Miracle-dz/UniFAR-FTUs huggingface dataset:
Course trajectories of anxiety disorders: Results from a 6-year follow-up in a general population study

Objective: Little is known about the course of anxiety disorders in the general population. This study provides insights into the course of anxiety disorders in the general population taking into account transition to residual symptoms and to other diagnostic categories. Methods: Using data from three waves of the Netherlands Mental Health Survey and Incidence Study-2 (NEMESIS-2; n = 6646), subjects with anxiety disorders (T0; n = 243) were divided into three mutually exclusive course trajectories according to their diagnostic status at 3-year (T1) and 6-year (T2) follow-up: remission group (no disorder at T2), intermittent course group (no disorder at T1 and disorder at T2) and chronic course group (disorder at all measurements). Transition to residual symptoms or other psychopathology were studied. In addition, predictors of course trajectories were assessed. Results: During 6-year follow-up, 77.8% of subjects achieved remission, 14.0% followed an intermittent course and 8.2% a chronic course. Of those in remission, residual anxiety symptoms remained in 46.6%, while 7.9% developed another disorder between T0 and T2. Compared with the remitting group, a chronic course was predicted by not living with a partner, multiple negative life events, neuroticism, lower mental functioning, severity of anxiety symptoms, use of mental health care and medication use. Limitations: The intermittent and chronic course groups were small, limiting statistical power. As a result, certain predictors may not have reached significance. Conclusions: In the general population at 6-year follow-up, 77.8% of subjects with anxiety disorders achieved remission. Because of transition to residual symptoms or another diagnostic category, only 52.4% of those subjects had a true favourable outcome.
Partnership between Primary Health and Social Care Services in the Long-Term Care of Older People with Dementia: A Vignette Study

Dementia is considered to be a significant cause of disability and dependency for older people worldwide and it raises difficulties in providing adequate formal and informal assistance. Research on the experience of long-term care (LTC)services for older people with dementia is scarce in Eastern European countries. This study aimed to understand the system of care for older people with dementia from the perspective of health and social care workers providing LTC services in Lithuania. A total of 72 primary health care and social care professionals from public and private institutions in Kaunas city participated in this study. One-to-one interviews were conducted with family physicians, community nurses, psychiatrists, psychiatric nurses, and social workers. A vignette situation of 2 fictitious patients with dementia and their informal caregiver was discussed during the interviews. Data were analyzed using thematic analysis by induction approach. The data revealed 2 main themes: LTC provision trajectory, and three-dimensional relationship perception in realization of LTC activities. LTC provision trajectory reflected activities performed as a response to the described situation embracing formal procedures for the endorsement of LTC needs as well as the range of LTC services. The three-dimensional perception of relationships in LTC services’ implementation reflected the participants’ personal approach toward LTC, relationship with different specialists, and the informal caregiver. Our study revealed the potential of complex measures that could be instrumental for the refinement of the caregiving process. First, a change in the additional care requirements endorsement logic is needed, shifting focus from medical diagnosis to functional abilities assessment. Second, to establish clear procedures for formal cooperation between the health and social care sectors in the trajectory of LTC service provision. Finally, to find an adequate balance between LTC and institutional care by creating a more comprehensive range of LTC services. A more consistent and coordinated delivery of services by both health and social care sectors seems to be an untapped resource for the improvement of the LTC potential.
Drosophila female reproductive tract gene expression reveals coordinated mating responses and rapidly evolving tissue-specific genes

