Apo structure of Mycobacterium tuberculosis 1-deoxy-d-xylulose 5-phosphate synthase DXPS: Dynamics and implications for inhibitor design.

The enzyme 1-deoxy-d-xylulose-5-phosphate synthase (DXPS) catalyses the first step of the MEP pathway, a key process for isoprenoid biosynthesis in bacteria that is absent in humans, making it a promising drug target. We present the structure of Mycobacterium tuberculosis DXPS in its apo form, obtained through a soaking method that removes thiamine diphosphate (ThDP) and metals from pre-formed crystals. The apo structure had three regions with absence of electron density near the active site that are unique to the apo form of the enzyme.

A reproducibility study on invasion in small pulmonary adenocarcinoma according to the WHO and a modified classification, supported by biomarkers.

Objectives: Evaluating invasion in non-mucinous adenocarcinoma (NMA) of the lung is crucial for accurate pT-staging. This study compares the World Health Organization (WHO) with a recently modified NMA classification.

Materials And Methods: A retrospective case-control study was conducted on small NMA pT1N0M0 cases with a 5-year follow-up.

Beyond Increasing Sample Sizes: Optimizing Effect Sizes in Neuroimaging Research on Individual Differences.

Linking neurobiology to relatively stable individual differences in cognition, emotion, motivation, and behavior can require large sample sizes to yield replicable results. Given the nature of between-person research, sample sizes at least in the hundreds are likely to be necessary in most neuroimaging studies of individual differences, regardless of whether they are investigating the whole brain or more focal hypotheses. However, the appropriate sample size depends on the expected effect size.

Safety, Efficacy and Pharmacokinetics of daily optimised doses of Rifampicin for the Treatment of Tuberculosis: A Systematic Review and Bayesian Network Meta-Analysis.

Background: Higher than standard doses of rifampicin could improve the treatment outcome of drug-susceptible tuberculosis without compromising the safety of patients.

Methods: We performed a systematic review of prospective clinical studies including adults with pulmonary and extrapulmonary TB receiving rifampicin doses above 10mg/kg/day. We extracted the data on overall adverse events (AE), hepatic AE, sputum culture conversion (SCC) at week 8, recurrence, mortality, and pharmacokinetics.

A systematic review of salivary gland hypofunction and/or xerostomia induced by non-surgical cancer therapies: prevention strategies.

Purpose: This systematic review aimed to assess the updated literature for the prevention of salivary gland hypofunction and xerostomia induced by non-surgical cancer therapies.

Methods: Electronic databases of MEDLINE/PubMed, EMBASE, and Cochrane Library were searched for randomized controlled trials (RCT) that investigated interventions to prevent salivary gland hypofunction and/or xerostomia. Literature search began from the 2010 systematic review publications from the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) up to February 2024.

Development and Validation of a Deep Learning Model Based on MRI and Clinical Characteristics to Predict Risk of Prostate Cancer Progression.

Purpose To validate a deep learning (DL) model for predicting the risk of prostate cancer (PCa) progression based on MRI and clinical parameters and compare it with established models. Materials and Methods This retrospective study included 1607 MRI scans of 1143 male patients (median age, 64 years; IQR, 59-68 years) undergoing MRI for suspicion of clinically significant PCa (csPCa) (International Society of Urological Pathology grade > 1) between January 2012 and May 2022 who were negative for csPCa at baseline MRI. A DL model was developed using baseline MRI and clinical parameters (age, prostate-specific antigen [PSA] level, PSA density, and prostate volume) to predict the time to PCa progression (defined as csPCa diagnosis at follow-up).

Measurement of Dehumanization, Self-Dehumanization, and Empathy as Mediating Factors Among Healthcare Professionals.

Background: Dehumanization refers to the tendency of individuals or groups to attribute fewer human characteristics to other individuals or groups (referred to as hetero-dehumanization) or to themselves (referred to as self-dehumanization). This phenomenon currently seems to predominate in the medical and nursing professions. Indeed, healthcare environments facilitate latent forms of dehumanization due to their structure, organization, and inherent professional demands.

Positive associations between mean ambient temperature and involuntary admissions to psychiatric facilities.

Background: Temperature increases in the context of climate change affect numerous mental health outcomes. One such relevant outcome is involuntary admissions as these often relate to severe (life)threatening psychiatric conditions. Due to a shortage of studies into this topic, relationships between mean ambient temperature and involuntary admissions have remained largely elusive.

Unhelpful Information About Low Back and Neck Pain on Physiotherapist's Websites.

Background: The internet is increasingly used as a primary source of information for patients with musculoskeletal pain. Private physiotherapy practices provide informative content on low back pain (LBP) and neck pain (NP) on their websites, but the extent to which this information is biopsychosocial, guidelines-consistent, and fear-inducing is unknown. The aim of this study was to analyse the information on websites of private physiotherapy practices in the Netherlands about LBP and NP regarding consistency with the guidelines and the biopsychosocial model and to explore the use of fear-inducing language.

A matched case-control study on polypharmacy and co-medications one year before drug treatment for Alzheimer's disease.

Background: Alzheimer's disease (AD) is the most prevalent form of dementia, characterized by amyloid-β plaques and neurofibrillary tangles. With an aging population, both AD and comorbidities are increasingly common. Managing comorbidities often requires multiple medications, leading to polypharmacy, defined as the concurrent use of five or more medications.

Evaluation of efficiency and effectiveness of different recruitment strategies for the FINGER-NL multidomain lifestyle intervention trial via the Dutch Brain Research Registry.

