Scara1 deficiency impairs clearance of soluble Amyloid-β by mononuclear phagocytes and accelerates Alzheimer’s-like disease progression

In Alzheimer’s disease soluble amyloid beta (sAβ) causes synaptic dysfunction and neuronal loss. Receptors involved in clearance of sAβ are not known. Here we use shRNA screening and identify the scavenger receptor Scara1 as a receptor for sAβ expressed on myeloid cells. To determine the role of Scara1 in clearance of sAβ in vivo, we cross Scara1 null mice with PS1-APP mice, a mouse model of Alzheimer’s disease and generate PS1-APP- Scara1-deficient mice. Scara1 deficiency markedly accelerates Aβ accumulation leading to increased mortality. In contrast, pharmacological upregulation of Scara1 expression on mononuclear phagocytes increases Aβ clearance. This approach is a potential treatment strategy for Alzheimer’s disease

Scara1 deficiency impairs clearance of soluble Amyloid-β by mononuclear phagocytes and accelerates Alzheimer’s-like disease progression

In Alzheimer’s disease soluble amyloid beta (sAβ) causes synaptic dysfunction and neuronal loss. Receptors involved in clearance of sAβ are not known. Here we use shRNA screening and identify the scavenger receptor Scara1 as a receptor for sAβ expressed on myeloid cells. To determine the role of Scara1 in clearance of sAβ in vivo, we cross Scara1 null mice with PS1-APP mice, a mouse model of Alzheimer’s disease and generate PS1-APP- Scara1-deficient mice. Scara1 deficiency markedly accelerates Aβ accumulation leading to increased mortality. In contrast, pharmacological upregulation of Scara1 expression on mononuclear phagocytes increases Aβ clearance. This approach is a potential treatment strategy for Alzheimer’s disease

Living Under Coronavirus and Injecting Drugs in Bristol (LUCID-B): a qualitative study of experiences of COVID-19 among people who inject drugs

BACKGROUND: : People who inject drugs (PWID) are a high-risk group for COVID-19 transmission and serious health consequences. Restrictions imposed in the UK in response to the pandemic led to rapid health and housing service alterations. We aimed to examine PWID experiences of: 1) challenges relating to the COVID-19 public health measures; 2) changes to opioid substitution therapy (OST) and harm reduction services; and 3) perceived effects of COVID-19 on drug use patterns and risk behaviour. METHODS: : Telephone semi-structured interviews were conducted with 28 PWID in Bristol, Southwest of England. Analysis followed a reflexive thematic analysis. RESULTS: : Concern about COVID-19 and adherence to public health guidance varied. Efforts made by services to continue providing support during the pandemic were appreciated and some changes were preferred, such as less frequent OST collection, relaxation of supervised consumption and needle and syringe programmes (NSP) home delivery. However, remote forms of contact were highlighted as less beneficial and more difficult to engage with than in-person contact. Public health guidance advising people to ‘stay home’ led to increased isolation, boredom, and time to ruminate which impacted negatively on mental health. Lockdown restrictions directly impacted on sources of income and routine. Changes in drug use were explained as a consequence of isolation and fewer interactions with peers, problems accessing drugs, reduced drug purity and reduced financial resources. CONCLUSION: : This study captures the significant impacts and challenges of the COVID-19 pandemic on the lives of PWID. While rapid adaptations to service delivery to help mitigate the risks of COVID-19 were appreciated and some changes such as relaxation of supervised daily OST consumption were viewed positively, barriers to access need further attention. Going forwards there may be opportunities to harness the positive aspects of some changes to services

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Incisional hernia following colorectal cancer surgery according to suture technique: Hughes Abdominal Repair Randomized Trial (HART).

BACKGROUND: Incisional hernias cause morbidity and may require further surgery. HART (Hughes Abdominal Repair Trial) assessed the effect of an alternative suture method on the incidence of incisional hernia following colorectal cancer surgery. METHODS: A pragmatic multicentre single-blind RCT allocated patients undergoing midline incision for colorectal cancer to either Hughes closure (double far-near-near-far sutures of 1 nylon suture at 2-cm intervals along the fascia combined with conventional mass closure) or the surgeon's standard closure. The primary outcome was the incidence of incisional hernia at 1 year assessed by clinical examination. An intention-to-treat analysis was performed. RESULTS: Between August 2014 and February 2018, 802 patients were randomized to either Hughes closure (401) or the standard mass closure group (401). At 1 year after surgery, 672 patients (83.7 per cent) were included in the primary outcome analysis; 50 of 339 patients (14.8 per cent) in the Hughes group and 57 of 333 (17.1 per cent) in the standard closure group had incisional hernia (OR 0.84, 95 per cent c.i. 0.55 to 1.27; P = 0.402). At 2 years, 78 patients (28.7 per cent) in the Hughes repair group and 84 (31.8 per cent) in the standard closure group had incisional hernia (OR 0.86, 0.59 to 1.25; P = 0.429). Adverse events were similar in the two groups, apart from the rate of surgical-site infection, which was higher in the Hughes group (13.2 versus 7.7 per cent; OR 1.82, 1.14 to 2.91; P = 0.011). CONCLUSION: The incidence of incisional hernia after colorectal cancer surgery is high. There was no statistical difference in incidence between Hughes closure and mass closure at 1 or 2 years. REGISTRATION NUMBER: ISRCTN25616490 (http://www.controlled-trials.com)

Prompt K_short production in pp collisions at sqrt(s)=0.9 TeV

The production of K_short mesons in pp collisions at a centre-of-mass energy of 0.9 TeV is studied with the LHCb detector at the Large Hadron Collider. The luminosity of the analysed sample is determined using a novel technique, involving measurements of the beam currents, sizes and positions, and is found to be 6.8 +/- 1.0 microbarn^-1. The differential prompt K_short production cross-section is measured as a function of the K_short transverse momentum and rapidity in the region 0 < pT < 1.6 GeV/c and 2.5 < y < 4.0. The data are found to be in reasonable agreement with previous measurements and generator expectations.Comment: 6+18 pages, 6 figures, updated author lis

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency–Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research

Observation of proton-tagged, central (semi)exclusive production of high-mass lepton pairs in pp collisions at 13 TeV with the CMS-TOTEM precision proton spectrometer

The process pp -> pl(+)l(-)p(()*()), with l(+)l(-) a muon or an electron pair produced at midrapidity with mass larger than 110 GeV, has been observed for the first time at the LHC in pp collisions at root s = 13 TeV. One of the two scattered protons is measured in the CMS-TOTEM precision proton spectrometer (CT-PPS), which operated for the first time in 2016. The second proton either remains intact or is excited and then dissociates into a low-mass state p*, which is undetected. The measurement is based on an integrated luminosity of 9.4 fb(-1) collected during standard, high-luminosity LHC operation. A total of 12 mu(+)/mu(-) and 8 e(+)e(-) pairs with m(l(+)l(-)) > 110 GeV, and matching forward proton kinematics, are observed, with expected backgrounds of 1.49 +/- 0.07 (stat) +/- 0.53 (syst) and 2.36 +/- 0.09 (stat) +/- 0.47(syst), respectively. This corresponds to an excess of more than five standard deviations over the expected background. The present result constitutes the first observation of proton-tagged gamma gamma collisions at the electroweak scale. This measurement also demonstrates that CT-PPS performs according to the design specifications.Peer reviewe

Measurement of single-diffractive dijet production in proton-proton collisions at root s=8 TeV with the CMS and TOTEM experiments

A Publisher's Erratum to this article was published on 03 May 2021. https://doi.org/10.1140/epjc/s10052-021-08863-wPeer reviewe