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Buch ; Online: Large Language Models Relearn Removed Concepts

Lo, Michelle / Cohen, Shay B. / Barez, Fazl

2024

Abstract: Advances in model editing through neuron pruning hold promise for removing undesirable concepts from large language models. However, it remains unclear whether models have the capacity to reacquire pruned concepts after editing. To investigate this, we ... ...

Abstract	Advances in model editing through neuron pruning hold promise for removing undesirable concepts from large language models. However, it remains unclear whether models have the capacity to reacquire pruned concepts after editing. To investigate this, we evaluate concept relearning in models by tracking concept saliency and similarity in pruned neurons during retraining. Our findings reveal that models can quickly regain performance post-pruning by relocating advanced concepts to earlier layers and reallocating pruned concepts to primed neurons with similar semantics. This demonstrates that models exhibit polysemantic capacities and can blend old and new concepts in individual neurons. While neuron pruning provides interpretability into model concepts, our results highlight the challenges of permanent concept removal for improved model \textit{safety}. Monitoring concept reemergence and developing techniques to mitigate relearning of unsafe concepts will be important directions for more robust model editing. Overall, our work strongly demonstrates the resilience and fluidity of concept representations in LLMs post concept removal.
Schlagwörter	Computer Science - Artificial Intelligence
Thema/Rubrik (Code)	006
Erscheinungsdatum	2024-01-03
Erscheinungsland	us
Dokumenttyp	Buch ; Online
Datenquelle	BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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Artikel ; Online: Functional annotation with expression validation identifies novel metastasis-relevant genes from post-GWAS risk loci in sporadic colorectal carcinomas.

Thean, Lai Fun / Wong, Michelle / Lo, Michelle / Tan, Iain / Wong, Evelyn / Gao, Fei / Tan, Emile / Tang, Choong Leong / Cheah, Peh Yean

Journal of medical genetics

2024 Band 61, Heft 3, Seite(n) 276–283

Abstract: Background: Colorectal cancer (CRC) is the third highest incidence cancer and is the leading cause of cancer mortality worldwide. Metastasis to distal organ is the major cause of cancer mortality. However, the underlying genetic factors are unclear. ... ...

Abstract	Background: Colorectal cancer (CRC) is the third highest incidence cancer and is the leading cause of cancer mortality worldwide. Metastasis to distal organ is the major cause of cancer mortality. However, the underlying genetic factors are unclear. This study aimed to identify metastasis-relevant genes and pathways for better management of metastasis-prone patients. Methods: A case-case genome-wide association study comprising 2677 sporadic Chinese CRC cases (1282 metastasis-positive vs 1395 metastasis-negative) was performed using the Human SNP6 microarray platform and analysed with the correlation/trend test based on the additive model. SNP variants with association testing -log10 p value ≥5 were imported into Functional Mapping and Annotation (FUMA) for functional annotation. Results: Glycolysis was uncovered as the top hallmark gene set. Transcripts from two of the five genes profiled, hematopoietic substrate 1 associated protein X 1 ( Conclusions: Combining genome-wide association testing with in silico functional annotation and wet-bench validation identified metastasis-relevant genes that could serve as features to develop subtype-specific metastasis-risk signatures for tailored management of patients with stage I-III CRC.
Mesh-Begriff(e)	Humans ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/pathology ; Genes, Neoplasm ; Polymorphism, Single Nucleotide/genetics ; Adaptor Proteins, Signal Transducing/genetics
Chemische Substanzen	HAX1 protein, human ; Adaptor Proteins, Signal Transducing
Sprache	Englisch
Erscheinungsdatum	2024-02-21
Erscheinungsland	England
Dokumenttyp	Journal Article
ZDB-ID	220881-7
ISSN	1468-6244 ; 0022-2593
ISSN (online)	1468-6244
ISSN	0022-2593
DOI	10.1136/jmg-2023-109517
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: ASO Author Reflections: Extracapsular Spread in Melanoma Lymphadenopathy: Prognostic Implications, Classification, and Management.

