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Klein et al. use mobility data to forecast COVID-19 admissions for five Massachusetts hospitals. Combining aggregated mobile device data about users’ contact patterns, commuting volume, and mobility range with COVID hospitalizations and test-positivity data increases the lead-time of accurate predictions for individual hospitals.

Abstract The extracellular matrix (ECM) constitutes the main acellular microenvironment of cells in almost all tissues and organs. The ECM not only provides mechanical support, but also mediates numerous biochemical interactions to guide cell survival, proliferation, differentiation, and migration. Thus, better understanding the everchanging temporal and spatial shifts in ECM composition and structure – the ECM dynamics – will provide fundamental insight regarding extracellular regulation of tissue homeostasis and how tissue states transition from one to another during diverse pathophysiological processes. This review outlines the mechanisms mediating ECM-cell interactions and highlights how changes in the ECM modulate tissue development and disease progression, using the lung as the primary model organ. We then discuss existing methodologies for revealing ECM compositional dynamics, with a particular focus on tracking newly synthesized ECM proteins. Finally, we discuss the ramifications ECM dynamics have on tissue engineering and how to implement spatial and temporal specific extracellular microenvironments into bioengineered tissues. Overall, this review communicates the current capabilities for studying native ECM dynamics and delineates new research directions in discovering and implementing ECM dynamics to push the frontier forward.

Objective:. To determine the accuracy of a predictive model for inpatient occupancy that was implemented at a large New England hospital to aid hospital recovery planning from the COVID-19 surge. Background:. During recovery from COVID surges, hospitals must plan for multiple patient populations vying for inpatient capacity, so that they maintain access for emergency department (ED) patients while enabling time-sensitive scheduled procedures to go forward. To guide pandemic recovery planning, we implemented a model to predict hospital occupancy for COVID and non-COVID patients. Methods:. At a quaternary care hospital in New England, we included hospitalizations from March 10 to July 12, 2020 and subdivided them into COVID, non-COVID nonscheduled (NCNS), and non-COVID scheduled operating room (OR) hospitalizations. For the recovery period from May 25 to July 12, the model made daily hospital occupancy predictions for each population. The primary outcome was the daily mean absolute percentage error (MAPE) and mean absolute error (MAE) when comparing the predicted versus actual occupancy. Results:. There were 444 COVID, 5637 NCNS, and 1218 non-COVID scheduled OR hospitalizations during the recovery period. For all populations, the MAPE and MAE for total occupancy were 2.8% or 22.3 hospitalizations per day; for general care, 2.6% or 17.8 hospitalizations per day; and for intensive care unit, 9.7% or 11.0 hospitalizations per day. Conclusions:. The model was accurate in predicting hospital occupancy during the recovery period. Such models may aid hospital recovery planning so that enough capacity is maintained to care for ED hospitalizations while ensuring scheduled procedures can efficiently return.

Abstract The long-term consequences of cancer and its therapy on the patients’ immune system years after cancer-free survival remain poorly understood. Here, we present an in-depth characterization of the bone marrow immune ecosystem of multiple myeloma long-term survivors, from initial diagnosis up to 17 years following a single therapy line and cancer-free survival. Using comparative single-cell analyses combined with molecular, genomic, and functional approaches, we demonstrate that multiple myeloma long-term survivors exhibit pronounced alterations in their bone marrow microenvironment associated with impaired immunity. These immunological alterations were frequently linked to an inflammatory immune circuit fueled by the long-term persistence or resurgence of residual myeloma cells. Notably, even in the complete absence of any detectable residual disease for decades, sustained changes in the immune system were observed, suggesting an irreversible ‘immunological scarring’ caused by the initial exposure to the cancer and therapy. Collectively, our study provides key insights into the molecular and cellular bone marrow ecosystem of long-term survivors of multiple myeloma, revealing both reversible and irreversible alterations in the immune compartment.