Abstract Sexual reproduction in internally fertilizing species requires complex coordination between female and male reproductive systems and among the diverse tissues of the female reproductive tract (FRT). Here, we report a comprehensive, tissue-specific investigation of Drosophila melanogaster FRT gene expression before and after mating. We identified expression profiles that distinguished each tissue, including major differences between tissues with glandular or primarily nonglandular epithelium. All tissues were enriched for distinct sets of genes possessing secretion signals that exhibited accelerated evolution, as might be expected for genes participating in molecular interactions between the sexes within the FRT extracellular environment. Despite robust transcriptional differences between tissues, postmating responses were dominated by coordinated transient changes indicative of an integrated systems-level functional response. This comprehensive characterization of gene expression throughout the FRT identifies putative female contributions to postcopulatory events critical to reproduction and potentially reproductive isolation, as well as the putative targets of sexual selection and conflict.
Relationship Between the Loudness Dependence of the Auditory Evoked Potential and the Severity of Suicidal Ideation in Patients with Major Depressive Disorder

Objective The loudness dependence of the auditory evoked potential (LDAEP) is a reliable indicator that is inversely related to central serotonergic activity, and recent studies have suggested an association between LDAEP and suicidal ideation. This study investigated differences in LDAEP between patients with major depressive disorder and high suicidality and those with major depressive disorder and low suicidality compared to healthy controls. Methods This study included 67 participants 23 patients with major depressive disorder with high suicidality (9 males, mean age 29.3 ± 15.7 years, total score of SSI-BECK ≥ 15), 22 patients with major depressive disorder with low suicidality (9 males, mean age 42.2 ± 14.4 years, total score of SSI-BECK ≤ 14), and 22 healthy controls (11 males, mean age 31.6 ± 8.7 years). Participants completed the following assessments Patient Health Questionnaire-9, Beck Depression Inventory-II, Beck Scale for Suicidal ideation, State Anxiety Scale of the State-Trait Anxiety Inventory, Beck Anxiety Inventory, and LDAEP (measured at electrode Cz). Results There were no sex-related differences among groups (p = 0.821). The high-suicidality group exhibited significantly higher LDAEP compared to the low-suicidality group (0.82 ± 0.79 vs. 0.26 ± 0.36, p = 0.014). No significant differences were found between the control and high-suicidality (p = 0.281) or the control and low-suicidality groups (p = 0.236). Conclusion LDAEP was applied to demonstrate the association between serotonergic activity and suicidal ideation and suicide risk in major depression and may be a candidate of biological marker for preventing suicide in this study.
Axial-SpineGAN: simultaneous segmentation and diagnosis of multiple spinal structures on axial magnetic resonance imaging images

Providing a simultaneous segmentation and diagnosis of the spinal structures on axial magnetic resonance imaging (MRI) images has significant value for subsequent pathological analyses and clinical treatments. However, this task remains challenging, owing to the significant structural diversity, subtle differences between normal and abnormal structures, implicit borders, and insufficient training data. In this study, we propose an innovative network framework called ‘Axial-SpineGAN’ comprising a generator, discriminator, and diagnostor, aiming to address the above challenges, and to achieve simultaneous segmentation and disease diagnosis for discs, neural foramens, thecal sacs, and posterior arches on axial MRI images. The generator employs an enhancing feature fusion module to generate discriminative features, i.e. to address the challenges regarding the significant structural diversity and subtle differences between normal and abnormal structures. An enhancing border alignment module is employed to obtain an accurate pixel classification of the implicit borders. The discriminator employs an adversarial learning module to effectively strengthen the higher-order spatial consistency, and to avoid overfitting owing to insufficient training data. The diagnostor employs an automated diagnosis module to provide automated recognition of spinal diseases. Extensive experiments demonstrate that these modules have positive effects on improving the segmentation and diagnosis accuracies. Additionally, the results indicate that Axial-SpineGAN has the highest Dice similarity coefficient (94.9% ± 1.8%) in terms of the segmentation accuracy and highest accuracy rate (93.9% ± 2.6%) in terms of the diagnosis accuracy, thereby outperforming existing state-of-the-art methods. Therefore, our proposed Axial-SpineGAN is effective and potential as a clinical tool for providing an automated segmentation and disease diagnosis for multiple spinal structures on MRI images.
Radiotherapy programs neutrophils to an antitumor phenotype by inducing mesenchymal-epithelial transition