Lo, Michelle / Peach, Howard / Moncrieff, Marc

Annals of surgical oncology

2020 Band 28, Heft 3, Seite(n) 1654–1655

Mesh-Begriff(e)	Humans ; Lymphadenopathy ; Melanoma/therapy ; Prognosis
Sprache	Englisch
Erscheinungsdatum	2020-10-20
Erscheinungsland	United States
Dokumenttyp	Journal Article
ZDB-ID	1200469-8
ISSN	1534-4681 ; 1068-9265
ISSN (online)	1534-4681
ISSN	1068-9265
DOI	10.1245/s10434-020-09197-9
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Sequencing in management of in-transit melanoma metastasis: Diphencyprone versus isolate limb infusion.

Lo, Michelle Ci / Garioch, Jennifer / Moncrieff, Marc Ds

Journal of plastic, reconstructive & aesthetic surgery : JPRAS

2020 Band 73, Heft 7, Seite(n) 1263–1267

Abstract: Background: In-transit metastases (ITMs) in melanoma are associated with poor prognosis, however a significant proportion of these patients survive for extended periods without further disease progression. We routinely use locoregional treatment e.g. ... ...

Abstract	Background: In-transit metastases (ITMs) in melanoma are associated with poor prognosis, however a significant proportion of these patients survive for extended periods without further disease progression. We routinely use locoregional treatment e.g. Diphencyprone (DPCP) and/or isolated limb infusion (ILI) as long-term palliation. This study aimed to identify correct sequencing of these therapies based on disease burden and progression. Method: Retrospective evaluation of all melanoma patients with ITMs treated with DPCP/ILI/both from 2010 to 2017 at our Cancer Centre was performed. Patients were initially assessed in a multidisciplinary setting and empirically prescribed DPCP for low-disease burden, ILI for high-disease burden. Patient demographics, tumour characteristics, response to therapy, ITM progression and patient outcomes were analysed. Results: 78 patients (M:F = 30:48), aged 47-95years (median 74years) treated with DPCP/ILI/both (n = 44/21/13) were identified. Progression-free survival (PFS) was significantly increased in patients responsive to DPCP or ILI as initial treatment. Patients who failed on DPCP and subsequently treated with ILI had a significantly increased PFS compared to DPCP alone (p = 0.026, HR = 0.048). This was not the case with patients who were treated with DPCP following failed ILI. All patients who failed to respond to the initial therapy progressed within 6 months. Conclusion: Our study shows that careful stratification ITM patients according to disease burden is fundamental to optimal outcomes. High-disease burden patients benefit from initial ILI; low-disease burden patients should commence on DPCP. ILI can be considered in DPCP patients who fail early. Systemic therapy should be considered when locoregional therapies fail after 12 months or after rapid relapse following ILI.
Mesh-Begriff(e)	Aged ; Aged, 80 and over ; Chemotherapy, Cancer, Regional Perfusion ; Cost of Illness ; Cyclopropanes/administration & dosage ; Disease Progression ; Female ; Humans ; Male ; Melanoma/drug therapy ; Melanoma/secondary ; Middle Aged ; Retrospective Studies ; Skin Neoplasms/drug therapy ; Skin Neoplasms/pathology
Chemische Substanzen	Cyclopropanes ; diphenylcyclopropenone (I7G14NW5EC)
Sprache	Englisch
Erscheinungsdatum	2020-03-17
Erscheinungsland	Netherlands
Dokumenttyp	Comparative Study ; Journal Article
ZDB-ID	2217750-4
ISSN	1878-0539 ; 1748-6815 ; 0007-1226
ISSN (online)	1878-0539
ISSN	1748-6815 ; 0007-1226
DOI	10.1016/j.bjps.2020.03.007
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Two-year retrospective cohort results on use of a dynamic unilateral brace for treatment of clubfoot: Can compliance and prevention of recurrence both be achieved?

Farrar, Emily J / Lo, Michelle / Groothoff, Luke / Cunningham, Jerald / Theuri, Joseph

Journal of rehabilitation and assistive technologies engineering

2022 Band 9, Seite(n) 20556683221112084

Abstract: Objectives: The Ponseti method has led to vast improvements in outcomes for infants born with clubfoot deformity, but challenges with compliance during the bracing phase of the protocol remain. Unilateral braces promise higher compliance but often have ... ...