Abstract Background Covid-19 healthcare worker testing, isolation and quarantine policies had to balance risks to patients from the virus and from staff absence. The emergence of the Omicron variant led to dangerous levels of key-worker absence globally. We evaluated whether using two manufacturers’ lateral flow tests (LFTs) concurrently improved SARS-CoV-2 Omicron detection significantly and was acceptable to hospital staff. In a nested study, to understand risks of return to work after a 5-day isolation/quarantine period, we examined virus culture 5–7 days after positive test or significant exposure. Methods Fully-vaccinated Liverpool (UK) University Hospitals staff participated (February-May 2022) in a random-order, open-label trial testing whether dual LFTs improved SARS-CoV-2 detection, and whether dual swabbing was acceptable to users. Participants used nose-throat swab Innova and nose-only swab Orient Gene LFTs in daily randomised order for 10 days. A user-experience questionnaire was administered on exit. Selected participants gave swabs for viral culture on days 5–7 after symptom onset or first positive test. Cultures were considered positive if cytopathic effect was apparent or SARS-CoV-2 N gene sub-genomic RNA was detected. Results Two hundred and twenty-six individuals reported 1466 pairs of LFT results. Tests disagreed in 127 cases (8.7%). Orient Gene was more likely (78 cf. 49; OR: 2.1, 1.1–4.1; P = 0.03) to be positive. If Innova was swabbed second, it was less likely to agree with a positive Orient Gene result (OR: 2.7, 1.3–5.2; P = 0.005); swabbing first with Innova made no significant difference (OR: 1.1, 0.5–2.3; P = 0.85). Orient Gene positive Innova negative result-pairs became more frequent over time (OR: 1.2, 1.1–1.3; P

Abstract Background Preclinical studies indicate that the systemic application of C1-inhibitor, clinically used to treat hereditary angioedema, reduces secondary brain injury after ischemic stroke. This study assessed the effect of C1-inhibitor on secondary brain injury after hemorrhagic stroke. Methods We used an established striatal whole-blood injection mouse model to mimic intracerebral hemorrhage-related secondary brain injury. Based on the spatiotemporal dynamics in our model, we calculated the necessary sample size (n = 24) and determined the most sensitive time point to detect potential group differences (48 h) prior to the experiments. The experimental setup, tissue processing and image analysis adhered to our published protocol. We randomized mice into three groups: C1-inhibitor treatment, placebo, and sham. Histology was standardized by taking eight anatomically predefined slices across the entire lesion. Lesion size, vascular leakage, and inflammatory responses were assessed using automated thresholding and dextran/ICAM1/CD45 intensity mapping. Investigators were blinded to group allocation during the experiment, tissue processing, and image analysis. Results Whole blood injection resulted in significantly larger lesion size and more pronounced vascular leakage and cellular inflammation compared to the sham group. However, there was no difference in lesion size or inflammatory markers between the C1-inhibitor and placebo groups. In addition, there was no difference in the inflammatory response of the choroid plexus, which has been identified as a central organ orchestrating inflammation after intracerebral hemorrhage. Conclusion The protective effect of C1-inhibitor might be isolated to pathophysiological processes with a predominant thromboinflammatory component, as in ischemia-reperfusion, but less so in permanent ischemia or intracerebral hemorrhage.

Abstract Age-related cataracts is a highly prevalent eye disorder that results in the clouding of the crystalline lens and is one of the leading causes of visual impairment and blindness. The disease is influenced by multiple factors including genetics, prolonged exposure to ultraviolet radiation, and a history of diabetes. However, the extent to which each of these factors contributes to the development of cataracts remains unclear. Our study identified 101 independent genome-wide significant loci, 57 of which are novel. We identified multiple genes and biological pathways associated with the cataracts, including four drug-gene interactions. Our results suggest a causal association between type 1 diabetes and cataracts. Also, we highlighted a surrogate measure of UV light exposure as a marker of cataract risk in adults.

