Amyotrophic lateral sclerosis caused by FUS mutations: advances with broad implications.

Autosomal dominant mutations in the gene encoding the DNA and RNA binding protein FUS are a cause of amyotrophic lateral sclerosis (ALS), and about 0·3-0·9% of patients with ALS are FUS mutation carriers. FUS-mutation-associated ALS (FUS-ALS) is characterised by early onset and rapid progression, compared with other forms of ALS. However, different pathogenic mutations in FUS can result in markedly different age at symptom onset and rate of disease progression.

App-Based Coaching to Prevent Addictive Behaviors in Vocational School Students: A Cluster Randomized Trial.

Purpose: This two-arm cluster randomized controlled trial evaluated the effectiveness of an app-based addiction prevention program in German vocational school students.

Methods: Schools from 5 German federal states were recruited. No eligibility criteria for classes were applied; enrollment decisions were made by school heads or teachers.

Comparison of GFR estimation in patients with diabetes mellitus using the EKFC and CKD-EPI equations.

Background: The estimation of glomerular filtration rate (eGFR) is essential in the early detection of diabetic nephropathy. We herein compare the performance of common eGFR formulas against a gold standard measurement of GFR in patients with diabetes mellitus.

Methods: GFR was measured in 93 patients with diabetes mellitus using iohexol clearance as the reference standard.

Deep CRISPR mutagenesis characterizes the functional diversity of TP53 mutations.

The mutational landscape of TP53, a tumor suppressor mutated in about half of all cancers, includes over 2,000 known missense mutations. To fully leverage TP53 mutation status for personalized medicine, a thorough understanding of the functional diversity of these mutations is essential. We conducted a deep mutational scan using saturation genome editing with CRISPR-mediated homology-directed repair to engineer 9,225 TP53 variants in cancer cells.

The molecular bacterial load assay predicts treatment responses in patients with pre-XDR/XDR-tuberculosis more accurately than GeneXpert Ultra MTB/Rif.

Objectives: Early detection of treatment failure is essential to improve the management of drug-resistant tuberculosis (DR-TB). We evaluated the molecular bacterial load assay (MBLA) in comparison to standard diagnostic tests for monitoring therapy of patients affected by drug-resistant TB.

Methods: The performance of MBLA in tracking treatment response in a prospective cohort of patients with pulmonary MDR/RR- and pre-XDR/XDR-TB was compared with mycobacterial culture, mycobacterial DNA detection using GeneXpert (Xpert) and microscopy detection of sputum acid-fast-bacilli.

Vocal and Facial Behavior During Affect Production in Autism Spectrum Disorder.

Purpose: We investigate the extent to which automated audiovisual metrics extracted during an affect production task show statistically significant differences between a cohort of children diagnosed with autism spectrum disorder (ASD) and typically developing controls.

Method: Forty children with ASD and 21 neurotypical controls interacted with a multimodal conversational platform with a virtual agent, Tina, who guided them through tasks prompting facial and vocal communication of four emotions-happy, angry, sad, and afraid-under conditions of high and low verbal and social cognitive task demands.

Results: Individuals with ASD exhibited greater standard deviation of the fundamental frequency of the voice with the minima and maxima of the pitch contour occurring at an earlier time point as compared to controls.

Frequency and neuropathology of HTT repeat expansions in FTD/ALS: co-existence rather than causation.

Introduction: While ≥ 40 CAG repeat expansions in HTT present a well-established cause of Huntington's disease (HD), an enrichment of HTT repeat expansions was recently reported also in patients with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), including FTD/ALS patients with additional HD neuropathology. This raises the question whether the phenotypic spectrum of HTT expansions can be extended to ALS and FTD, and whether HTT should be considered as a new causative gene of FTD/ALS. If HTT repeat expansions were indeed systematically related to FTD/ALS, one would expect an increased frequency of HTT carriers in FTD/ALS, who can clinically/neuropathologically not be explained better than by the presence of the HTT repeat expansions.

Pushing a bistable [2]rotaxane out of equilibrium and isolation of the metastable-state co-conformation.

Incorporating a steric barrier between the two stations in a bistable [2]rotaxane based on monopyrrolotetrathiafulvalene and cyclobis(paraquat--phenylene) allows the high-energy metastable-state co-conformation to be physically isolated following a single redox cycle, thus making it possible to store energy (4.4 J L) and to follow its interconversion back to the ground-state co-conformation.

The seventh blind test of crystal structure prediction: structure generation methods.

A seventh blind test of crystal structure prediction was organized by the Cambridge Crystallographic Data Centre featuring seven target systems of varying complexity: a silicon and iodine-containing molecule, a copper coordination complex, a near-rigid molecule, a cocrystal, a polymorphic small agrochemical, a highly flexible polymorphic drug candidate, and a polymorphic morpholine salt. In this first of two parts focusing on structure generation methods, many crystal structure prediction (CSP) methods performed well for the small but flexible agrochemical compound, successfully reproducing the experimentally observed crystal structures, while few groups were successful for the systems of higher complexity. A powder X-ray diffraction (PXRD) assisted exercise demonstrated the use of CSP in successfully determining a crystal structure from a low-quality PXRD pattern.

Alternative techniques for cardiopulmonary resuscitation in extreme environments - A scoping review.

