bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhaled corticosteroids andStenotrophomonas maltophiliain outpatients with chronic obstructive pulmonary disease: a retrospective cohort study
Authors: Rønn Christian , Kamstrup Peter , Heerfordt Christian Kjer , Sivapalan Pradeesh , Eklöf Josefin , Boel Jonas Bredtoft , Ostergaard Christian , Dessau Ram Benny , Moberg Mia , Janner Julie , Ulrik Charlotte Suppli , Jensen Jens-Ulrik Stæhr
Published: June 2024

Objectives

Inhaled corticosteroids (ICS) are widely used in patients with chronic obstructive pulmonary disease (COPD). However, ICS are associated with an increased risk of adverse effects.

We aimed to determine whether an association between a lower respiratory tract culture withStenotrophomonas maltophiliaand increasing ICS dosing in patients with COPD exists.

Design

An observational cohort study of outpatients with COPD in Denmark between 2010 and 2018.

ICS exposure was categorised into four groups based on average daily consumption 1 year prior to inclusion: no use, low ICS dose (≤400 µg), moderate ICS dose (400–800 µg) and high ICS dose (>800 µg). Dose–response relationship was investigated by a multivariable Cox proportional hazards regression.

Results

Of the total 22 689 patients, 459 had lower respiratory tract cultures positive forS. maltophilia. The HR ofS. maltophiliaincreased with increasing daily ICS dose: low ICS dose HR 2.6 (95% CI 1.6 to 4.0), moderate ICS dose HR 3.0 (95% CI 1.9 to 4.6) and high ICS dose HR 5.7 (95% CI 3.8 to 8.5).

Conclusions

We found that ICS was associated with a high, dose-dependent increased hazard ofS. maltophiliain outpatients with COPD. High dose users had a nearly six times increased hazard compared with non-users of ICS. When appropriate, attempts at de-escalating ICS treatment should be made.
Extracorporeal photopheresis (ECP) in the treatment of chronic lung allograft dysfunction (CLAD): a prospective, multicentre, open-label, randomised controlled trial studying the addition of ECP to standard care in the treatment of bilateral lung transplant patients with CLAD (E-CLAD UK)
Authors: Fisher Andrew J , White Michael , Goudie Nicola , Kershaw Anneka , Phillipson Julia , Bardgett Michelle , Lally Joanne , Bevin-Nicholls Alex , Chadwick Thomas , Bryant Andrew , Russell Sian , Smith Hesther , Frisby Laura , Errington Rebecca , Carby Martin , Thompson Richard , Santhanakrishnan Karthik , Parmar Jasvir , Lordan James L , Vale Luke , Hancock Helen , Exley Catherine , Gennery Andrew R , Wason James MS
Published: June 2024

Background

Long-term survival after lung transplantation is limited compared with other organ transplants. The main cause is development of progressive immune-mediated damage to the lung allograft. This damage, which can develop via multiple immune pathways, is captured under the umbrella term chronic lung allograft dysfunction (CLAD). Despite the availability of powerful immunosuppressive drugs, there are presently no treatments proven to reverse or reliably halt the loss of lung function caused by CLAD. The aim of the E-CLAD UK trial is to determine whether the addition of immunomodulatory therapy, in the form of extracorporeal photopheresis (ECP), to standard care is more efficacious at stabilising lung function in CLAD compared with standard care alone.

Methods and analysis

E-CLAD UK is a Phase II clinical trial of an investigational medicinal product (Methoxsalen) delivered to a buffy coat prepared via an enclosed ECP circuit. Target recruitment is 90 bilateral lung transplant patients identified as having CLAD and being treated at one of the five UK adult lung transplant centres. Participants will be randomised 1:1 to intervention plus standard of care, or standard of care alone. Intervention will comprise nine ECP cycles spread over 20 weeks, each course involving two treatments of ECP on consecutive days. All participants will be followed up for a period of 24 weeks.

The primary outcome is lung function stabilisation derived from change in forced expiratory volume in one second and forced vital capacity at 12 and 24 weeks compared with baseline at study entry. Other parameters include change in exercise capacity, health-related quality of life and safety. A mechanistic study will seek to identify molecular or cellular markers linked to treatment response and qualitative interviews will explore patient experiences of CLAD and the ECP treatment.

A patient and public advisory group is integral to the trial from design to implementation, developing material to support the consent process and interview materials.

Ethics and dissemination

The East Midlands—Derby Research Ethics Committee has provided ethical approval (REC 22/EM/0218). Dissemination will be via publications, patient-friendly summaries and presentation at scientific meetings.

Trial registration number

EudraCT number 2022-002659-20;NCT10615985.
Cessation of Smoking Trial in the Emergency Department (COSTED): a multicentre randomised controlled trial
Authors: Pope Ian , Clark Lucy V , Clark Allan , Ward Emma , Belderson Pippa , Stirling Susan , Parrott Steve , Li Jinshuo , Coats Tim , Bauld Linda , Holland Richard , Gentry Sarah , Agrawal Sanjay , Bloom Benjamin Michael , Boyle Adrian A , Gray Alasdair J , Morris M Geraint , Livingstone-Banks Jonathan , Notley Caitlin
Published: June 2024

Background

Supporting people to quit smoking is one of the most powerful interventions to improve health. The Emergency Department (ED) represents a potentially valuable opportunity to deliver a smoking cessation intervention if it is sufficiently resourced. The objective of this trial was to determine whether an opportunistic ED-based smoking cessation intervention can help people to quit smoking.

Methods

In this multicentre, parallel-group, randomised controlled superiority trial conducted between January and August 2022, adults who smoked daily and attended one of six UK EDs were randomised to intervention (brief advice, e-cigarette starter kit and referral to stop smoking services) or control (written information on stop smoking services). The primary outcome was biochemically validated abstinence at 6 months.

