Miracle-dz/UniFAR-FTUs huggingface dataset:
Integrated molecular profiling of patient‐derived ovarian cancer models identifies clinically relevant signatures and tumor vulnerabilities

High‐grade serous ovarian carcinoma (HGSOC) is a highly aggressive and intractable neoplasm, mainly because of its rapid dissemination into the abdominal cavity, a process that is favored by tumor‐associated peritoneal ascites. The precise molecular alterations involved in HGSOC onset and progression remain largely unknown due to the high biological and genetic heterogeneity of this tumor. We established a set of different tumor samples (termed the As11‐set) derived from a single HGSOC patient, consisting of peritoneal ascites, primary tumor cells, ovarian cancer stem cells (OCSC) and serially propagated tumor xenografts. The As11‐set was subjected to an integrated RNA‐seq and DNA‐seq analysis which unveiled molecular alterations that marked the different types of samples. Our profiling strategy yielded a panel of signatures relevant in HGSOC and in OCSC biology. When such signatures were used to interrogate the TCGA dataset from HGSOC patients, they exhibited prognostic and predictive power. The molecular alterations also identified potential vulnerabilities associated with OCSC, which were then tested functionally in stemness‐related assays. As a proof of concept, we defined PI3K signaling as a novel druggable target in OCSC.
Practising the ethics of person‐centred care balancing ethical conviction and moral obligations

Abstract Person‐centred care is founded on ethics as a basis for organizing care. In spite of healthcare systems claiming that they have implemented person‐centred care, patients report less satisfaction with care. These contrasting results require clarification of how to practice person‐centred ethics using Paul Ricoeur's ‘Little ethics’, summarized as: ‘aiming for the good life, with and for others in just institutions’. In this ethic Kantian morality is at once subordinate and complementary to Aristotelian ethics because the ethical goal needs to be critically assessed and passed through the examination of the norm in each care situation. This paper presents examples that describes a person‐centred care practice that balance a critical review of care activities based on a conviction of aiming for patients' wellbeing. In contrast to patients' experiences of person‐centred care in real life, research projects have shown that if the clinical performers comprehend and apply the practice of person‐centred ethics, patients report positive outcomes. The implementation of person‐centred care therefore demands that stakeholders and managers enables and requires that healthcare staff study ethics in the same way as studying for example pharmacology is required when handling patients' medicines.
A Systematic Review of the Effectiveness of Bisphosphonates for Otosclerosis

Objective: To systematically review the evidence for the use of bisphosphonate therapy in otosclerosis through clinically relevant outcomes. Databases Reviewed: MEDLINE, EMBASE, PubMed, and CINAHL databases were searched up to July 12, 2021. Methods: RCTs and cohort studies investigating the effect of bisphosphate therapy on adults or children diagnosed with otosclerosis were included. The risk of bias within trials was examined using the ROB2 tool for RCTs, and the ROBINS-I for non-RCTs. Results: Three studies reported over five publications were included in the systematic review. Data from one RCT at 6 months did not demonstrate any improvement nor deterioration in audiological outcomes in participants treated with Sodium Alendronate. Data from MRI in this group demonstrated improvements in the SI of the otosclerotic foci at the RAOW compared to participants taking placebo. In another RCT, improvements in audiological outcomes were seen at 12 and 24 months in individuals treated with Etidronate Sodium. Long-term data from a retrospective cohort study demonstrated stabilisation of hearing in individuals with otosclerosis and progressive SNHL. Conclusion: There is insufficient evidence to recommend the routine use of bisphosphonates in otosclerosis patients at present. Long-term retrospective data has suggested a role for bisphosphonates in the subset of patients with deteriorating sensorineural hearing loss with the aim of hearing stabilisation. Adequately powered RCTs with long term follow up will be required to evaluate this further.
Maintained P2Y12 inhibitor monotherapy after shorter‐duration of dual antiplatelet therapy in patients undergoing coronary drug‐eluting stents implantation: An updated meta‐analysis of randomized trials

