image to link drawing evaluations with memory performance for both groups. We found that both groups showed comparable visual recognition memory performance; however, the artist group showed increased recall memory performance. Moreover, they produced drawings that were both better quality and more similar to the original image. Individually, participants whose drawings were rated as better showed higher recognition accuracy. Results from Study 2 also have practical implications for the usage of drawing as a tool for measuring free recall - the majority of the drawings were recognizable, and raters showed a high level of consistency during their evaluation of the drawings. Taken together, we found that artists have better visual recall memory than laypeople.

• MeSH
• Adult MeSH
• Humans MeSH
• Young Adult MeSH
• Mental Recall * physiology   MeSH
• Recognition, Psychology * physiology   MeSH
• Pattern Recognition, Visual * physiology   MeSH
• Students * MeSH
• Art * MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH