Safety and Tolerability of Pivmecillinam During More Than Four Decades of Clinical Experience: A Systematic Review.

The recent US Food and Drug Administration approval of pivmecillinam-an oral prodrug of the amidinopenicillin antibiotic mecillinam-presents a valuable opportunity to address the need for new treatments for uncomplicated urinary tract infection (uUTI). We report findings of a systematic literature review of the safety profile of pivmecillinam/mecillinam based on more than 40 years' experience, mainly in Europe and Canada, to describe its tolerability profile and identify any important safety signals. In total, 110 eligible publications were identified describing use of pivmecillinam/mecillinam as monotherapy or in combination, for treatment of uUTI or other infectious conditions.

Bone-Induced Her2 Promotes Secondary Metastasis in HR+/Her2- Breast Cancer.

Bone metastases can disseminate to secondary sites and promote breast cancer progression creating additional clinical challenges. The mechanisms contributing to secondary metastasis are barely understood. Here, we evaluate the prediction power of Her2-expressing (Her2E) circulating tumor cells (CTCs) after analyzing over 13,000 CTCs from a cohort of 137 metastatic breast cancer (MBC) patients with initial HR+/Her2- status and employ preclinical models of bone metastasis (BM) to validate the role of Her2E CTCs in multi-organ metastases.

Endopiriform neurons projecting to ventral CA1 are a critical node for recognition memory.

The claustrum complex is viewed as fundamental for higher-order cognition; however, the circuit organization and function of its neuroanatomical subregions are not well understood. We demonstrated that some of the key roles of the CLA complex can be attributed to the connectivity and function of a small group of neurons in its ventral subregion, the endopiriform (EN). We identified a subpopulation of EN neurons by their projection to the ventral CA1 (EN.

Paradoxical dominant negative activity of an immunodeficiency-associated activating variant.

encodes three regulatory subunits of class IA phosphoinositide 3-kinase (PI3K), each associating with any of three catalytic subunits, namely p110α, p110β, or p110δ. Constitutional mutations cause diseases with a genotype-phenotype relationship not yet fully explained: heterozygous loss-of-function mutations cause SHORT syndrome, featuring insulin resistance and short stature attributed to reduced p110α function, while heterozygous activating mutations cause immunodeficiency, attributed to p110δ activation and known as APDS2. Surprisingly, APDS2 patients do not show features of p110α hyperactivation, but do commonly have SHORT syndrome-like features, suggesting p110α hypofunction.

Mixed representations of choice direction and outcome by GABA/glutamate cotransmitting neurons in the entopeduncular nucleus.

The basal ganglia (BG) are an evolutionarily conserved and phylogenetically old set of sub-cortical nuclei that guide action selection, evaluation, and reinforcement. The entopeduncular nucleus (EP) is a major BG output nucleus that contains a population of GABA/glutamate cotransmitting neurons (EP) that specifically target the lateral habenula (LHb) and whose function in behavior remains mysterious. Here, we use a probabilistic switching task that requires an animal to maintain flexible relationships between action selection and evaluation to examine when and how GABA/glutamate cotransmitting neurons contribute to behavior.

Aberrant FGF signaling promotes granule neuron precursor expansion in SHH subgroup infantile medulloblastoma.

Mutations in Sonic Hedgehog (SHH) signaling pathway genes, for example, (SUFU), drive granule neuron precursors (GNP) to form medulloblastomas (MB). However, how different molecular lesions in the Shh pathway drive transformation is frequently unclear, and mutations in the cerebellum seem distinct. In this study, we show that fibroblast growth factor 5 (FGF5) signaling is integral for many infantile MB cases and that expression is uniquely upregulated in infantile MB tumors.

Revealing the Water Structure at Neutral and Charged Graphene/Water Interfaces through Quantum Simulations of Sum Frequency Generation Spectra.

The structure and dynamics of water at charged graphene interfaces fundamentally influence molecular responses to electric fields with implications for applications in energy storage, catalysis, and surface chemistry. Leveraging the realism of the MB-pol data-driven many-body potential and advanced path-integral quantum dynamics, we analyze the vibrational sum frequency generation (vSFG) spectrum of graphene/water interfaces under varying surface charges. Our quantum simulations reveal a distinctive dangling OH peak in the vSFG spectrum at neutral graphene, consistent with recent experimental findings yet markedly different from those of earlier studies.