It is well known that high in‐stent thrombotic risk due to the superimposition of a platelet‐rich thrombus was considered as the main origin of major adverse cardiac events after stent implantation. The clinical management of antiplatelet therapy strategy after percutaneous coronary intervention (PCI) remains controversial. This study is sought to explore the efficacy and safety of a maintained P2Y12 inhibitor monotherapy after shorter‐duration of dual antiplatelet therapy (DAPT) in these patients.
The magnitude of LFA-1/ICAM-1 forces fine-tune TCR-triggered T cell activation

T cells defend against cancer and viral infections by rapidly scanning the surface of target cells seeking specific peptide antigens. This key process in adaptive immunity is sparked upon T cell receptor (TCR) binding of antigens within cell-cell junctions stabilized by integrin (LFA-1)/intercellular adhesion molecule–1 (ICAM-1) complexes. A long-standing question in this area is whether the forces transmitted through the LFA-1/ICAM-1 complex tune T cell signaling. Here, we use spectrally encoded DNA tension probes to reveal the first maps of LFA-1 and TCR forces generated by the T cell cytoskeleton upon antigen recognition. DNA probes that control the magnitude of LFA-1 force show that F>12 pN potentiates antigen-dependent T cell activation by enhancing T cell–substrate engagement. LFA-1/ICAM-1 mechanical events with F>12 pN also enhance the discriminatory power of the TCR when presented with near cognate antigens. Overall, our results show that T cells integrate multiple channels of mechanical information through different ligand-receptor pairs to tune function.
X-ray Induced Fragmentation of Protonated Cystine

We demonstrate site-specific X-ray induced fragmentation across the sulfur L-edge of protonated cystine, the dimer of the amino acid cysteine. Ion yield NEXAFS were performed in the gas phase using electrospray ionization (ESI) in combination with an ion trap. The interpretation of the sulfur L-edge NEXAFS spectrum is supported by Restricted Open-Shell Configuration Interaction (ROCIS) calculations. The fragmentation pathway of triply charged cystine ions was modeled by Molecular Dynamics (MD) simulations. We have deduced a possible pathway of fragmentation upon excitation and ionization of S 2p electrons. The disulfide bridge breaks for resonant excitation at lower photon energies but remains intact upon higher energy resonant excitation and upon ionization of S 2p. The larger fragments initially formed subsequently break into smaller fragments.
The transmission game: Testing behavioral interventions in a pandemic-like simulation

During pandemics, effective nonpharmaceutical interventions encourage people to adjust their behavior in fast-changing environments in which exponential dynamics aggravate the conflict between the individual benefits of risk-taking and its social costs. Policy-makers need to know which interventions are most likely to promote socially advantageous behaviors. We designed a tool for initial evaluations of the effectiveness of large-scale interventions, the transmission game framework, which integrates simulations of outbreak dynamics into large-group experiments with monetary stakes. In two studies (n = 700), we found substantial differences in the effectiveness of five behavioral interventions. A simple injunctive-norms message proved most effective, followed by two interventions boosting participants’ ability to anticipate the consequences of risky behavior. Interventions featuring descriptive norms or concurrent risk information failed to reduce risk-taking.
Analysis of a Vertical Interconnection Access by Using Longitudinal Wave Concept Iteratve Process (LWCIP)

A new formulation of the Wave Concept Iterative Process (WCIP) method is presented in this work. This approach uses an analysis with the longitudinal components instead of the transverse components. This approach includes decomposing the transverse TM modes into two longitudinal terms: the TM and TEM modes. This approach is applied to model a Vertical Interconnect Access VIA hole. The current density behavior is studied in the two cases with and without VIA hole. Also this method is used to study a SIW slot antenna. Compared to those obtained by available published data, our results show that the proposed method gives convincing results.
Single Virus Detection on Silicon Photonic Crystal Random Cavities.

