Integrative determination of atomic structure of mutant huntingtin exon 1 fibrils implicated in Huntington disease.

Neurodegeneration in Huntington's disease (HD) is accompanied by the aggregation of fragments of the mutant huntingtin protein, a biomarker of disease progression. A particular pathogenic role has been attributed to the aggregation-prone huntingtin exon 1 (HTTex1), generated by aberrant splicing or proteolysis, and containing the expanded polyglutamine (polyQ) segment. Unlike amyloid fibrils from Parkinson's and Alzheimer's diseases, the atomic-level structure of HTTex1 fibrils has remained unknown, limiting diagnostic and treatment efforts.

Cesarean section: One procedure, varied techniques. Detailed observations of 1013 first cesarean sections in a tertiary hospital in Ghana.

Objective: Cesarean sections (CS) are among the most performed surgical procedures in the world. Small variations in surgical techniques could have a significant impact on a global scale, for example, in postoperative complications. In the present study we aimed to observe and audit every single step used during first time CS.

Environmental Conditions Modulate Warming Effects on Plant Litter Decomposition Globally.

Empirical studies worldwide show that warming has variable effects on plant litter decomposition, leaving the overall impact of climate change on decomposition uncertain. We conducted a meta-analysis of 109 experimental warming studies across seven continents, using natural and standardised plant material, to assess the overarching effect of warming on litter decomposition and identify potential moderating factors. We determined that at least 5.

A Socioecological Approach to Support the Transition to Adult Care for Youth With Medical Complexity: Family Perspectives and Recommendations.

Introduction: The transition from paediatric to adult health care (i.e., 'health care transition') poses many challenges for youth with medical complexity (YMC) and their families.

Trends in initial pharmacological COPD treatment in primary care (2010-2021): a population-based study using the PHARMO Data Network.

Background: Pharmacological treatment is a cornerstone of chronic obstructive pulmonary disease (COPD) management, with general practitioners providing the most care. However, the lack of data on prescribing trends in initial pharmacotherapy in primary care hinders the understanding of how scientific and technical developments impact patient care and may also perpetuate suboptimal practices. Hence, this study aims to analyze trends in the initial pharmacological treatment of newly diagnosed COPD patients in Dutch primary care from 2010 to 2021.

Psychosocial and cognitive determinants of 10-year depressive symptom trajectories in patients with cardiovascular disease: The SMART-Medea Study.

Background: Middle-aged and older adults presenting clinically relevant depressive symptoms are often undiagnosed. Understanding the determinants of late-life depressive symptoms could improve prognosis. Further, individuals with manifest cardiovascular disease (CVD) are at an increased risk of depression.

Breaking Bad News to Learners: How Well Does the SPIKES Clinical Model Translate?

When health professions learners do not meet standards on assessments, educators need to share this information with the learners and determine next steps to improve their performance. Those conversations can be difficult, and educators may lack confidence or skill in holding them. For clinician-educators with experience sharing challenging news with patients, using an analogy from clinical settings may help with these conversations in the education context.

The case for neurons: a no-go theorem for consciousness on a chip.

We apply the methodology of no-go theorems as developed in physics to the question of artificial consciousness. The result is a no-go theorem which shows that under a general assumption, called dynamical relevance, Artificial Intelligence (AI) systems that run on contemporary computer chips cannot be conscious. Consciousness is dynamically relevant, simply put, if, according to a theory of consciousness, it is relevant for the temporal evolution of a system's states.

Talking Cancer-Cancer Talking: A Linguistic and Thematic Analysis of Patient Narratives.

To explore "the lived experience" of patients with cancer through narratives, in-depth interviews with 20 patients were conducted in the patients' homes-"at the kitchen table." Interviews were audio-recorded, transcribed, and analyzed following the Linguistic Inquiry and Word Count (LIWC) methodology. Thematic Analysis was used to explore themes in the narratives.

Changes in nutritional status and effectiveness of the dietary intervention of multimodal prehabilitation for patients with colorectal cancer: A secondary analysis of the PREHAB randomized clinical trial.

Background & Aims: Prehabilitation is a preoperative multimodal program including exercise, nutritional, and psychological support. Little is known about changes in nutritional status during prehabilitation.

Methods: This secondary analysis of the PREHAB trial aims to assess changes in nutritional status and explore the effectiveness of a four-week nutritional intervention.

The efficacy of longer-term lebrikizumab treatment in patients with moderate-to-severe atopic dermatitis who did not meet protocol-defined response criteria at week 16 in two randomized controlled clinical trials.

Background: Lebrikizumab demonstrated statistically significant improvements in patients with moderate-to-severe atopic dermatitis at week 16 with a durable response up to week 52.

Objective: To investigate the efficacy of lebrikizumab-treated patients at 52 weeks who did not achieve the ADvocate1 and ADvocate2 protocol-defined response criteria (≥75% improvement in the Eczema Area and Severity Index [EASI 75] or Investigator Global Assessment [IGA] 0/1 with ≥2-point improvement without rescue medication) after 16 weeks.

Methods: This analysis includes observed data for patients who received lebrikizumab every 2 weeks during the induction period, did not achieve the protocol-defined response, and subsequently received open-label lebrikizumab treatment.

Syndromic Retinitis Pigmentosa.

Retinitis pigmentosa (RP) is a progressive inherited retinal dystrophy, characterized by the degeneration of photoreceptors, presenting as a rod-cone dystrophy. Approximately 20-30% of patients with RP also exhibit extra-ocular manifestations in the context of a syndrome. This manuscript discusses the broad spectrum of syndromes associated with RP, pathogenic mechanisms, clinical manifestations, differential diagnoses, clinical management approaches, and future perspectives.