Background Neutrophils can play a pro-tumor or anti-tumor role depending on the tumor microenvironment. The effects of concurrent treatment with granulocyte colony-stimulating factor (G-CSF) and radiotherapy (RT) on neutrophils have not yet to be described. Methods Hypofractionated radiation of 8 Gy ×3 fractions was administered with or without recombinant G-CSF to Lewis lung carcinoma tumor-bearing C57BL/6 model mice. The activation status of cytotoxic T cells in the mice was measured, along with the levels of tumor-associated neutrophils, cytotoxic T cells, and Treg cells. Tumor growth, survival, cytokine expression, and signaling pathways underlying anti-tumor effects of tumor-associated neutrophils after treatment were also studied. To ascertain the effects of concurrent RT and G-CSF on tumor-associated neutrophils, neutrophil depletion was performed. Results RT affected early neutrophil infiltration, which is the first-line immune response. Subsequently, enhanced accumulation of lymphocytes, particularly CD8 cytotoxic T cells, was observed. Notably, lymphocytic infiltration was inhibited by neutrophil depletion but enhanced by G-CSF treatment. RT generated persistent DNA damage, as evidenced by an accumulation of phosphorylation of histone H2AX (γH2AX), and subsequently triggered inflammatory chemokine secretion. The chemokines CXCL1, CXCL2, and CCL5 were upregulated in both radiation-treated cells and the corresponding supernatants. Neutrophils that were newly recruited after RT improved radiosensitivity by inhibiting epithelial–mesenchymal transition via the reactive oxygen species-mediated PI3K/Akt/Snail signaling pathway, and G-CSF treatment enhanced this effect. Conclusions The results of this study suggest that RT activates neutrophil recruitment and polarizes newly recruited neutrophils toward an antitumor phenotype, which is enhanced by the concurrent administration of G-CSF. Mesenchymal-epithelial transition induced by reactive oxygen species accumulation plays a major role in this process. Thus, the polarization of tumor-associated neutrophils might play a role in future cancer immunotherapies.
GSDet: Object Detection in Aerial Images Based on Scale Reasoning

Variations in both object scale and style under different capture scenes (e.g., downtown, port) greatly enhance the difficulties associated with object detection in aerial images. Although ground sample distance (GSD) provides an apparent clue to address this issue, no existing object detection methods have considered utilizing this useful prior knowledge. In this paper, we propose the first object detection network to incorporate GSD into the object detection modeling process. More specifically, built on a two-stage detection framework, we adopt a GSD identification subnet converting the GSD regression into a probability estimation process, then combine the GSD information with the sizes of Regions of Interest (RoIs) to determine the physical size of objects. The estimated physical size can provide a powerful prior for detection by reweighting the weights from the classification layer of each category to produce RoI-wise enhanced features. Furthermore, to improve the discriminability among categories of similar size and make the inference process more adaptive, the scene information is also considered. The pipeline is flexible enough to be stacked on any two-stage modern detection framework. The improvement over the existing two-stage object detection methods on the DOTA dataset demonstrates the effectiveness of our method.
ELISA detection of MPO-DNA complexes in human plasma is error-prone and yields limited information on neutrophil extracellular traps formed in vivo