Results

An intention-to-treat analysis included 972 of 1443 people screened for inclusion (484 in the intervention group, 488 in the control group). Of 975 participants randomised, 3 were subsequently excluded, 17 withdrew and 287 were lost to follow-up. The 6-month biochemically-verified abstinence rate was 7.2% in the intervention group and 4.1% in the control group (relative risk 1.76; 95% CI 1.03 to 3.01; p=0.038). Self-reported 7-day abstinence at 6 months was 23.3% in the intervention group and 12.9% in the control group (relative risk 1.80; 95% CI 1.36 to 2.38; p<0.001). No serious adverse events related to taking part in the trial were reported.

Conclusions

An opportunistic smoking cessation intervention comprising brief advice, an e-cigarette starter kit and referral to stop smoking services is effective for sustained smoking abstinence with few reported adverse events.

Trial registration number

NCT04854616
.
At the deep end: towards a social emergency medicine
Authors: McHenry Ryan , Aspden Cath , Quinn Joanna , Loughrey John Paul , Chung David
Published: June 2024

People experiencing the highest levels of social deprivation are more likely to present to emergency care across the spectrum of disease severity, and to have worse outcomes following acute illness. Emergency medicine in the UK and Europe has lagged behind other regions in incorporating social emergency medicine into practice. There is evidence that emergency clinicians have the potential to mitigate health inequalities, through advocacy and intervention supported by high-quality research, while also acknowledging the limitations intrinsic to the environment in which they work.
Molecular assessment of intratumoral immune cell subsets and potential mechanisms of resistance to odronextamab, a CD20×CD3 bispecific antibody, in patients with relapsed/refractory B-cell non-Hodgkin lymphoma
Authors: Brouwer-Visser Jurriaan , Fiaschi Nathalie , Deering Raquel P , Cygan Kamil J , Scott Darius , Jeong Se , Boucher Lauren , Gupta Namita T , Gupta Suraj , Adler Christina , Topp Max S , Bannerji Rajat , Duell Johannes , Advani Ranjana H , Flink Dina M , Chaudhry Aafia , Thurston Gavin , Ambati Srikanth R , Jankovic Vladimir
Published: June 2024

Background

Patients with relapsed/refractory B-cell non-Hodgkin lymphoma (R/R B-NHL) have a significant need for effective treatment options. Odronextamab is an Fc-silenced, human, CD20×CD3 bispecific antibody that targets CD20-expressing cells via T-cell-mediated cytotoxicity independent of T-cell/major histocompatibility complex interaction. Phase I results in patients with R/R B-NHL demonstrated that odronextamab monotherapy could achieve deep and durable responses with a generally manageable safety profile (ELM-1;NCT02290951). As part of a biomarker analysis of the same study, we investigated potential biomarkers and mechanisms of resistance to odronextamab.

Methods

Patients with R/R B-NHL enrolled in ELM-1 received one time per week doses of intravenous odronextamab for 4×21 day cycles, then doses every 2 weeks thereafter. Patient tumor biopsies were obtained at baseline, on-treatment, and at progression. Immune cell markers were analyzed by immunohistochemistry, flow cytometry, single-cell RNA sequencing, and whole genome sequencing.

Results

Baseline tumor biopsies showed that almost all patients had high proportions of B cells that expressed the CD20 target antigen, whereas expression of other B-cell surface antigens (CD19, CD22, CD79b) was more variable. Responses to odronextamab in patients with diffuse large B-cell lymphoma were not related to the relative level of baseline CD20 expression, cell of origin, or high-risk molecular subtype. A potential link was observed between greater tumor programmed cell death-ligand 1 expression and increased likelihood of response to odronextamab. Similarly, a trend was observed between clinical response and increased levels of CD8 T cells and regulatory T cells at baseline. We also identified an on-treatment pharmacodynamic shift in intratumoral immune cell subsets. Finally, loss of CD20 expression through inactivating gene mutations was identified as a potential mechanism of resistance in patients who were treated with odronextamab until progression, as highlighted in two detailed patient cases reported here.

Conclusions

This biomarker analysis expands on clinical findings of odronextamab in patients with R/R B-NHL, providing verification of the suitability of CD20 as a therapeutic target, as well as evidence for potential mechanisms of action and resistance.
COVID-19 and the vaccine tax: an egalitarian, market-based approach to the global vaccine inequality
Authors: Albertsen Andreas
Published: June 2024

The global inequality in the distribution of vaccines is unjust. As countries scrambled to ensure enough vaccines, the world’s poorest were left to fend for themselves, and the generosity meant to mitigate this through COVAX was not sufficiently forthcoming. In light of this, I proposed a vaccine tax, which obligates those willing and able to pay to protect their own population to contribute to protecting those residing in the world’s low-income countries. Petrovic has offered an important critique of this proposal, questioning both the fairness and the efficiency of the tax. However, when properly specified, the vaccine tax is not vulnerable to these critiques.
ZFHX3
variants cause childhood partial epilepsy and infantile spasms with favourable outcomes
Authors: He Ming-Feng , Liu Li-Hong , Luo Sheng , Wang Juan , Guo Jia-Jun , Wang Peng-Yu , Zhai Qiong-Xiang , He Su-Li , Zou Dong-Fang , Liu Xiao-Rong , Li Bing-Mei , Ma Hai-Yan , Qiao Jing-Da , Zhou Peng , He Na , Yi Yong-Hong , Liao Wei-Ping
Published: June 2024

Background

The
ZFHX3
gene plays vital roles in embryonic development, cell proliferation, neuronal differentiation and neuronal death. This study aims to explore the relationship between
ZFHX3
variants and epilepsy.