Abstract The role of adaptive immunity in long-term outcomes in early breast cancer is increasingly recognised. Standard (neo)adjuvant chemotherapy can have adverse effects on immune cells. We conducted a retrospective longitudinal study of full blood counts (FBC) of 200 patients receiving (neo)adjuvant chemotherapy for early breast cancer at a single institution. FBC results at four time points from pre-treatment to 12 months post-chemotherapy were analysed. Flow cytometry was performed for patients with matched pre- and post-chemotherapy peripheral blood mononuclear cell samples. A significant decrease in absolute lymphocyte count at 12 months post-chemotherapy was observed (p

Abstract Background Chronic pain is reported by between 30 and 71% of people with haemophilia (PWH). Exercise is shown to be effective for pain management in other arthritides, but it remains unclear if such an approach is effective or acceptable to PWH. The aim of this study was to evaluate the feasibility and acceptability of a telerehabilitation exercise intervention for PWH living with chronic pain. Methods This was a multisite, non-randomised, pre-post feasibility design, with a nested qualitative study. People with severe haemophilia > 18 years, living with chronic pain, were recruited. The intervention comprised 12 low-impact/moderate intensity, individualised exercise sessions and 3 knowledge-sharing and discussion sessions. Primary objectives assessed according to predefined progression criteria were as follows: (a) recruitment rate (5 participants enrolled per site over 8 weeks), (b) adherence (≥ 75% participants would adhere to ≥ 75% of sessions), (c) follow-up rate (≥ 75% completion of self-reported measures), (d) fidelity (intervention delivered as described in protocol) and (e) safety (≤ 30% participants would report adverse events). Acceptability was evaluated from thematic analysis of post-intervention participant interviews. Preliminary evaluation of self-reported pain, function and quality of life (QoL) was a secondary objective. Results were reported using descriptive statistics integrated with qualitative findings. Results Ten PWH were recruited and completed the intervention. Nine agreed to be interviewed post intervention. Attendance at individual sessions was 84.5% compared to 52.1% for the group sessions. Outcome measures were successfully completed for 100% at baseline, 70% at intervention end and 60% at 3-month follow-up. No serious adverse events were recorded. Group median values in outcome measures (pain, function, QoL) showed minimal change post intervention. Participant interviews highlighted high levels of enjoyment, confidence in continuing exercises independently and positive views of virtual delivery and condition-specific exercise. Conclusions Recruitment rate and safety met the predefined progression criteria. Fidelity partially met the progression criteria, but the follow-up rate for self-reported measures did not. The study was acceptable to both participants and physiotherapists. Further intervention development is needed to review approaches to outcome measure collection and refine the usefulness of the knowledge-sharing sessions. Trial registration The study was prospectively registered on 9 July 2021: International Standard Randomised Controlled Trial Number ISRCTN 17454597.

We identified a novel human circovirus in an immunocompromised 66-year-old woman with sudden onset of self-limiting hepatitis. We detected human circovirus 1 (HCirV-1) transcripts in hepatocytes and the HCirV-1 genome long-term in the patient’s blood, stool, and urine. HCirV-1 is an emerging human pathogen that persists in susceptible patients.

Introduction: Nailfold video-capillaroscopy (NVC) is a non-invasive cost-effective technique involving the microscopic examination of small blood vessels of the distal nailfold with a magnification device. It provides valuable information regarding the microcirculation including anomalies such as tortuous or dilated capillaries, hemorrhages, and avascular areas, which can characterize connective tissue diseases. The utility of NVC in the diagnosis and monitoring of systemic sclerosis (SSc) has been investigated in numerous studies allowing the distinction of the specific microvascular pattern of scleroderma from different conditions other than scleroderma (non-scleroderma pattern). Sarcoidosis (SA) is a systemic inflammatory disease that can affect various organs, including the lungs, skin, and lymph nodes. The purpose of our review was to evaluate the current state of the art in the use of NVC in the diagnosis of SA, to understand the indications for its use and any consequent advantages in the management of the disease in different settings in terms of benefits for patients. Materials and Methods: We searched for the key terms “sarcoidosis” and “video-capillaroscopy” in a computerized search of Pub-Med, extending the search back in time without setting limits. We provided a critical overview of the literature, based on a precise evaluation. After our analysis, we examined the six yielded works looking for answers to our questions. Results: Few studies have evaluated that microcirculation is often compromised in SA, with alterations in blood flow and consequent tissue damage. Discussion: Basing on highlighted findings, NVC appears to be a useful tool in the initial evaluation of sarcoidosis patients. Furthermore, capillaroscopy is useful in the evaluation of the coexistence of sarcoidosis and scleroderma spectrum disorder or overlap syndromes. Conclusions: In conclusions, no specific pattern has been described for sarcoidosis, and further re-search is needed to fully understand the implications of nailfold capillaroscopy find-ings in this disease and to establish standardized guidelines for its use in clinical practice.