Age- and sex-related differences in social competence and emotion labeling in pre-adolescence.

Identification of facial expressions is important to navigate social interactions and associates with developmental outcomes. It is presumed that social competence, behavioral emotion labeling and neural emotional face processing are related, but this has rarely been studied. Here, we investigated these interrelations and their associations with age and sex, in the YOUth cohort (1055 children, 8-11 years old).

The Dual Dynamical Foundation of Orthodox Quantum Mechanics.

This paper combines mathematical, philosophical, and historical analyses in a comprehensive investigation of the dynamical foundations of the formalism of orthodox quantum mechanics. The results obtained include: (i) A deduction of the canonical commutation relations (CCR) from the tenets of Matrix Mechanics; (ii) A discussion of the meaning of Schrödinger's first derivation of the wave equation that not only improves on Joas and Lehner's 2009 investigation on the subject, but also demonstrates that the CCR follow of necessity from Schrödinger's first derivation of the wave equation, thus correcting the common misconception that the CCR were only posited by Schrödinger to pursue equivalence with Matrix Mechanics; (iii) A discussion of the mathematical facts and requirements involved in the equivalence of Matrix and Wave Mechanics that improves on F. A.

Rewriting the Quantum "Revolution".

This paper is a critical analysis of the structure of the quantum revolution. I consider the factual question of how, historically and theoretically, the classical gave way to the quantum, and I argue for an answer that shows, contra Thomas Kuhn's influential philosophy of science, that it is the logic, and not the sociology and psychology, of research that correctly explains the classical-to-the-quantum paradigm shift. My approach is based not on archival studies but on a careful reading, in their original historical context, of Max Planck's and Albert Einstein's well-known papers; the burden of my argument, which at points will be outspoken, consists, then, in identifying and removing the impediments that prevent us from reading these papers in themselves.

Assessing COVID-19 transmission through school and family networks using population-level registry data from the Netherlands.

Understanding the impact of different types of social interactions is key to improving epidemic models. Here, we use extensive registry data-including PCR test results and population-level networks-to investigate the impact of school, family, and other social contacts on SARS-CoV-2 transmission in the Netherlands (June 2020-October 2021). We isolate and compare different contexts of potential SARS-CoV-2 transmission by matching pairs of students based on their attendance at the same or different primary school (in 2020) and secondary school (in 2021) and their geographic proximity.

Evaluating MicroRNAs as diagnostic tools for lymph node metastasis in breast cancer: Findings from a systematic review and meta-analysis.

Lymph node metastasis (LNM) significantly affects the prognosis and clinical management of breast cancer (BC) patients. This systematic review and meta-analysis aim to identify microRNAs (miRNAs) associated with LNM in BC and evaluate their potential diagnostic and prognostic value. Following PRISMA guidelines, a comprehensive literature search was conducted in PubMed, Web of Science, and SCOPUS databases, to assess the role of miRNAs in LNM BC.

The influence of the dynamic context of the pandemic on the predictive performance of mortality predictions over time in older patients hospitalised for COVID-19.

Objective: During the COVID-19 pandemic, dynamic factors such as governmental policies, improved treatment and prevention options and viral mutations changed the incidence of outcomes and possibly changed the relation between predictors and outcomes. The aim of the present study was to assess whether the dynamic context of the pandemic influenced the predictive performance of mortality predictions over time in older patients hospitalised for COVID-19.

Study Design And Setting: The COVID-OLD study, a multicentre cohort study in the Netherlands, included COVID-19 patients aged 70 years and older hospitalised during the first (early 2020), second (late 2020), third (late 2021) or fourth wave (early 2022).

Nucleosomal asymmetry shapes histone mark binding and promotes poising at bivalent domains.

Promoters of developmental genes in embryonic stem cells (ESCs) are marked by histone H3 lysine 4 trimethylation (H3K4me3) and H3K27me3 in an asymmetric nucleosomal conformation, with each sister histone H3 carrying only one of the two marks. These bivalent domains are thought to poise genes for timely activation upon differentiation. Here, we show that asymmetric bivalent nucleosomes recruit repressive H3K27me3 binders but fail to enrich activating H3K4me3 binders, thereby promoting a poised state.

Reusing routine electronic health record data for nationwide COVID-19 surveillance in nursing homes: barriers, facilitators, and lessons learned.

Background: At the beginning of the COVID-19 pandemic in 2020, little was known about the spread of COVID-19 in Dutch nursing homes while older people were particularly at risk of severe symptoms. Therefore, attempts were made to develop a nationwide COVID-19 repository based on routinely recorded data in the electronic health records (EHRs) of nursing home residents. This study aims to describe the facilitators and barriers encountered during the development of the repository and the lessons learned regarding the reuse of EHR data for surveillance and research purposes.

Implementing HIV teams to improve HIV indicator condition-guided testing in general practitioner centers in the Netherlands.

Background: HIV indicator condition-guided testing is recommended by guidelines to identify undiagnosed HIV infections. However, general practitioners (GPs) frequently see patients for indicator conditions without testing them for HIV. The aim of this study was to evaluate whether implementing HIV teams, using trained GP ambassadors, promoted local HIV indicator condition-guided testing practices in urban GP centers in the Netherlands.

Seed tuber microbiome can predict growth potential of potato varieties.

Potato vigour, the growth potential of seed potatoes, is a key agronomic trait that varies significantly across production fields due to factors such as genetic background and environmental conditions. Seed tuber microbiomes are thought to influence plant health and crop performance, yet the precise relationships between microbiome composition and potato vigour remain unclear. Here we conducted microbiome sequencing on seed tuber eyes and heel ends from 6 potato varieties grown in 240 fields.