Abstract	Objectives: The Ponseti method has led to vast improvements in outcomes for infants born with clubfoot deformity, but challenges with compliance during the bracing phase of the protocol remain. Unilateral braces promise higher compliance but often have led to unacceptably high recurrence. Methods: We have developed a novel unilateral brace for clubfoot deformity that strategically applies patient-specific, anatomically-targeted forces to the lower limb to maintain correction. We retrospectively reviewed the cases of 26 patients with minimum follow-up of 24 months. The data were analyzed for recurrence rates, caregiver-reported compliance, and differences in Pirani score, dorsiflexion, abduction, hindfoot eversion, and resting rotation between initial and final follow-up. Results: Most patients ( Conclusions: This novel unilateral brace for maintenance of clubfoot correction after Ponseti treatment demonstrates rates of recurrence rates and caregiver-reported compliance at 2 years of follow up that are comparable to outcomes with traditional bilateral foot abduction orthoses.
Sprache	Englisch
Erscheinungsdatum	2022-07-03
Erscheinungsland	England
Dokumenttyp	Journal Article
ZDB-ID	2819384-2
ISSN	2055-6683 ; 2055-6683
ISSN (online)	2055-6683
ISSN	2055-6683
DOI	10.1177/20556683221112084
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Morphological profiling by high-throughput single-cell biophysical fractometry.

Zhang, Ziqi / Lee, Kelvin C M / Siu, Dickson M D / Lo, Michelle C K / Lai, Queenie T K / Lam, Edmund Y / Tsia, Kevin K

Communications biology

2023 Band 6, Heft 1, Seite(n) 449

Abstract: Complex and irregular cell architecture is known to statistically exhibit fractal geometry, i.e., a pattern resembles a smaller part of itself. Although fractal variations in cells are proven to be closely associated with the disease-related phenotypes ... ...

Abstract	Complex and irregular cell architecture is known to statistically exhibit fractal geometry, i.e., a pattern resembles a smaller part of itself. Although fractal variations in cells are proven to be closely associated with the disease-related phenotypes that are otherwise obscured in the standard cell-based assays, fractal analysis with single-cell precision remains largely unexplored. To close this gap, here we develop an image-based approach that quantifies a multitude of single-cell biophysical fractal-related properties at subcellular resolution. Taking together with its high-throughput single-cell imaging performance (~10,000 cells/sec), this technique, termed single-cell biophysical fractometry, offers sufficient statistical power for delineating the cellular heterogeneity, in the context of lung-cancer cell subtype classification, drug response assays and cell-cycle progression tracking. Further correlative fractal analysis shows that single-cell biophysical fractometry can enrich the standard morphological profiling depth and spearhead systematic fractal analysis of how cell morphology encodes cellular health and pathological conditions.
Mesh-Begriff(e)	Humans ; Lung Neoplasms
Sprache	Englisch
Erscheinungsdatum	2023-04-24
Erscheinungsland	England
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2399-3642
ISSN (online)	2399-3642
DOI	10.1038/s42003-023-04839-6
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Reconstructive burden and financial implications of wider excision margins for invasive primary cutaneous melanoma.

Lo, Michelle Chin / Heaton, Martin J / Snelling, Andrew / Moncrieff, Marc Ds

Journal of plastic, reconstructive & aesthetic surgery : JPRAS

2019 Band 73, Heft 2, Seite(n) 313–318

Abstract: Background: For invasive primary cutaneous melanoma, wider excision is advocated to reduce local recurrence risk and improve patient outcomes. Excision detail is controversial, especially in intermediate- and high-risk primary melanoma (AJCC pT2-pT4). ... ...

