Miracle-dz/UniFAR-FTUs huggingface dataset:
Prevention of eating disorders: 2021 in review

ABSTRACT This review of 19 prevention-related publications in Eating Disorders during 2021 is framed by four models: (1) Mental Health Intervention Spectrum: health promotion → types of prevention → case identification/referral → treatment; (2) the prevention cycle: rationale and theory, shaped by critical reviews → clarifying risk and protective factors → program innovation and feasibility studies → efficacy and effectiveness research → program dissemination; (3) links between disordered eating (DE) and eating disorders (EDs); and (4) Kraemer and Jacobi’s criteria for variable, causal risk factors (RFs). Twelve articles demonstrated the strengths and limitations of cross-sectional investigations of RFs for DE and EDs: five explored the role of trauma in activating genetic and psychological RFs (e.g., anxiety and experiential avoidance), while five suggest other variables meriting further evaluation: ergogenic supplement use, “feeling fat,” internalized weight bias, food insecurity, and compulsive exercising. One article presents a pilot program that reduced risk factors in a high-risk group: professional ballerinas. Implications of the absence of efficacy, effectiveness, dissemination, and advocacy studies, along with the need to develop tailored programs for various high-risk groups, are discussed.
Two wars on one front: Experiences of gynaecological cancer patients in the COVID‐19 pandemic

Abstract Objective The aim of this study is to explore the experiences of gynaecological cancer patients during the COVID‐19 pandemic from their own perspectives. Methods The study is a descriptive study with a qualitative design based on thematic analysis. We conducted the study with 17 women with gynaecological cancer and receiving chemotherapy in the Medical Oncology and Chemotherapy Unit of Kütahya Training and Research Hospital. The data were collected between April 2021 and May 2021 via an in‐depth individual interview form. The COREQ checklist was followed in the study. Results As a result of the interviews, we identified four main themes: the impacts of COVID‐19 on life, the impact of COVID‐19 on cancer treatment, the biggest fear during the COVID‐19 pandemic and the metaphors of struggling with cancer during the COVID‐19 pandemic. Conclusion The disruption of treatment services during the COVID‐19 pandemic and women's fear of infection by the virus led to delays in cancer diagnosis and treatment. This situation caused the women's state of health to deteriorate, and the resultant regret and sadness that they experienced had an adverse effect on their mental health. Furthermore, women's self‐isolation due to the fear of infection by the virus had a negative effect on their psychosocial health. Telehealth services should be provided for cancer patients to obtain accurate information and to easily access information about treatment processes during the pandemic, and telepsychological hotlines and peer support groups should be established to improve the psychosocial health of patients.
Mitochondria signaling pathways in allergic asthma

Mitochondria, as the powerhouse organelle of cells, are greatly involved in regulating cell signaling pathways, including those related to the innate and acquired immune systems, cellular differentiation, growth, death, apoptosis, and autophagy as well as hypoxic stress responses in various diseases. Asthma is a chronic complicated airway disease characterized by airway hyperresponsiveness, eosinophilic inflammation, mucus hypersecretion, and remodeling of airway. The asthma mortality and morbidity rates have increased worldwide, so understanding the molecular mechanisms underlying asthma progression is necessary for new anti-asthma drug development. The lung is an oxygen-rich organ, and mitochondria, by sensing and processing O2, contribute to the generation of ROS and activation of pro-inflammatory signaling pathways. Asthma pathophysiology has been tightly associated with mitochondrial dysfunction leading to reduced ATP synthase activity, increased oxidative stress, apoptosis induction, and abnormal calcium homeostasis. Defects of the mitochondrial play an essential role in the pro-remodeling mechanisms of lung fibrosis and airway cells’ apoptosis. Identification of mitochondrial therapeutic targets can help repair mitochondrial biogenesis and dysfunction and reverse related pathological changes and lung structural remodeling in asthma. Therefore, we here overviewed the relationship between mitochondrial signaling pathways and asthma pathogenic mechanisms.
Elevated MCU Expression by CaMKIIδB Limits Pathological Cardiac Remodeling

