The Human Cell Atlas from a cell census to a unified foundation model.

With the convergence in exciting advances in molecular and spatial profiling methods and new computational approaches leveraging artificial intelligence and machine learning (AI/ML), the construction of cell atlases is progressing from data collection to atlas integration and beyond. Here, we explore five ways in which cell atlases, including the Human Cell Atlas, are already revealing valuable biological insights, and how they are poised to provide even greater benefits in the coming years. In particular, we discuss cell atlases as censuses of cells; as 3D maps of cells in the body, across modalities and scales; as maps connecting genotype causes to phenotype effects; as 4D maps of development; and, ultimately, as foundation models of biology unifying all these aspects and helping to transform medicine.

Exploring the motivations, expectations, and experience of graduate-entry nursing students: A qualitative research study.

Current research demonstrates a sparsity of United Kingdom-focused research into graduate-entry nursing programmes, as well as a need for further research into motivations and expectations of graduate-entry nursing students. The aim of this study was to explore a graduate-entry nursing programme from a student perspective, with a specific focus on a) motivations for enrolling, b) expectations of the programme, and c) experience of the programme to date. A qualitative descriptive design was utilised.

Shaping Perceptions and Inspiring Future Neurosurgeons: The Value of a Hands-On Simulated Aneurysm Clipping Workshops at a Student-Organized Neurosurgical Conference.

 Early exposure to niche specialities, like neurosurgery, is essential to inform decisions about future training in these specialities. This study assesses the impact of a hands-on simulated aneurysm clipping workshop on medical students' and junior doctors' perceptions of neurosurgery at a student-organized neurosurgical conference.  Ninety-six delegates were sampled from a hands-on workshop involving hydrogel three-dimensional printed aneurysms clipping using surgical microscopes.

Penn Medicine Lancaster General Health's Ambulatory Care Evolution.

Hospital and health system leaders alike are increasing their efforts to implement an ambulatory care strategy. The move is understandable: Innovative and well-funded competitors are entering their markets, payers are demanding lower-cost options, and patients are seeking affordability and convenience.Healthcare organizations must consider several imperatives when identifying a long-term ambulatory strategy that is both successful and sustainable.

Radical Pleasure: Feminist Digital Storytelling by, with, and for Women Living with HIV.

Despite the fact that HIV can be controlled with medication to undetectable levels where it cannot be passed on, stigmatization of women living with HIV persists. Such stigmatization pivots on stereotypes around sex and sexism and has force in women's lives. Our aim was to create an inspirational resource for women living with HIV regarding sex, relationships, and sexuality: www.

Supervised pulmonary rehabilitation using minimal or specialist exercise equipment in COPD: a propensity-matched analysis.

Background: Many trials supporting the benefits of pulmonary rehabilitation (PR) have used specialist exercise equipment, such as treadmills and cycle ergometers. However, access to specialist equipment may not be feasible in some settings. There is growing interest in delivering PR programmes with minimal, low-cost equipment, but uncertainty remains regarding their efficacy compared with programmes using specialist equipment.

Anxiety and depression in bronchiectasis: Response to pulmonary rehabilitation and minimal clinically important difference of the Hospital Anxiety and Depression Scale.

The aims of the study were to evaluate the responsiveness of Hospital Anxiety and Depression Scale-Anxiety (HADS-A) subscale and HADS-Depression (HADS-D) subscale to pulmonary rehabilitation (PR) in patients with bronchiectasis compared to a matched group of patients with chronic obstructive pulmonary disease (COPD) and provide estimates of the minimal clinically important difference (MCID) of HADS-A and HADS-D in bronchiectasis. Patients with bronchiectasis and at least mild anxiety or depression (HADS-A ≥ 8 or/and HADS-D ≥ 8), as well as a propensity score-matched control group of patients with COPD, underwent an 8-week outpatient PR programme (two supervised sessions per week). Within- and between-group changes were calculated in response to PR.

The timing and quality of antenatal care received by women attending a primary care centre in Iquitos, Peru: A facility exit survey.

Background: Maternal mortality is high in Loreto, Peru, but can be reduced by high quality antenatal care. Indicators for the quality of antenatal care received include the timing (with respect to gestational age) and number of antenatal appointments attended, the delivery of antenatal services and health information, and women's perceptions about their care. This study investigated these indicators amongst women receiving antenatal care in predominantly the San Juan Bautista district of Iquitos, Loreto.

Home versus outpatient pulmonary rehabilitation in COPD: a propensity-matched cohort study.

Home-based exercise has been proposed as an equivalent treatment strategy to supervised outpatient pulmonary rehabilitation (PR), but it is not known whether its implementation into clinical practice produces similar benefits to those observed in trials. We compared the real-world responses of 154 patients with COPD undergoing home-based exercise with a matched group attending supervised PR. We observed smaller improvements in exercise capacity with home-based exercise compared with PR, but similar improvements in quality of life.

King's Brief Interstitial Lung Disease questionnaire: responsiveness and minimum clinically important difference.

Health status is increasingly used in clinical practice to quantify symptom burden and as a clinical trial end-point in patients with interstitial lung disease (ILD). The King's Brief Interstitial Lung Disease (KBILD) questionnaire is a brief, validated 15-item, disease-specific, health-related quality of life questionnaire that is increasingly used in clinical trials, but little data exist regarding the minimum clinically important difference (MCID). Using pulmonary rehabilitation as a model, we aimed to determine the responsiveness of KBILD and provide estimates of the MCID.