Background: Cardiopulmonary resuscitation (CPR) is essential for saving lives during cardiac arrest, but performing CPR in extreme environments poses unique challenges. In scenarios ranging from hypogravity or microgravity to confined spaces like aeroplanes and underwater scenarios, traditional CPR techniques may be inadequate. This scoping review aims to identify alternative chest compression techniques, synthesise current knowledge, and pinpoint research gaps in resuscitation for cardiac arrest in extreme conditions.

Continental-scale associations of Arabidopsis thaliana phyllosphere members with host genotype and drought.

Plants are colonized by distinct pathogenic and commensal microbiomes across different regions of the globe, but the factors driving their geographic variation are largely unknown. Here, using 16S ribosomal DNA and shotgun sequencing, we characterized the associations of the Arabidopsis thaliana leaf microbiome with host genetics and climate variables from 267 populations in the species' native range across Europe. Comparing the distribution of the 575 major bacterial amplicon variants (phylotypes), we discovered that microbiome composition in A.

Surgically treated acute knee dislocations with knee stiffness perform equally as well as non-stiff knees when treated with arthroscopic arthrolysis.

Purpose: Postoperative knee stiffness is a common issue in multiligament knee injuries (MLKIs). This study aims to compare outcomes between MLKI patients who underwent postoperative arthroscopic lysis of arthrofibrosis (LOA) for limited range of motion (ROM) and those who did not.

Methods: Thirty-one patients (10 IIIM, nine IIIL and 12 IV) were included in this retrospective clinical study with acute type III or IV knee dislocations, while two patients were lost to follow up.

Characteristics, outcomes and health care utilization of patients with acute myeloid leukemia aged 70 years or older: A single-center retrospective analysis.

The overall prognosis of older patients with acute myeloid leukemia (AML) is dismal. Only a small subgroup experiences long-term survival. The discrimination between patients who are candidates for potentially curative approaches and those who are not is crucial since - in addition to differences in terms of AML-directed treatment - different policies concerning intensive care unit (ICU) admission and involvement of specialized palliative care (SPC) seem obvious.

Multimodal speech biomarkers for remote monitoring of ALS disease progression.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that severely impacts affected persons' speech and motor functions, yet early detection and tracking of disease progression remain challenging. The current gold standard for monitoring ALS progression, the ALS functional rating scale - revised (ALSFRS-R), is based on subjective ratings of symptom severity, and may not capture subtle but clinically meaningful changes due to a lack of granularity. Multimodal speech measures which can be automatically collected from patients in a remote fashion allow us to bridge this gap because they are continuous-valued and therefore, potentially more granular at capturing disease progression.

Development of Delivery Systems with Prebiotic and Neuroprotective Potential of Industrial-Grade L.

This study delves into the transformative effects of supercritical carbon dioxide (scCO) cannabis extracts and prebiotic substances (dextran, inulin, trehalose) on gut bacteria, coupled with a focus on neuroprotection. Extracts derived from the Białobrzeska variety of Cannabis sativa, utilising supercritical fluid extraction (SFE), resulted in notable cannabinoid concentrations (cannabidiol (CBD): 6.675 ± 0.

The effect of longer epidural duration after open pancreaticoduodenectomy on pain and mobilisation: A retrospective single-centre analysis.

Background: The optimal length of epidural use following open pancreaticoduodenectomy has not been defined. The aim of this study was to investigate whether the length of patient-controlled epidural analgesia affected pain and ability to mobilise on epidural termination following open pancreaticoduodenectomy in the context of enhanced recovery after surgery.

Methods: A retrospective single-centre cohort analysis was performed between November 2015 and December 2021 on patients who underwent open pancreaticoduodenectomy.

Quality of life from childhood to adulthood: Perspectives from adult patients with pediatric-onset intestinal failure.

Adult patients with pediatric onset short bowel syndrome (SBS) or intestinal failure (IF) have been described as a distinct population warranting further research. The aim of this exploratory study aimed was to offer initial insights into this population's navigation of childhood, adolescence, and transition into adulthood. Both quantitative and qualitative data were collected from a convenience sample of adults with pediatric-onset SBS/IF using a disease-specific pilot survey; 14 questionnaires were completed.

Insight from Electrochemical Analysis in the Radical Cation State of a Monopyrrolotetrathiafulvalene-Based [2]Rotaxane.

Mechanically interlocked molecules are a class of compounds used for controlling directional movement when barriers can be raised and lowered using external stimuli. Applied voltages can turn on redox states to alter electrostatic barriers but their use for directing motion requires knowledge of their impact on the kinetics. Herein, we make the first measurements on the movement of cyclobis(paraquat-p-phenylene) (CBPQT) across the radical-cation state of monopyrrolotetrathiafulvalene (MPTTF) in a [2]rotaxane using variable scan-rate electrochemistry.

Combining Multiple Multimodal Speech Features into an Interpretable Index Score for Capturing Disease Progression in Amyotrophic Lateral Sclerosis.

Multiple speech biomarkers have been shown to carry useful information regarding Amyotrophic Lateral Sclerosis (ALS) pathology. We propose a two-step framework to compute optimal linear combinations (indexes) of these biomarkers that are more discriminative and noise-robust than the individual markers, which is important for clinical care and pharmaceutical trial applications. First, we use a hierarchical clustering based method to select representative speech metrics from a dataset comprising 143 people with ALS and 135 age- and sex-matched healthy controls.