Trafficking through the blood-brain barrier is directed by core and outer surface components of layer-by-layer nanoparticles.

Drug-carrying nanoparticles are a promising strategy to deliver therapeutics into the brain, but their translation requires better characterization of interactions between nanomaterials and endothelial cells of the blood-brain barrier (BBB). Here, we use a library of 18 layer-by-layer electrostatically assembled nanoparticles (NPs) to independently assess the impact of NP core and surface materials on in vitro uptake, transport, and intracellular trafficking in brain endothelial cells. We demonstrate that NP core stiffness determines the magnitude of transport, while surface chemistry directs intracellular trafficking.

The diversity and ecological significance of microbial traits potentially involved in B biosynthesis in the global ocean.

Cobalamin (B), an essential nutrient and growth cofactor for many living organisms on Earth, can be fully synthesized only by selected prokaryotes in nature. Therefore, microbial communities related to B biosynthesis could serve as an example subsystem to disentangle the underlying ecological mechanisms balancing the function and taxonomic make-up of complex functional assemblages. By anchoring microbial traits potentially involved in B biosynthesis, we depict the biogeographic patterns of B biosynthesis genes and the taxa harboring them in the global ocean, despite the limitations of detecting de novo B synthesizers via metagenomes alone.

Sensor-integrated brain-on-a-chip platforms: Improving the predictive validity in neurodegenerative research.

Affecting millions of individuals worldwide, neurodegenerative diseases (NDDs) pose a significant and growing health concern in people over the age of 60 years. Contributing to this trend are the steady increase in the aging population coupled with a persistent lack of disease-altering treatment strategies targeting NDDs. The absence of efficient therapeutics can be attributed to high failure rates in clinical trials and the ineptness of animal models in preceding preclinical studies.

Assessment of respiratory rate monitoring in the emergency department.

Objectives: This study aimed to compare the different respiratory rate (RR) monitoring methods used in the emergency department (ED): manual documentation, telemetry, and capnography.

Methods: This is a retrospective study using recorded patient monitoring data. The study population includes patients who presented to a tertiary care ED between January 2020 and December 2022.

Ultrasound-guided puncture into newborn rat brain.

Since the brain structure of neonatal rats was not fully formed during the first 4 days, it cannot be detected using ultrasound. The objective of this study was to investigate the use of ultrasound to guide puncture in the normal coronal brain structure and determine the puncture depth of the location of the cortex, hippocampus, lateral ventricle, and striatum of newborn rats of 5-15 days. The animal was placed in a prone position.

Cancer vaccines in the clinic.

Vaccines are an important tool in the rapidly evolving repertoire of immunotherapies in oncology. Although cancer vaccines have been investigated for over 30 years, very few have achieved meaningful clinical success. However, recent advances in areas such antigen identification, formulation development and manufacturing, combination therapy regimens, and indication and patient selection hold promise to reinvigorate the field.

Exploring the Use of Natural Language Processing for Objective Assessment of Disorganized Speech in Schizophrenia.

Objective: Measurement-based care tools in psychiatry are useful for symptom monitoring and detecting response to treatment, but methods for quick and objective measurement are lacking especially for acute psychosis. The aim of this study was to explore potential language markers, detected by natural language processing (NLP) methods, as a means to objectively measure the severity of psychotic symptoms of schizophrenia in an acute clinical setting.

Methods: Twenty-two speech samples were collected from seven participants who were hospitalized for schizophrenia, and their symptoms were evaluated over time with SAPS/SANS and TLC scales.

A three-dimensional method for morphological analysis and flow velocity estimation in microvasculature on-a-chip.

Three-dimensional (3D) imaging techniques (e.g., confocal microscopy) are commonly used to visualize in vitro models, especially microvasculature on-a-chip.

Automated detection of progressive speech changes in early Alzheimer's disease.

Unlabelled: Speech and language changes occur in Alzheimer's disease (AD), but few studies have characterized their longitudinal course. We analyzed open-ended speech samples from a prodromal-to-mild AD cohort to develop a novel composite score to characterize progressive speech changes. Participant speech from the Clinical Dementia Rating (CDR) interview was analyzed to compute metrics reflecting speech and language characteristics.

