Miracle-dz/UniFAR-FTUs huggingface dataset:
Perceived Benefits of MDMA-Assisted Psychotherapy beyond Symptom Reduction: Qualitative Follow-Up Study of a Clinical Trial for Individuals with Treatment-Resistant PTSD

ABSTRACT We present select findings from a long-term follow-up qualitative study of MDMA-assisted psychotherapy for veterans, firefighters, and police officers suffering from chronic, treatment-resistant PTSD. Semi-structured qualitative interviews were conducted at participants’ one-year follow-up after a recently completed phase 2 clinical trial. Available interviews from 19 of 24 participants were analyzed. This qualitative analysis sought to complement, clarify, and expand upon the quantitative findings obtained from the Clinician Administered PTSD Scale (CAPS-IV) and supported by the Long-Term Follow-Up (LTFU) Questionnaire. Pertinent data from interview transcripts were coded and analyzed using an interpretative phenomenological analysis (IPA) methodological framework. We explore prominent thematic elements from participant accounts to better understand the outcomes experienced in this trial. All participants reported experiencing lasting personal benefits and enhanced quality of life that extend beyond quantifiable symptom reduction. We explore a range of treatment benefits beyond symptom reduction to highlight the utility of qualitative investigations of the process and effects of MDMA-assisted psychotherapy. Limitations and challenges encountered in conducting this study are discussed along with recommendations for improved qualitative research protocols in future clinical trials.
ETS1 is coexpressed with ZEB2 and mediates ZEB2‐induced epithelial‐mesenchymal transition in human tumors

Epithelial‐mesenchymal transition (EMT) is an embryonic program that is reactivated in cancer and regulates the invasion and metastasis of tumor cells. Zinc finger E‐box binding homeobox 2 (ZEB2) induces EMT by upregulating matrix metalloproteinases (MMP), yet MMP genes lack ZEB2 binding motif in their promoters. Recently, expression of MMPs was associated to the activation of ETS1 transcription factor; however, a link between ZEB2 and ETS proto‐oncogene 1, transcription factor (ETS1) remains to be elucidated. Hence, we investigated the transcriptional regulation of ETS1 by ZEB2 after our initial observation that ZEB2 and ETS1 are coexpressed in hepatocellular carcinoma cells (HCCs). Chromatin immunoprecipitation and luciferase reporter assays clearly showed that ZEB2 binds to E‐box sequences on the promoter of ETS1. Elevated expression of ETS1 was found in DLD‐ZEB2 and A431‐ZEB2 inducible systems, and knockdown of ZEB2 caused an explicit downregulation of ETS1 in shZEB2‐SNU398 and shZEB2‐SK‐HEP‐1 cells. Repression of ETS1 expression in ZEB2‐induced conditions substantially impaired the migration and invasive capacities of DLD1 cells. Mechanistically, knockdown of ETS1 in ZEB2‐expressing cells resulted in the downregulation of established ZEB2 targets TWIST and MMP9. Correlation analyses in HCC lines, cancer complementary DNA arrays, and The Cancer Genome Atlas RNA‐sequencing data set revealed that ZEB2 and ETS1 are coexpressed, and their expressions in human tumors show a highly significant positive correlation. Our results demonstrated that ZEB2 acts as an upstream regulator of ETS1 and, in turn, ETS1 maintains ZEB2‐induced EMT. These findings add another level of complexity to the understanding of ZEB2 in the invasion and metastasis of cancer cells, and put ZEB2/ETS1 axis as a novel therapeutic target in human malignancies.
MRI-based synthetic CT generation using semantic random forest with iterative refinement