On-chip silicon microcavity sensors are advantageous for the detection of virus and biomolecules due to their compactness and the enhanced light-matter interaction with the analyte. While their theoretical sensitivity is at the single-molecule level, the fabrication of high quality (Q) factor silicon cavities and their integration with optical couplers remain as major hurdles in applications such as single virus detection. Here, label-free single virus detection using silicon photonic crystal random cavities is proposed and demonstrated. The sensor chips consist of free-standing silicon photonic crystal waveguides and do not require pre-fabricated defect cavities or optical couplers. Residual fabrication disorder results in Anderson-localized cavity modes which are excited by a free space beam. The Q ≈105 is sufficient for observing discrete step-changes in resonance wavelength for the binding of single adenoviruses (≈50 nm radius). The authors' findings point to future applications of CMOS-compatible silicon sensor chips supporting Anderson-localized modes that have detection capabilities at the level of single nanoparticles and molecules.
Precision targeting tumor cells using cancer-specific InDel mutations with CRISPR-Cas9

Significance The targeted killing of cancer cells without affecting surrounding normal cells is the most desirable approach for cancer therapy; however, it cannot be easily achieved, owing to the shared properties of normal and cancer cells. Using CRISPR-Cas9 targeting multiple cancer-specific mutations, we developed an innovative approach called cancer-specific insertions and deletions attacker that can induce targeted cancer cell death by simultaneous and multiple DNA double-strand breaks. As demonstrated in cell lines, cancer patient–driven cells and xenografts, the concept proposed in this study may become a potential approach for personalized cancer treatments.
Cohort differences in the development of civic engagement during adolescence.

Investigating whether changing societal circumstances have altered the development of civic engagement, this study compared developmental changes from mid- to late adolescence (i.e., age 15-18) across two cohorts of representative Swiss samples (born in1991, N = 1258, Mage T1 = 15.30, 54% female, 33% migration background representing diverse ethnicities; born in 2000, N = 930, Mage T1 = 15.32, 51% female; 33% migration background). Findings from latent multigroup models revealed similar levels in attitudes about social justice in both cohorts, remaining stable over time. Adolescents reported lower levels of political efficacy and informal helping in the cohort born in 2000. Both aspects slightly increased during adolescence. Informal helping had a steeper increase in the 1991 compared to the 2000 cohort, suggesting developmental differences between cohorts.
Unveiling the phantom: What neuroimaging has taught us about phantom limb pain

Phantom limb pain (PLP) is a complicated condition with diverse clinical challenges. It consists of pain perception of a previously amputated limb. The exact pain mechanism is disputed and includes mechanisms involving cerebral, peripheral, and spinal origins. Such controversy limits researchers’ and clinicians’ ability to develop consistent therapeutics or management. Neuroimaging is an essential tool that can address this problem. This review explores diffusion tensor imaging, functional magnetic resonance imaging, electroencephalography, and magnetoencephalography in the context of PLP. These imaging modalities have distinct mechanisms, implications, applications, and limitations. Diffusion tensor imaging can outline structural changes and has surgical applications. Functional magnetic resonance imaging captures functional changes with spatial resolution and has therapeutic applications. Electroencephalography and magnetoencephalography can identify functional changes with a strong temporal resolution. Each imaging technique provides a unique perspective and they can be used in concert to reveal the true nature of PLP. Furthermore, researchers can utilize the respective strengths of each neuroimaging technique to support the development of innovative therapies. PLP exemplifies how neuroimaging and clinical management are intricately connected. This review can assist clinicians and researchers seeking a foundation for applications and understanding the limitations of neuroimaging techniques in the context of PLP.
Work From Home or Bring Home the Work? Burnout and Procrastination in Brazilian Workers During the COVID-19 Pandemic