Methods

Whole-exome sequencing was performed in a cohort of 378 patients with partial (focal) epilepsy. A
Drosophila Zfh2
knockdown model was used to validate the association between
ZFHX3
and epilepsy.

Results

Compound heterozygous
ZFHX3
variants were identified in eight unrelated cases. The burden of
ZFHX3
variants was significantly higher in the case cohort, shown by multiple/specific statistical analyses. In
Zfh2
knockdown flies, the incidence and duration of seizure-like behaviour were significantly greater than those in the controls. The
Zfh2
knockdown flies exhibited more firing in excitatory neurons. All patients presented partial seizures. The five patients with variants in the C-terminus/N-terminus presented mild partial epilepsy. The other three patients included one who experienced frequent non-convulsive status epilepticus and two who had early spasms. These three patients had also neurodevelopmental abnormalities and were diagnosed as developmental epileptic encephalopathy (DEE), but achieved seizure-free after antiepileptic-drug treatment without adrenocorticotropic-hormone/steroids. The analyses of temporal expression (genetic dependent stages) indicated that
ZFHX3
orthologous were highly expressed in the embryonic stage and decreased dramatically after birth.

Conclusion

ZFHX3
is a novel causative gene of childhood partial epilepsy and DEE. The patients of infantile spasms achieved seizure-free after treatment without adrenocorticotropic-hormone/steroids implies a significance of genetic diagnosis in precise treatment. The genetic dependent stage provided an insight into the underlying mechanism of the evolutional course of illness.
Disease-specific variant interpretation highlighted the genetic findings in 2325 Japanese patients with retinitis pigmentosa and allied diseases
Authors: Goto Kensuke , Koyanagi Yoshito , Akiyama Masato , Murakami Yusuke , Fukushima Masatoshi , Fujiwara Kohta , Iijima Hanae , Yamaguchi Mitsuyo , Endo Mikiko , Hashimoto Kazuki , Ishizu Masataka , Hirakata Toshiaki , Mizobuchi Kei , Takayama Masakazu , Ota Junya , Sajiki Ai Fujita , Kominami Taro , Ushida Hiroaki , Fujita Kosuke , Kaneko Hiroki , Ueno Shinji , Hayashi Takaaki , Terao Chikashi , Hotta Yoshihiro , Murakami Akira , Kuniyoshi Kazuki , Kusaka Shunji , Wada Yuko , Abe Toshiaki , Nakazawa Toru , Ikeda Yasuhiro , Momozawa Yukihide , Sonoda Koh-Hei , Nishiguchi Koji M
Published: June 2024

Background

As gene-specific therapy for inherited retinal dystrophy (IRD) advances, unified variant interpretation across institutes is becoming increasingly important. This study aims to update the genetic findings of 86 retinitis pigmentosa (RP)-related genes in a large number of Japanese patients with RP by applying the standardised variant interpretation guidelines for Japanese patients with IRD (J-IRD-VI guidelines) built upon the American College of Medical Genetics and Genomics and the Association for Molecular Pathology rules, and assess the contribution of these genes in RP–allied diseases.

Methods

We assessed 2325 probands with RP (n=2155, including n=1204 sequenced previously with the same sequencing panel) and allied diseases (n=170, newly analysed), including Usher syndrome, Leber congenital amaurosis and cone-rod dystrophy (CRD). Target sequencing using a panel of 86 genes was performed. The variants were interpreted according to the J-IRD-VI guidelines.

Results

A total of 3564 variants were detected, of which 524 variants were interpreted as pathogenic or likely pathogenic. Among these 524 variants, 280 (53.4%) had been either undetected or interpreted as variants of unknown significance or benign variants in our earlier study of 1204 patients with RP. This led to a genetic diagnostic rate in 38.6% of patients with RP, with
EYS
accounting for 46.7% of the genetically solved patients, showing a 9% increase in diagnostic rate from our earlier study. The genetic diagnostic rate for patients with CRD was 28.2%, with RP-related genes significantly contributing over other allied diseases.

Conclusion

A large-scale genetic analysis using the J-IRD-VI guidelines highlighted the population-specific genetic findings for Japanese patients with IRD; these findings serve as a foundation for the clinical application of gene-specific therapies.
Encephalocraniocutaneous lipomatosis phenotype associated with mosaic biallelic pathogenic variants in theNF1gene
Authors: Smeijers Steven , Brems Hilde , Verhaeghe Alexander , van Paesschen Wim , van Loon Johannes , Van der Auweraer Seppe , Sciot Raf , Thal Dietmar Rudolf , Lagae Lieven , Legius Eric , Theys Tom
Published: June 2024

