bluuebunny/crossref_metadata_2025_split huggingface dataset:
SARS-CoV-2 lineage B.1.1.7 is associated with greater disease severity among hospitalised women but not men: multicentre cohort study
Authors: Stirrup Oliver , Boshier Florencia , Venturini Cristina , Guerra-Assunção José Afonso , Alcolea-Medina Adela , Beckett Angela , Charalampous Themoula , da Silva Filipe Ana , Glaysher Sharon , Khan Tabassum , Kulasegaran Shylini Raghavendran , Kele Beatrix , Monahan Irene , Mollett Guy , Parker Matthew , Pelosi Emanuela , Randell Paul , Roy Sunando , Taylor Joshua , Weller Sophie , Wilson-Davies Eleri , Wade Phillip , Williams Rachel ,   The COG-UK-HOCI Variant substudy consortium,   The COVID-19 Genomics UK (COG-UK) consortium, Copas Andrew , Cutino-Moguel Maria-Teresa , Freemantle Nick , Hayward Andrew C , Holmes Alison , Hughes Joseph , Mahungu Tabitha , Nebbia Gaia , Partridge David , Pope Cassie , Price James , Robson Samuel , Saeed Kordo , de Silva Thushan , Snell Luke , Thomson Emma , Witney Adam A , Breuer Judith 
Published: September 2021

BackgroundSARS-CoV-2 lineage B.1.1.7 has been associated with an increased rate of transmission and disease severity among subjects testing positive in the community. Its impact on hospitalised patients is less well documented.MethodsWe collected viral sequences and clinical data of patients admitted with SARS-CoV-2 and hospital-onset COVID-19 infections (HOCIs), sampled 16 November 2020 to 10 January 2021, from eight hospitals participating in the COG-UK-HOCI study. Associations between the variant and the outcomes of all-cause mortality and intensive therapy unit (ITU) admission were evaluated using mixed effects Cox models adjusted by age, sex, comorbidities, care home residence, pregnancy and ethnicity.FindingsSequences were obtained from 2341 inpatients (HOCI cases=786) and analysis of clinical outcomes was carried out in 2147 inpatients with all data available. The HR for mortality of B.1.1.7 compared with other lineages was 1.01 (95% CI 0.79 to 1.28, p=0.94) and for ITU admission was 1.01 (95% CI 0.75 to 1.37, p=0.96). Analysis of sex-specific effects of B.1.1.7 identified increased risk of mortality (HR 1.30, 95% CI 0.95 to 1.78, p=0.096) and ITU admission (HR 1.82, 95% CI 1.15 to 2.90, p=0.011) in females infected with the variant but not males (mortality HR 0.82, 95% CI 0.61 to 1.10, p=0.177; ITU HR 0.74, 95% CI 0.52 to 1.04, p=0.086).InterpretationIn common with smaller studies of patients hospitalised with SARS-CoV-2, we did not find an overall increase in mortality or ITU admission associated with B.1.1.7 compared with other lineages. However, women with B.1.1.7 may be at an increased risk of admission to intensive care and at modestly increased risk of mortality.
Prospective, double-blind diagnostic multicentre study of confocal laser endomicroscopy for wheat sensitivity in patients with irritable bowel syndrome
Authors: Bojarski Christian , Tangermann Paul , Barmeyer Christian , Buchkremer Juliane , Kiesslich Ralf , Ellrichmann Mark , Schreiber Stefan , Schmidt Carsten , Stallmach Andreas , Roehle Robert , Loddenkemper Christoph , Daum Severin , Siegmund Britta , Schumann Michael , Ullrich Reiner 
Published: September 2021

