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

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

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

Low-Cost Flexible Nano-Sulfide/Carbon Composite Counter Electrode for Quantum-Dot-Sensitized Solar Cell

Cu2S nanocrystal particles were in situ deposited on graphite paper to prepare nano-sulfide/carbon composite counter electrode for CdS/CdSe quantum-dot-sensitized solar cell (QDSC). By optimization of deposition time, photovoltaic conversion efficiency up to 3.08% was obtained. In the meantime, this composite counter electrode was superior to the commonly used Pt, Au and carbon counter electrodes. Electrochemical impedance spectra further confirmed that low charge transfer resistance at counter electrode/electrolyte interface was responsible for this, implied the potential application of this composite counter electrode in high-efficiency QDSC