The Effectiveness of Pressure Injury Prevention Education for Patient Care Technicians in an Adult Acute Care Setting: A Quality Improvement Project.

Purpose: The purpose of this quality improvement project was to determine whether hospital-acquired pressure injuries (HAPIs) could be prevented by implementing an educational tool kit for patient care technicians (PCTs).

Participants And Setting: Data were collected from 24 PCTs and 43 patients in a 26-bed inpatient adult acute care unit at an academic medical center in the mid-Atlantic region of the United States.

Approach: Outcome data were collected over an 8-week period from September to November 2021.

Epitaxial Electrodeposition of Zinc on Different Single Crystal Copper Substrates for High Performance Aqueous Batteries.

The aqueous zinc metal battery holds great potential for large-scale energy storage due to its safety, low cost, and high theoretical capacity. However, challenges such as corrosion and dendritic growth necessitate controlled zinc deposition. This study employs epitaxy to achieve large-area, dense, and ultraflat zinc plating on textured copper foil.

Spontaneous Formation of Single-Crystalline Spherulites in a Chiral 2D Hybrid Perovskite.

In two-dimensional (2D) chiral metal-halide perovskites (MHPs), chiral organic spacers induce structural chirality and chiroptical properties in the metal-halide sublattice. This structural chirality enables reversible crystalline-glass phase transitions in (-NEA)PbBr, a prototypical chiral 2D MHP where NEA represents 1-(1-naphthyl)ethylammonium. Here, we investigate two distinct spherulite states of (-NEA)PbBr, exhibiting either radial-like or stripe-like banded patterns depending on the annealing conditions of the amorphous film.

Spin Chains with Highly Quantum Character through Strong Covalency in CaCrN.

The insulating transition metal nitride CaCrN consists of sheets of triangular [CrN] units with symmetry that are connected via quasi-1D zigzag chains. Due to strong covalency between Cr and N, Cr ions are unusually low-spin, and = 1/2. Magnetic susceptibility measurements reveal dominant quasi-1D spin correlations with very large nearest-neighbor antiferromagnetic exchange = 340 K and yet no sign of magnetic order down to = 0.

Sensitivity of Lung Point-of-Care Ultrasound (POCUS) to Predict Oxygen Requirements in Emerging Viral Infections.

Objectives: The prognostic characteristics of lung point-of-care ultrasound (L-POCUS) to predict respiratory decompensation in patients with emerging infections remains unstudied. Our objective was to examine whether scored lung ultrasounds predict hypoxia among a nonhypoxic, ambulatory population of patients with COVID-19.

Methods: This was a diagnostic case-control study.

Rome Foundation Working Team Report: Consensus Statement on the Design and Conduct of Behavioural Clinical Trials for Disorders of Gut-Brain Interaction.

Background: Brain-gut behaviour therapies (BGBT) have gained widespread acceptance as therapeutic modalities for the management of disorders of gut-brain interaction (DGBI). However, existing treatment evaluation methods in the medical field fail to capture the specific elements of scientific rigour unique to behavioural trial evaluation.

Aims: To offer the first consensus on the development and testing of BGBT in DGBI.

Healthcare Contact Days Pre- and Post-Liver Transplant in Patients with Cirrhosis: A National Cohort Study.

Introduction: "Healthcare contact days" is a patient-centered quantitative proxy for time toxicity, which can be informative for liver transplant (LT) decision-making. We aimed to (i) quantify contact days in patients with cirrhosis pre- and post-LT; (ii) identify clinical and demographic features associated with contact days.

Methods: Using a national health system database, we calculated healthcare contact days (inpatient, outpatient hospital [e.

Real-world trends and future projections of the prevalence of cirrhosis and hepatic encephalopathy among commercially and Medicare-insured adults in the United States.

Objectives: Describing cirrhosis and hepatic encephalopathy (HE) burden over time can inform clinical management and resource allocation. Using health care claims data, this observational study examined recent trends in the prevalence of cirrhosis and HE and associated health care resource utilization among commercially and Medicare-insured adults in the United States (US).

Methods: Data from the MarketScan Commercial Claims and Encounters Database and 100% Medicare Research Identifiable Files were analyzed (2007-2020).