Background: Calcium (Ca2+) is a key regulator of energy metabolism. Impaired Ca2+ homeostasis damages mitochondria, causing cardiomyocyte death, pathological hypertrophy, and heart failure. This study investigates the regulation and the role of the mitochondrial Ca2+ uniporter (MCU) in chronic stress-induced pathological cardiac remodeling. Methods: MCU knockout or transgenic mice were infused with isoproterenol (ISO; 10 mg/kg per day, 4 weeks). Cardiac hypertrophy and remodeling were evaluated by echocardiography and histology. Primary cultured rodent adult cardiomyocytes were treated with ISO (1 nmol/L, 48 hours). Intracellular Ca2+ handling and cell death pathways were monitored. Adenovirus-mediated gene manipulations were used in vitro. Results: Chronic administration of the β-adrenergic receptor agonist ISO increased the levels of the MCU and the MCU complex in cardiac mitochondria, raising mitochondrial Ca2+ concentrations, in vivo and in vitro. ISO also upregulated MCU without affecting its regulatory proteins in adult cardiomyocytes. It is interesting that ISO-induced cardiac hypertrophy, fibrosis, contractile dysfunction, and cardiomyocyte death were exacerbated in global MCU knockout mice. Cardiomyocytes from knockout mice or overexpressing a dominant negative MCU exhibited defective intracellular Ca2+ handling and activation of multiple cell death pathways. Conversely, cardiac-specific overexpression of MCU maintained intracellular Ca2+ homeostasis and contractility, suppressed cell death, and prevented ISO-induced heart hypertrophy. ISO upregulated MCU expression through activation of Ca2+/calmodulin kinase II δB (CaMKIIδB) and promotion of its nuclear translocation via calcineurin-mediated dephosphorylation at serine 332. Nuclear CaMKIIδB phosphorylated CREB (cAMP-response element binding protein), which bound the Mcu promoter to enhance Mcu gene transcription. Conclusions: The β-adrenergic receptor/CaMKIIδB/CREB pathway upregulates Mcu gene expression in the heart. MCU upregulation is a compensatory mechanism that counteracts stress-induced pathological cardiac remodeling by preserving Ca2+ homeostasis and cardiomyocyte viability.
Are deaths from COVID-19 associated with higher rates of prolonged grief disorder (PGD) than deaths from other causes?

Abstract With the COVID-19 pandemic prompting predictions of a “grief pandemic,” rates and risks for Prolonged Grief Disorder (PGD) warrant further investigation. Data were collected online from 1470 respondents between October 2020 and July 2021. Shorter time since death, deaths of siblings and “others,” and deaths from accidents and homicides were positively associated with potential risk of probable PGD; deaths of extended family and from dementia were negatively associated with probable PGD. When compared directly to deaths from COVID-19, natural causes of death were associated with lower potential risk of probable PGD, while deaths from unnatural causes were associated with higher potential risk.
Comparison between Nasal and Nasopharyngeal Swabs for SARS-CoV-2 Rapid Antigen Detection in an Asymptomatic Population, and Direct Confirmation by RT-PCR from the Residual Buffer

