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Article ; Online: COVID-19 infection in primary central nervous system lymphoma treatment: Who is most at risk?

Lim, Sean H

2022 Volume 199, Issue 4, Page(s) 480–481

MeSH term(s)	Humans ; COVID-19 ; Central Nervous System Neoplasms/therapy ; Central Nervous System Neoplasms/pathology ; Lymphoma, Large B-Cell, Diffuse/pathology ; Central Nervous System/pathology
Language	English
Publishing date	2022-08-26
Publishing country	England
Document type	Journal Article
ZDB-ID	80077-6
ISSN	1365-2141 ; 0007-1048
ISSN (online)	1365-2141
ISSN	0007-1048
DOI	10.1111/bjh.18416
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Article ; Online: Two approaches to tackling COVID-19 in patients with blood cancer.

Wijaya, Ratna / Lim, Sean H

Nature cancer

2023 Volume 4, Issue 1, Page(s) 5–6

MeSH term(s)	Humans ; COVID-19 ; Hematologic Neoplasms/complications ; Hematologic Neoplasms/epidemiology ; Hematologic Neoplasms/therapy ; Neoplasms/epidemiology ; Neoplasms/therapy ; Patients
Language	English
Publishing date	2023-02-09
Publishing country	England
Document type	Journal Article ; Comment
ISSN	2662-1347
ISSN (online)	2662-1347
DOI	10.1038/s43018-022-00505-8
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Article ; Online: Agonist Antibodies for Cancer Immunotherapy: History, Hopes, and Challenges.

Lim, Sean H / Beers, Stephen A / Al-Shamkhani, Aymen / Cragg, Mark S

Clinical cancer research : an official journal of the American Association for Cancer Research

2023 Volume 30, Issue 9, Page(s) 1712–1723

Abstract: Immunotherapy is among the most promising new treatment modalities to arise over the last two decades; antibody drugs are delivering immunotherapy to millions of patients with many different types of cancer. Initial success with antibody therapeutics ... ...

Abstract	Immunotherapy is among the most promising new treatment modalities to arise over the last two decades; antibody drugs are delivering immunotherapy to millions of patients with many different types of cancer. Initial success with antibody therapeutics came in the form of direct targeting or cytotoxic antibodies, such as rituximab and trastuzumab, which bind directly to tumor cells to elicit their destruction. These were followed by immunomodulatory antibodies that elicit antitumor responses by either stimulating immune cells or relieving tumor-mediated suppression. By far the most successful approach in the clinic to date has been relieving immune suppression, with immune checkpoint blockade now a standard approach in the treatment of many cancer types. Despite equivalent and sometimes even more impressive effects in preclinical models, agonist antibodies designed to stimulate the immune system have lagged behind in their clinical translation. In this review, we document the main receptors that have been targeted by agonist antibodies, consider the various approaches that have been evaluated to date, detail what we have learned, and consider how their anticancer potential can be unlocked.
MeSH term(s)	Humans ; Neoplasms/immunology ; Neoplasms/drug therapy ; Neoplasms/therapy ; Immunotherapy/methods ; Animals ; Antineoplastic Agents, Immunological/therapeutic use ; Antineoplastic Agents, Immunological/pharmacology
Chemical Substances	Antineoplastic Agents, Immunological
Language	English
Publishing date	2023-12-28
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	1225457-5
ISSN	1557-3265 ; 1078-0432
ISSN (online)	1557-3265
ISSN	1078-0432
DOI	10.1158/1078-0432.CCR-23-1014
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Zs.A 4223: Show issues

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Article ; Online: Dexamphetamine increased speech and visual unimodal illusions in healthy participants without affecting temporal binding window.

Voon, Fui-Ling / Loffman, Sean J / Lim, Mark J H / Lee, Joseph W Y / Iyyalol, Rajan / Martin-Iverson, Mathew T

Human psychopharmacology

2024 Volume 39, Issue 3, Page(s) e2896

Abstract: Objective: Stimuli received beyond a very short timeframe, known as temporal binding windows (TBWs), are perceived as separate events. In previous audio-visual multisensory integration (McGurk effect) studies, widening of TBWs has been observed in ... ...

