Evaluation of machine-learning methods for ligand-based virtual screening

Machine-learning methods can be used for virtual screening by analysing the structural characteristics of molecules of known (in)activity, and we here discuss the use of kernel discrimination and naive Bayesian classifier (NBC) methods for this purpose. We report a kernel method that allows the processing of molecules represented by binary, integer and real-valued descriptors, and show that it is little different in screening performance from a previously described kernel that had been developed specifically for the analysis of binary fingerprint representations of molecular structure. We then evaluate the performance of an NBC when the training-set contains only a very few active molecules. In such cases, a simpler approach based on group fusion would appear to provide superior screening performance, especially when structurally heterogeneous datasets are to be processed

Direct Probing of Gap States and Their Passivation in Halide Perovskites by High-Sensitivity, Variable Energy Ultraviolet Photoelectron Spectroscopy

Direct detection of intrinsic defects in halide perovskites (HaPs) by standard methods utilizing optical excitation is quite challenging, due to the low density of defects in most samples of this family of materials (≤10^{15} cm^{–3} in polycrystalline thin films and ≤10^{11} cm^{–3} in single crystals, except melt-grown ones). While several electrical methods can detect defect densities 2 eV) HaPs. By measuring HaP layers on both hole- and electron-contact layers, as well as single crystals without contacts, we conclude that the observed deep defects are intrinsic to the Br-based HaP, and we propose a passivation route via the incorporation of a 2D-forming ligand into the precursor solution

Sex differences in nucleus accumbens transcriptome profiles associated with susceptibility versus resilience to subchronic variable stress

Depression and anxiety disorders are more prevalent in females, but the majority of research in animal models, the first step in finding new treatments, has focused predominantly on males. Here we report that exposure to subchronic variable stress (SCVS) induces depression-associated behaviors in female mice, whereas males are resilient as they do not develop these behavioral abnormalities. In concert with these different behavioral responses, transcriptional analysis of nucleus accumbens (NAc), a major brain reward region, by use of RNA sequencing (RNA-seq) revealed markedly different patterns of stress regulation of gene expression between the sexes. Among the genes displaying sex differences was DNA methyltransferase 3a (Dnmt3a), which shows a greater induction in females after SCVS. Interestingly, Dnmt3a expression levels were increased in the NAc of depressed humans, an effect seen in both males and females. Local overexpression of Dnmt3a in NAc rendered male mice more susceptible to SCVS, whereas Dnmt3a knock-out in this region rendered females more resilient, directly implicating this gene in stress responses. Associated with this enhanced resilience of female mice upon NAc knock-out of Dnmt3a was a partial shift of the NAc female transcriptome toward the male pattern after SCVS. These data indicate that males and females undergo different patterns of transcriptional regulation in response to stress and that a DNA methyltransferase in NAc contributes to sex differences in stress vulnerability

The Swift Surge of Perovskite Photovoltaics

The breakthrough early 1990s dye sensitization of mesoscopic TiO2 films along with a regenerative iodide redox couple led to the explosive growth of dye-sensitized solar cell (DSC) research. The pioneering work of Grätzel and colleagues also made it possible to develop a solid-state DSSC with spiro-oMETAD as the hole conductor and thus replace the liquid electrolyte in the cell. Research efforts of Konenkamp and others further initiated the search for the “extremely thin absorber” (ETA) nanostructured solar cell, using TiO2 as the electron conductor, an inorganic absorber, and a hole conductor. Another major research thrust was by Weller, Kamat, Zaban, Nozik, Hodes, and others, who employed inorganic quantum dots (e.g., CdS and CdSe) as sensitizers. While discussing developments in sensitized solar cells, it is important to note the contributions of early visionaries like Gerischer, Sutin, and Bard, who were first to establish the concepts of sensitization using dye molecules and semiconductor nanostructures

Patients’ ability to treat anaphylaxis using adrenaline autoinjectors: a randomized controlled trial