Nasal swabbing for SARS-CoV-2 (COVID-19) comes with many benefits but is slightly less sensitive than traditional nasopharyngeal swabbing; however, confirmatory lab-based testing could be performed directly from the residual buffer from either sample type. ABSTRACT Containment measures employed during the COVID-19 pandemic included prompt recognition of cases, isolation, and contact tracing. Bilateral nasal (NA) swabs applied to a commercial antigen-based rapid diagnostic test (Ag-RDT) offer a simpler and more comfortable alternative to nasopharyngeal (NP) collection; however, little is known about the sensitivity of this method in an asymptomatic population. Participants in community-based asymptomatic testing sites were screened for SARS-CoV-2 using an Ag-RDT with NP sampling. Positive individuals returned for confirmatory molecular testing and consented to repeating the Ag-RDT using a bilateral NA swab for comparison. Residual test buffer (RTB) from Ag-RDTs was subjected to real-time reverse transcription-PCR (RT-PCR). Of 123,617 asymptomatic individuals, 197 NP Ag-RDT-positive participants were included, with 175 confirmed positive by RT-PCR. Of these cases, 154 were identified from the NA swab collection with Ag-RDT, with a sensitivity of 88.0% compared to the NP swab collection. Stratifying results by RT-PCR cycle threshold demonstrated that sensitivity of the nasal collection method varied based on the cycle threshold (CT) value of the paired RT-PCR sample. RT-PCR testing on the RTB from the Ag-RDT using NP and NA swab collections resulted in 100.0% and 98.7% sensitivity, respectively. NA swabs provide an adequate alternative to NP swab collection for use with Ag-RDT, with the recognition that the test is most sensitive in specimens with high viral loads. With the high sensitivity of RT-PCR testing on RTB from Ag-RDT, a more streamlined approach to confirmatory testing is possible without recollection or use of paired collections strategies. IMPORTANCE Nasal swabbing for SARS-CoV-2 (COVID-19) comes with many benefits but is slightly less sensitive than traditional nasopharyngeal swabbing; however, confirmatory lab-based testing could be performed directly from the residual buffer from either sample type.
Studying the Effects of Congruence of Auditory and Visual Stimuli on Virtual Reality Experiences

Studies in virtual reality (VR) have introduced numerous multisensory simulation techniques for more immersive VR experiences. However, although they primarily focus on expanding sensory types or increasing individual sensory quality, they lack consensus in designing appropriate interactions between different sensory stimuli. This paper explores how the congruence between auditory and visual (AV) stimuli, which are the sensory stimuli typically provided by VR devices, affects the cognition and experience of VR users as a critical interaction factor in promoting multisensory integration. We defined the types of (in)congruence between AV stimuli, and then designed 12 virtual spaces with different types or degrees of congruence between AV stimuli. We then evaluated the presence, immersion, motion sickness, and cognition changes in each space. We observed the following key findings: 1) there is a limit to the degree of temporal or spatial incongruence that can be tolerated, with few negative effects on user experience until that point is exceeded; 2) users are tolerant of semantic incongruence; 3) a simulation that considers synesthetic congruence contributes to the user's sense of immersion and presence. Based on these insights, we identified the essential considerations for designing sensory simulations in VR and proposed future research directions.
Ferroelectric tunnel junctions : memristors for neuromorphic computing

Classical computer architectures are optimized to process pre-formatted information in a deterministic way and therefore struggle to treat unorganized natural data (images, sounds, etc.). As these become more and more important, the brain inspires new, neuromorphic computer circuits such as neural networks. Their energy-efficient hardware implementations will greatly benefit from nanodevices, called memristors, whose small size could enable the high synaptic connectivity degree observed in the brain.In this work, we concentrate on memristors based on ferroelectric tunnel junctions that are composed of an ultrathin ferroelectric film between two metallic electrodes. We show that the polarization reversal in BiFeO3 films can induce resistance contrasts as high as 10^4 and how mixed domain states are connected to intermediate resistance levels.Changing the electrode materials provides insights into their influence on the electrostatic barrier and dynamic properties of these memristors. Single-shot switching experiments reveal very fast polarization switching which we further investigate in cumulative measurements. Their analysis in combination with piezoresponse force microscopy finally allows us to establish a model describing the memristor dynamics under arbitrary voltage signals. After the demonstration of an important learning rule for neural networks, called spike-timing-dependent plasticity, we successfully predict new, previously unexplored learning curves. This constitutes an important step towards the realization of unsupervised self-learning hardware neural networks.
Dupilumab for the treatment of atopic dermatitis: real-world data from the Czech Republic BIOREP registry