Abstract	Objective: Stimuli received beyond a very short timeframe, known as temporal binding windows (TBWs), are perceived as separate events. In previous audio-visual multisensory integration (McGurk effect) studies, widening of TBWs has been observed in people with schizophrenia. The present study aimed to determine if dexamphetamine could increase TBWs in unimodal auditory and unimodal visual illusions that may have some validity as experimental models for auditory and visual hallucinations in psychotic disorders. Methods: A double-blind, placebo-controlled, counter-balanced crossover design with permuted block randomisation for drug order was followed. Dexamphetamine (0.45 mg/kg, PO, q.d.) was administered to healthy participants. Phantom word illusion (speech illusion) and visual-induced flash illusion/VIFI (visual illusion) tests were measured to determine if TBWs were altered as a function of delay between stimuli presentations. Word emotional content for phantom word illusions was also analysed. Results: Dexamphetamine significantly increased the total number of phantom words/speech illusions (p < 0.01) for pooled 220-1100 ms ISIs in kernel density estimation and the number of positive valence words heard (beta = 2.20, 95% CI [1.86, 2.55], t = 12.46, p < 0.001) with a large effect size (std. beta = 1.05, 95% CI [0.89, 1.22]) relative to placebo without affecting the TBWs. For the VIFI test, kernel density estimation for pooled 0-801 ms ISIs showed a significant difference (p < 0.01) in the data distributions of number of target flash (es) perceived by participants after receiving dexamphetamine as compared with placebo. Conclusions: Overall, healthy participants who were administered dexamphetamine (0.45 mg/kg, PO, q.d.) experienced increases in auditory and visual illusions in both phantom word illusion and VIFI tests without affecting their TBWs.
MeSH term(s)	Humans ; Double-Blind Method ; Male ; Adult ; Cross-Over Studies ; Female ; Illusions/drug effects ; Illusions/physiology ; Young Adult ; Dextroamphetamine/pharmacology ; Dextroamphetamine/administration & dosage ; Visual Perception/drug effects ; Visual Perception/physiology ; Hallucinations/chemically induced ; Time Factors ; Photic Stimulation/methods ; Central Nervous System Stimulants/pharmacology ; Central Nervous System Stimulants/administration & dosage ; Acoustic Stimulation ; Speech Perception/drug effects ; Auditory Perception/drug effects ; Auditory Perception/physiology ; Adolescent
Chemical Substances	Dextroamphetamine (TZ47U051FI) ; Central Nervous System Stimulants
Language	English
Publishing date	2024-02-14
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Randomized Controlled Trial
ZDB-ID	632931-7
ISSN	1099-1077 ; 0885-6222
ISSN (online)	1099-1077
ISSN	0885-6222
DOI	10.1002/hup.2896
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Article: Evaluation of Surface Properties and Separation Performance of NF and RO Membranes for Phthalates Removal.

Lim, En Qi / Seah, Mei Qun / Lau, Woei Jye / Hasbullah, Hasrinah / Goh, Pei Sean / Ismail, Ahmad Fauzi / Emadzadeh, Daryoush

Membranes

2023 Volume 13, Issue 4

Abstract: ... indicated that the surface of the NF3 membrane was severely covered by foulants after 4-h filtration of DBP ...

Abstract	Many studies indicated that phthalates, a common plasticizer, lurk silently in water bodies and can potentially harm living organisms. Therefore, removing phthalates from water sources prior to consumption is crucial. This study aims to evaluate the performance of several commercial nanofiltrations (NF) (i.e., NF3 and Duracid) and reverse osmosis (RO) membranes (i.e., SW30XLE and BW30) in removing phthalates from simulated solutions and further correlate the intrinsic properties of membranes (e.g., surface chemistry, morphology, and hydrophilicity) with the phthalates removal. Two types of phthalates, i.e., dibutyl phthalate (DBP) and butyl benzyl phthalate (BBP), were used in this work, and the effects of pH (ranging from 3 to 10) on the membrane performance were studied. The experimental findings showed that the NF3 membrane could yield the best DBP (92.5-98.8%) and BBP rejection (88.7-91.7%) regardless of pH, and these excellent results are in good agreement with the surface properties of the membrane, i.e., low water contact angle (hydrophilicity) and appropriate pore size. Moreover, the NF3 membrane with a lower polyamide cross-linking degree also exhibited significantly higher water flux compared to the RO membranes. Further investigation indicated that the surface of the NF3 membrane was severely covered by foulants after 4-h filtration of DBP solution compared to the BBP solution. This could be attributed to the high concentration of DBP presented in the feed solution owing to its high-water solubility (13 ppm) compared to BBP (2.69 ppm). Further research is still needed to study the effect of other compounds (e.g., dissolved ions and organic/inorganic matters that might be present in water) on the performance of membranes in removing phthalates.
Language	English
Publishing date	2023-04-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2614641-1
ISSN	2077-0375
ISSN	2077-0375
DOI	10.3390/membranes13040413
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Article ; Online: Tailored risk assessment and forecasting in intermittent claudication.