Layer-by-layer interleukin-12 nanoparticles drive a safe and effective response in ovarian tumors.

Ovarian cancer is especially deadly, challenging to treat, and has proven refractory to known immunotherapies. Cytokine therapy is an attractive strategy to drive a proinflammatory immune response in immunologically cold tumors such as many high grade ovarian cancers; however, this strategy has been limited in the past due to severe toxicity. We previously demonstrated the use of a layer-by-layer (LbL) nanoparticle (NP) delivery vehicle in subcutaneous flank tumors to reduce the toxicity of interleukin-12 (IL-12) therapy upon intratumoral injection.

Sprayable tissue adhesive with biodegradation tuned for prevention of postoperative abdominal adhesions.

Adhesions are dense, fibrous bridges that adjoin tissue surfaces due to uncontrolled inflammation following postoperative mesothelial injury. A widely used adhesion barrier material in Seprafilm often fails to prevent transverse scar tissue deposition because of its poor mechanical properties, rapid degradation profile, and difficulty in precise application. Solution blow spinning (SBS), a polymer fiber deposition technique, allows for the placement of in situ tissue-conforming and tissue-adherent scaffolds with exceptional mechanical properties.

Causes and consequences of pair-bond disruption in a sex-skewed population of a long-lived monogamous seabird.

Many animals form long-term monogamous pair bonds, and the disruption of a pair bond (through either divorce or widowhood) can have significant consequences for individual vital rates (survival, breeding, and breeding success probabilities) and life-history outcomes (lifetime reproductive success [LRS], life expectancy). Here, we investigated the causes and consequences of pair-bond disruption in wandering albatross (). State-of-the-art statistical and mathematical approaches were developed to estimate divorce and widowhood rates and their impacts on vital rates and life-history outcomes.

A comparative study of flow cytometry-sorted communities and shotgun viral metagenomics in a Singapore municipal wastewater treatment plant.

Traditional or "bulk" viral enrichment and amplification methods used in viral metagenomics introduce unavoidable bias in viral diversity. This bias is due to shortcomings in existing viral enrichment methods and overshadowing by the more abundant viral populations. To reduce the complexity and improve the resolution of viral diversity, we developed a strategy coupling fluorescence-activated cell sorting (FACS) with random amplification and compared this to bulk metagenomics.

Illustrated State-of-the-Art Capsules of the ISTH 2022 Congress.

The ISTH London 2022 Congress is the first held (mostly) face-to-face again since the COVID-19 pandemic took the world by surprise in 2020. For 2 years we met virtually, but this year's in-person format will allow the ever-so-important and quintessential creativity and networking to flow again. What a pleasure and joy to be able to see everyone! Importantly, all conference proceedings are also streamed (and available recorded) online for those unable to travel on this occasion.

The low overpotential regime of acidic water oxidation part I: the importance of O detection.

The high overpotential required for the oxygen evolution reaction (OER) represents a significant barrier for the production of closed-cycle renewable fuels and chemicals. Ruthenium dioxide is among the most active catalysts for OER in acid, but the activity at low overpotentials can be difficult to measure due to high capacitance. In this work, we use electrochemistry - mass spectrometry to obtain accurate OER activity measurements spanning six orders of magnitude on a model series of ruthenium-based catalysts in acidic electrolyte, quantifying electrocatalytic O production at potential as low as 1.

MUlticenter STudy of tissue plasminogen activator (alteplase) use in COVID-19 severe respiratory failure (MUST COVID): A retrospective cohort study.

Background: Few therapies exist to treat severe COVID-19 respiratory failure once it develops. Given known diffuse pulmonary microthrombi on autopsy studies of COVID-19 patients, we hypothesized that tissue plasminogen activator (tPA) may improve pulmonary function in COVID-19 respiratory failure.

Methods: A multicenter, retrospective, observational study of patients with confirmed COVID-19 and severe respiratory failure who received systemic tPA (alteplase) was performed.