Encephalocraniocutaneous lipomatosis (ECCL) is a sporadic congenital condition characterised by ocular, cutaneous and central nervous system involvement. Mosaic activating variants inFGFR1andKRAShave been reported in several individuals with this syndrome. We report on a patient with neurofibromatosis type 1 (NF1) with a germline pathogenic variant in theNF1gene and an ECCL phenotype, suggesting ECCL to be part of a spectrum of malformations associated withNF1pathogenic variants. An anatomical hemispherectomy was performed for intractable epilepsy. Through genetic analysis of blood, cerebral tissue and giant cell lesions in both jaws, we identified the germlineNF1pathogenic variant in all samples and a second-hit pathogenicNF1variant in cerebral tissue and both giant cell lesions. BothNF1variants were located on different alleles resulting in somatic mosaicism for a biallelicNF1inactivation originating in early embryogenesis (second-hit mosaicism or Happle type 2 mosaicism). The biallelic deficit inNF1in the left hemicranium explains the severe localised, congenital abnormality in this patient. Identical first and second-hit variants in a giant cell lesion of both upper and lower jaws provide confirmatory evidence for an early embryonic second hit involving at least the neural crest. We suggest that the ECCL phenotype may be part of a spectrum of congenital problems associated with mosaicNF1nullisomy originating during early embryogenesis. The biallelicNF1inactivation during early embryogenesis mimics the severe activation of the RAS-MAPK pathway seen in ECCL caused by embryonic mosaic activatingFGFR1andKRASvariants in the cranial region. We propose that distinct mechanisms of mosaicism can cause the ECCL phenotype through convergence on the RAS-MAPK pathway.
Dynamics of synaptic damage in severe traumatic brain injury revealed by cerebrospinal fluid SNAP-25 and VILIP-1
Authors: olde Heuvel Florian , Li Zhenghui , Riedel Daniel , Halbgebauer Steffen , Oeckl Patrick , Mayer Benjamin , Gotzman Nina , Shultz Sandy , Semple Bridgette , Tumani Hayrettin , Ludolph Albert C , Boeckers Tobias Maria , Morganti-Kossmann Cristina , Otto Markus , Roselli Francesco
Published: June 2024

Background

Biomarkers of neuronal, glial cells and inflammation in traumatic brain injury (TBI) are available but they do not specifically reflect the damage to synapses, which represent the bulk volume of the brain. Experimental models have demonstrated extensive involvement of synapses in acute TBI, but biomarkers of synaptic damage in human patients have not been explored.

Methods

Single-molecule array assays were used to measure synaptosomal-associated protein-25 (SNAP-25) and visinin-like protein 1 (VILIP-1) (along with neurofilament light chain (NFL), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), glial fibrillar acidic protein (GFAP), interleukin-6 (IL-6) and interleukin-8 (IL-8)) in ventricular cerebrospinal fluid (CSF) samples longitudinally acquired during the intensive care unit (ICU) stay of 42 patients with severe TBI or 22 uninjured controls.

Results

CSF levels of SNAP-25 and VILIP-1 are strongly elevated early after severe TBI and decline in the first few days. SNAP-25 and VILIP-1 correlate with inflammatory markers at two distinct timepoints (around D1 and then again at D5) in follow-up. SNAP-25 and VILIP-1 on the day-of-injury have better sensitivity and specificity for unfavourable outcome at 6 months than NFL, UCH-L1 or GFAP. Later elevation of SNAP-25 was associated with poorer outcome.

Conclusion

Synaptic damage markers are acutely elevated in severe TBI and predict long-term outcomes, as well as, or better than, markers of neuroaxonal injury. Synaptic damage correlates with initial injury and with a later phase of secondary inflammatory injury.
Blood pressure status, trajectories and cardiovascular disease: the CoLaus|PsyCoLaus prospective study
Authors: Chocron Yaniv , Rousakis Markos , Vollenweider Peter , Vaucher Julien , Marques-Vidal Pedro-Manuel
Published: June 2024

Background

High blood pressure (BP) is a major risk factor for cardiovascular disease (CVD). Adequate treatment of high BP should reduce the risk of CVD, but this association has seldom been assessed in a general population setting.

Methods

Population-based prospective study conducted in Lausanne, Switzerland, with a follow-up between 2003 and 2021. Participants were categorised as normal BP, untreated high BP, treated and uncontrolled BP and treated and controlled BP. Total and CVD mortality as well as any CVD event were assessed.

Results

5341 participants (65% normal, 17.4% untreated, 8.8% treated and uncontrolled and 8.8% treated and controlled) were included. After a median follow-up of 14 years (IQR: 11–15), 575 CVD events occurred. Relative to participants with normal BP, multivariable-adjusted HRs (and 95% CI) for total CVD were 1.38 (1.11 to 1.72) for untreated, 1.35 (1.04 to 1.76) for treated and uncontrolled and 1.50 (1.15 to 1.95) for treated and controlled. The corresponding HRs for CVD mortality (112 events) were 0.94 (0.52 to 1.70), 1.77 (1.00 to 3.12) and 2.52 (1.50 to 4.23), respectively. For total mortality (677 events), the HRs were 1.24 (1.01 to 1.52), 1.26 (0.99 to 1.60) and 1.27 (0.99 to 1.62), respectively. Sensitivity analysis using BP status during a 5-year period and categorising participants as always normal, always treated and uncontrolled, always treated and controlled and other led to similar findings.

Conclusion

Over a long follow-up period of 14 years, BP control was not associated with reduction of CVD events, CVD-related or total mortality. This finding should help define further studies on factors affecting CVD and mortality in people treated for hypertension in the general population.
Cooled versus conventional radiofrequency treatment of the genicular nerves for chronic knee pain: 12-month and cost-effectiveness results from the multicenter COCOGEN trial
Authors: Belba Amy , Vanneste Thibaut , Kallewaard Jan Willem , van Kuijk Sander MJ , Gelissen Marloes , Emans Peter , Bellemans Johan , Smeets Kristof , Van Boxem Koen , Sommer Micha , Kimman Merel , Van Zundert Jan
Published: June 2024

Background

Radiofrequency (RF) treatment of the genicular nerves reduces chronic knee pain in patients with osteoarthritis (OA) or persistent postsurgical pain (PPSP) after total knee arthroplasty (TKA). The objective of this study is to compare long-term outcomes of cooled and conventional RF and perform an economic evaluation.