Ravindhran, Bharadhwaj / Prosser, Jonathon / Lim, Arthur / Mishra, Bhupesh / Lathan, Ross / Hitchman, Louise H / Smith, George E / Carradice, Daniel / Chetter, Ian C / Thakker, Dhaval / Pymer, Sean

BJS open

2024 Volume 8, Issue 1

Abstract: Background: Guidelines recommend cardiovascular risk reduction and supervised exercise therapy as the first line of treatment in intermittent claudication, but implementation challenges and poor patient compliance lead to significant variation in ... ...

Abstract	Background: Guidelines recommend cardiovascular risk reduction and supervised exercise therapy as the first line of treatment in intermittent claudication, but implementation challenges and poor patient compliance lead to significant variation in management and therefore outcomes. The development of a precise risk stratification tool is proposed through a machine-learning algorithm that aims to provide personalized outcome predictions for different management strategies. Methods: Feature selection was performed using the least absolute shrinkage and selection operator method. The model was developed using a bootstrapped sample based on patients with intermittent claudication from a vascular centre to predict chronic limb-threatening ischaemia, two or more revascularization procedures, major adverse cardiovascular events, and major adverse limb events. Algorithm performance was evaluated using the area under the receiver operating characteristic curve. Calibration curves were generated to assess the consistency between predicted and actual outcomes. Decision curve analysis was employed to evaluate the clinical utility. Validation was performed using a similar dataset. Results: The bootstrapped sample of 10 000 patients was based on 255 patients. The model was validated using a similar sample of 254 patients. The area under the receiver operating characteristic curves for risk of progression to chronic limb-threatening ischaemia at 2 years (0.892), risk of progression to chronic limb-threatening ischaemia at 5 years (0.866), likelihood of major adverse cardiovascular events within 5 years (0.836), likelihood of major adverse limb events within 5 years (0.891), and likelihood of two or more revascularization procedures within 5 years (0.896) demonstrated excellent discrimination. Calibration curves demonstrated good consistency between predicted and actual outcomes and decision curve analysis confirmed clinical utility. Logistic regression yielded slightly lower area under the receiver operating characteristic curves for these outcomes compared with the least absolute shrinkage and selection operator algorithm (0.728, 0.717, 0.746, 0.756, and 0.733 respectively). External calibration curve and decision curve analysis confirmed the reliability and clinical utility of the model, surpassing traditional logistic regression. Conclusion: The machine-learning algorithm successfully predicts outcomes for patients with intermittent claudication across various initial treatment strategies, offering potential for improved risk stratification and patient outcomes.
MeSH term(s)	Humans ; Intermittent Claudication/therapy ; Chronic Limb-Threatening Ischemia ; Reproducibility of Results ; Exercise Therapy ; Risk Assessment
Language	English
Publishing date	2024-02-27
Publishing country	England
Document type	Journal Article
ISSN	2474-9842
ISSN (online)	2474-9842
DOI	10.1093/bjsopen/zrad166
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Article ; Online: 2-Year Clinical and Echocardiography Follow-Up of Transcatheter Mitral Valve Replacement With the Transapical Intrepid System.