Abstract	Background: For invasive primary cutaneous melanoma, wider excision is advocated to reduce local recurrence risk and improve patient outcomes. Excision detail is controversial, especially in intermediate- and high-risk primary melanoma (AJCC pT2-pT4). Guidance varies from sizes 1 to 3 cm (translating into large defects of 2-6 cm). The aim of this study was to determine the reconstructive and resource burden of wider excision margins (EMs). Methods: Data analysis from our prospective database (2008-2017) included 1184 patients (563F:621 M) with cutaneous melanoma (pT1b-pT4b). Procedure tariff data were sourced from our financial services department. Results: Two hundred twenty-nine patients had a narrower EM (1 cm) and 995 (80.7%) had a wider EM (2-3 cm). Reconstructive requirement significantly increased with a wider EM collectively (11.3% vs 29.3%, odds ratio (OR) = 3.2; p < 0.0001), in the extremities (15.2% vs 42.0%; p < 0.0001), and in the head and neck (H&N) (23.5 % vs 64.7%; p < 0.0001). Reconstruction significantly increased hospitalisation rates (26.6% vs 63.0%, OR = 4.7; p < 0.0001) collectively, in the H&N (26.8 % vs 53.9%), and in the upper (18.9 % vs 42.3%) and lower extremities (34.8% vs 77.3%). Narrower EMs significantly reduced hospitalisation rates in the upper and lower extremities (7.1% vs 28.5%; p = 0.004, 37.9% vs 58.5%; p = 0.005, respectively). Overall procedure cost significantly increased by £180 (mean, p < 0.0001) and £346 (median, p = 0.0004) per patient when reconstruction was required. Conclusions: Our data suggest substantial impact of wider EM on patients, which more than doubled in the functionally and cosmetically sensitive extremities and the H&N region. Reconstructions add significant financial and healthcare service burden. Without randomised controlled trial (RCT) evidence demonstrating increased efficacy of wider EM, narrower EM is advocated whilst awaiting future planned RCT results specifically investigating on this.
Mesh-Begriff(e)	Cohort Studies ; Cost of Illness ; Female ; Humans ; Male ; Margins of Excision ; Melanoma/pathology ; Melanoma/surgery ; Neoplasm Invasiveness ; Reconstructive Surgical Procedures/economics ; Reconstructive Surgical Procedures/methods ; Retrospective Studies ; Skin Neoplasms/pathology ; Skin Neoplasms/surgery
Sprache	Englisch
Erscheinungsdatum	2019-10-02
Erscheinungsland	Netherlands
Dokumenttyp	Journal Article
ZDB-ID	2217750-4
ISSN	1878-0539 ; 1748-6815 ; 0007-1226
ISSN (online)	1878-0539
ISSN	1748-6815 ; 0007-1226
DOI	10.1016/j.bjps.2019.09.035
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Extracapsular Spread in Melanoma Lymphadenopathy: Prognostic Implications, Classification, and Management.

Lo, Michelle / Robinson, Alyss / Wade, Ryckie / Peach, Howard / Dewar, Donald / Heaton, Martin / Moncrieff, Marc

Annals of surgical oncology

2020 Band 28, Heft 3, Seite(n) 1642–1653

Abstract: Background: Extracapsular spread (ECS) is recognized to be a high-risk factor in melanoma patients with macrometastatic (N+) nodal disease; however, ECS risk in sentinel lymph node (SLN) biopsy, micrometastatic stage III disease is ambiguous.: ... ...

Abstract	Background: Extracapsular spread (ECS) is recognized to be a high-risk factor in melanoma patients with macrometastatic (N+) nodal disease; however, ECS risk in sentinel lymph node (SLN) biopsy, micrometastatic stage III disease is ambiguous. Objective: The aim of this study was to examine ECS incidence and its prognostic significance. Methods: A two-center, retrospective analysis of all patients with micro/macrometastatic lymphadenopathy undergoing nodal surgery from 2008 to 2014 was performed. Patient demographics, tumor characteristics, nodal ECS status, and patient outcomes were collected. Results: Overall, 515 patients with nodal disease were identified (males/females = 277/238); median age was 63 years (range 17-94). There was an increased frequency of ECS disease in N+ disease compared with SLN+ disease (52.4% vs. 16.2%; p < 0.0001). The absolute disease-specific survival (DSS) difference for SLN+ patients was approximately 30% at 10 years (66.2% vs. 37.2%; p < 0.0001), and the prognosis of SLN+/ECS+ patients was identical to N+/ECS- patients. Multivariate analysis demonstrated that ECS status was an independent prognostic indicator for DSS (hazard ratio 2.47, 95% confidence interval 1.87-3.26; p < 0.0001) in patients with SLN+ disease. There were significant differences in nodal burden according to ECS status between the SLN+ and N+ subgroups suggestive of differing biology in ECS+ tumors. Conclusion: We found that ECS is a significant DSS, progression-free survival, and overall survival indicator in SLN+ and N+ disease. We demonstrated that ECS upstages stage III disease, similar to ulceration in primary melanoma (stage I/II disease). A simplified staging system substituting ECS for N stage accurately stages patients according to prognosis.
Mesh-Begriff(e)	Adolescent ; Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Lymphadenopathy ; Lymphatic Metastasis ; Male ; Melanoma/pathology ; Middle Aged ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Sentinel Lymph Node Biopsy ; Skin Neoplasms/pathology ; Survival Rate ; Young Adult
Sprache	Englisch
Erscheinungsdatum	2020-09-17
Erscheinungsland	United States
Dokumenttyp	Journal Article
ZDB-ID	1200469-8
ISSN	1534-4681 ; 1068-9265
ISSN (online)	1534-4681
ISSN	1068-9265
DOI	10.1245/s10434-020-09099-w
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel: KRAS-specific antibody binds to KRAS protein inside colorectal adenocarcinoma cells and inhibits its localization to the plasma membrane.

