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Previous studies on the natural history of long-COVID have been few and selective. Without comparison groups, disease progression cannot be differentiated from symptoms originating from other causes. The Long-COVID in Scotland Study (Long-CISS) is a Scotland-wide, general population cohort of adults who had laboratory-confirmed SARS-CoV-2 infection matched to PCR-negative adults. Serial, self-completed, online questionnaires collected information on pre-existing health conditions and current health six, 12 and 18 months after index test. Of those with previous symptomatic infection, 35% reported persistent incomplete/no recovery, 12% improvement and 12% deterioration. At six and 12 months, one or more symptom was reported by 71.5% and 70.7% respectively of those previously infected, compared with 53.5% and 56.5% of those never infected. Altered taste, smell and confusion improved over time compared to the never infected group and adjusted for confounders. Conversely, late onset dry and productive cough, and hearing problems were more likely following SARS-CoV-2 infection. The long-term natural history of long-COVID is not well understood. In this population-based cohort study from Scotland, the authors describe symptom prevalence and health-related quality of life up to 18 months after a positive SARS-CoV-2 test and compare with matched test-negative controls. [ABSTRACT FROM AUTHOR]

Long-COVID prevalence estimates vary widely and should take account of symptoms that would have occurred anyway. Here we determine the prevalence of symptoms attributable to SARS-CoV-2 infection, taking account of background rates and confounding, in a nationwide population cohort study of 198,096 Scottish adults. 98,666 (49.8%) had symptomatic laboratory-confirmed SARS-CoV-2 infections and 99,430 (50.2%) were age-, sex-, and socioeconomically-matched and never-infected. While 41,775 (64.5%) reported at least one symptom 6 months following SARS-CoV-2 infection, this was also true of 34,600 (50.8%) of those never-infected. The crude prevalence of one or more symptom attributable to SARS-CoV-2 infection was 13.8% (13.2%,14.3%), 12.8% (11.9%,13.6%), and 16.3% (14.4%,18.2%) at 6, 12, and 18 months respectively. Following adjustment for potential confounders, these figures were 6.6% (6.3%, 6.9%), 6.5% (6.0%, 6.9%) and 10.4% (9.1%, 11.6%) respectively. Long-COVID is characterised by a wide range of symptoms that, apart from altered taste and smell, are non-specific. Care should be taken in attributing symptoms to previous SARS-CoV-2 infection.Determining the prevalence of Long COVID is challenging because many symptoms attributed to the syndrome could have other causes. Here, the authors estimate the prevalence of Long COVID in Scotland by comparing rates of symptoms reported by people with and without history of SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

The aim of the present study is to produce flexible, flame-retardant, water-resistant and biodegradable composite materials. The ultimate goal of this research is to develop simple processes for the production of bio-based materials capable of replacing non-degradable substrates in printed circuit board. Cellulose was chosen as a renewable resource, and dissolved in 1-ethyl-3-methylimidazolium acetate ionic liquid to prepare a cellulosic continuous film. Since flame retardancy is an important criterion for electronic device applications and cellulose is naturally flammable, we incorporated ammonium polyphosphate (APP) as a flame-retardant filler to increase the flame retardancy of the produced materials. The developed material achieved a UL-94 HB rating in the flammability test, while the cellulose sample without APP failed the test. Two hydrophobic agents, ethyl 2-cyanoacrylate and trichloro(octadecyl)silane were applied by a simple dip-coating technique to impart hydrophobicity to the cellulose-APP composites. Dynamic mechanical analysis indicated that the mechanical properties of the cellulosic materials were not significantly affected by the addition of APP or the hydrophobic agents. Moreover, the biodegradability of the cellulosic materials containing APP increased owing to the presence of the cellulase enzyme. The hydrophobic coating slightly decreased the biodegradability of cellulose-APP, but it was still higher than that of pure cellulose film. [ABSTRACT FROM AUTHOR]