Target delineation for radiation therapy treatment planning often benefits from magnetic resonance imaging (MRI) in addition to x-ray computed tomography (CT) due to MRI’s superior soft tissue contrast. MRI-based treatment planning could reduce systematic MR-CT co-registration errors, medical cost, radiation exposure, and simplify clinical workflow. However, MRI-only based treatment planning is not widely used to date because treatment-planning systems rely on the electron density information provided by CTs to calculate dose. Additionally, air and bone regions are difficult to separategiven their similar intensities in MR imaging. The purpose of this work is to develop a learning-based method to generate patient-specific synthetic CT (sCT) from a routine anatomical MRI for use in MRI-only radiotherapy treatment planning. An auto-context model with patch-based anatomical features was integrated into a classification random forest to generate and improve semantic information. The semantic information along with anatomical features was then used to train a series of regression random forests based on the auto-context model. After training, the sCT of a new MRI can be generated by feeding anatomical features extracted from the MRI into the well-trained classification and regression random forests. The proposed algorithm was evaluated using 14 patient datasets withT1-weighted MR and corresponding CT images of the brain. The mean absolute error (MAE), peak signal-to-noise ratio (PSNR), and normalized cross correlation (NCC) were 57.45 ± 8.45 HU, 28.33 ± 1.68 dB, and 0.97 ± 0.01. We also compared the difference between dose maps calculated on the sCT and those on the original CT, using the same plan parameters. The average DVH differences among all patients are less than 0.2 Gy for PTVs, and less than 0.02 Gy for OARs. The sCT generation by the proposed method allows for dose calculation based MR imaging alone, and may be a useful tool for MRI-based radiation treatment planning.
“I don’t want them to know”: how stigma creates dilemmas for engagement with Treat-all HIV care for people living with HIV in Eswatini

“Treat-all” programmes aim to improve clinical outcomes and to reduce HIV transmission through regular HIV testing and immediate offer of antiretroviral therapy (ART) for those diagnosed HIV-positive, irrespective of immunological status and symptoms of disease. Global narratives on the benefits of Treat-all anticipate reduced HIV-related stigma and increased “normalisation” of HIV with Treat-all implementation, whereby HIV is remoulded as a manageable, chronic condition where stigmatising symptoms can be concealed. Drawing on Goffman’s stigma work, we aimed to investigate how stigma may influence the engagement of clinically asymptomatic people living with HIV (PLHIV) with Treat-all HIV care in Shiselweni, Eswatini (formerly Swaziland). This longitudinal research comprised 106 interviews conducted from August 2016 to September 2017, including repeated interviews with 30 PLHIV, and one-off interviews with 20 healthcare workers. Data were analysed thematically using NVivo 11, drawing upon principles of grounded theory to generate findings inductively from participants’ accounts. Stigma was pervasive within the narratives of PLHIV, framing their engagement with treatment and care. Many asymptomatic PLHIV were motivated to initiate ART in order to maintain a “discreditable” status, by preventing the development of visible and exposing symptoms. However, engagement with treatment and care services could itself be exposing. PLHIV described the ways in which these “invisibilising” benefits and exposing risks of ART were continually assessed and navigated over time. Where the risk of exposure was deemed too great, this could lead to intermittent treatment-taking, and disengagement from care. Addressing HIV related stigma is crucial to the success of Treat-all, and should thus be a core component of HIV responses.
Structural characterization of the Imm52 family protein TsiT in Pseudomonas aeruginosa

The bacterial type VI secretion system (T6SS) utilizes many toxic effectors to gain advantage over interbacterial competition and eukaryotic host infection. Meanwhile, the cognate immunity proteins of these effectors are employed to protect themselves from the virulence. TseT and TsiT form an effector‐immunity (E‐I) protein pair secreted by T6SS of Pseudomonas aeruginosa. TseT is toxic for other bacteria, whereas TsiT can suppress the virulence of TseT. Here, we report the crystal structure of TsiT at 1.6 Å resolution. TsiT is a typical α + β class protein and belongs to a novel Imm52 protein family of the polymorphic toxin system. Apart from TsiT, only one structure of the Imm52 family proteins is present in the Protein Data Bank (PDB), but that structure is not characterized and shares low sequence identity with TsiT. We characterized the basic features of TsiT structure and identified conserved residues of the Imm52 family proteins according to homology comparison. Our work provided structural information of a new protein family and should aid future functional studies.
Revision of the taxonomic status of Synthesium elongatum (Ozaki, 1935) (Brachycladiidae), an intestinal digenean of narrow-ridged finless porpoise (Neophocaena asiaeorientalis)