Abstract Background Dupilumab has been approved to treat moderate-to-severe atopic dermatitis; however, the data in a real-world setting are still limited. Objective To analyze the effectiveness and safety of dupilumab. Methods This was a real-life Czech multicenter retrospective study from patients treated with dupilumab for severe AD. Results A total of 360 patients were included. At 16 weeks, 66.6, 34.1, and 5.5% of patients achieved EASI75/90 and EASI100, respectively. Improvement continued with the time, and the proportion of patients with EASI75/90 and EASI100 increased to 89.5, 55.6, and 12.9% after one year of treatment and reached 95.8, 60.4, and 27.1% in the second year of therapy, respectively. A significant reduction was observed in the DLQI scores. The most common adverse events were infections in 5.8% of patients, followed by ocular complications in 2.5% of patients. Persistence rates were 98.2% at four months to 93.1% at month 24, and lack of effectiveness was the most common reason for discontinuation. Conclusion This real-life study confirmed the effectiveness and safety of dupilumab in a real-life setting during the COVID-19 pandemic. Our study revealed a higher frequency of infections and a lower conjunctivitis frequency than other real-life studies and clinical trials.
Aberrant Fibrin Clot Structure Visualized Ex Vivo in Critically Ill Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Infection

OBJECTIVES: Disseminated fibrin-rich microthrombi have been reported in patients who died from COVID-19. Our objective is to determine whether the fibrin clot structure and function differ between critically ill patients with or without COVID-19 and to correlate the structure with clinical coagulation biomarkers. DESIGN: A cross-sectional observational study. Platelet poor plasma was used to analyze fibrin clot structure; the functional implications were determined by quantifying clot turbidity and porosity. SETTING: ICU at an academic medical center and an academic laboratory. PATIENTS: Patients admitted from July 1 to August 1, 2020, to the ICU with severe acute respiratory syndrome coronavirus 2 infection confirmed by reverse transcription-polymerase chain reaction or patients admitted to the ICU with sepsis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Blood was collected from 36 patients including 26 ICU patients with COVID-19 and 10 ICU patients with sepsis but without COVID-19 at a median of 11 days after ICU admission (interquartile range, 3–16). The cohorts were similar in age, gender, body mass index, comorbidities, Sequential Organ Failure Assessment (SOFA) score, and mortality. More patients with COVID-19 (100% vs 70%; p = 0.003) required anticoagulation. Ex vivo fibrin clots formed from patients with COVID-19 appeared to be denser and to have smaller pores than those from patients with sepsis but without COVID-19 (percent area of fluorescent fibrin 48.1% [SD, 16%] vs 24.9% [SD, 18.8%]; p = 0.049). The turbidity and flow-through assays corroborated these data; fibrin clots had a higher maximum turbidity in patients with COVID-19 compared with patients without COVID-19 (0.168 vs 0.089 OD units; p = 0.003), and it took longer for buffer to flow through these clots (216 vs 103 min; p = 0.003). In patients with COVID-19, d-dimer levels were positively correlated with percent area of fluorescent fibrin (ρ = 0.714, p = 0.047). Denser clots (assessed by turbidity and thromboelastography) and higher SOFA scores were independently associated with delayed clot lysis. CONCLUSIONS: We found aberrant fibrin clot structure and function in critically ill patients with COVID-19. These findings may contribute to the poor outcomes observed in COVID-19 patients with widespread fibrin deposition.
LINE-1 expression in cancer correlates with p53 mutation, copy number alteration, and S phase checkpoint