Abstract The global crisis of antimicrobial resistance (AMR) necessitates the development of broad-spectrum antibacterial drugs effective against multi-drug resistant (MDR) pathogens. BWC0977, a Novel Bacterial Topoisomerase Inhibitor (NBTI) selectively inhibits bacterial DNA replication via inhibition of DNA gyrase and topoisomerase IV. BWC0977 exhibited a minimum inhibitory concentration (MIC90) of 0.03–2 µg/mL against a global panel of MDR Gram-negative bacteria including Enterobacterales and non-fermenters, Gram-positive bacteria, anaerobes and biothreat pathogens. BWC0977 retains activity against isolates resistant to fluoroquinolones (FQs), carbapenems and colistin and demonstrates efficacy against multiple pathogens in two rodent species with significantly higher drug levels in the epithelial lining fluid of infected lungs. In healthy volunteers, single-ascending doses of BWC0977 administered intravenously ( https://clinicaltrials.gov/study/NCT05088421 ) was found to be safe, well tolerated (primary endpoint) and achieved dose-proportional exposures (secondary endpoint) consistent with modelled data from preclinical studies. Here, we show that BWC0977 has the potential to treat a range of critical-care infections including MDR bacterial pneumonias.

This study focused on visitors undertaking recreational activities at two important wetland conservation reserves with two main aims: to understand if visitors recognize the significant role of wetlands as vital bird habitat, and to understand the importance of birds as part of the visitor experience. We surveyed 511 visitors at two internationally significant urban wetlands in Perth, Western Australia. Results indicated that respondents valued wetland areas for exercising, aesthetic values, utility of infrastructure and general amenity, as well as the presence of birds. Some respondents perceived that the wetlands were important for birds and the presence of birds was generally rated highly. Results further indicated that while birds were generally not the focus of visitor experience, birds were an important component of that experience. We conclude that most visitors will generally support management actions aimed at conserving the wetlands and birdlife, and management actions do not need to consider a range of differing views across different recreational activities. Thus, understanding the extent that different recreational users of urban wetlands value birds and bird habitat provides vital insights into management approaches for conservation.

Abstract Background Acute kidney injury (AKI) is common in critical cases of coronavirus disease 2019 (COVID-19) and associated with worse outcome. Dysregulated neutrophil extracellular trap (NET) formation is one of several suggested pathophysiological mechanisms involved in the development of COVID-19 associated AKI. The corticosteroid dexamethasone was implemented as a standard treatment for severe COVID-19 as of June 2020. A sub-analysis of a prospective observational single center study was performed to evaluate the effect of corticosteroid treatment on AKI development and NET markers in critical cases of COVID-19. Results Two hundred and ten adult patients admitted to intensive care at a tertiary level hospital due to respiratory failure or shock secondary to SARS-CoV-2-infection between March 13th 2020 and January 14th 2021 were included in the study. Ninety-seven of those did not receive corticosteroids. One hundred and thirteen patients were treated with corticosteroids [dexamethasone (n = 98) or equivalent treatment (n = 15)], but the incidence of AKI was assessed only in patients that received corticosteroids before any registered renal dysfunction (n = 63). Corticosteroids were associated with a lower incidence of AKI (19% vs 55.8%, p