ObjectiveA considerable proportion of patients with irritable bowel syndrome (IBS) may be wheat-sensitive and respond to a gluten-free diet (GFD) although they do not have coeliac disease. However, a diagnostic test for wheat sensitivity (WS) is missing. Our study evaluated the diagnostic accuracy (sensitivity and specificity) of confocal laser endomicroscopy (CLE) for the identification of WS as primary outcome.DesignIn this prospective, double-blind diagnostic study 147 non-coeliac patients fulfilling the Rome III criteria for IBS were tested by CLE for duodenal changes after wheat (index test), soy, yeast or milk exposure. Patients with IBS responding to 2 months of GFD were classified as having WS (reference test) using response criteria recommended by regulatory bodies for pharmaceutical trials of patients with IBS. After 2 months, CLE results were unblinded and patients were advised to exclude those food components that had led to a positive CLE reaction. The clinical response was assessed at follow-up after 6 and 12 months.ResultsOf 130 patients who completed the study per protocol, 74 (56.9%) responded to GFD and were classified as WS after 2 months, and 38 of these 74 patients were correctly identified by CLE (sensitivity 51.4%; 97.5% CI: 38.7% to 63.9%). A total of 38 of 56 patients without WS were correctly identified by CLE (specificity 67.9%; 97.5% CI: 52.9% to 79.9%). At 6 months follow-up, CLE correctly identified 49 of 59 food-sensitive patients (sensitivity 83.1%; 97.5% CI: 69.9% to 91.3%) but specificity was only 32% (97.5% CI: 15.7% to 54.3%).ConclusionIn light of the high proportion of patients with IBS responding to GFD, the diagnostic accuracy of CLE is too low to recommend widespread use of this invasive procedure.Trail registration numberThis study was registered as clinical trial in the German Registry for Clinical Studies (DRKS00010123).
Effect of a multidisciplinary Severe Immunotherapy Complications Service on outcomes for patients receiving immune checkpoint inhibitor therapy for cancer
Authors: Zubiri Leyre , Molina Gabriel E , Mooradian Meghan J , Cohen Justine , Durbin Sienna M , Petrillo Laura , Boland Genevieve M , Juric Dejan , Dougan Michael , Thomas Molly F , Faje Alex T , Rengarajan Michelle , Guidon Amanda C , Chen Steven T , Okin Daniel , Medoff Benjamin D , Nasrallah Mazen , Kohler Minna J , Schoenfeld Sara R , Leaf Rebecca K , Sise Meghan E , Neilan Tomas G , Zlotoff Daniel A , Farmer Jocelyn R , Bardia Aditya , Sullivan Ryan J , Blum Steven M , Semenov Yevgeniy R , Villani Alexandra-Chloé , Reynolds Kerry L 
Published: September 2021

BackgroundIn 2017, Massachusetts General Hospital implemented the Severe Immunotherapy Complications (SIC) Service, a multidisciplinary care team for patients hospitalized with immune-related adverse events (irAEs), a unique spectrum of toxicities associated with immune checkpoint inhibitors (ICIs). This study’s objectives were to evaluate the intervention’s (1) effect on patient outcomes and healthcare utilization, and (2) ability to collect biological samples via a central infrastructure, in order to study the mechanisms responsible for irAEs.MethodsA hospital database was used to identify patients who received ICIs for a malignancy and were hospitalized with severe irAEs, before (April 2, 2016–October 3, 2017) and after (October 3, 2017–October 24, 2018) SIC Service initiation. The primary outcome was readmission rate after index hospitalization. Secondary outcomes included length of stay (LOS) for admissions, corticosteroid and non-steroidal second-line immunosuppression use, ICI discontinuation, and inpatient mortality.ResultsIn the pre-SIC period, 127 of 1169 patients treated with ICIs were hospitalized for irAEs; in the post-SIC period, 122 of 1159. After SIC service initiation, reductions were observed in irAE readmission rate (14.8% post-SIC vs 25.9% pre-SIC; OR 0.46; 95% CI 0.22 to 0.95; p=0.036) and readmission LOS (median 6 days post-SIC vs 7 days pre-SIC; 95% CI −16.03 to –0.14; p=0.046). No significant pre-initiation and post-initiation differences were detected in corticosteroid use, second-line immunosuppression, ICI discontinuation, or inpatient mortality rates. The SIC Service collected 789 blood and tissue samples from 234 patients with suspected irAEs.ConclusionsThis is the first study to report that establishing a highly subspecialized care team focused on irAEs is associated with improved patient outcomes and reduced healthcare utilization. Furthermore, the SIC Service successfully integrated blood and tissue collection safety into routine care.
A step forward, but still inadequate: Australian health professionals’ views on the genetics and life insurance moratorium
Authors: Tiller Jane M , Keogh Louise A , McInerney-Leo Aideen M , Belcher Andrea , Barlow-Stewart Kristine , Boughtwood Tiffany , Gleeson Penny , Dowling Grace , Prince Anya , Bombard Yvonne , Joly Yann , Delatycki Martin , Winship Ingrid M , Otlowski Margaret , Lacaze Paul 
Published: September 2021