Significance In addition to canonical genes, our genomes encode repetitive copies of the LINE-1 retrotransposon. These elements duplicate themselves by cutting a single-strand break in genomic DNA and then reverse transcribing a new LINE-1 DNA copy into that breakpoint. In most contexts, LINE-1 elements are epigenetically repressed, but they are dramatically derepressed in many cancers, where they have the potential to impact genome integrity. We probed publicly available multiomic data from the CPTAC to identify the DNA damage response correlates of LINE-1 expression and validated the potential for LINE-1 overexpression to trigger RAD50 phosphorylation—a key step in an S phase double-strand break response pathway that we found to be highly correlated with LINE-1 expression in endometrial cancer. Retrotransposons are genomic DNA sequences that copy themselves to new genomic locations via RNA intermediates; LINE-1 is the only active and autonomous retrotransposon in the human genome. The mobility of LINE-1 is largely repressed in somatic tissues but is derepressed in many cancers, where LINE-1 retrotransposition is correlated with p53 mutation and copy number alteration (CNA). In cell lines, inducing LINE-1 expression can cause double-strand breaks (DSBs) and replication stress. Reanalyzing multiomic data from breast, ovarian, endometrial, and colon cancers, we confirmed correlations between LINE-1 expression, p53 mutation status, and CNA. We observed a consistent correlation between LINE-1 expression and the abundance of DNA replication complex components, indicating that LINE-1 may also induce replication stress in human tumors. In endometrial cancer, high-quality phosphoproteomic data allowed us to identify the DSB-induced ATM-MRN-SMC S phase checkpoint pathway as the primary DNA damage response (DDR) pathway associated with LINE-1 expression. Induction of LINE-1 expression in an in vitro model led to increased phosphorylation of MRN complex member RAD50, suggesting that LINE-1 directly activates this pathway.
Serial reproduction of narratives preserves emotional appraisals

ABSTRACT We conducted the largest multiple-iteration retelling study to date (12,840 participants and 19,086 retellings) with two different studies that test how emotional appraisals are transmitted across retellings. We use a novel Bayesian model that tracks changes across retellings. Study 1 examines the preservation of appraisals of happy and sad stories and finds that retellings preserve the story’s degree of happiness and sadness even when length shrinks and aspects of story coherence and rationalisation deteriorate. Study 2 compared the transmission of appraisals of happiness and sadness with embarrassment, disgust, and risk. Appraisals of happiness, sadness, and also embarrassment showed high appraisal preservation, while disgust and risk were not well preserved. We conclude that participants in our studies encoded happy and sad stories by encapsulating the events and details into an overall emotional appraisal of the story and that this processing strategy might also apply to stories involving other emotions like embarrassment. The emotional appraisal played a key role in retelling by helping to guide the selection, invention, and ordering of the story elements. Hence, we posit that emotion appraisals can operate as anchors for remembering and retelling stories, thus playing an important role in narrative communication.
Deciphering the endometrial niche of human thin endometrium at single-cell resolution

Significance Thin endometrium is the most common reason for uterine infertility and refractory gynecological diseases due to its complexity in pathogenesis and adverse pregnancy outcomes. Here, we profile cells from normal and thin endometrium at single-cell resolution to investigate the sophisticated alterations in the local microenvironment that occur in thin endometrium. Increased cellular senescence, collagen overdeposition, and significant down-regulation of gene expression related to cell proliferation are observed and confirmed. Moreover, we demonstrate aberrant activation of the SEMA3 pathway accompanied by dampened EGF, PTN, and TWEAK signaling pathways in thin endometrium. These findings aid in understanding the mechanisms of thin endometrium and provide new tools to rejuvenate the atrophic endometrium for female fertility preservation and successful pregnancy. Thin endometrium has been widely recognized as a critical cause of infertility, recurrent pregnancy loss, and placental abnormalities; however, access to effective treatment is a formidable challenge due to the rudimentary understanding of the pathogenesis of thin endometrium. Here, we profiled the transcriptomes of human endometrial cells at single-cell resolution to characterize cell types, their communications, and the underlying mechanism of endometrial growth in normal and thin endometrium during the proliferative phase. Stromal cells were the most abundant cell type in the endometrium, with a subpopulation of proliferating stromal cells whose cell cycle signaling pathways were compromised in thin endometrium. Both single-cell RNA sequencing and experimental verification revealed cellular senescence in the stroma and epithelium accompanied by collagen overdeposition around blood vessels. Moreover, decreased numbers of macrophages and natural killer cells further exacerbated endometrial thinness. In addition, our results uncovered aberrant SEMA3, EGF, PTN, and TWEAK signaling pathways as causes for the insufficient proliferation of the endometrium. Together, these data provide insight into therapeutic strategies for endometrial regeneration and growth to treat thin endometrium.