Molecular mechanisms reconstruction from single-cell multi-omics data with HuMMuS.

MOTIVATION: The molecular identity of a cell results from a complex interplay between heterogeneous molecular layers. Recent advances in single-cell sequencing technologies have opened the possibility to measure such molecular layers of regulation. RESULTS: Here, we present HuMMuS, a new method for inferring regulatory mechanisms from single-cell multi-omics data. Differently from the state-of-the-art, HuMMuS captures cooperation between biological macromolecules and can easily include additional layers of molecular regulation. We benchmarked HuMMuS with respect to the state-of-the-art on both paired and unpaired multi-omics datasets. Our results proved the improvements provided by HuMMuS in terms of transcription factor (TF) targets, TF binding motifs and regulatory regions prediction. Finally, once applied to snmC-seq, scATAC-seq and scRNA-seq data from mouse brain cortex, HuMMuS enabled to accurately cluster scRNA profiles and to identify potential driver TFs. AVAILABILITY AND IMPLEMENTATION: HuMMuS is available at https://github.com/cantinilab/HuMMuS.

Minimal Change Disease: Pathogenetic Insights from Glomerular Proteomics.

The mechanism underlying podocyte dysfunction in minimal change disease (MCD) remains unknown. This study aimed to shed light on the potential pathophysiology of MCD using glomerular proteomic analysis. Shotgun proteomics using label-free quantitative mass spectrometry was performed on formalin-fixed, paraffin-embedded (FFPE) renal biopsies from two groups of samples: control (CTR) and MCD. Glomeruli were excised from FFPE renal biopsies using laser capture microdissection (LCM), and a single-pot solid-phase-enhanced sample preparation (SP3) digestion method was used to improve yield and protein identifications. Principal component analysis (PCA) revealed a distinct separation between the CTR and MCD groups. Forty-eight proteins with different abundance between the two groups (p-value ≤ 0.05 and |FC| ≥ 1.5) were identified. These may represent differences in podocyte structure, as well as changes in endothelial or mesangial cells and extracellular matrix, and some were indeed found in several of these structures. However, most differentially expressed proteins were linked to the podocyte cytoskeleton and its dynamics. Some of these proteins are known to be involved in focal adhesion (NID1 and ITGA3) or slit diaphragm signaling (ANXA2, TJP1 and MYO1C), while others are structural components of the actin and microtubule cytoskeleton of podocytes (ACTR3 and NES). This study suggests the potential of mass spectrometry-based shotgun proteomic analysis with LCM glomeruli to yield valuable insights into the pathogenesis of podocytopathies like MCD. The most significantly dysregulated proteins in MCD could be attributable to cytoskeleton dysfunction or may be a compensatory response to cytoskeleton malfunction caused by various triggers.

Self-help support: The Alzheimer's telephone from the user's perspective.

Background: Telephone counseling is an important form of support for informal carers of persons with dementia. The quality and benefit of this kind of service have rarely been evaluated in Germany. Methods: We developed a survey to assess the quality of telephone counseling. We conducted an online survey among 201 users of the telephone hotline "Alzheimer-Telefon" (Alzheimer's telephone service) provided by the German Alzheimer's Association after the consultation. The aim of the study was to determine whether this form of telephone support meets certain quality criteria and the callers' needs. Results: Of the 201 participants, 80% were female. The mean age of the callers was 51 years. 74% of cases were one-off consultations; 26% of the callers sought advice twice or more often. The most common reasons for calling included behavioral changes (45%) and finding a nursing home (41%). Other family members were significantly (p=0.036) more likely to seek local respite options. Based on the 201 online questionnaires evaluated, most callers were highly satisfied with the counseling services provided by the Alzheimer's telephone service. Those seeking advice were particularly satisfied with the appreciative and empathetic communication style of the advisors and their professional competence. This also applies to the accessibility of the telephone. More than three quarters were fully satisfied with the information they received. Almost half of the callers were sure that the advice would help to solve their issue. 14% of people seeking advice were uncertain about how to implement the suggested solutions.A further survey would be worthwhile to determine to what extent the topics of the consultation can be implemented. The feedback from relatives who use the Alzheimer's telephone repeatedly could be used for this purpose - the repetition rate is currently 25% and the trend is rising. Results could be interesting for successful counseling and for the development of further support services. Conclusion: The telephone hotline is a useful component of dementia care in Germany and an important contribution to the National Dementia Strategy.