Identification of an Alternating-Access Dynamics Mutant of EmrE with Impaired Transport.

Proteins that perform active transport must alternate the access of a binding site, first to one side of a membrane and then to the other, resulting in the transport of bound substrates across the membrane. To better understand this process, we sought to identify mutants of the small multidrug resistance transporter EmrE with reduced rates of alternating access. We performed extensive scanning mutagenesis by changing every amino acid residue to Val, Ala, or Gly, and then screening the drug resistance phenotypes of the resulting mutants.

Comparative genomics of 16 spp. that tolerate multiple heavy metals and antibiotics.

A total of 16 different strains of spp. were isolated from contaminated soil and enriched on the carcinogen, hexavalent chromium [Cr(VI)]. The majority of the isolates (11 of the 16) were able to tolerate concentrations (0.

Variation in lung function as a marker of adherence to oral and inhaled medication in cystic fibrosis.

The aim of this study was to characterise adherence in an adult population with cystic fibrosis (CF) and to investigate if variation in lung function was a predictor of adherence to treatment.The adherence of patients aged ≥16 years from an adult CF centre was measured by medication possession ratio (MPR) and self-report. Patients were assigned to one of three adherence categories (<50%, 50 to <80%, ≥80%) by their composite score (MPR).

Community nurse-led initiation of antiviral therapy for chronic hepatitis C in people who inject drugs does not increase uptake of or adherence to treatment.

Background: Chronic hepatitis C is common in people who inject drugs (PWID) and this population serves as a reservoir for infection. Treatment levels are low among this group, ranging from 1 to 19%. We explored whether a nurse-initiated community treatment model increased uptake of and adherence to interferon-based therapies.

Fungal contamination of nebuliser devices used by people with cystic fibrosis.

Background: Poor nebuliser hygiene can result in bacterial contamination and risk of infections. The aim of this study was to assess the prevalence of fungal contamination of nebulisers used by adults with cystic fibrosis.

Methods: A total of 170 nebulisers from 149 subjects were screened by wetting a sterile cotton swab with sterile water and swabbing each drug chamber.

Structures of an apo and a binary complex of an evolved archeal B family DNA polymerase capable of synthesising highly cy-dye labelled DNA.

Thermophilic DNA polymerases of the polB family are of great importance in biotechnological applications including high-fidelity PCR. Of particular interest is the relative promiscuity of engineered versions of the exo- form of polymerases from the Thermo- and Pyrococcales families towards non-canonical substrates, which enables key advances in Next-generation sequencing. Despite this there is a paucity of structural information to guide further engineering of this group of polymerases.

Imaging conditioned fear circuitry using awake rodent fMRI.

Functional magnetic resonance imaging (fMRI) is a powerful method for exploring emotional and cognitive brain responses in humans. However rodent fMRI has not previously been applied to the analysis of learned behaviour in awake animals, limiting its use as a translational tool. Here we have developed a novel paradigm for studying brain activation in awake rats responding to conditioned stimuli using fMRI.

Managing C difficile relapses in the community.

Nurses face several challenges in caring for patients with recurrent episodes of C difficile in the community. This article reports on the development of a clinical pathway to meet the needs of older patients and their families.

Structures of hepatitis B virus cores presenting a model epitope and their complexes with antibodies.

The core shell of hepatitis B virus is a potent immune stimulator, giving a strong neutralizing immune response to foreign epitopes inserted at the immunodominant region, located at the tips of spikes on the exterior of the shell. Here, we analyze structures of core shells with a model epitope inserted at two alternative positions in the immunodominant region. Recombinantly expressed core protein assembles into T=3 and T=4 icosahedral shells, and atomic coordinates are available for the T=4 shell.

NSAID inhibition of prostate cancer cell migration is mediated by Nag-1 Induction via the p38 MAPK-p75(NTR) pathway.

The nonsteroidal anti-inflammatory drugs (NSAID) R-flurbiprofen and ibuprofen have been shown to induce expression of p75(NTR) (neurotrophin receptor) in prostate cancer cell lines. p75(NTR), a tumor necrosis factor receptor superfamily member, is a proapoptotic protein that functions as a tumor suppressor in the human prostate. Expression of p75(NTR) is lost as prostate cancer progresses and is minimal in several metastatic prostate cancer cell lines.

Search for the associated production of the standard-model Higgs Boson in the all-hadronic channel.

We report on a search for the standard-model Higgs boson in pp collisions at square root(s) = 1.96 TeV using an integrated luminosity of 2.0 fb(-1).

First observation of B(s)(0) --> D(s)(+/-)K(-/+) and measurement of the ratio of branching fractions B(B(s)(0) --> D(s)(+/-)K(-/+)/B(B(s)(0) --> D(s)(+)pi(-)).

A combined mass and particle identification fit is used to make the first observation of the decay B(s)(0) --> D(s)(+/-)K(-/+) and measure the branching fraction of B(s)(0) --> D(s)(+/-)K(-/+) relative to B(s)(0) --> D(s)(+)pi(-). This analysis uses 1.2 fb(-1) integrated luminosity of pp collisions at square root(s) = 1.