Bapat, Vinayak / Weiss, Eric / Bajwa, Tanvir / Thourani, Vinod H / Yadav, Pradeep / Thaden, Jeremy J / Lim, D Scott / Reardon, Michael / Pinney, Sean / Adams, David H / Yakubov, Steven J / Modine, Thomas / Redwood, Simon R / Walton, Antony / Spargias, Konstantinos / Zhang, Angie / Mack, Michael / Leon, Martin B

JACC. Cardiovascular interventions

2024

Abstract: Background: Thirty-day outcomes with the investigational Intrepid transapical (TA) transcatheter mitral valve replacement (TMVR) system have previously demonstrated good technical success, but longer-term outcomes in larger cohorts need to be evaluated.! ...

Abstract	Background: Thirty-day outcomes with the investigational Intrepid transapical (TA) transcatheter mitral valve replacement (TMVR) system have previously demonstrated good technical success, but longer-term outcomes in larger cohorts need to be evaluated. Objectives: The authors sought to evaluate the 2-year safety and performance of the Intrepid TA-TMVR system in patients with symptomatic, ≥moderate-severe mitral regurgitation (MR) and high surgical risk. Methods: Patient eligibility was determined by local heart teams and approved by a central screening committee. Clinical events were adjudicated by an independent clinical events committee. Echocardiography was evaluated by an independent core laboratory. Results: The cohort included 252 patients that were enrolled at 58 international sites before February 2021 as part of the global Pilot Study (n = 95) or APOLLO trial (primary cohort noneligible + TA roll-ins, n = 157). Mean age was 74.2 years, mean STS-PROM was 6.3%, 60.3% were male, and 80.6% were in NYHA functional class III/IV. Most presented with secondary MR (70.1%), and nearly all had ≥moderate-severe MR (98.4%). All-cause mortality was 13.1% (30-day), 27.3% (1-year), and 36.2% (2-year). The 30-day ≥major bleeding event rate was 22.3%. Heart failure rehospitalization was 9.6% (30-day) and 36.2% (2-year). At 2 years, >50% of patients were alive with improvement in NYHA functional class (82.1%, class I/II), and all patients with available echocardiograms had ≤mild MR. Conclusions: This analysis represents the largest reported TA-TMVR experience with the longest follow-up in high-risk ≥moderate-severe MR patients. Early mortality and heart failure rehospitalizations were significant, exacerbated by early TA-related bleeding events; however, meaningful improvements in clinical outcomes and marked reductions in MR severity were observed through 2 years.
Language	English
Publishing date	2024-04-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	2452157-7
ISSN	1876-7605 ; 1936-8798
ISSN (online)	1876-7605
ISSN	1936-8798
DOI	10.1016/j.jcin.2024.02.033
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Article ; Online: Predicting COVID-19 infection risk in people who are immunocompromised by antibody testing.

Wijaya, Ratna / Johnson, Marina / Campbell, Nicola / Stuart, Beth / Kelly, Adam / Tipler, Nicole / Menne, Tobias / Ahearne, Matthew J / Willimott, Victoria / Al-Naeeb, Anna Bowzyk / Fox, Christopher P / Collins, Graham P / O'Callaghan, Ann / Davies, Andrew J / Goldblatt, David / Lim, Sean H

Lancet (London, England)

2023 Volume 402, Issue 10396, Page(s) 99–102

MeSH term(s)	Humans ; COVID-19 ; Immunocompromised Host ; Antibodies, Viral ; COVID-19 Testing
Chemical Substances	Antibodies, Viral
Language	English
Publishing date	2023-06-29
Publishing country	England
Document type	Letter
ZDB-ID	3306-6
ISSN	1474-547X ; 0023-7507 ; 0140-6736
ISSN (online)	1474-547X
ISSN	0023-7507 ; 0140-6736
DOI	10.1016/S0140-6736(23)01180-7
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Article ; Online: Optimizing therapy in advanced-stage Hodgkin lymphoma.

Lim, Sean H / Johnson, Peter W M

Blood

2018 Volume 131, Issue 15, Page(s) 1679–1688

Abstract: The treatment of Hodgkin lymphoma has evolved continuously since the introduction of extended-field radiotherapy in the 1960s to involved-field and then involved-node radiotherapy, multiagent chemotherapy, combined chemoradiotherapy, risk-adapted and ... ...