Methods

The COCOGEN trial is a double-blinded, non-inferiority, pilot, randomized controlled trial that compared the effects up to 12 months of cooled and conventional RF in patients with chronic knee pain suffering from OA or PPSP after TKA following a 1:1 randomization rate. Outcomes were knee pain, functionality, quality of life, emotional health, medication use, and adverse events. A trial-based economic evaluation was performed with a 12-month societal perspective. Here, the primary outcome was the incremental costs per quality-adjusted life year (QALY).

Results

41 of the 49 included patients completed the 12-month follow-up. One patient in the PPSP cooled RF group had substantial missing data at 12-month follow-up. The proportion of patients with ≥50% pain reduction at 12 months was 22.2% (4/18) in patients treated with conventional RF versus 22.7% (5/22) in patients treated with cooled RF (p>0.05). There was a statistically significant difference in the mean absolute numerical rating scale at 12 months after cooled RF and conventional RF in patients with PPSP (p=0.02). Differences between other outcomes were not statistically significant. The health economic analysis indicated that cooled RF resulted in lower costs and improved QALYs compared with conventional RF in PPSP but not in OA. There were no serious adverse events.

Conclusions

Both RF treatments demonstrated in approximately 22% of patients a ≥50% pain reduction at 12 months. In patients with PPSP, contrary to OA, cooled RF seems to be more effective than conventional RF. Additionally, cooled RF has in patients with PPSP, as opposed to OA, greater effectiveness at lower costs compared with conventional RF.

Trial registration number

NCT03865849
.
Association between sinusitis and incident rheumatic diseases: a population-based study
Authors: Kronzer Vanessa L , Davis John M , Hanson Andrew C , Sparks Jeffrey A , Myasoedova Elena , Duarte-Garcia Ali , Hinze Alicia M , Makol Ashima , Koster Mattew J , Vassallo Robert , Warrington Kenneth J , Wright Kerry , Crowson Cynthia S
Published: June 2024

Objectives

To determine whether antecedent sinusitis is associated with incident rheumatic disease.

Methods

This population-based case–control study included all individuals meeting classification criteria for rheumatic diseases between 1995 and 2014. We matched three controls to each case on age, sex and length of prior electronic health record history. The primary exposure was presence of sinusitis, ascertained by diagnosis codes (positive predictive value 96%). We fit logistic regression models to estimate ORs for incident rheumatic diseases and disease groups, adjusted for confounders.

Results

We identified 1729 incident rheumatic disease cases and 5187 matched controls (mean age 63, 67% women, median 14 years electronic health record history). After adjustment, preceding sinusitis was associated with increased risk of several rheumatic diseases, including antiphospholipid syndrome (OR 7.0, 95% CI 1.8 to 27), Sjögren’s disease (OR 2.4, 95% CI 1.1 to 5.3), vasculitis (OR 1.4, 95% CI 1.1 to 1.9) and polymyalgia rheumatica (OR 1.4, 95% CI 1.0 to 2.0). Acute sinusitis was also associated with increased risk of seronegative rheumatoid arthritis (OR 1.8, 95% CI 1.1 to 3.1). Sinusitis was most associated with any rheumatic disease in the 5–10 years before disease onset (OR 1.7, 95% CI 1.3 to 2.3). Individuals with seven or more codes for sinusitis had the highest risk for rheumatic disease (OR 1.7, 95% CI 1.3 to 2.4). In addition, the association between sinusitis and incident rheumatic diseases showed the highest point estimates for never smokers (OR 1.7, 95% CI 1.3 to 2.2).

Conclusions

Preceding sinusitis is associated with increased incidence of rheumatic diseases, suggesting a possible role for sinus inflammation in their pathogenesis.
Rationale and design of ProUrokinase in Mild IsChemic strokE (PUMICE): a multicentre, prospective, randomised, open-label, blinded-endpoint controlled trial
Authors: Xiong Yunyun , Hao Manjun , Pan Yuesong , Duan Chunmiao , Feng Xueyan , Li Hao , Wu Na , Wang Liyuan , Meng Xia , Zhao Xingquan , Wang Yongjun
Published: June 2024

Background and purpose

Recombinant human prourokinase (rhPro-UK) is a new generation of specific plasminogen activator, that is non-inferior to alteplase in acute ischemic stroke. We aimed to investigate the efficacy and safety of rhPro-UK compared with standard medical treatment in acute mild ischemic stroke within 4.5 hours of symptom onset.

Methods and design

Prourokinase in mild ischemic stroke is a multicentre, prospective, randomised, open-label, blinded-endpoint controlled trial. Patients who had an acute ischemic stroke within 4.5 hours from symptom onset and with baseline National Institutes of Health Stroke Scale (NIHSS) score ≤ 5 will be recruited. Patients will be randomly assigned (1:1) to receive intravenous rhPro-UK (35 mg) or standard medical treatment. The follow-up duration will be 90 days. The calculated sample size is 1446.

Study outcomes

Primary efficacy outcome is an excellent functional outcome, defined as a modified Rankin Scale (mRS) score ≤ 1 at 90 days. Secondary efficacy outcomes include ordinal distribution of mRS at 90 days, mRS score ≤ 2 at 90 days, early neurological improvement at 24 hours (a decrease of NIHSS score ≥ 4 points compared with baseline or NIHSS score ≤ 1 point), Barthel index of 75–100 points at 90 days, quality of life at 90 days, and activities of daily living at 90 days. Safety outcomes are symptomatic intracranial haemorrhage within 36 hours, mortality at 90 days, moderate and severe systematic bleeding at 90 days, and adverse events/serious adverse events within 90 days.

Discussion

This large phase III randomised clinical trial will answer the question of whether thrombolysis is beneficial for acute mild ischemic stroke, and may provide evidence for rhPro-UK in patients had an acute mild ischemic stroke within 4.5 hours of symptom onset.