Where to locate COVID-19 mass vaccination facilities?

The outbreak of COVID-19 led to a record-breaking race to develop a vaccine. However, the limited vaccine capacity creates another massive challenge: how to distribute vaccines to mitigate the near-end impact of the pandemic? In the United States in particular, the new Biden administration is launching mass vaccination sites across the country, raising the obvious question of where to locate these clinics to maximize the effectiveness of the vaccination campaign. This paper tackles this question with a novel data-driven approach to optimize COVID-19 vaccine distribution.

Heal the Healers: A pilot study evaluating the feasibility, acceptability, and exploratory efficacy of a Transcendental Meditation intervention for emergency clinicians during the coronavirus disease 2019 pandemic.

Objective: Emergency clinicians face elevated rates of burnout that result in poor outcomes for clinicians, patients, and health systems. The objective of this single-arm pilot study was to evaluate the feasibility of a Transcendental Meditation (TM) intervention for emergency clinicians during the coronavirus disease 2019 (COVID-19) pandemic and to explore the potential effectiveness in improving burnout, sleep, and psychological health.

Methods: Emergency clinicians (physicians, nurses, and physician-assistants) from 2 urban hospitals were recruited to participate in TM instruction (8 individual or group in-person and remote sessions) for 3 months.

Biomaterials and nanomedicine for bone regeneration: Progress and future prospects.

Bone defects pose a heavy burden on patients, orthopedic surgeons, and public health resources. Various pathological conditions cause bone defects including trauma, tumors, inflammation, osteoporosis, and so forth. Auto- and allograft transplantation have been developed as the most commonly used clinic treatment methods, among which autologous bone grafts are the golden standard.

Coping with darkness: The adaptive response of marine picocyanobacteria to repeated light energy deprivation.

The picocyanobacteria and are found throughout the ocean's euphotic zone, where the daily light:dark cycle drives their physiology. Periodic deep mixing events can, however, move cells below this region, depriving them of light for extended periods of time. Here, we demonstrate that members of these genera can adapt to tolerate repeated periods of light energy deprivation.

Moving ecological and biogeochemical transitions across the North Pacific.

In the North Pacific Ocean, nutrient rich surface waters flow south from the subpolar gyre through a transitional region and into the subtropics. Along the way, nutrients are used, recycled, and exported, leading to lower biomass and a commensurate change in ecosystem structure moving southward. We focus on the region between the two gyres (the Transition Zone) using a coupled biophysical ocean model, remote sensing, floats, and cruise data to explore the nature of the physical, biogeochemical, and ecological fields in this region.

Cell therapies in the clinic.

Cell therapies have emerged as a promising therapeutic modality with the potential to treat and even cure a diverse array of diseases. Cell therapies offer unique clinical and therapeutic advantages over conventional small molecules and the growing number of biologics. Particularly, living cells can simultaneously and dynamically perform complex biological functions in ways that conventional drugs cannot; cell therapies have expanded the spectrum of available therapeutic options to include key cellular functions and processes.

A virucidal face mask based on the reverse-flow reactor concept for thermal inactivation of SARS-CoV-2.

While facial coverings reduce the spread of SARS-CoV-2 by viral filtration, masks capable of viral inactivation by heating can provide a complementary method to limit transmission. Inspired by reverse-flow chemical reactors, we introduce a new virucidal face mask concept driven by the oscillatory flow of human breath. The governing heat and mass transport equations are solved to evaluate virus and CO transport.

Gemcitabine and doxorubicin in immunostimulatory monophosphoryl lipid A liposomes for treating breast cancer.

Cancer therapy is increasingly shifting toward targeting the tumor immune microenvironment and influencing populations of tumor infiltrating lymphocytes. Breast cancer presents a unique challenge as tumors of the triple-negative breast cancer subtype employ a multitude of immunosilencing mechanisms that promote immune evasion and rapid growth. Treatment of breast cancer with chemotherapeutics has been shown to induce underlying immunostimulatory responses that can be further amplified with the addition of immune-modulating agents.