Over the past years, neutrophil extracellular traps (NETs) were shown to contribute to states of acute and chronic inflammatory disease. They are composed of expelled chromatin and decorated by neutrophil-derived proteins. Therefore, the analysis of DNA complexes with myeloperoxidase (MPO) by ELISA has become an attractive tool to measure NET formation in in vitro and in vivo samples. When we used a published MPO-DNA ELISA protocol and included an isotype control for the anti-MPO coating antibody, we observed high assay specificity for in vitro prepared NET samples, whereas the specificity for in vivo plasma samples was low. In addition, the assay failed to detect in vitro generated MPO-DNA complexes when spiked into plasma. Therefore, we set out to improve the specificity of the MPO-DNA ELISA for plasma samples. We found that the use of Fab fragments or immunoglobulins from different species or reversal of the antibody pair led to either a high background or a low dynamic range of detection that did not improve the specificity for plasma samples. Also, the use of higher plasma dilutions or pre-clearing of plasma immunoglobulins were ineffective. Finally, we found that a commercial reagent designed to block human anti-mouse antibodies and multivalent substances increased the detection window between the MPO antibody and isotype control for highly diluted plasma. We applied this modified ELISA protocol to analyze MPO-DNA complexes in human blood samples of acute and chronic inflammatory conditions. While markers of neutrophil activation and NET formation such as MPO, elastase and citrullinated histone H3 correlated significantly, we observed no correlation with the levels of MPO-DNA complexes. Therefore, we conclude that ELISA measurements of MPO-DNA complexes in human plasma are highly questionable regarding specificity of NET detection. In general, plasma analyses by ELISA should more frequently include isotype controls for antibodies to demonstrate target specificity.
Sleep macroarchitecture but not obstructive sleep apnea is independently associated with cognitive function in only older men of a population‐based cohort

Evidence linking obstructive sleep apnea with cognitive dysfunction predominantly comes from clinical or select community samples. We investigated the independent cross‐sectional association of obstructive sleep apnea and sleep macroarchitecture parameters with cognitive function in unselected community‐dwelling middle‐aged and older men. Four hundred and seventy‐seven Florey Adelaide Male Ageing Study participants underwent successful home‐based polysomnography. They also completed cognitive testing, including the inspection time task, Fuld object memory evaluation, trail‐making test A and B, and mini‐mental state examination. Multivariable regression models examined independent cross‐sectional associations of obstructive sleep apnea and sleep macroarchitecture parameters with cognitive function. In univariable analyses, a higher apnea–hypopnea index and percentage of total sleep time with oxygen saturation <90% were associated with worse trail‐making test A performance (both p < .05). A higher apnea–hypopnea index was also associated with worse trail‐making test B performance and slower inspection time (both p < .05). In adjusted analyses, obstructive sleep apnea and sleep macroarchitecture parameters were not associated with cognitive function (all p > .05). In age‐stratified analysis in men ≥65 years, greater stage 1 sleep was independently associated with worse trail‐making test A performance, whereas greater stage 3 sleep was independently associated with better trail‐making test A performance (both p < .05). Our findings suggest that obstructive sleep apnea is not independently associated with cognitive function. In older, but not younger, men, light sleep was associated with worse attention, whereas deep sleep was associated with better attention. Longitudinal population‐based cohort studies are needed to determine if obstructive sleep apnea and disrupted sleep macroarchitecture independently predict prospective cognitive dysfunction and decline.
Treatment Strategies and Outcomes for Osteochondritis Dissecans of the Capitellum

Background: The optimum management of osteochondritis dissecans (OCD) of the capitellum is a widely debated subject. Purpose: To better understand the efficacy of different surgical modalities and nonoperative treatment of OCD as assessed by radiological and clinical outcomes and return to sports. Study Design: Systematic review; Level of evidence, 4. Methods: A systematic review of all treatment studies published between January 1975 and June 2020 was performed following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A total of 76 clinical studies, including 1463 patients, were suitable for inclusion. Aggregate analysis and subgroup analysis of individual patient data were performed to compare the functional and radiographic outcomes between the various nonoperative and surgical treatment options for capitellar OCD. A unified grading system (UGS; grades 1-4) was developed from existing validated classification systems to allow a comparison of patients with similar-grade OCD lesions in different studies according to their treatment. Patient-level data were available for 352 patients. The primary outcome measures of interest were patient-reported functional outcome, range of motion (ROM), and return to sports after treatment. The influences of the capitellar physeal status, location of the lesion, and type of sports participation were also assessed. Each outcome measure was evaluated according to the grade of OCD and treatment method (debridement/microfracture, fragment fixation, osteochondral autograft transplantation [OATS], or nonoperative treatment). Results: No studies reported elbow scores or ROM for nonoperatively treated patients. All surgical modalities resulted in significantly increased postoperative ROM and elbow scores for stable (UGS grades 1 and 2) and unstable lesions (UGS grades 3 and 4). There was no significant difference in the magnitude of improvement or overall scores according to the type of surgery for stable or unstable lesions. Return to sports was superior with nonoperative treatment for stable lesions, whereas surgical treatment was superior for unstable lesions. Patients with an open capitellar physis had superior ROM for stable and unstable lesions, but there was no correlation with lesion location and the outcomes of OATS versus fragment fixation for high-grade lesions. Conclusion: Nonoperative treatment was similar in outcomes to surgical treatment for low-grade lesions, whereas surgical treatment was superior for higher grade lesions. There is currently insufficient evidence to support complex reconstructive techniques for high-grade lesions compared with microfracture/debridement alone.
Nursing intervention to prevent delirium in critically ill adults.