Patient Reported Outcome Measurement (PROM) under real-life conditions of non-curable cancer outpatients with the Integrated Palliative Outcome Scale (IPOS) and NCCN-Distress Thermometer - A mixed methods study.

Objective: Prospective cohort study to test the real-life feasibility of longitudinal patient-reported outcome measurement PROM (Integrated Palliative Outcome Scale IPOS, and NCCN Distress Thermometer DT) required for outpatients with non-curable lung or prostate cancer in comprehensive cancer centers. Methods: Assessment with paper-based IPOS and DT was observed for 15 months. We analyzed response to patients' distress (requests for supportive and palliative services) following PROM. Focus groups to comprehensively explore the user experience of patients, informal caregivers and health care professionals (HCP) supplemented the analysis. Results: Ninety-seven percent (125/129) of the patients received a questionnaire once, but quarterly assessment as recommended by certification committees was achieved only in 50% and 31% of prostate and lung cancer patients. Although both instruments were well accepted, only IPOS showed a high content validity, because some patients had difficulties in understanding the DT. Patients felt comfortable with completing the PROM, and HCP found PROM helped to structure the patient encounter. Due to organizational deficiencies in the handling of the instruments and operationalization of reactions to identified distress, the referrals to supportive and palliative services were rare. Conclusion: To facilitate consequences from PROM it should be a standardized intervention rather than assessment alone. Innovation: The patient perspective improves the implementation of PROM under real-life clinical conditions.

From greenwashing to screenwashing?

In this viewpoint, we introduce the term 'screenwashing', which describes the phenomenon whereby social media platforms, such as TikTok and Instagram, pretend to be more socially responsible than they actually are. That is, social media platforms pretend to be thoughtful about children's health and the prevention of problematic social media use, but this often turns out to be nothing more than "a lick of paint". We describe how features like the one-hour notification on TikTok and Instagram are considered screenwashing and why we believe so. Screenwashing, an unethical practice, has the potential to mislead parents and young users. Consequently, we advocate for increased government intervention to protect our youth from the potential hazards associated with problematic social media use.

Eficacia de la técnica de distracción contingente con material auditivo en el comportamiento de pacientes entre 4 y 6 años de edad / Efficacy of contingent distraction technique with auditive material on the behavior of patients between 4 and 6 yeras old

El objetivo de este estudio fue evaluar la eficacia de la técnica de distracción contingente con el uso de material auditivo. Se seleccionaron 18 pacientes entre 4 y 6 años de edad que requirieran tratamiento odontológico restaurador con el uso de anestesia local. A los pacientes se les realizó una cita control donde se utilizaron técnicas de manejo convencionales y luego una cita experimental donde se aplicaron técnicas convencionales en combinación con la técnica de distracción contingente. Las demás condiciones experimentales tales como el operador, la hora, el sitio de atención y el tipo de tratamiento fueron iguales en ambas citas. Todos los procedimientos fueron filmados y editados. Dos odontopediatras previamente calibrados observaron los videos editados y calificaron el comportamiento global y durante tres periodos de tratamiento (inicial, intermedio, final) utilizando la Escala de Frankl. Al comparar tanto el comportamiento global como el de cada uno de los periodos de tratamiento entre la cita control y experimental, los resultados revelaron diferencias estadísticamente significativas de acuerdo con la prueba de Rangos de Friedman, que indicaban que la técnica fue efectiva. En conclusión, los hallazgos de esta investigación sugieren que la técnica de distracción contingente es eficaz para mejorar el comportamiento de pacientes entre 4 y 6 años de edad que requieran tratamiento odontológico...