Aim: To assess lung function in patients with persistent dyspnea 1 year after mild coronavirus disease 2019 (COVID-19) and compare with those hospitalized with moderate or critical COVID-19. Methods: Adults with confirmed severe acute respiratory syndrome coronavirus-2 infection with mild COVID-19 and persistent dyspnea (n = 18) or with moderate (n = 34) or critical COVID-19 (n = 19) were followed up 11–13 months after initial infection. Inclusion criteria were age < 65 years, no smoking history, and no preexisting respiratory diseases. Sociodemographic and clinical data were collected, and patients underwent spirometry and measurement of diffusing capacity for carbon monoxide (DLCO). Results: The non-hospitalized patients were significantly younger and more often female compared with those in the moderate and critical groups (P = 0.002 and P < 0.001, respectively). No significant differences in comorbidities or body mass index (BMI) were noted between severity groups. An obstructive spirometry pattern (ratio of forced expiratory volume during the first exhalation second to forced vital capacity under the lower limit of normal (LLN)) was found in 5.6, 5.9, and 5.3% of patients in the mild, moderate, and critical groups, respectively (P = 0.995). Abnormal DLCO (< LLN) rates were seen in 5.6, 16.7, and 47.4% in the mild, moderate, and critical groups, respectively (P = 0.018). DLCO, expressed as a z-score, was significantly lower in the critical group compared with the mild group after adjustment for age, sex, and BMI. Conclusion: Only a few subjects with mild COVID-19 and persistent dyspnea had abnormal lung function 1 year after initial infection, assessed based on spirometry and DLCO measurements. An obstructive spirometry pattern at 1-year follow-up was uncommon even in patients with moderate or critical COVID-19. Impaired DLCO was more common in patients with critical COVID-19.

Mucosa-associated lymphoid tissue (MALT) lymphomas are slow-growing B-cell lymphomas mainly diagnosed in the stomach and termed gastric MALT lymphoma (G-MALT). Despite histological evaluation, immunostaining, and additional B-cell clonality analysis by fragment analysis, a clear-cut diagnosis is not feasible in all cases, especially for clinical follow-up of patients after treatment. We examined clonally rearranged immunoglobulin heavy- and light-chain gene sequences of 36 genomic DNA samples from six different patients obtained at different time points over the course of several years using the OncomineTM B-cell receptor pan-clonality next-generation sequencing (NGS) assay. Each case consisted of samples diagnosed with G-MALT and samples without evidence of lymphoma, based on histological examinations. We show a robust correlation (100%) of the results between the applied NGS method and histology-diagnosed G-MALT-positive patients. We also detected malignant clonotypes in samples where histology assessment failed to provide clear evidence of G-MALT (15 out of 19 samples). Furthermore, this method revealed malignant clonotypes much earlier in the disease course, with NGS of the immunoglobulin light chain being crucial in complementing immunoglobulin heavy-chain analysis. Hence, the value of NGS in routine lymphoma diagnostics is greatly significant and can be explored in order to provide better diagnoses and proffer the early detection of lymphoma relapse.

AbstractThe study aimed to determine the main factors that predicted users’ intention to continue using mobile food delivery apps during the COVID-19 pandemic. The moderating role of user experience was also explored. Data were obtained from 411 users of mobile food delivery apps in South Africa, using the purposive sampling technique. The lens of the integrated modified unified theory of acceptance and use of technology (UTAUT2) and the task technology fit (TTF) were used for this research. The results indicate that users’ continuance intentions are influenced by performance expectancy and habit, and that hedonic motivation and TTF are insignificant predictors. Performance expectancy mediates between TTF and continuance intention, and user experience moderates the relationship between predictors (TTF, hedonic motivation, habit) and continuance intention. Restaurant owners can use the findings of this study to design winning strategies that mix both technology features and mental perceptions to build a stronger client base during crises and future business possibilities.