This cross-sectional study highlights that working from home (WFH) may have more advantages than disadvantages in ideal conditions during the COVID-19 pandemic. However, work-life imbalances and social and gender inequalities seem to be key aspects regarding distress and burnout among workers WFH, especially in women with small children. Objective: To investigate burnout and procrastination in a sample of Brazilian workers during the COVID-19 pandemic according to their current work mode. Methods: This cross-sectional study used data from an online survey conducted in 2020: 435 workers were included. The Copenhagen Burnout Inventory and the Irrational Procrastination Scale were used to access burnout and procrastination respectively. Results: There was no difference between workers working from home (WFH) and at face-to-face work regarding burnout symptoms. However, the WFH group had higher levels of procrastination. Clinically significant levels of burnout were associated with being female, increased childcare load and living with children under 12years old. Conclusions: WFH may have more advantages than disadvantages in ideal conditions. However, work-life imbalances seem to be a key aspect regarding distress among workers WFH, especially in women with small children.
External Validation of the 2003 Leibovich Prognostic Score in Patients Randomly Assigned to SORCE, an International Phase III Trial of Adjuvant Sorafenib in Renal Cell Cancer

PURPOSE The 2003 Leibovich score guides prognostication and selection to adjuvant clinical trials for patients with locally advanced renal cell carcinoma (RCC) after nephrectomy. We provide a robust external validation of the 2003 Leibovich score using contemporary data from SORCE, an international, randomized trial of sorafenib after excision of primary RCC. METHODS Data used to derive the 2003 Leibovich score were compared with contemporary data from SORCE. Discrimination and calibration of the metastasis-free survival outcome were assessed in data from patients with clear-cell RCC, using Cox proportional hazards regression, Kaplan-Meier curves, and calculation of Harrell's c indexes. Secondary analyses involved three important SORCE groups: patients with any non–clear-cell subtype, papillary, and chromophobe carcinomas. RESULTS Four hundred seven recurrences occurred in 982 patients in the Leibovich cohort and 520 recurrences were recorded in 1,445 patients in the primary SORCE cohort. Clear discrimination between intermediate-risk and high-risk SORCE cohorts was shown; hazard ratio 2.74 (95% CI, 2.29 to 3.28), c-index 0.63 (95% CI, 0.61 to 0.65). A hazard ratio of 0.61 (95% CI, 0.53 to 0.70) confirmed poor calibration of the two cohorts. Discrimination was observed in secondary populations, with c-indexes of 0.64 (95% CI, 0.59 to 0.69) for non–clear-cell RCC, 0.63 (95% CI, 0.56 to 0.69) for papillary RCC, and 0.65 (95% CI, 0.55 to 0.76) for chromophobe RCC. CONCLUSION The 2003 Leibovich score discriminates between intermediate-risk and high-risk clear-cell and non–clear-cell RCC groups in contemporary data, supporting its use for risk stratification in adjuvant clinical trials. Over time, metastasis-free survival for patients with locally advanced RCC has improved. Contemporary data from adjuvant RCC trials should be used to improve prognostication for patients with RCC. Read how we have shown that the 2003 Leibovich score demonstrates discriminative accuracy in contemporary clear-cell and non–clear-cell RCC patient cohorts, supporting its continued use to guide discussions on patient prognosis and risk-stratification in clinical trials.
Positive-case follow up for lymphatic filariasis after a transmission assessment survey in Haiti

Background Lymphatic filariasis (LF) has been targeted for global elimination as a public health problem since 1997. The primary strategy to interrupt transmission is annual mass drug administration (MDA) for ≥5 years. The transmission assessment survey (TAS) was developed as a decision-making tool to measure LF antigenemia in children to determine when MDA in a region can be stopped. The objective of this study was to investigate potential sampling strategies for follow-up of LF-positive children identified in TAS to detect evidence of ongoing transmission. Methodology/Principle findings Nippes Department in Haiti passed TAS 1 with 2 positive cases and stopped MDA in 2015; however, 8 positive children were found during TAS 2 in 2017, which prompted a more thorough assessment of ongoing transmission. Purposive sampling was used to select the closest 50 households to each index case household, and systematic random sampling was used to select 20 households from each index case census enumeration area. All consenting household members aged ≥2 years were surveyed and tested for circulating filarial antigen (CFA) using the rapid filarial test strip and for Wb123-specific antibodies using the Filaria Detect IgG4 ELISA. Among 1,927 participants, 1.5% were CFA-positive and 4.5% were seropositive. CFA-positive individuals were identified for 6 of 8 index cases. Positivity ranged from 0.4–2.4%, with highest positivity in the urban commune Miragoane. Purposive sampling found the highest number of CFA-positives (17 vs. 9), and random sampling found a higher percent positive (2.4% vs. 1.4%). Conclusions/Significance Overall, both purposive and random sampling methods were reasonable and achievable methods of TAS follow-up in resource-limited settings. Both methods identified additional CFA-positives in close geographic proximity to LF-positive children found by TAS, and both identified strong signs of ongoing transmission in the large urban commune of Miragoane. These findings will help inform standardized guidelines for post-TAS surveillance.
Bisphenol F exposure affects mouse oocyte in vitro maturation through inducing oxidative stress and DNA damage