Trial registration number

ISRCTN05507645
Personalized ctDNA for Monitoring Disease Status in Head and Neck Squamous Cell Carcinoma
Authors: Hanna Glenn J. , Dennis Michael J. , Scarfo Nicole , Mullin Michelle S. , Sethi Rosh K.V. , Sehgal Kartik , Annino Donald J. , Goguen Laura A. , Haddad Robert I. , Tishler Roy B. , Margalit Danielle N. , Uppaluri Ravindra , Schoenfeld Jonathan D. , Rettig Eleni M.
Published: June 2024

Purpose:

Many patients with locoregionally advanced human papillomavirus–negative head and neck squamous cell carcinoma (HNSCC) relapse. ctDNA has the potential to identify minimal residual disease, but its clinical utility for virus-negative HNSCC is not well understood.

Experimental Design:

We retrospectively evaluated a personalized, commercial ctDNA assay (Signatera, Natera) during clinical care of patients treated for predominantly newly diagnosed human papillomavirus–negative HNSCC. Signatera utilizes 16-plex PCR from matched tumor and blood. Objectives were to understand ctDNA detectability and correlate changes posttreatment with disease outcomes.

Results:

Testing was successful in 100/116 (86%) patients (median age: 65 years, 68% male, 65% smokers); testing failed in 16 (14%) because of insufficient tissue. Oral cavity (55, 47%) tumors were most common; most had stage III to IV disease (82, 71%), whereas 17 (15%) had distant metastases. Pretreatment, 75/100 patients with successful testing (75%) had detectable ctDNA (range: 0.03–4049.69 mean tumor molecules/mL). No clinical features predicted ctDNA detectability or levels (multivariate analysis). At a median follow-up of 5.1 months (range: 0.2–15.1), 55 (55%) had >1 test result (range: 1–7; 194 samples). Of 55 patients, 17 (31%) remained ctDNA positive after starting treatment. Progression-free survival was significantly worse for patients who were ctDNA positive versus ctDNA negative posttreatment (HR, 7.33; 95% confidence interval, 3.12–17.2; P < 0.001); 1-year overall survival was 89.1% versus 100%, respectively (HR, 7.46; 95% confidence interval, 0.46–119.5; P = 0.155).

Conclusions:

Tumor-informed ctDNA testing is feasible in nonviral HNSCC. ctDNA positivity is an indicator of disease progression and associated with inferior survival. Further research is warranted to understand whether ctDNA may be leveraged to guide therapy in HNSCC.
Supplementary Table S3 from Translational and Therapeutic Evaluation of RAS-GTP Inhibition by RMC-6236 in RAS-Driven Cancers
Authors: Jiang Jingjing , Jiang Lingyan , Maldonato Benjamin J. , Wang Yingyun , Holderfield Matthew , Aronchik Ida , Winters Ian P. , Salman Zeena , Blaj Cristina , Menard Marie , Brodbeck Jens , Chen Zhe , Wei Xing , Rosen Michael J. , Gindin Yevgeniy , Lee Bianca J. , Evans James W. , Chang Stephanie , Wang Zhican , Seamon Kyle J. , Parsons Dylan , Cregg James , Marquez Abby , Tomlinson Aidan C.A. , Yano Jason K. , Knox John E. , Quintana Elsa , Aguirre Andrew J. , Arbour Kathryn C. , Reed Abby , Gustafson W. Clay , Gill Adrian L. , Koltun Elena S. , Wildes David , Smith Jacqueline A.M. , Wang Zhengping , Singh Mallika
Published: June 2024

Supplementary Table S3 shows PK and/or PD data of RMC-6236 in subcutaneous xenograft tumors, intracranially implanted xenograft tumors, normal brain from naüve mice, and ear skin and colon from xenograft tumor bearing mice.
Table S1 from B7-H3–Targeting Chimeric Antigen Receptors Epstein-Barr Virus–specific T Cells Provides a Tumor Agnostic Off-The-Shelf Therapy Against B7-H3–positive Solid Tumors
Authors: Yeo Siok Ping , Kua Lindsay , Tan Jin Wei , Lim Joanna Kristyn , Wong Fiona HS , Santos May Delos , Poh Chek Meng , Goh Angeline XH , Koh Xin Yu , Zhou Xiaohua , Rajarethinam Ravisankar , Chen Qingfeng , Her Zhisheng , Horak Ivan D. , Low Lionel , Tan Kar Wai
Published: June 2024

Supplementary table 1
Supplementary figure 7 from B7-H3–Targeting Chimeric Antigen Receptors Epstein-Barr Virus–specific T Cells Provides a Tumor Agnostic Off-The-Shelf Therapy Against B7-H3–positive Solid Tumors
Authors: Yeo Siok Ping , Kua Lindsay , Tan Jin Wei , Lim Joanna Kristyn , Wong Fiona HS , Santos May Delos , Poh Chek Meng , Goh Angeline XH , Koh Xin Yu , Zhou Xiaohua , Rajarethinam Ravisankar , Chen Qingfeng , Her Zhisheng , Horak Ivan D. , Low Lionel , Tan Kar Wai
Published: June 2024

Supplementary figure 7
Supplementary figure 6 from B7-H3–Targeting Chimeric Antigen Receptors Epstein-Barr Virus–specific T Cells Provides a Tumor Agnostic Off-The-Shelf Therapy Against B7-H3–positive Solid Tumors
Authors: Yeo Siok Ping , Kua Lindsay , Tan Jin Wei , Lim Joanna Kristyn , Wong Fiona HS , Santos May Delos , Poh Chek Meng , Goh Angeline XH , Koh Xin Yu , Zhou Xiaohua , Rajarethinam Ravisankar , Chen Qingfeng , Her Zhisheng , Horak Ivan D. , Low Lionel , Tan Kar Wai
Published: June 2024