Second-Generation Energy Decomposition Analysis of Intermolecular Interaction Energies from the Second-Order Mo̷ller-Plesset Theory: An Extensible, Orthogonal Formulation with Useful Basis Set Convergence for All Terms.

Energy decomposition analysis (EDA) based on density functional theory (DFT) and self-consistent field (SCF) calculations has become widely used for understanding intermolecular interactions. This work reports a new approach to EDA for post-SCF wave functions based on closed-shell restricted second-order Mo̷ller-Plesset (MP2) together with an efficient implementation that generalizes the successful SCF-level second-generation absolutely localized molecular orbital EDA approach, ALMO-EDA-II, and improves upon MP2 ALMO-EDA-I. The new MP2 ALMO-EDA-II provides distinct energy contributions for a frozen interaction energy containing permanent electrostatics and Pauli repulsions, polarized energy-yielding induced electrostatics, dispersion-corrected energy, and the fully relaxed energy, which describes charge transfer.

Quantum Dynamics Simulations of Exciton Polariton Transport.

Recent experiments have shown that exciton transport can be significantly enhanced through hybridization with confined photonic modes in a cavity. The light-matter hybridization generates exciton-polariton (EP) bands, whose group velocity is significantly larger than the excitons. Dissipative mechanisms that affect the constituent states of EPs, such as exciton-phonon coupling and cavity loss, have been observed to reduce the group velocities in experiments.

Food access and the severity of newly diagnosed pediatric inflammatory bowel disease.

Objectives: Inflammatory bowel disease (IBD) results from genetic susceptibility, gut microbiome, and environmental factors. Diet, one modifiable environmental factor, has been linked to the increased prevalence of IBD. This study aimed to evaluate a potential association between food deserts and disease severity at diagnosis.

Computational Investigation of the Role of Metal Center Identity in Cytochrome P450 Enzyme Model Reactivity.

Mononuclear Fe enzymes such as heme-containing cytochrome P450 enzymes catalyze a variety of C-H activation reactions under ambient conditions, and they represent an attractive platform for engineering reactivity through changes to the native enzyme. Using density functional theory, we study both native Fe and non-native group 8 (Ru, Os) and group 9 (Ir) metal centers in an active site model of P450. We quantify how changing the metal changes spin state preferences throughout the catalytic cycle.

Time-Varying Spatial Propagation of Brain Networks in fMRI Data.

Spontaneous neural activity coherently relays information across the brain. Several efforts have been made to understand how spontaneous neural activity evolves at the macro-scale level as measured by resting-state functional magnetic resonance imaging (rsfMRI). Previous studies observe the global patterns and flow of information in rsfMRI using methods such as sliding window or temporal lags.

Glow Discharge Optical Emission Coded Aperture Spectroscopy.

Glow discharge optical emission spectrometry (GDOES) allows fast and simultaneous multielemental analysis directly from solids and depth profiling down to the nanometer scale, which is critical for thin-film (TF) characterization. Nevertheless, operating conditions for the best limits of detection (LODs) are compromised in lieu of the best sputtering crater shapes for depth resolution. In addition, the fast transient signals from ultra-TFs do not permit the optimal sampling statistics of bulk analysis such that LODs are further compromised.

Autoantibodies cause nociceptive sensitization in a mouse model of degenerative osteoarthritis.

Previous preclinical and translational studies suggest that tissue trauma related to bony fracture and intervertebral disk disruption initiates the formation of pronociceptive antibodies that support chronic musculoskeletal pain conditions. This study tested this hypothesis in the monosodium iodoacetate (MIA) mouse model of osteoarthritis (OA) and extended the findings using OA patient samples. Monosodium iodoacetate was injected unilaterally into the knees of male and female wild-type (WT) and muMT mice (lacking B cells) to induce articular cartilage damage.

Improving estimation efficiency for survival data analysis by integrating a coarsened time-to-event outcome from an external study.

In the era of big data, increasing availability of data makes combining different data sources to obtain more accurate estimations a popular topic. However, the development of data integration is often hindered by the heterogeneity in data forms across studies. In this paper, we focus on a case in survival analysis where we have primary study data with a continuous time-to-event outcome and complete covariate measurements, while the data from an external study contain an outcome observed at regular intervals, and only a subset of covariates is measured.