Bisphenol F (BPF), a substitute for bisphenol A (BPA), is progressively used to manufacture various consumer products. Despite the established reproductive toxicity of BPF, the underlying mechanisms remain to elucidate. This in‐vitro study deep in sighted the BPF toxicity on mouse oocyte meiotic maturation and quality. After treating oocytes with BPF (300 μM), the oocyte meiotic progression was blocked, accentuated by a reduced rate in the first polar body extrusion (PBE). Next, we illustrated that BPF induced α‐tubulin hyper‐acetylation disrupted the spindle assembly and chromosome alignment. Concurrently, BPF resulted in severe oxidative stress and DNA damage, which triggered the early apoptosis in mouse oocytes. Further, altered epigenetic modifications following BPF exposure were proved by increased H3K27me3 levels. Concerning the toxic effects on spindle structure, oxidative stress, and DNA damage in mouse oocytes, BPF toxicity was less severe to oocyte maturation and spindle structure than BPA and induced low oxidative stress. However, compared with BPA, oocytes treated with BPF were more prone to DNA damage, indicating not less intense or even more severe toxic effects of BPF than BPA on some aspects of oocytes maturation. In brief, the present study established that like wise to BPA, BPF could inhibit meiotic maturation and reduce oocyte quality, suggesting it is not a safe substitute for BPA.
The impact of the COVID-19 pandemic on engagement in activities of daily living in persons with acquired brain injury

ABSTRACT Primary Objectives This study examined (a) the impact of coronavirus disease-2019 (COVID-19) pandemic on engagement in activity participation in persons with acquired brain injury (ABI); and (b) whether changes in activity participation during the pandemic were associated participants’ health-related quality of life (HRQoL). Research Design Exploratory online survey study. Methods Eighty-seven respondents with ABI and 98 healthy adults (HA) participated in this study. Engagement in activity participation during COVID-19 was calculated as a percentage of the activities participants performed before the pandemic. Main Results Participants with ABI modified their activities less than HA in order to maintain level of engagement in activity participation. They stopped performing more activities during the pandemic compared to HA and compared to their pre-pandemic engagement. Both groups continued to do similar percentage of activities without modifications compared to before the pandemic. Better HRQoL in both groups was predicted by a larger percentage of activities continued and fewer activities stopped. Conclusion Results emphasize the importance of addressing activity participation changes during situations where there are disruptions of the individual’s habits and routines in order to minimize negative consequences of such changes.
A nonparametric approach to confidence intervals for concordance index and difference between correlated indices

ABSTRACT Concordance refers to the probability that subjects with high values on one variable also have high values on another variable. This index has wide application in practice, as a measure of effect size in group-comparison studies, an index of accuracy in diagnostic studies, and a discrimination index for prediction models. Herein, we provide a unified framework for statistical inference involving concordance indices for standard variables of binary, ordinal, and continuous types. In particular, we develop confidence interval procedures for a single concordance index and differences between two correlated indices. Simulation results show that procedures based on logit-transformation for a single index and Fisher’s -transformation for a difference between indices perform very well in terms of coverage and tail errors even when the sample size is as small as 30, unless the concordance is high and the standard is a binary variable for which at least 50 subjects are needed. We illustrate the procedures for a variety of standard variables with previously published data. Illustrative SAS code is provided.