Abstract	The treatment of Hodgkin lymphoma has evolved continuously since the introduction of extended-field radiotherapy in the 1960s to involved-field and then involved-node radiotherapy, multiagent chemotherapy, combined chemoradiotherapy, risk-adapted and response-adapted modulation, and, most recently, introduction of antibody-drug conjugates and immune checkpoint-blocking antibodies. These changes have translated into progressively increasing cure rates, so that 10-year survival figures now exceed 80%, compared with <50% 40 years ago. The challenge now is how to improve upon success while maintaining, or if possible improving, the quality of life for survivors. Steering between undertreatment, with the risk of avoidable recurrences, and overtreatment, with the risk of unnecessary toxicity, remains complex because control of the lymphoma and the probability of survival are no longer closely linked. This requires trials with long follow-up and continuous reappraisal of the interaction between the illness; the method used to define risk, and the type of treatment involved. One important factor in this is age: outcomes in older patients have not improved at the same rate as those in the population under 60 years of age, reflecting the need for different approaches. Recently, treatment has moved from being primarily risk-based, using baseline characteristics such as anatomical stage and severity of the illness, to a more dynamic approach that takes account of the response to therapy, using functional imaging to make an early appraisal, with the option to modulate subsequent treatment. The results of several trials indicate that this has advantages, but a combination of risk- and response-adaptation is probably ideal.
MeSH term(s)	Age Factors ; Disease-Free Survival ; Hodgkin Disease/diagnosis ; Hodgkin Disease/mortality ; Hodgkin Disease/therapy ; Humans ; Quality of Life ; Survival Rate
Language	English
Publishing date	2018-03-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood-2017-09-772640
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Article ; Online: Identifying Mitral Valve Prolapse at Risk for Arrhythmias and Fibrosis From Electrocardiograms Using Deep Learning.

Tison, Geoffrey H / Abreau, Sean / Barrios, Joshua / Lim, Lisa J / Yang, Michelle / Crudo, Valentina / Shah, Dipan J / Nguyen, Thuy / Hu, Gene / Dixit, Shalini / Nah, Gregory / Arya, Farzin / Bibby, Dwight / Lee, Yoojin / Delling, Francesca N

JACC. Advances

2023 Volume 2, Issue 6

Abstract: Background: Mitral valve prolapse (MVP) is a common valvulopathy, with a subset developing sudden cardiac death or cardiac arrest. Complex ventricular ectopy (ComVE) is a marker of arrhythmic risk associated with myocardial fibrosis and increased ... ...

Abstract	Background: Mitral valve prolapse (MVP) is a common valvulopathy, with a subset developing sudden cardiac death or cardiac arrest. Complex ventricular ectopy (ComVE) is a marker of arrhythmic risk associated with myocardial fibrosis and increased mortality in MVP. Objectives: The authors sought to evaluate whether electrocardiogram (ECG)-based machine learning can identify MVP at risk for ComVE, death and/or myocardial fibrosis on cardiac magnetic resonance (CMR) imaging. Methods: A deep convolutional neural network (CNN) was trained to detect ComVE using 6,916 12-lead ECGs from 569 MVP patients from the University of California-San Francisco between 2012 and 2020. A separate CNN was trained to detect late gadolinium enhancement (LGE) using 1,369 ECGs from 87 MVP patients with contrast CMR. Results: The prevalence of ComVE was 28% (160/569). The area under the receiver operating characteristic curve (AUC) of the CNN to detect ComVE was 0.80 (95% CI: 0.77-0.83) and remained high after excluding patients with moderate-severe mitral regurgitation [0.80 (95% CI: 0.77-0.83)] or bileaflet MVP [0.81 (95% CI: 0.76-0.85)]. AUC to detect all-cause mortality was 0.82 (95% CI: 0.77-0.87). ECG segments relevant to ComVE prediction were related to ventricular depolarization/repolarization (early-mid ST-segment and QRS from V Conclusions: CNN-analyzed 12-lead ECGs can detect MVP at risk for ventricular arrhythmias, death and/or fibrosis and can identify novel ECG correlates of arrhythmic risk. ECG-based CNNs may help select those MVP patients requiring closer follow-up and/or a CMR.
Language	English
Publishing date	2023-08-05
Publishing country	United States
Document type	Journal Article
ISSN	2772-963X
ISSN (online)	2772-963X
DOI	10.1016/j.jacadv.2023.100446
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