OBJECTIVE To determine the effectiveness of a nursing intervention for delirium prevention in critically ill patients. METHOD A quasi-experimental study was conducted with a non-equivalent control group and with evaluation before and after the intervention. 157 Patients were part of the intervention group and 134 of the control group. Patients were followed-up until they were discharged from the ICU or died. The incidence of delirium in both groups was compared. Additionally, the effect measures were adjusted for the propensity score. RESULTS The incidence and incidence rate of delirium in the control group were 20.1% and 33.1 per 1000 person-days (CI 95% 22.7 to 48.3) and in the intervention group was 0.6% and 0.64 per 1000 person-days (CI 95% 0.22 to 11.09), respectively. The crude Hazard Ratio was 0.06 (CI 95% 0,008 to 0,45) and adjusted 0.07 (CI 95% 0,009 to 0,60). The number needed to be treated was six. CONCLUSION Low incidence of delirium in critically ill patients intervened demonstrated the effectiveness of interventions. The average intervention time was 4 days with a 15-minutes dedication for each patient.
Quantification of P-Glycoprotein in the Gastrointestinal Tract of Humans and Rodents: Methodology, Gut Region, Sex, and Species Matter

Intestinal efflux transporters affect the gastrointestinal processing of many drugs but further data on their intestinal expression levels are required. Relative mRNA expression and relative and absolute protein expression data of transporters are commonly measured by real-time polymerase chain reaction (RT-PCR), Western blot and mass spectrometry-based targeted proteomics techniques. All of these methods, however, have their own strengths and limitations, and therefore, validation for optimized quantification methods is needed. As such, the identification of the most appropriate technique is necessary to effectively translate preclinical findings to first-in-human trials. In this study, the mRNA expression and protein levels of the efflux transporter P-glycoprotein (P-gp) in jejunal and ileal epithelia of 30 male and female human subjects, and the duodenal, jejunal, ileal and colonic tissues in 48 Wistar rats were quantified using RT-PCR, Western blot and liquid chromatography-tandem mass spectrometry (LC-MS/MS). A similar sex difference was observed in the expression of small intestinal P-gp in humans and Wistar rats where P-gp was higher in males than females with an increasing trend from the proximal to the distal parts in both species. A strong positive linear correlation was determined between the Western blot data and LC-MS/MS data in the small intestine of humans (R2 = 0.85). Conflicting results, however, were shown in rat small intestinal and colonic P-gp expression between the techniques (R2 = 0.29 and 0.05, respectively). In RT-PCR and Western blot, an internal reference protein is experimentally required; here, beta-actin was used which is innately variable along the intestinal tract. Quantification via LC-MS/MS can provide data on P-gp expression without the need for an internal reference protein and consequently, can give higher confidence on the expression levels of P-gp along the intestinal tract. Overall, these findings highlight similar trends between the species and suggest that the Wistar rat is an appropriate preclinical animal model to predict the oral drug absorption of P-gp substrates in the human small intestine.