Miracle-dz/UniFAR-FTUs huggingface dataset:
Prostate cancer and novel pharmacological treatment options–what’s new for 2022?

ABSTRACT Introduction Androgen deprivation therapy (ADT) plus Androgen Receptor Target Agents (ARTAs) or docetaxel are the actual standard of care in prostate cancer (PC). Several therapeutic options are available for pretreated patients: cabazitaxel, olaparib, and rucaparib for BRCA mutations, Radium-223 for selected patients with symptomatic bone metastasis, sipuleucel T, and 177 LuPSMA-617. Areas covered This review the new potential therapeutic approaches and the most impacting recent published trials to provide an overview on the future management of PC. Expert opinion Currently, there is a growing interest in the potential role of triplet therapies encompassing ADT, chemotherapy, and ARTAs. These strategies, explored in different settings, appeared to be particularly promising in metastatic hormone-sensitive PC. Recent trials investigating ARTAs plus poly(adenosine diphosphate–ribose) polymerase (PARPi) inhibitor provided helpful insights for patients with metastatic castration resistant disease, regardless of homologous recombination genes status. Otherwise, the publication of the complete data is awaited, and more evidence is required. In advanced settings, several combination approaches are under investigation, to date with contradictory results, such as immunotherapy plus PARPi or chemotherapy. The radionuclide 177Lu-PSMA-617 proved successful outcomes in pretreated mCRPC patients. Additional studies will better clarify the appropriate candidates to each strategy and the correct treatments’ sequence.
Projection of diffusions on submanifolds: Application to mean force computation

We consider the problem of sampling a Boltzmann‐Gibbs probability distribution when this distribution is restricted (in some suitable sense) on a submanifold Σ of ℝn implicitly defined by N constraints q1(x) = ⃛ = qN(x) = 0 (N < n). This problem arises, for example, in systems subject to hard constraints or in the context of free energy calculations. We prove that the constrained stochastic differential equations (i.e., diffusions) proposed in [7, 13] are ergodic with respect to this restricted distribution. We also construct numerical schemes for the integration of the constrained diffusions. Finally, we show how these schemes can be used to compute the gradient of the free energy associated with the constraints. © 2007 Wiley Periodicals, Inc.
Structural properties of isolated early-type galaxies. The dependence of scaling relations on environment

Aims. In order to investigate whether gravitational interactions between galaxies are able to modify their structural properties, we determine the Kormendy relation (KR) for a sample of isolated early-type galaxies (ETG) for which we have measured several photometric parameters. This relation is compared with that obtained for a sample of ETG of the Coma Cluster, and with that obtained for a sample of perturbed S0 galaxies contained within high-density environments. Methods. Using very strict physical isolation criteria we selected a sample of 82 E and S0 galaxies from the CfA catalogue, in the redshift range 5000 km s −1 ≤ cz < 10 000 km s −1 . We obtained the photometric parameters, (re, � SB e� ) and total magnitude for 21 galaxies in the B filter and for 23 in the Gunn r filter. Results. The main result we obtained is that the KR is the same for isolated galaxies and for galaxies in high-density environments or in interaction. In addition we found evidence that the intrinsic dispersion of the KR depends on the magnitude range within which the galaxies are contained (larger dispersion for larger magnitude range), and not on the degree of gravitational interaction to which these galaxies are subjected.
Osteoarticular Involvement in Childhood Brucellosis: Evaluation of Clinical, Laboratory and Radiologic Features of 185 Cases