Introduction: Recruitment of participants for intervention studies is challenging. We evaluated the effectiveness and efficiency of a participant recruitment campaign through an online registry for the FINGER-NL study, a multi-domain lifestyle intervention trial targeting cognitively healthy individuals aged 60-79 with dementia prevention potential. Additionally, we explored which recruitment strategy successfully reached individuals from underrepresented groups in research.

The Auditory Environment at Early Intervention Groups for Young Children With Hearing Loss: Signal to Noise Ratio, Background Noise, and Reverberation.

Objectives: One important aspect in facilitating language access for children with hearing loss (HL) is the auditory environment. An optimal auditory environment is characterized by high signal to noise ratios (SNRs), low background noise levels, and low reverberation times. In this study, the authors describe the auditory environment of early intervention groups specifically equipped for young children with HL.

A machine learning model accurately identifies glycogen storage disease Ia patients based on plasma acylcarnitine profiles.

Background: Glycogen storage disease (GSD) Ia is an ultra-rare inherited disorder of carbohydrate metabolism. Patients often present in the first months of life with fasting hypoketotic hypoglycemia and hepatomegaly. The diagnosis of GSD Ia relies on a combination of different biomarkers, mostly routine clinical chemical markers and subsequent genetic confirmation.

Alkaline phosphatase decline and pain response as predictors of overall survival benefit in patients treated with radium-223: a post hoc analysis of the REASSURE study.

Background: Alkaline phosphatase (ALP) declines and pain responses can occur during radium-223 (Ra) treatment, but their association with treatment outcomes is unclear.

Methods: For patients with metastatic castration-resistant prostate cancer treated with Ra in the REASSURE study, we investigated whether ALP decline (Week 12) and/or pain response (during treatment) are associated with improved overall survival (OS). The Brief Pain Inventory-Short Form (BPI-SF) was used to assess pain at baseline and pain response (in patients with baseline BPI-SF score ≥2).

The Long-Term Uptake of Home Spirometry in Regular Cystic Fibrosis Care: Retrospective Multicenter Observational Study.

Background: Home spirometers have been widely implemented in the treatment of people with cystic fibrosis (CF). Frequent spirometry measurements at home could lead to earlier detection of exacerbations. However, previous research indicates that the long-term use of home spirometry is not well maintained by people with CF.

Neurobiological mechanisms of antidepressant properties of psilocybin: A systematic review of blood biomarkers.

Psilocybin represents a novel therapeutic approach for individuals with major depressive disorder (MDD) who do not respond to conventional antidepressant treatment. Investigating the influence of psilocybin on the pathophysiological processes involved in MDD could enhance our neurobiological understanding of the presumed antidepressant action mechanism. This systematic review aims to summarize the results of human studies investigating changes in blood-based biomarkers of MDD to guide future research on potentially relevant analytes that could be monitored in clinical trials.

Harnessing machine learning algorithms for the prediction and optimization of various properties of polylactic acid in biomedical use: a comprehensive review.

Machine learning (ML) has emerged as a transformative tool in various industries, driving advancements in key tasks like classification, regression, and clustering. In the field of chemical engineering, particularly in the creation of biomedical devices, personalization is essential for ensuring successful patient recovery and rehabilitation. Polylactic acid (PLA) is a material with promising potential for applications like tissue engineering, orthopedic implants, drug delivery systems, and cardiovascular stents due to its biocompatibility and biodegradability.

Status of Sepsis Care in European Hospitals: Results from an International Cross-Sectional Survey.

Rationale: Early detection, standardized therapy, adequate infrastructure and strategies for quality improvement should constitute essential components of every hospital's sepsis plan.

Objectives: To investigate the extent to which recommendations from the sepsis guidelines are implemented and the availability of infrastructure for the care of patients with sepsis in acute hospitals.

Methods: A multidisciplinary cross-sectional questionnaire was used to investigate sepsis care in hospitals.

Knee position affects medial gastrocnemius and soleus activation during dynamic plantarflexion: no evidence for an inter-muscle compensation in healthy young adults.

Knee joint position influences ankle torque, but it is unclear whether the soleus compensates to counteract the reductions in gastrocnemius output during knee-flexed versus knee-extended plantarflexions. Therefore, the purpose of this study was to determine the effects of knee joint position and plantarflexion contraction velocity on ankle plantarflexion torque and electromyography activity of the medial gastrocnemius and soleus in healthy young adults. Healthy male participants (n=30) performed concentric plantar flexions in a custom-built dynamometer from 15° dorsiflexion to 30° plantarflexion at gradually increasing velocities during each contraction at 30, 60, 120, 180, and 210° s-1 in a supine position with the knee fully extended and while kneeling with the knee fixed in 90° flexion.

Sex-specific risk factors for new-onset heart failure: the PREVEND study at 25 years.

Background And Aims: Current estimates for the lifetime risk to develop heart failure with either a reduced (HFrEF) or preserved ejection fraction (HFpEF) and their associated risk factors are derived from two studies from the USA. The sex-specific lifetime risk and population attributable fraction of potentially modifiable risk factors for incident HFpEF and HFrEF are described in a large European community-based cohort with 25 years of follow-up.

Methods: A total of 8558 participants from the PREVEND cohort were studied at baseline from 1997 onwards and followed until 2022 for cases of new-onset HFrEF (ejection fraction < 50%) and HFpEF (ejection fraction ≥ 50%) by assessment of hospital records.

Loss-of-function GHSR variants are associated with short stature and low IGF-I.

Context: The growth hormone (GH) secretagogue receptor, encoded by GHSR, is expressed on somatotrophs of the pituitary gland. Stimulation with its ligand ghrelin, as well as its constitutive activity, enhances GH secretion. Studies in knock-out mice suggest that heterozygous loss-of-function of GHSR is associated with decreased GH response to fasting, but patient observations in small case reports have been equivocal.