Purpose To examine patients’ experiences of receiving care on an ICU for COVID-19 and the subsequent rehabilitation process. Methods An explorative and inductive design was used. Participants were recruited from two university hospitals in Sweden. Patients admitted to the ICU due to COVID-19 from March 2020 to April 2021, who enrolled in the ICU follow-up, and understood and spoke Swedish were invited to participate. In total, 20 participants completed a semi-structured interview, of whom 18 were included in the thematic analysis. Results The analysis resulted in two themes: “An isolated world with silver linings” and “Recovery in the wake of the pandemic”. Findings show that patients cared for on an ICU for COVID-19 during the pandemic felt safe but experienced a sense of vulnerability. After discharge, physical rehabilitation was a slow process with frustrating day-to-day fluctuations. Mentally, participants felt isolated, fatigued, and emotionally sensitive. Patients reported that love and support from family and friends were crucial for the recovery process. Conclusions This study highlights the challenges of recovering from COVID-19, emphasizing the importance of continued support from health care, public services, family and friends. It provides important insights into patients’ experiences and can inform future healthcare strategies and policies.

Canine cutaneous histiocytoma (CCH) is a tumor that originates from dermal Langerhans cells and affects particularly young dogs. The common spontaneous regression of CCH makes it an interesting model in comparative oncology research. Previous studies have indicated that anti-tumor immune responses may be involved, but details remain speculative to date. Here, we asked which specific immuno-oncological dynamics underlie spontaneous regression of CCH on mRNA and protein levels. QuantSeq 3′ mRNA sequencing with functional over-representation analysis and an nCounter RNA hybridization assay were employed on 21 formalin-fixed, paraffin-embedded CCH samples representing three different tumor stages (dataset information: GSE261387—Immuno-Oncologic Profiling by Stage-Dependent Transcriptome and Proteome Analyses of Spontaneously Regressing Canine Cutaneous Histiocytoma—OmicsDI). Nine additional samples were subjected to matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). Surprisingly, only minor stage-specific differences were found. When we investigated expression of B7 family ligands and CD28 family receptors holding co-stimulatory and -inhibitory functions, respectively, we found a higher abundance of CD80, CD86, CTLA4 and CD28, which may trigger a balanced activation of lymphocyte-mediated immune responses. CD80 and CD86 expressing cells were further quantified by in situ hybridization and compared with data from three cases of canine histiocytic sarcoma (HS), a malignant tumor variant originating from antigen-presenting interstitial dendritic cells. A stage-specific increase of CD80 expressing cells was recorded in CCH from the tumor bottom to the top, while CD86 was continuously and homogenously expressed at high levels. Overall expression of CD80 in CCH was similar to that in HS (73.3 ± 37.4% vs 62.1 ± 46.4%), while significantly more CD86 expressing tumor cells were found in CCH (94.7 ± 10.3%) when compared to HS (57.6 ± 11.0%). Our data suggest that major immuno-oncological pathways are not regulated during regression of CCH on the mRNA or protein levels as detectable by the methods used. Instead, our data provide further evidence supporting previous hypotheses towards a role of immune stimulatory B7 family ligands and CD28 family receptors in the regression of CCH.

The manipulation of dipolar interactions within ultracold molecular ensembles represents a pivotal advancement in experimental physics, aiming at the emulation of quantum phenomena unattainable through mere contact interactions. Our study uncovers regimes of multiband occupation which allow to probe more realistic, complex long-range interacting lattice models with ultracold dipolar simulators. By mapping out experimentally relevant ranges of potential depths, interaction strengths, particle fillings, and geometric configurations, we calculate the agreement between the state prepared in the quantum simulator and a target lattice state. We do so by separately calculating numerically exact many-body wave functions in the continuous space and single- or multiband lattice representations, and building their many-body state overlaps. Our findings reveal that for shallow lattices and stronger interactions above half filling, multiband population increases, resulting in fundamentally different ground states than the ones observed in simple lowest-band descriptions, e.g., striped vs checkerboard states. A wide range of probed parameter regimes in its turn provides a systematic and quantitative blueprint for realizing multiband states with two-dimensional quantum simulators employing ultracold dipolar molecules.