Backgrounds: Brucellosis is a systemic zoonotic disease. Osteoarticular (OA) system involvement is a common complication and the predominant manifestation of brucellosis in children. We aimed to evaluate the epidemiologic, demographic, clinical characteristics, and laboratory and radiologic findings of children with brucellosis and how these related to OA involvement. Methods: This retrospective cohort study consisted of all consecutive children and adolescents diagnosed as having brucellosis who were admitted to the pediatric infectious disease department of University of Health Sciences Van Research and Training Hospital between August 1, 2017, and December 31, 2018, in Turkey. Results: A total of 185 patients diagnosed as having brucellosis were evaluated, 50.8% had OA involvement (n = 94). Seventy-two patients (76.6%) exhibited peripheral arthritis involvement, among of them, hip arthritis (63.9%; n = 46) was the most common manifestation, followed by arthritis of knee (30.6%; n = 22), shoulder (4.2%; n = 3) and elbow (4.2%; n = 3). A total of 31 patients (33.0%) had sacroiliac joint involvement. Seven patients (7.4%) had spinal brucellosis. Erythrocyte sedimentation rate level above 20 mm/h at admission and age were independent predictor of OA involvement (respectively odds ratio [OR] = 2.82; 95% confidential interval [CI] = 1.41–5.64, ORperyear = 1.10; 95% CI: 1.01–1.19). Increasing age was associated types of OA involvement. Conclusion: A half of brucellosis cases had OA involvement. These results can help physicians to make early identification and diagnosis of childhood OA brucellosis who present with arthritis and arthralgia to enable the disease to be treated in time.
Relativistic microburst storm characteristics: Combined satellite and ground‐based observations

[1] We report a comparison of Solar Anomalous Magnetospheric Particle Explorer detected relativistic electron microbursts and short-lived subionospheric VLF perturbations termed FAST events, observed at Sodankyla Geophysical Observatory, Finland, during 2005. We show that only strong geomagnetic disturbances can produce FAST events, which is consistent with the strong link between storms and relativistic microbursts. Further, the observed FAST event perturbation decay times were consistent with ionospheric recovery from bursts of relativistic electron precipitation. However, the one-to-one correlation in time between microbursts and FAST events was found to be very low (∼1%). We interpret this as confirmation that microbursts have small ionospheric footprints and estimate the individual precipitation events to be <4 km radius. In contrast, our study strongly suggests that the region over which microbursts occur during storm event periods can be at least ∼90° in longitude (∼6 h in magnetic local time). This confirms earlier estimates of microburst storm size, suggesting that microbursts could be a significant loss mechanism for radiation belt relativistic electrons during geomagnetic storms. Although microbursts are observed at a much higher rate than FAST events, the ground-based FAST event data can provide additional insight into the conditions required for microburst generation and the time variation of relativistic precipitation.
Near and Far Transfer Effects of Computerized Progressive Attention Training (CPAT) Versus Mindfulness Based Stress Reduction (MBSR) Practice Among Adults With ADHD

Objective: The present study evaluated the near (attention) and far (reading, ADHD symptoms, learning, and quality of life) transfer effects of a Computerized Progressive Attention Training (CPAT) versus Mindfulness Based Stress Reduction (MBSR) practice among adults with ADHD compared to a passive group. Method: Fifty-four adults participated in a non-fully randomized controlled trial. Participants in the intervention groups completed eight 2-hr weekly training sessions. Outcomes were assessed before, immediately after, and 4 months post-intervention, using objective tools: attention tests, eye-tracker, and subjective questionnaires. Results: Both interventions showed near-transfer to various attention functions. The CPAT produced far-transfer effects to reading, ADHD symptoms, and learning while the MBSR improved the self-perceived quality of life. At follow-up, all improvements except for ADHD symptoms were preserved in the CPAT group. The MBSR group showed mixed preservations. Conclusion: Both interventions have beneficial effects, however only the CPAT group exhibited improvements compared to the passive group.
Pathoclinical associations between panic disorders and the brain-derived neurotrophic factor Val66Met polymorphism: an updated meta-analysis