Synthesium elongatum (Brachycladiidae) is an intestinal digenean described from the finless porpoise (Neophocaena asiaeorientalis) in Japan. Few records of this species exist and there is a remarkable morphological similarity between S. elongatum and S. tursionis, such that a synonymy between the species has been suggested previously. However, no morphological and/or molecular analysis has been carried out to clarify the taxonomic status of S. elongatum. In this study, we collected specimens of Synthesium sp. from N. asiaeorientalis in western Japan. The specimens possess lobed testes within the third quarter of the body, a round ovary, and vitellaria extending to level of uterine field, which are diagnostic characters for both S. elongatum and S. tursionis. They were morphologically identified to S. elongatum or S. tursionis due to the fact that the available morphometric data for both species overlap remarkably. A molecular analysis of the mitochondrial ND3 gene showed that the pairwise nucleotide distances between these specimens and S. tursionis were small, and phylogenetic analysis showed that these specimens and S. tursionis are in the same clade. Therefore, it was indicated that S. elongatum and S. tursionis are the same species and, consequently, S. elongatum is a synonym of S. tursionis.
Tailored and Adaptive Computerized Cognitive Training in Older Adults at Risk for Dementia: A Randomized Controlled Trial.

BACKGROUND Computerized Cognitive Training (CCT) has been shown to improve cognitive function in older adults with mild cognitive impairment (MCI) or mood-related neuropsychiatric symptoms (MrNPS), but many questions remain unresolved. OBJECTIVE To evaluate the extent to which CCT benefits older adults with both MCI and MrNPS, and its effects on meta-cognitive and non-cognitive outcomes, as well as establish whether adapting difficulty levels and tailoring to individuals' profile is superior to generic training. METHODS Older adults with MCI (n = 9), MrNPS (n = 11), or both (MCI+, n = 25) were randomized into a home-based individually-tailored and adaptive CCT (n = 21) or an active control condition (AC; n = 23) in a double-blind design. Interventions lasted 8-12 weeks and outcomes were assessed after the intervention, and at a 3-month follow-up. RESULTS Participants in both conditions reported greater satisfaction with their everyday memory following intervention and at follow-up. However, participants in the CCT condition showed greater improvement on composite measures of memory, learning, and global cognition at follow-up. Participants with MrNPS in the CCT condition were also found to have improved mood at 3-month follow-up and reported using fewer memory strategies at the post-intervention and follow-up assessments. There was no evidence that participants with MCI+ were disadvantaged relative to the other diagnostic conditions. Finally, informant-rated caregiver burden declined at follow-up assessment in the CCT condition relative to the AC condition. CONCLUSIONS Home-based CCT with adaptive difficulty and personal tailoring appears superior to more generic CCT in relation to both cognitive and non-cognitive outcomes. Mechanisms of treatment effect and future directions are discussed.
Investigating racial differences in clusters of adverse childhood experiences.

Many researchers have examined the cumulative effects of adverse childhood experiences (ACEs) and found that higher levels of ACEs increase the risk for worsening health conditions. Recent research has moved beyond the simple counting of ACEs, to develop a more nuanced understanding of the ways in which ACEs are experienced. Despite evidence that ACEs are experienced differentially by race, limited attention has been paid to these differences. The objective of the current study is to understand whether groupings of ACEs are experienced similarly across racial groups. A subsample of Latinx, Black, and White children were drawn from the National Survey of Children's Health 2016 data release was used as the sample (N = 43,711). The primary measure included in the study were 9 ACE indicators available in the survey. We use descriptive and latent class analysis to examine whether similar clusters of ACEs appear across racial groups. We found that White children had lower exposure to specific ACEs as well as total number of ACEs compared to non-Latinx Black and Latinx Children. In addition, there was not configural similarity between race/ethnic groups and the latent class structure of ACE exposure varies by child race/ethnicity, suggesting important differences by child race. Understanding the disparities in children's experiences can inform screening and intervention development. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Small molecule‐facilitated anion transporters in cells for a novel therapeutic approach to cystic fibrosis