Supplementary figure 6
Supplementary figure 5 from B7-H3–Targeting Chimeric Antigen Receptors Epstein-Barr Virus–specific T Cells Provides a Tumor Agnostic Off-The-Shelf Therapy Against B7-H3–positive Solid Tumors
Authors: Yeo Siok Ping , Kua Lindsay , Tan Jin Wei , Lim Joanna Kristyn , Wong Fiona HS , Santos May Delos , Poh Chek Meng , Goh Angeline XH , Koh Xin Yu , Zhou Xiaohua , Rajarethinam Ravisankar , Chen Qingfeng , Her Zhisheng , Horak Ivan D. , Low Lionel , Tan Kar Wai
Published: June 2024

Supplementary figure 5
Terapia ocupacional, assistência social e o trabalho socioassistencial com pessoas com deficiências: relato de experiência em um Centro-Dia
Authors: Basso Ana Carolina Souza , Bezerra Waldez Cavalcante , Silva Júlia Cássia da Costa , Beserra Larissa de Oliveira , Borba Patrícia Leme de Oliveira
Published: June 2024

This article aims to describe and analyze the work with people with disabilities in a Day-care Center of the Brazilian Welfare Policy System, based on an internship experience in occupational therapy carried out in the city of Rio de Janeiro in the year 2022. Taking as a basis a critical Marxian perspective and the theoretical-methodological framework of social occupational therapy, three categories of discussion were outlined, namely: social needs and objectives of professional action; the methodologies and resources used; the challenges in constructing the work: the contradictions involving the social assistance policy and the overcoming of clinical practices, both in terms of reading social needs and responding to the demands presented by service users. The experience showed that there is coherence and relevance between the objectives of the work and the purposes of the Welfare Policy, in addition to activities being an element that enhances actions, imparting a differentiated quality to the professional practice of occupational therapists in this social policy. We reflect that social occupational therapy is a coherent framework to inform social assistance work in this professional context.
A terapia ocupacional no SUAS: produção e divulgação de conteúdos fomentados por uma comunidade de práticas
Authors: Bardi Giovanna , Oliveira Marina Leandrini de , Soares Carla Regina Silva , Santamaria Larissa Mazzotti , Correa Emanuelle Oliveira , Borges Laís Souza
Published: June 2024

The insertion and growth of occupational therapists in the Unified Social Assistance System have generated demands for professional training and dissemination in Brazil. In view of this, the Community of Practice in Occupational Therapy was organized for professionals working in this field. Among its various actions, there was the creation of a Blog and an Instagram account. This article aims to report the trajectory of the creation and maintenance of social media as Community of Practice strategies for the dissemination and visibility of occupational therapy in this policy. 131 publications were identified on the Blog, the majority of which dealt with general topics about SUAS, while 35.2% addressed specific population groups. Instagram had 118 publications and 1425 followers. Analysis of Instagram metrics revealed reach of 1,872 accounts and 7,280 impressions. The Community of Practices initiative highlights the importance of Occupational Therapy in this system, aiming to increase visibility and exchange of knowledge between professionals. In this way, these tools represent successful strategies to strengthen and disseminate the work of occupational therapy in this context through the recognition of methodological strategies, in addition to providing support for consistent action in the field of social assistance.
Rescue Stenting after Unsuccessful Recanalization of Endovascular Thrombectomy of the Posterior Circulation: A Systematic Review and Meta Analysis
Authors: Brake Aaron , Danso Emmanuel , Liu William , Galate Vince , Fry Lane , Abraham Michael
Published: June 2024

Background

The role of rescue stenting (RS) in acute ischemic strokes due to intracranial atherosclerotic disease–related large vessel occlusion is an area of active investigation. This study evaluates the efficacy and safety of RS under these circumstances.

Methods

A systematic literature review, conforming to Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines, was conducted across PubMed, EMBASE, Cochrane, and OVID databases. Common and random effects analyses were conducted to compare outcomes including modified Rankin Scale score, 90‐day mortality, and symptomatic intracranial hemorrhage between patients receiving and those not receiving RS after failed endovascular thrombectomy within posterior circulation.

Results

Ten studies comprising 1202 patients (730 RS, 472 control) were analyzed. RS was associated with a statistically significant improvement in functional outcomes, evidenced by a higher proportion of patients achieving modified Rankin Scale score ≤2 at 90 days (32.74% versus 21.19% in controls;
P
<0.001). Additionally, RS showed a significant reduction in 90‐day mortality (33.28% versus 54.66% in controls;
P
<0.001) and a lower incidence of symptomatic intracranial hemorrhage (3.74% versus 9.49% in controls;
P
<0.001).