Lam, Kuen Kuen / Low, Yee Syuen / Lo, Michelle / Wong, Michelle / Leong Tang, Choong / Tan, Emile / Chok, Aik Yong / Seow-En, Isaac / Wong, Siew Heng / Cheah, Peh Yean

Frontiers in oncology

2023 Band 13, Seite(n) 1036871

Abstract: Colorectal cancer (CRC) is the third highest incidence cancer and a leading cause of cancer mortality worldwide. To date, chemotherapeutic treatment of advanced CRC that has metastasized has a dismayed success rate of less than 30%. Further, most (80%) ... ...

Abstract	Colorectal cancer (CRC) is the third highest incidence cancer and a leading cause of cancer mortality worldwide. To date, chemotherapeutic treatment of advanced CRC that has metastasized has a dismayed success rate of less than 30%. Further, most (80%) sporadic CRCs are microsatellite-stable and are refractory to immune checkpoint blockade therapy. KRAS is a gatekeeper gene in colorectal tumorigenesis. Nevertheless, KRAS is 'undruggable' due to its structure. Thus, focus has been diverted to develop small molecule inhibitors for its downstream effector such as ERK/MAPK. Despite intense research efforts for the past few decades, no small molecule inhibitor has been in clinical use for CRC. Antibody targeting KRAS itself is an attractive alternative. We developed a transient
Sprache	Englisch
Erscheinungsdatum	2023-03-27
Erscheinungsland	Switzerland
Dokumenttyp	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2023.1036871
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel: StarmapVis: An interactive and narrative visualisation tool for single-cell and spatial data.

Ma, Shichao / Fang, Xiunan / Yao, Yu / Li, Jianfu / Morgan, Daniel C / Xia, Yongyan / Kwok, Crystal S M / Lo, Michelle C K / Siu, Dickson M D / Tsia, Kevin K / Yang, Andrian / Ho, Joshua W K

Computational and structural biotechnology journal

2023 Band 21, Seite(n) 1598–1605

Abstract: Current single-cell visualisation techniques project high dimensional data into 'map' views to identify high-level structures such as cell clusters and trajectories. New tools are needed to allow the transversal through the high dimensionality of single- ... ...

Abstract	Current single-cell visualisation techniques project high dimensional data into 'map' views to identify high-level structures such as cell clusters and trajectories. New tools are needed to allow the transversal through the high dimensionality of single-cell data to explore the single-cell local neighbourhood. StarmapVis is a convenient web application displaying an interactive downstream analysis of single-cell expression or spatial transcriptomic data. The concise user interface is powered by modern web browsers to explore the variety of viewing angles unavailable to 2D media. Interactive scatter plots display clustering information, while the trajectory and cross-comparison among different coordinates are displayed in connectivity networks. Automated animation of camera view is a unique feature of our tool. StarmapVis also offers a useful animated transition between two-dimensional spatial omic data to three-dimensional single cell coordinates. The usability of StarmapVis is demonstrated by four data sets, showcasing its practical usability. StarmapVis is available at: https://holab-hku.github.io/starmapVis.
Sprache	Englisch
Erscheinungsdatum	2023-02-14
Erscheinungsland	Netherlands
Dokumenttyp	Journal Article
ZDB-ID	2694435-2
ISSN	2001-0370
ISSN	2001-0370
DOI	10.1016/j.csbj.2023.02.023
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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