BackgroundIn 2019, the Australian life insurance industry introduced a partial moratorium (ban) limiting the use of genetic test results in life insurance underwriting. The moratorium is industry self-regulated and applies only to policies below certain financial limits (eg, $500 000 of death cover).MethodsWe surveyed Australian health professionals (HPs) who discuss genetic testing with patients, to assess knowledge of the moratorium; reported patient experiences since its commencement; and HP views regarding regulation of genetic discrimination (GD) in Australia.ResultsBetween April and June 2020, 166 eligible HPs responded to the online survey. Of these, 86% were aware of the moratorium, but <50% had attended related training/information sessions. Only 16% answered all knowledge questions correctly, yet 69% believed they had sufficient knowledge to advise patients. Genetics HPs’ awareness and knowledge were better than non-genetics HPs’ (p<0.05). There was some reported decrease in patients delaying/declining testing after the moratorium’s introduction, however, 42% of HPs disagreed that patients were more willing to have testing post-moratorium. Although many (76%) felt the moratorium resolved some GD concerns, most (88%) still have concerns, primarily around self-regulation, financial limits and the moratorium’s temporary nature. Almost half (49%) of HPs reported being dissatisfied with the moratorium as a solution to GD. The majority (95%) felt government oversight is required, and 93% felt specific Australian legislation regarding GD is required.ConclusionWhile the current Australian moratorium is considered a step forward, most HPs believe it falls short of an adequate long-term regulatory solution to GD in life insurance.
Efficacy of combined use of a stent retriever and aspiration catheter in mechanical thrombectomy for acute ischemic stroke
Authors: Okuda Tomohiro , Arimura Koichi , Matsuo Ryu , Tokunaga So , Hara Kenta , Yamaguchi Shinya , Yoshida Hidenori , Kurogi Ryota , Kameda Katsuharu , Ito Osamu , Tsumoto Tomoyuki , Iihara Koji , Mizokami Taichiro , Uwatoko Takeshi , Nishimura Ataru , Iwaki Katsuma , Mizoguchi Masahiro 
Published: September 2021

BackgroundThe efficacy of combined stent retriever (SR) and aspiration catheter (AC; combined technique: CBT) use for acute ischemic stroke (AIS) is unclear. We investigated the safety and efficacy of single-unit CBT (SCBT)—retrieving the thrombus as a single unit with SR and AC into the guide catheter—compared with single use of either SR or contact aspiration (CA).MethodsWe analysed 763 consecutive patients who underwent mechanical thrombectomy for AIS between January 2013 and January 2020, at six comprehensive stroke centers. Patients were divided into SCBT and single device (SR/CA) groups. The successful recanalization with first pass (SRFP) and other procedural outcomes were compared between groups.ResultsOverall, 240 SCBT and 301 SR/CA (SR 128, CA 173) patients were analyzed. SRFP (modified Thrombolysis In Cerebral Infarction (mTICI) ≥2c, 43.3% vs 27.9%, p<0.001; mTICI 3, 35.8% vs 25.5%, p=0.009) and final mTICI ≥2b recanalization (89.1% vs 82.0%, p=0.020) rates were significantly higher, puncture-to-reperfusion time was shorter (median (IQR) 43 (31.5–69) vs 55 (38–82.2) min, p<0.001), and the number of passes were fewer (mean±SD 1.72±0.92 vs 1.99±1.01, p<0.001) in the SCBT group. Procedural complications were similar between the groups. In subgroup analysis, SCBT was more effective in women, cardioembolic stroke patients, and internal carotid artery and M2 occlusions.ConclusionsSCBT increases the SRFP rate and shortens the puncture-to-reperfusion time without increasing procedural complications.
Non-ischemic cerebral enhancing lesions after intracranial aneurysm endovascular repair: a retrospective French national registry
Authors: Shotar Eimad , Labeyrie Marc-Antoine , Biondi Alessandra , Velasco Stéphane , Saliou Guillaume , Boulouis Grégoire , Daumas-Duport Benjamin , Bourcier Romain , Janot Kevin , Herbreteau Denis , Michelozzi Caterina , Premat Kevin , Redjem Hocine , Bricout Nicolas , Thouant Pierre , Arteaga Charles , Pierot Laurent , Tahon Florence , Boubagra Kamel , Ikka Leon , Chabert Emmanuel , Lenck Stéphanie , Guédon Alexis , Consoli Arturo , Saleme Suzana , di Maria Federico , Ferré Jean-Christophe , Eugene Francois , Anxionnat René , Marnat Gaultier , Guetarni Zakaria , Sourour Nader-Antoine , Dormont Didier , Clarençon Frédéric 
Published: September 2021