With increasing numbers infected by SARS-CoV-2, understanding long-COVID is essential to inform health and social care support. A Scottish population cohort of 33,281 laboratory-confirmed SARS-CoV-2 infections and 62,957 never-infected individuals were followed-up via 6, 12 and 18-month questionnaires and linkage to hospitalization and death records. Of the 31,486 symptomatic infections,1,856 (6%) had not recovered and 13,350 (42%) only partially. No recovery was associated with hospitalized infection, age, female sex, deprivation, respiratory disease, depression and multimorbidity. Previous symptomatic infection was associated with poorer quality of life, impairment across all daily activities and 24 persistent symptoms including breathlessness (OR 3.43, 95% CI 3.29–3.58), palpitations (OR 2.51, OR 2.36–2.66), chest pain (OR 2.09, 95% CI 1.96–2.23), and confusion (OR 2.92, 95% CI 2.78–3.07). Asymptomatic infection was not associated with adverse outcomes. Vaccination was associated with reduced risk of seven symptoms. Here we describe the nature of long-COVID and the factors associated with it. In this population-based cohort study from Scotland, the authors investigate the prevalence of symptoms in the post-acute phase of COVID-19 infection compared to matched uninfected controls. They identify persistent symptoms associated with infection and identify factors associated with failure to recover. [ABSTRACT FROM AUTHOR]

Neutralizing antibody function provides a foundation for the efficacy of vaccines and therapies1–3. Here, using a robust in vitro Ebola virus (EBOV) pseudo-particle infection assay and a well-defined set of solid-phase assays, we describe a wide spectrum of antibody responses in a cohort of healthy survivors of the Sierra Leone EBOV outbreak of 2013–2016. Pseudo-particle virus-neutralizing antibodies correlated with total anti-EBOV reactivity and neutralizing antibodies against live EBOV. Variant EBOV glycoproteins (1995 and 2014 strains) were similarly neutralized. During longitudinal follow-up, antibody responses fluctuated in a ‘decay–stimulation–decay’ pattern that suggests de novo restimulation by EBOV antigens after recovery. A pharmacodynamic model of antibody reactivity identified a decay half-life of 77–100 days and a doubling time of 46–86 days in a high proportion of survivors. The highest antibody reactivity was observed around 200 days after an individual had recovered. The model suggests that EBOV antibody reactivity declines over 0.5–2 years after recovery. In a high proportion of healthy survivors, antibody responses undergo rapid restimulation. Vigilant follow-up of survivors and possible elective de novo antigenic stimulation by vaccine immunization should be considered in order to prevent EBOV viral recrudescence in recovering individuals and thereby to mitigate the potential risk of reseeding an outbreak.In many survivors of Ebola virus infection, antibody responses show long-term patterns of decline followed by restimulation, possibly owing to recrudescence of persisting virus. [ABSTRACT FROM AUTHOR]

Printable and biodegradable printed circuit boards (PCBs) prepared by using cellulose as the continuous matrix, laponite as flame retardant filler with various weight ratio (0, 5, 10 and 20 wt% with respect to the α-cellulose quantity used to prepare the composites) and 1-ethyl-3-methylimidazolium acetate ([emim][OAc]) as the recoverable dissolution medium. Prepared cellulose-composites were subjected into physical, chemical, thermal, mechanical and biodegradation analyses to check the suitability of the cellulose-laponite composite for biodegradable electronic application. The addition of laponite into cellulose increased the degradation temperature, flame retardancy and decreased the mechanical properties of the cellulose-laponite composites. The surface nature of the cellulose composite converted from hydrophilic to hydrophobic (contact angle value increased in the range from 50° to 112°) by treating with relatively small amount of hydrophobizing agent (< 1 wt%). The conductive ink printing experiments on the composites explaining the role of hydrophobizing agent and laponite in the composites. Biodegradability of the cellulose was evaluated by enzyme treatments and derived the effect of laponite, hydrophobic agent and conductive ink. [ABSTRACT FROM AUTHOR]

Combining surface chemical modification of cellulose to introduce positively charged trimethylammonium groups by reaction with glycidyltrimethylammonium chloride (GTMAC) allowed for direct attachment of mammalian MG-63 cells, without addition of protein modifiers, or ligands. Very small increases in the surface charge resulted in significant increases in cell attachment: at a degree of substitution (DS) of only 1.4%, MG-63 cell attachment was > 90% compared to tissue culture plastic, whereas minimal attachment occurred on unmodified cellulose. Cell attachment plateaued above DS of ca. 1.85% reflecting a similar trend in surface charge, as determined from ζ-potential measurements and capacitance coupling (electric force microscopy). Cellulose film stiffness was modulated by cross linking with glyoxal (0.3–2.6% degree of crosslinking) to produce a range of materials with surface shear moduli from 76 to 448 kPa (measured using atomic force microscopy). Cell morphology on these materials could be regulated by tuning the stiffness of the scaffolds. Thus, we report tailored functionalised biomaterials based on cationic cellulose that can be tuned through surface reaction and glyoxal crosslinkin+g, to influence the attachment and morphology of cells. These scaffolds are the first steps towards materials designed to support cells and to regulate cell morphology on implanted biomaterials using only scaffold and cells, i.e. without added adhesion promoters. [ABSTRACT FROM AUTHOR]