Prior studies have indicated the pathological role of brain-derived neurotrophic factor (BDNF) gene polymorphism in panic disorders (PD). A functionally less active BDNF Val66Met mutant was previously detected in PD patients with different ethnic backgrounds. However, the results remain inconclusive or inconsistent. A meta-analysis was used to explore the consistency of the BDNF Val66Met mutant’s association with PD irrespective of the subject’s ethnicity. Relevant case-controlled full-length clinical and preclinical reports were retrieved by database searching, and 11 articles involving 2203 cases and 2554 controls were systematically selected per the standard inclusion criteria. Eleven articles were finally included that explored the relationship between the Val66Met polymorphism and PD risk susceptibility. Statistical analysis revealed a significant genetic association of the mutation, allele frequencies, and genotype distributions of BDNF with PD onset. Our findings demonstrated that the BDNF Val66Met is a susceptibility factor of PD.
Dementia among older people with schizophrenia: an update on recent studies

Purpose of review This narrative review examines recently published research that examines the prevalence, underlying causes, and treatments for dementia among people with schizophrenia. Recent findings People with schizophrenia have high rates of dementia, compared with the general population, and cognitive decline has been observed 14 years prior to onset of psychosis with accelerated decline in middle age. Underlying mechanisms of cognitive decline in schizophrenia include low cognitive reserve, accelerated cognitive aging, cerebrovascular disease and medication exposure. Although pharmacologic, psychosocial and lifestyle interventions show early promise for preventing and mitigating cognitive decline, few studies have been conducted in older people with schizophrenia. Summary Recent evidence supports accelerated cognitive decline and brain changes in middle-aged and older people with schizophrenia, relative to the general population. More research in older people with schizophrenia is needed to tailor existing cognitive interventions and develop novel approaches for this vulnerable and high-risk group.
Stimulated Raman forward scattering and the relativistic modulational instability of light waves in rarefied plasma

The modulational instability of copropagating light waves was studied recently by McKinstrie and Bingham [Phys. Fluids B 1, 230 (1989)], who applied their general theory to the study of the relativistic modulational instability (RMI) of light waves in the beat‐wave accelerator. However, in rarefied plasma, the RMI merges with stimulated Raman forward scattering. The longitudinal RMI is suppressed over most of its expected range and the study of secondary instabilities in the beat‐wave accelerator must be amended accordingly. A preliminary analysis indicates that stimulated Raman backward scattering is likely to be important in current beat‐wave experiments, while near‐resonant stimulated Raman forward scattering and near‐forward stimulated Raman scattering could be important in proposed beat‐wave experiments.
Anesthetic management of patients with peripartum cardiomyopathy

Purpose of review Cardiovascular disease is increasingly emerging as a cause of peripartum morbidity and mortality. Peripartum cardiomyopathy (PPCM) is defined as pregnancy-related heart failure with a reduced left ventricular ejection fraction <45%. PPCM develops in the peripartum phase and is not an aggravation of an existing prepregnancy cardiomyopathy. Anesthesiologists typically encounter these patients in the peripartum phase in a variety of settings and should be aware of this pathology and its implications for the perioperative management of parturients. Recent findings PPCM has been investigated increasingly over the last few years. Significant progress has been made in the assessment of global epidemiology, pathophysiological mechanisms, genetics and treatment. Summary Although PPCM is an overall rare pathology, patients can potentially be encountered by any anesthesiologist in many different settings. Therefore, it is important to be aware of this disease and understand the basic implications for anesthetic management. Severe cases often require early referral to specialized centers for advanced hemodynamic monitoring and pharmacological or mechanical circulatory support.
Benefit From a Humanitarian Pediatric Congenital Heart Surgery Program Over a 10-Year Period