Conclusion

RS for acute ischemic stroke in the context of intracranial atherosclerotic diseaserelated posterior circulation large vessel occlusion after failed endovascular thrombectomy is associated with improved functional outcomes, reduced mortality, and decreased symptomatic intracranial hemorrhage rates. These findings suggest RS as a beneficial intervention in this patient population. However, the retrospective nature of the included studies and their heterogeneity underline the need for further research, particularly through randomized controlled trials.
Training school students in information evaluation
Authors: Shenton Andrew
Published: June 2024

The importance of the skill of source evaluation within information literacy (IL) has grown hugely in the last fifty years and now few aspects of IL receive greater attention. It was subject to little coverage in the early days but today a multitude of specialist appraisal tools have been devised to help users make assessments of the material they encounter, at a time when the information to which people are exposed differs more than ever in terms of its types, originators and calibre. Many of the evaluation frameworks, though, are variations on a theme. In the future, we may make progress by encouraging young people to develop their own mental models for appraising information, after they have explored disparate frameworks that have emerged from the ideas of writers who have taken particular interest in contrasting types of material.
Fostering self-reflection on library instruction
Authors: Silberberg Eric
Published: June 2024

This study demonstrates that a library instruction observation instrument can effectively foster critical self-reflection among academic library faculty and staff on their teaching practices. The paper outlines the instrument's design, which gathers low inference observations on instructors’ use of questioning as a pedagogical strategy based on recommendations from the LIS and education literature. To test and refine the instrument's design, the instructors’ utilised the instrument to collect data from classes taught by five participating instructors, who, during post-observation interviews, engaged in thoughtful reflections on their class planning, student participation, and teaching philosophy. They also provided valuable critiques of the usefulness of the instrument. Through analysing the observee reflections and the data from the observation instrument, this study aims to provide academic libraries with a method to incorporate an observation instrument in a peer observation program.
Navigating tomorrow's classroom
Authors: Hutchinson Elizabeth
Published: June 2024

This article explores the transformative impact of Artificial Intelligence (AI) on information literacy (IL) in schools, advocating for a paradigm shift. It emphasises the role of school librarians in leveraging AI, especially through the Framework Of Skills for Inquiry Learning (FOSIL), to seamlessly integrate IL into the curriculum. Addressing librarian hesitancy towards AI, the article stresses the urgency for librarians to embrace the technology and position themselves as essential guides in navigating ethical considerations. The discussion underscores the importance of inquiry-based learning, aligning with IL goals and preparing students for an AI-driven future. It envisions a collaborative future where librarians, armed with clear roles and frameworks like FOSIL, actively contribute to shaping education. The article calls for collective exploration by educators, librarians, and policymakers to ensure a holistic approach in preparing students for the challenges and opportunities of the future.
Information literacy now
Authors: Saunders Laura
Published: June 2024

Librarians have long been at the forefront of information literacy (IL), helping to develop and codify definitions and standards and advocating for its importance across situations and domains. The explosion of attention to mis- and disinformation in recent years has highlighted the need for these skills and competencies. At the same time, critics have raised and lamented the focus on processes and tasks over critical thinking and questioned the efficacy of IL instructional programs. The current landscape of IL seems to be defined by a continuous evolution of the concept, along with calls for more interdisciplinary research and attention to the psychological and neuroscience aspects of information evaluation.
The self-tracking information literacy practices of LGBTQ+ students
Authors: McKinney Pamela , Peacock Corin , Cox Andrew
Published: June 2024

This paper explores the self-tracking information literacy practices of LGBTQ+ students, how the practices connect to LGBTQ+ identities, and whether these practices are perceived as empowering. Six semi-structured interviews were conducted with students who identified as LGBTQ+ self-trackers. Four previously discovered dimensions of IL in self-tracking framed the design. Collaborative thematic analysis revealed participants find it useful to monitor their physical health and tracking supports mental health, which is experienced as empowering. The heteronormative assumptions of apps influenced their perceived usefulness. There was some distrust about how apps used data, but this risk was accepted, typically because the convenience of the app outweighed privacy concerns. Data sharing took place—restricted due to self-consciousness or fear of judgement—and embraced when there was a feeling of working towards a shared goal. IL in this landscape is related to developing critical awareness of when and how self-tracking can support health goals; the limitations of apps and devices, particularly for those undergoing transition; privacy implications; and the nuances of social sharing.
Archives as the prologues of information literacy
Authors: Whitworth Andrew
Published: June 2024

Through analysing how information literate practitioners emerged in the pre-digital era, how they were taught and how they communicated their understandings of practice, we can better appreciate how these actors helped shape contemporary information landscapes. Such studies can be conducted through the resources in special collections of libraries and archives. Case studies of medieval scholarly practice, and the history of the island of St Helena, are presented as examples of where these archival sources reveal the influence of historic information (literate and illiterate) practice on modern information landscapes.
Flourishing in an ocean of information
Authors: Hughes Hilary
Published: June 2024

Over 50 years we have built a mature information literacy (IL) discipline through dedicated, innovative research and practice. Drawing on recent Australian referendum experience, I consider current challenges to expanding our contribution across society. These include limited government and public recognition of IL, its opaque image, fragmentation into separate literacies, and lack of a connective conceptual thread. Looking forward, to provoke fresh thinking and extend our disciplinary horizons, I present a personal vision of information literacy for wellbeing with individuals and communities flourishing in an ocean of information and a confluence of literacies, empowered by informed learning
“Do as I say, not as I do…”
Authors: Vong Silvia
Published: June 2024

It is important to align what we teach with how we teach information literacy (IL), otherwise we may inadvertently engage with what Hipple et al. (2021) identify as the pedagogy of hypocrisy through neoliberal pressure in higher education. This occurs when there is a misalignment between the values and principles behind what we teach and the pedagogical approaches we take when teaching. For example, when teaching IL concepts that intend to engage with social justice themes around access privilege and information, the pedagogy of hypocrisy can occur when we simply demonstrate how to access library resources on the library’s website, without engaging in critical conversations about systems that contribute to inequities in access within society. To counter this, Hipple et al. (2021) suggest that those who teach must critically reflect on who they teach for, examine how they use and activate (or co-opt) social justice language, and name dominant and oppressive structures. This paper builds on Hipple's argument to suggest ways of recognising the pedagogy of hypocrisy within IL practices, and argues that this recognition is key to countering hegemonic ideologies within LIS teaching.