BackgroundNon-ischemic cerebral enhancing (NICE) lesions are exceptionally rare following aneurysm endovascular therapy (EVT).ObjectiveTo investigate the presenting features and longitudinal follow-up of patients with NICE lesions following aneurysm EVT.MethodsPatients included in a retrospective national multicentre inception cohort were analysed. NICE lesions were defined, using MRI, as delayed onset punctate, nodular or annular foci enhancements with peri-lesion edema, distributed in the vascular territory of the aneurysm EVT, with no other confounding disease.ResultsFrom a pool of 58 815 aneurysm endovascular treatment procedures during the study sampling period (2006–2019), 21/37 centres identified 31 patients with 32 aneurysms of the anterior circulation who developed NICE lesions (mean age 45±10 years). Mean delay to diagnosis was 5±9 months, with onset occurring a month or less after the index EVT procedure in 10 out of 31 patients (32%). NICE lesions were symptomatic at time of onset in 23 of 31 patients (74%). After a mean follow-up of 25±26 months, 25 patients (81%) were asymptomatic or minimally symptomatic without disability (modified Rankin Scale (mRS) score 0–1) at last follow-up while 4 (13%) presented with mild disability (mRS score 2). Clinical follow-up data were unavailable for two patients. Follow-up MRI (available in 27 patients; mean time interval after onset of 22±22 months) demonstrated persistent enhancement in 71% of cases.ConclusionsThe clinical spectrum of NICE lesions following aneurysm EVT therapy spans a wide range of neurological symptoms. Clinical course is most commonly benign, although persistent long-term enhancement is frequent.
Perceived sources of occupational burn-out and embitterment among front-line health workers for COVID-19 control in Gyeonggi province, South Korea: a qualitative study
Authors: Kang Bee-Ah , Kwon Sijoung , You Myoungsoon , Lee Heeyoung 
Published: September 2021

ObjectivesFront-line health workers (FHWs) for COVID-19 control in South Korea have implemented a labour-intensive contact tracing programme, which places them at high risk for mental health problems. However, a few studies have examined mental health conditions in this population. We employed a qualitative approach to understand the factors perceived as causes of burn-out and embitterment among temporary FHWs to provide recommendations for supporting the workforce.MethodsWe recruited 20 FHWs to participate in semistructured focus group interviews through purposive sampling. The sample size was determined on the basis of data saturation. We collected data from October to November 2020, audiorecording and transcribing the interviews. Data analysis was conducted manually, applying the principles of grounded theory.ResultsFive levels of perceived sources of occupational burn-out and embitterment emerged. FHWs showed considerable mistrust of patients and faced ethical dilemmas in accessing and disclosing personal information. Poor collaboration with community health centre workers and interested parties as well as inadequate organisational support aggravated their conditions. Lack of social recognition and employment instability also presented challenges for FHWs’ mental health.ConclusionsThe current pandemic response system imposes great moral and emotional burdens on the workforce, prompting the need for initiatives to safeguard the values and needs of those who represent the backbone of the system. This study suggests that multilevel strategies, including providing organisational support and establishing contingency plans for workforce management and resource distribution, may improve FHWs’ mental health outcomes as well as the health system for emergency preparedness.
Spatiotemporal evolution of large igneous provinces and their related rifts in the North China craton: role in craton breakup and destruction
Authors: Peng Peng , Xu Huiru , Wang Chong , Su Xiangdong , Sun Fengbo , Wang Xinping 
Published: September 2021

Abstract

The North China craton is encircled by four successive triple-conjugated rifts, which are respectively the centres of large igneous provinces (LIPs) of bimodal compositions, i.e. Xiong'er rift (south,
c.
1.78 Ga Taihang LIP), Yanliao rift (north,
c.
1.32 Ga Yanliao LIP), Xuhuai rift (east,
c.
1.23 Ga Licheng and
c.
0.92 Ga Dashigou LIPs) and Langshan rift (west,
c.
0.82 Ga Qianlishan LIP). These rifts are genetically related to their contemporaneous LIPs based on their consistent geometry. Spatial migration of these rifts and LIPs indicates their propagation from along one marginal side to the opposite side of the craton, which may have resulted in the sequential breakup of the proto-North China craton from one side to the other during 1.8–0.8 Ga. However, the observation that the lithosphere under the LIP-associated rift regions is less destroyed (decratonized) in the Mesozoic indicates a possible role of LIPs in strengthening intracratonic steady state. This study shows that LIPs may change craton stability in either direction.
Massively Parallel Computation via Remote Memory Access
Authors: Behnezhad Soheil , Dhulipala Laxman , Esfandiari Hossein , Łącki Jakub , Mirrokni Vahab , Schudy Warren 
Published: September 2021