We report the ability of cellulose to support cells without the use of matrix ligands on the surface of the material, thus creating a two-component system for tissue engineering of cells and materials. Sheets of bacterial cellulose, grown from a culture medium containing Acetobacter organism were chemically modified with glycidyltrimethylammonium chloride or by oxidation with sodium hypochlorite in the presence of sodium bromide and 2,2,6,6-tetramethylpipiridine 1-oxyl radical to introduce a positive, or negative, charge, respectively. This modification process did not degrade the mechanical properties of the bulk material, but grafting of a positively charged moiety to the cellulose surface (cationic cellulose) increased cell attachment by 70% compared to unmodified cellulose, while negatively charged, oxidised cellulose films (anionic cellulose), showed low levels of cell attachment comparable to those seen for unmodified cellulose. Only a minimal level of cationic surface derivitisation (ca 3% degree of substitution) was required for increased cell attachment and no mediating proteins were required. Cell adhesion studies exhibited the same trends as the attachment studies, while the mean cell area and aspect ratio was highest on the cationic surfaces. Overall, we demonstrated the utility of positively charged bacterial cellulose in tissue engineering in the absence of proteins for cell attachment. [ABSTRACT FROM AUTHOR]

Correction to: I Nature Communications i https://doi.org/10.1038/s41467-022-33415-5, published online 12 October 2022 The original version of this Article contained an error in the Discussion, which incorrectly read 'Lack of recovery was associated with more severe infection, older age, female gender, black and South Asian ethnic groups, deprivation, pre-existing respiratory disease and multimorbidity but pre-infection vaccination was associated with reduced risk of some persistent symptoms.'. The correct version states "white ethnicity" in place of "black and South Asian ethnic groups". This has been corrected in both the PDF and HTML versions of the Article. The original article can be found online at https://doi.org/10.1038/s41467-022-33415-5. [Extracted from the article]

Circulating tumor cells are commonly observed in the peripheral blood of advanced breast cancer patients. We tested the feasibility of tumor cell detection in the cerebrospinal fluid (CSF) and studied its clinical relevance in leptomeningeal metastasis (LM) of breast cancer. CSF samples were collected from 38 metastatic breast cancer patients known or suspected to have LM. Control CSF samples were collected from 14 individuals without solid tumor malignancy. We used a modified CellSearch™ assay and an alternative EPCAM-based method involving immunomagnetic enrichment followed by flow cytometry (IE/FC) to enumerate CSF tumor cells (CSFTCs). CSFTCs were assayed at time of LM diagnosis and over the course of LM-directed therapy. We analyzed a total of 102 CSF samples with modified CellSearch™. The CSFTC counts were strongly correlated with the corresponding IE/FC results (Pearson's r = 0.94). Twenty-eight out of 30 samples in which malignant cells were identified by CSF cytology were CSFTC-positive by modified CellSearch™. Baseline CSFTC levels from 21 patients eventually diagnosed with LM were significantly higher than the controls ( p = 0.0202), whereas 13 patients deemed not to have LM showed CSFTC results indistinguishable from the controls. In patients with serial samples, it was possible to monitor CSFTC levels as a potential biomarker of treatment response. CSFTC detection using a modified CellSearch™ assay demonstrated high sensitivity in detecting malignant cells in CSF and may be a promising method for diagnosing LM and monitoring LM during treatment. [ABSTRACT FROM AUTHOR]