Cystic fibrosis (CF) is a lethal autosomal recessive genetic disease that originates from the defective function of the CF transmembrane conductance regulator (CFTR) protein, a cAMP‐dependent anion channel involved in fluid transport across epithelium. Because small synthetic transmembrane anion transporters (anionophores) can replace the biological anion transport mechanisms, independent of genetic mutations in the CFTR, such anionophores are candidates as new potential treatments for CF.
Imaging of proteoglycan and water contents in human articular cartilage with full‐body CT using dual contrast technique

Assessment of cartilage composition via tomographic imaging is critical after cartilage injury to prevent post‐traumatic osteoarthritis. Diffusion of cationic contrast agents in cartilage is affected by proteoglycan loss and elevated water content. These changes have opposite effects on diffusion and, thereby, reduce the diagnostic accuracy of cationic agents. Here, we apply, for the first time, a clinical full‐body CT for dual contrast imaging of articular cartilage. We hypothesize that full‐body CT can simultaneously determine the diffusion and partitioning of cationic and non‐ionic contrast agents and that normalization of the cationic agent partition with that of the non‐ionic agent minimizes the effect of water content and tissue permeability, especially at early diffusion time points. Cylindrical (d = 8 mm) human osteochondral samples (n = 45; four cadavers) of a variable degenerative state were immersed in a mixture of cationic iodinated CA4+ and non‐charged gadoteridol contrast agents and imaged with a full‐body CT scanner at various time points. Determination of contrast agents’ distributions within cartilage was possible at all phases of diffusion. At early time points, gadoteridol, and CA4+ distributed throughout cartilage with lower concentrations in the deep cartilage. At ≥24 h, the gadoteridol concentration remained nearly constant, while the CA4+ concentration increased toward deep cartilage. Normalization of the CA4+ partition with that of gadoteridol significantly (p < 0.05) enhanced correlation with proteoglycan content and Mankin score at the early time points. To conclude, the dual contrast technique was found advantageous over single contrast imaging enabling more sensitive diagnosis of cartilage degeneration. © 2019 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. J Orthop Res 9999:1–12, 2019.
Materials for Photovoltaics: State of Art and Recent Developments

In recent years, photovoltaic cell technology has grown extraordinarily as a sustainable source of energy, as a consequence of the increasing concern over the impact of fossil fuel-based energy on global warming and climate change. The different photovoltaic cells developed up to date can be classified into four main categories called generations (GEN), and the current market is mainly covered by the first two GEN. The 1GEN (mono or polycrystalline silicon cells and gallium arsenide) comprises well-known medium/low cost technologies that lead to moderate yields. The 2GEN (thin-film technologies) includes devices that have lower efficiency albeit are cheaper to manufacture. The 3GEN presents the use of novel materials, as well as a great variability of designs, and comprises expensive but very efficient cells. The 4GEN, also known as “inorganics-in-organics”, combines the low cost/flexibility of polymer thin films with the stability of novel inorganic nanostructures (i.e., metal nanoparticles and metal oxides) with organic-based nanomaterials (i.e., carbon nanotubes, graphene and its derivatives), and are currently under investigation. The main goal of this review is to show the current state of art on photovoltaic cell technology in terms of the materials used for the manufacture, efficiency and production costs. A comprehensive comparative analysis of the four generations is performed, including the device architectures, their advantages and limitations. Special emphasis is placed on the 4GEN, where the diverse roles of the organic and nano-components are discussed. Finally, conclusions and future perspectives are summarized.
PIK3CA mutations in ductal carcinoma in situ and adjacent invasive breast cancer.