Background: The charity organization Kinderherzen retten e.V. (KHR) enables humanitarian congenital heart surgery for pediatric patients from low- and middle-income countries at the University Heart Center Freiburg, Germany. The aim of this study was to assess periprocedural and mid-term outcomes of these patients for evaluation of KHR sustainability. Methods: Part one of the study comprised retrospective medical chart analyses of the periprocedural course of all KHR-treated children from 2008 to 2017, and part two a prospective evaluation of their mid-term outcome, assessed by questionnaires concerning survival, medical history, mental and physical development, and socioeconomic situation. Results: Of the 100 consecutively presented children from 20 countries (median age 3.25 years), 3 patients were not invasively treatable, 89 underwent cardiovascular surgery, and 8 received a catheter intervention only. There were no periprocedural deaths. Median postoperative duration of mechanical ventilation, intensive care stay, and total hospital stay was 7 (interquartile range [IQR] 4-21) hours, 2 (IQR 1-3) days, and 12 (IQR 10-16) days, respectively. Mid-term postoperative follow-up demonstrated a 5-year survival probability of 94.4%. The majority of patients received continued medical care in their home country (86.2% of patients), were in good mental and physical condition (96.5% and 94.7% of patients, respectively), and able to engage in age-appropriate education/employment (98.3% of patients). Conclusions: Cardiac, neurodevelopmental, and socioeconomic outcomes of patients treated via KHR was satisfactory. Thorough pre-visit evaluation and close contact with local physicians are crucial when providing this high-quality, sustainable, and viable therapeutic option for these patients.
Characterizing the exposure–response relationship of idecabtagene vicleucel in patients with relapsed/refractory multiple myeloma

Idecabtagene vicleucel (ide‐cel; bb2121) is a B‐cell maturation antigen–directed chimeric antigen receptor (CAR) T cell therapy approved for treatment of patients with heavily pretreated relapsed and refractory multiple myeloma. This analysis evaluated exposure–response (ER) relationships of ide‐cel with key efficacy end points and safety events. Ide‐cel exposure data were available from 127 patients treated at target doses of 150, 300, or 450 × 106 CAR+ T cells from the phase II KarMMa study (NCT03361748). Key exposure metrics, including area under the curve of the transgene level from 0 to 28 days and maximum transgene level, were calculated using noncompartmental methods. Logistic regression models, using both linear and maximum response function of exposure on the logit scale, were evaluated to quantify observed ER trends, and modified by including statistically significant individual covariates in a stepwise regression analysis. There was wide overlap of exposures across the target doses. ER relationships were observed for the overall and complete response rates, with higher response rates associated with higher exposures. Model‐based evaluations identified female sex and baseline serum monoclonal protein less than or equal to 10 g/L as predictive of a higher objective response rate and a higher complete response rate, respectively. ER relationships were observed for safety events of cytokine release syndrome requiring tocilizumab or corticosteroids. The established ER models were used to quantify the ide‐cel dose–response, which showed a positive benefit–risk assessment for the range of ide‐cel exposures associated with the target dose range of 150–450 × 106 CAR+ T cells.
Viral dew: Phase separation and the formation of viral replication compartments

Cellular life is based on compartmentalization to sequester biochemical reactions. Two kinds of cellular compartments exist: membrane-enclosed and membrane-less compartments. The cytoplasm of eukaryotic cells harbors many membrane-enclosed compartments, such as the endoplasmic reticulum, lysosomes, and peroxisomes. At the same time, the cytoplasm and especially the nucleus are compartmentalized by membrane-less structures, such as nucleoli, promyelocytic leukemia nuclear bodies (PML-NBs), nuclear speckles, and others. Not surprisingly, viruses hijack both compartment types to facilitate their replication. While the genesis of membrane-enclosed compartments has been studied for decades, research only recently focused on the biophysical properties of membrane-less compartments. Here, we outline the basic principles of their formation and how viruses generate such compartments for replication and morphogenesis. As excellent in-depth reviews have recently been published [1–3], this article is meant to serve as a brief introduction to the field.
The HOPX and BLBP landscape and gliogenic regions in developing human brain