We introduce the
Adaptive Massively Parallel Computation
(AMPC) model, which is an extension of the
Massively Parallel Computation
(MPC) model. At a high level, the AMPC model strengthens the MPC model by storing all messages sent within a round in a distributed data store. In the following round, all machines are provided with random read access to the data store, subject to the same constraints on the total amount of communication as in the MPC model. Our model is inspired by the previous empirical studies of distributed graph algorithms [8, 30] using MapReduce and a distributed hash table service [17].

This extension allows us to give new graph algorithms with much lower round complexities compared to the best-known solutions in the MPC model. In particular, in the AMPC model we show how to solve maximal independent set in
O
(1) rounds and connectivity/minimum spanning tree in
O
(log log

m
/
n

n
rounds both using
O
(
n
δ
) space per machine for constant δ < 1. In the same memory regime for MPC, the best-known algorithms for these problems require poly log
n
rounds. Our results imply that the 2-C
YCLE
conjecture, which is widely believed to hold in the MPC model, does not hold in the AMPC model.
Efficient Parallel 3D Computation of the Compressible Euler Equations with an Invariant-domain Preserving Second-order Finite-element Scheme
Authors: Maier Matthias , Kronbichler Martin 
Published: September 2021

We discuss the efficient implementation of a high-performance second-order collocation-type finite-element scheme for solving the compressible Euler equations of gas dynamics on unstructured meshes. The solver is based on the
convex-limiting
technique introduced by Guermond et al. (SIAM J. Sci. Comput. 40, A3211–A3239, 2018). As such, it is
invariant-domain preserving
; i.e., the solver maintains important physical invariants and is guaranteed to be stable without the use of ad hoc tuning parameters. This stability comes at the expense of a significantly more involved algorithmic structure that renders conventional high-performance discretizations challenging. We develop an algorithmic design that allows SIMD vectorization of the compute kernel, identify the main ingredients for a good node-level performance, and report excellent weak and strong scaling of a hybrid thread/MPI parallelization.
RTK-Dependent Inducible Degradation of Mutant PI3Kα Drives GDC-0077 (Inavolisib) Efficacy
Authors: Song Kyung W. , Edgar Kyle A. , Hanan Emily J. , Hafner Marc , Oeh Jason , Merchant Mark , Sampath Deepak , Nannini Michelle A. , Hong Rebecca , Phu Lilian , Forrest William F. , Stawiski Eric , Schmidt Stephen , Endres Nicholas , Guan Jane , Wallin Jeffrey J. , Cheong Jonathan , Plise Emile G. , Lewis Phillips Gail D. , Salphati Laurent , Heffron Timothy P. , Olivero Alan G. , Malek Shiva , Staben Steven T. , Kirkpatrick Donald S. , Dey Anwesha , Friedman Lori S. 
Published: September 2021

AbstractPIK3CA is one of the most frequently mutated oncogenes; the p110a protein it encodes plays a central role in tumor cell proliferation. Small-molecule inhibitors targeting the PI3K p110a catalytic subunit have entered clinical trials, with early-phase GDC-0077 studies showing antitumor activity and a manageable safety profile in patients with PIK3CA-mutant breast cancer. However, preclinical studies have shown that PI3K pathway inhibition releases negative feedback and activates receptor tyrosine kinase signaling, reengaging the pathway and attenuating drug activity. Here we discover that GDC-0077 and taselisib more potently inhibit mutant PI3K pathway signaling and cell viability through unique HER2-dependent mutant p110a degradation. Both are more effective than other PI3K inhibitors at maintaining prolonged pathway suppression. This study establishes a new strategy for identifying inhibitors that specifically target mutant tumors by selective degradation of the mutant oncoprotein and provide a strong rationale for pursuing PI3Kα degraders in patients with HER2-positive breast cancer.Significance:The PI3K inhibitors GDC-0077 and taselisib have a unique mechanism of action; both inhibitors lead to degradation of mutant p110a protein. The inhibitors that have the ability to trigger specific degradation of mutant p110a without significant change in wild-type p110a protein may result in improved therapeutic index in PIK3CA-mutant tumors.See related commentary by Vanhaesebroeck et al., p. 20.This article is highlighted in the In This Issue feature, p. 1