PIK3CA is one of the most frequently mutated genes in invasive breast cancer (IBC). These mutations are generally associated with hyper-activation of the phosphatidylinositol 3-kinase signaling pathway, which is negatively regulated by the tumor suppressor PTEN. Data is limited regarding the variant allele frequency (VAF) of PIK3CA and PTEN expression during various stages of breast carcinogenesis. Therefore, the aim of this study was to gain insight into PIK3CA VAF and associated PTEN expression during the progression from ductal carcinoma in situ (DCIS) to IBC. We isolated DNA from DCIS tissue and synchronous IBC. These samples were pre- screened for PIK3CA hotspot mutations using the SNaPshot assay and, if positive, validated and quantified by digital PCR. PTEN expression was evaluated by immunohistochemistry using the Histo-score (H-score). Differences in PIK3CA VAF and PTEN H-scores between DCIS and IBC were analyzed. We detected a significantly higher VAF of PIK3CA in the DCIS component compared to the adjacent IBC component (p=0.007). The expression of PTEN was significantly higher in DCIS compared to the IBC component in cases with a wild type (WT) PIK3CA status (p=0.007), while it remained similar in both components when PIK3CA was mutated. In conclusion, our data suggest that PIK3CA mutations could be essential specifically in early stages of breast carcinogenesis. In addition, these mutations do not-co-occur with PTEN expression during DCIS progression to IBC in the majority of patients. These results may contribute to further unraveling the process of breast carcinogenesis and this could aid development of patient-specific treatment.
Generating Robust and Informative Nonclinical In Vitro and In Vivo Bacterial Infection Model Efficacy Data To Support Translation to Humans

In June 2017, the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, organized a workshop entitled “Pharmacokinetics-Pharmacodynamics (PK/PD) for Development of Therapeutics against Bacterial Pathogens. ” The aims were to discuss details of various PK/PD models and identify sound practices for deriving and utilizing PK/PD relationships to design optimal dosage regimens for patients. Workshop participants encompassed individuals from academia, industry, and government, including the United States Food and Drug Administration. ABSTRACT In June 2017, the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, organized a workshop entitled “Pharmacokinetics-Pharmacodynamics (PK/PD) for Development of Therapeutics against Bacterial Pathogens. ” The aims were to discuss details of various PK/PD models and identify sound practices for deriving and utilizing PK/PD relationships to design optimal dosage regimens for patients. Workshop participants encompassed individuals from academia, industry, and government, including the United States Food and Drug Administration. This and the accompanying review on clinical PK/PD summarize the workshop discussions and recommendations. Nonclinical PK/PD models play a critical role in designing human dosage regimens and are essential tools for drug development. These include in vitro and in vivo efficacy models that provide valuable and complementary information for dose selection and translation from the laboratory to human. It is crucial that studies be designed, conducted, and interpreted appropriately. For antibacterial PK/PD, extensive published data and expertise are available. These have been leveraged to develop recommendations, identify common pitfalls, and describe the applications, strengths, and limitations of various nonclinical infection models and translational approaches. Despite these robust tools and published guidance, characterizing nonclinical PK/PD relationships may not be straightforward, especially for a new drug or new class. Antimicrobial PK/PD is an evolving discipline that needs to adapt to future research and development needs. Open communication between academia, pharmaceutical industry, government, and regulatory bodies is essential to share perspectives and collectively solve future challenges.
Serum iron concentration as a marker of inflammation in young cows that underwent dehorning operation

This study aimed to assess the usefulness of serum iron (Fe) concentration as a marker of inflammation caused by the dehorning operation. Five young Holstein cows aged 205.0 ± 10.7 days and weighing 207.2 ± 24.1 kg underwent the dehorning operation. Blood samples were withdrawn before dehorning (pre) and at time periods of t=0.5, 2, 4, 6, 8, 12, 24, and 48 hr. The serum amyloid A (SAA) concentration was significantly high at t=48 hr (P<0.01). The serum Fe concentration significantly decreased, reaching 90.0 ± 36.4 µg/dl at t=24 hr (P<0.001). Therefore, serum Fe concentration showed significant and negative correlation with SAA concentration (r2=0.500, P<0.01). In conclusion, serum Fe concentration is a useful marker of inflammation in young cows that have undergone the dehorning operation.