Circulating tumor cells (CTCs) are prognostic in all stages of breast cancer. However, since they are extremely rare, little is known about the molecular nature of these cells. We report a novel strategy for the isolation and expression profiling of pure populations of CTCs derived from peripheral blood. We developed a method to isolate CTCs based on immunomagnetic capture followed by fluorescence-activated cell sorting (IE/FACS). After assay validation using the BT474 cell line spiked into blood samples in vitro, RNA from CTCs isolated from the blood of five metastatic breast cancer (MBC) patients was linearly amplified and subjected to gene expression profiling via cDNA microarrays. We isolated a range of 9-993 captured CTCs from five MBC patients' blood and profiled their RNA in comparison to a diverse panel of primary breast tumors ( n = 55). Unsupervised hierarchical clustering revealed that CTC profiles clustered with more aggressive subtypes of primary breast tumors and were readily distinguishable from peripheral blood (PB) and normal epithelium. Differential expression analysis revealed CTCs to have downregulated apoptosis, and they were distinguishable from PB by the relative absence of immune-related signals. As expected, CTCs from MBC had significantly higher risk of recurrence scores than primary tumors (p = 0.0073). This study demonstrates that it is feasible to isolate CTCs from PB with high purity through IE/FACS and profile them via gene expression analysis. Our approach may inform the discovery of therapeutic predictors and be useful for real-time identification of emerging resistance mechanisms in MBC patients. [ABSTRACT FROM AUTHOR]

Preclinical data have demonstrated that the combination of antihuman epidermal growth factor receptor-2 (anti-HER2) and antivascular endothelial growth factor (anti-VEGF)-targeted agents has antitumor activity; these data indicate certain patients with HER2-overexpressing breast cancer may derive clinical benefit from this combination. The purpose of this single-arm phase II study was to determine the efficacy and safety of the dual-targeting combination of lapatinib and bevacizumab. Women with HER2-overexpressing advanced breast cancer received 1,500 mg oral lapatinib daily plus 10 mg/kg IV bevacizumab every 2 weeks. The primary endpoint was progression-free survival (PFS) at week 12; secondary endpoints included overall tumor response rate (ORR), clinical benefit rate (CBR), duration of response, time-to-response, PFS, and safety. Circulating tumor cells (CTC) and circulating endothelial cells (CEC) were measured at baseline and during study treatment as potential response markers. Fifty-two patients with stage IV disease were enrolled. The 12-week investigator-assessed PFS rate was 69.2% (95% confidence interval [CI]: 54.9, 81.3). Median PFS was 24.7 weeks (95% CI: 20.4, 35.1), and the CBR was 30.8% (95% CI: 18.7, 45.1). Of 45 patients with measurable disease, 6 were determined to have a partial response per Response Evaluation Criteria in Solid Tumors (ORR: 13.3%; 95% CI: 5.1, 26.8). The most common adverse events (AEs) included diarrhea, rash, and fatigue; most of these were either grade 1 or 2. Clinical responses were correlated with decreases in CTC and CEC. Lapatinib plus bevacizumab was active in patients with HER2-overexpressing breast cancer. The AE profile of the combination was consistent with the known profiles for these agents. [ABSTRACT FROM AUTHOR]

Purpose: No standard of care exists for patients with metastatic pancreatic cancer following progression on first-line chemotherapy. Based on potential for additive or synergistic activity by concurrent inhibition of VEGF and EGFR, we conducted a phase II study evaluating the combination of bevacizumab plus erlotinib in this patient population. Methods: Patients with metastatic pancreatic adenocarcinoma, ECOG performance status 0-1, and previous exposure to 1-3 systemic therapies (at least one gemcitabine-based) were eligible. Treatment consisted of bevacizumab 15 mg/kg every 21 days plus erlotinib 150 mg daily. Results: Thirty-six patients were enrolled, including eight who had previously received VEGF-targeted therapy and nine prior erlotinib. Median number of treatment cycles was 2 (range, 1-7). Common toxicities included rash (72%), diarrhea (25%), venous thromboembolic events (15%), and hypertension (11%). One patient demonstrated partial response and seven others stable disease for >2 cycles. CA19-9 decline ≥25% was observed in 4/26 patients with baseline levels >2 x ULN. Estimated median time to progression was 40 days (95% CI, 35-41 days) and median survival 102 days (95% CI, 74-117 days), with a 6-month survival rate of 22%. Baseline concentration of circulating endothelial cells (CD45/CD34/CD31) was inversely associated with overall survival. Conclusions: The combination of bevacizumab and erlotinib is safe but relatively ineffective in patients with gemcitabine-refractory metastatic pancreatic cancer. Future studies should focus on refining subsets of patients in this challenging population likely to benefit from treatment beyond first-line. [ABSTRACT FROM AUTHOR]