Outer radial glial cells (oRGs) give rise to neurons and glial cells and contribute to cell migration and expansion in developing neocortex. HOPX has been described as a marker of oRGs and possible actor in glioblastomas. Recent years' evidence points to spatiotemporal differences in brain development which may have implications for the classification of cell types in the central nervous system and understanding of a range of neurological diseases. Using the Human Embryonic/Fetal Biobank, Institute of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark, HOPX and BLBP immunoexpression was investigated in developing frontal, parietal, temporal and occipital human neocortex, other cortical areas and brain stem regions to interrogate oRG and HOPX regional heterogeneity. Furthermore, usage of high‐plex spatial profiling (Nanostring GeoMx® DSP) was tested on the same material. HOPX marked oRGs in several human developing brain regions as well as cells in known gliogenic areas but did not completely overlap with BLBP or GFAP. Interestingly, limbic structures (e.g. olfactory bulb, indusium griseum, entorhinal cortex, fimbria) showed more intense HOPX immunoreactivity than adjacent neocortex and in cerebellum and brain stem, HOPX and BLBP seemed to stain different cell populations in cerebellar cortex and corpus pontobulbare. DSP screening of corresponding regions indicated differences in cell type composition, vessel density and presence of apolipoproteins within and across regions and thereby confirming the importance of acknowledging time and place in developmental neuroscience.
Data analysis considerations in probing single quantum dot fluorescence intermittency

The fluorescence intermittency of single, bare, CdSe/ZnS quantum dots was probed using single molecule confocal microscopy and found to demonstrate power law kinetics. Various threshold values and line fitting parameters are employed in the data analysis and their effects on the extracted power law exponents, moff and mon, are presented. The threshold is found to be critical in determining moff while having no significant effect on mon. The mean plus 2σ threshold, calculated from the background noise in the measurement, results in a more negative moff slope in comparison to the mean plus 3σ or mean plus 4σ thresholds. This is likely due to the mean plus 2σ threshold lying within the background noise outliers which mimic short on events. In contrast, the mean plus 4σ threshold is above 99.99% of the background noise while adequately below the fluorescence signal. Additionally, it is found that fitting only the ten most probable data points rather than all the data points in the log-log probability density graphs results in no significant change in moff and mon.
The Role of the Likelihood Function in the Estimation of Chaos Models

The estimation problem for chaos models defined by deterministic differential equations is discussed, and the important role of the maximum likelihood method in the inferential study of chaos models is highlighted. The usefulness of the likelihood function in the inferential study of chaos is confirmed with numerical examples from the Lorenz chaos model and the Rikitake two disk dynamo chaos model.
Lesbian, gay, bisexual, transgender and or queer patient experiences in Canadian primary care and emergency departments: a literature review

Abstract This literature review synthesises existing evidence and offers a thematic analysis of primary care and emergency department experiences of lesbian, gay, bisexual, transgender, queer and/or any other sexual or gender minority (LGBTQ+) individuals in Canada. Articles detailing first-person primary or emergency care experiences of LGBTQ + patients were included from EMBASE, MEDLINE, PsycINFO and CINHAL. Studies published before 2011, focused on the COVID-19 pandemic, unavailable in English, non-Canadian, specific to other healthcare settings, and/or only discussing healthcare provider experiences were excluded. Critical appraisal was performed following title/abstract screening and full-text review by three reviewers. Of sixteen articles, half were classified as general LGBTQ + experiences and half as trans-specific experiences. Three overarching themes were identified: discomfort/disclosure concerns, lack of positive space signalling, and lack of healthcare provider knowledge. Heteronormative assumptions were a key theme among general LGBTQ + experiences. Trans-specific themes included barriers to accessing care, the need for self-advocacy, care avoidance, and disrespectful communication. Only one study reported positive interactions. LGBTQ + patients continue to have negative experiences within Canadian primary and emergency care – at the provider level and due to system constraints. Increasing culturally competent care, healthcare provider knowledge, positive space signals, and decreasing barriers to care can improve LGBTQ + experiences.