BACKGROUND: Previous work has shown patients commonly misuse adrenaline autoinjectors (AAI). It is unclear whether this is due to inadequate training, or poor device design. We undertook a prospective randomized controlled trial to evaluate ability to administer adrenaline using different AAI devices. METHODS: We allocated mothers of food‐allergic children prescribed an AAI for the first time to Anapen or EpiPen using a computer‐generated randomization list, with optimal training according to manufacturer's instructions. After one year, participants were randomly allocated a new device (EpiPen, Anapen, new EpiPen, JEXT or Auvi‐Q), without device‐specific training. We assessed ability to deliver adrenaline using their AAI in a simulated anaphylaxis scenario six weeks and one year after initial training, and following device switch. Primary outcome was successful adrenaline administration at six weeks, assessed by an independent expert. Secondary outcomes were success at one year, success after switching device, and adverse events. RESULTS: We randomized 158 participants. At six weeks, 30 of 71 (42%) participants allocated to Anapen and 31 of 73 (43%) participants allocated to EpiPen were successful – RR 1.00 (95% CI 0.68–1.46). Success rates at one year were also similar, but digital injection was more common at one year with EpiPen (8/59, 14%) than Anapen (0/51, 0%, P = 0.007). When switched to a new device without specific training, success rates were higher with Auvi‐Q (26/28, 93%) than other devices (39/80, 49%; P < 0.001). CONCLUSIONS: AAI device design is a major determinant of successful adrenaline administration. Success rates were low with several devices, but were high using the audio‐prompt device Auvi‐Q

The good, the bad and the ugly

This paper discusses the neo-logicist approach to the foundations of mathematics by highlighting an issue that arises from looking at the Bad Company objection from an epistemological perspective. For the most part, our issue is independent of the details of any resolution of the Bad Company objection and, as we will show, it concerns other foundational approaches in the philosophy of mathematics. In the first two sections, we give a brief overview of the "Scottish" neo-logicist school, present a generic form of the Bad Company objection and introduce an epistemic issue connected to this general problem that will be the focus of the rest of the paper. In the third section, we present an alternative approach within philosophy of mathematics, a view that emerges from Hilbert's Grundlagen der Geometrie (1899, Leipzig: Teubner; Foundations of geometry (trans.: Townsend, E.). La Salle, Illinois: Open Court, 1959.). We will argue that Bad Company-style worries, and our concomitant epistemic issue, also affects this conception and other foundationalist approaches. In the following sections, we then offer various ways to address our epistemic concern, arguing, in the end, that none resolves the issue. The final section offers our own resolution which, however, runs against the foundationalist spirit of the Scottish neo-logicist program

Experiences of patients and health care professionals on the quality of telephone follow-up care during the COVID-19 pandemic:a large qualitative study in a multidisciplinary academic setting

OBJECTIVE: To evaluate the perceived quality of follow-up telephone consultations (TCs) from the perspective of patients and healthcare professionals (HCPs) of multiple medical disciplines during the COVID-19 pandemic. DESIGN: A qualitative study using semi-structured interviews and reflexive thematic analysis. SETTING: Seven medical disciplines (general dermatology, dermato-oncology, head and neck oncology, internal medicine, medical oncology, gynaecological oncology and surgical oncology) at a large university hospital in the Netherlands. PARTICIPANTS: Patients who received and HCPs who provided TCs as a substitute for outpatient follow-up appointments during the COVID-19 pandemic. RESULTS: Eighty-two patients and 58 HCPs were interviewed. Predominantly, patients and HCPs were satisfied with the quality of care by TCs. They regarded TCs as efficient, accessible and of acceptable quality, provided there was an established patient-HCP relationship, medical complaints were absent and physical examination was not indicated. However, most patients were worried about the accuracy of their health assessment in the absence of physical examination and non-verbal communication. Both patients and HCPs wish to use TCs in the future alternatively with face-to-face consultations. CONCLUSION: This study concludes that TCs seem a valuable contribution to the context of follow-up care and could partially replace face-to-face consultations. TCs can be performed in stable, chronic patients with whom a doctor-patient relationship has already been established. Face-to-face consultations are considered more appropriate in the case of new patients, challenging or emotionally charged consultations and when clinically relevant physical examination is indicated. Due to the context-dependent nature of experiences of patients and HCPs, TCs should be used with an individually customised approach based on patient and disease specifics, in which shared decision-making plays an extensive role. Before major implementation is considered, sufficient data on the safety regarding missed diagnoses or cancer recurrences should be assembled first