JESSICA AURELIA WONG - Academia.edu (original) (raw)

Papers by JESSICA AURELIA WONG

Research paper thumbnail of Tumors of the esophagus

Research paper thumbnail of SF3B1 Mutation Alters The Selection Of 3' RNA Splice Sites In Chronic Lymphocytic Leukemia

Blood, 2013

Large-scale cancer sequencing efforts have enabled the discovery of previously unknown paths to c... more Large-scale cancer sequencing efforts have enabled the discovery of previously unknown paths to carcinogenesis. In chronic lymphocytic leukemia (CLL), these initiatives have identified highly recurrent mutations in the core spliceosome component SF3B1 at restricted sites (i.e. 50% at K700E), implicating a role of altered RNA splicing in CLL. Mutated SF3B1 has been associated with adverse clinical outcome in CLL and a higher incidence in refractory/relapsed CLL. However, mechanistic insights into downstream paths affected by mutated SF3B1 and its role in the oncogenic phenotype are still lacking. To this end, we first examined if mutated SF3B1 alters known disrupted pathways in CLL. We tested the effect of expressing constructs encoding full-length mutated vs. wild-type SF3B1 into hematopoietic cell lines on established pathway readout assays but observed no discernible changes in cell cycle, Notch or Wnt signaling. On the other hand, given the key role of SF3B1 in pre-mRNA splicing,...

Research paper thumbnail of Carcinoma of the esophagus

Research paper thumbnail of Is exercise effective for the management of subacromial impingement syndrome and other soft tissue injuries of the shoulder? A systematic review by the Ontario Protocol for Traffic Injury Management (OPTIMa) Collaboration

Manual Therapy, 2015

Is exercise effective for the management of subacromial impingement syndrome and other soft tissu... more Is exercise effective for the management of subacromial impingement syndrome and other soft tissue injuries of the shoulder? A systematic review by the Ontario Protocol for Traffic Injury Management (OPTIMa) Collaboration,

Research paper thumbnail of Are non-steroidal anti-inflammatory drugs effective for the management of neck pain and associated disorders, whiplash-associated disorders, or non-specific low back pain? A systematic review of systematic reviews by the Ontario Protocol for Traffic Injury Management (OPTIMa) Collaboration

European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society, 2015

To evaluate the effectiveness of non-steroidal anti-inflammatory drugs (NSAIDs) for the managemen... more To evaluate the effectiveness of non-steroidal anti-inflammatory drugs (NSAIDs) for the management of neck pain and associated disorders (NAD), whiplash-associated disorders, and non-specific low back pain (LBP) with or without radiculopathy. We systematically searched six databases from 2000 to 2014. Random pairs of independent reviewers critically appraised eligible systematic reviews using the Scottish Intercollegiate Guidelines Network criteria. We included systematic reviews with a low risk of bias in our best evidence synthesis. We screened 706 citations and 14 systematic reviews were eligible for critical appraisal. Eight systematic reviews had a low risk of bias. For recent-onset NAD, evidence suggests that intramuscular NSAIDs lead to similar outcomes as combined manipulation and soft tissue therapy. For NAD (duration not specified), oral NSAIDs may be more effective than placebo. For recent-onset LBP, evidence suggests that: (1) oral NSAIDs lead to similar outcomes to plac...

Research paper thumbnail of Spontaneous conus medullaris infarction in a 79 year-old female with cardiovascular risk factors: a case report

The Journal of the Canadian Chiropractic Association, 2012

To detail the case of a 79 year-old female who presented with sudden bilateral neurological defic... more To detail the case of a 79 year-old female who presented with sudden bilateral neurological deficits of the lower extremities and was later diagnosed with non-traumatic conus medullaris infarction. The purpose of this case report is to inform primary contact practitioners of the presentation, diagnosis and the associated risk factors of this condition in order to facilitate prompt management. Spinal cord infarction presenting as low back pain with a high degree of bilateral loss of motor strength, sensation and reflexes in the lower extremities and bowel/bladder dysfunction, in a patient with previous coronary artery bypass graft surgery and renal insufficiency. Referral to emergency within hours of symptom onset allowed for immediate assessment, management and relatively favourable partial recovery. Although rare, conus medullaris infarction is potentially devastating and requires an appropriate clinical index of suspicion for timely diagnosis, treatment and optimal neurological re...

Research paper thumbnail of Sternal insufficiency fracture related to steroid-induced osteoporosis: A case report

The Journal of the Canadian Chiropractic Association, 2013

Osteoporosis often results in fractures, deformity and disability. A rare but potentially challen... more Osteoporosis often results in fractures, deformity and disability. A rare but potentially challenging complication of osteoporosis is a sternal insufficiency fracture. This case report details a steroid-induced osteoporotic male who suffered a sternal insufficiency fracture after minimal trauma. Prompt diagnosis and appropriate management resulted in favourable outcome for the fracture, though a sequalae involving a myocardial infarction ensued with his osteoporosis and complex health history. The purpose of this case report is to heighten awareness around distinct characteristics of sternal fractures in osteoporotic patients. Discussion focuses on the incidence, mechanism, associated factors and diagnostic challenge of sternal insufficiency fractures. This case report highlights the role primary contact practitioners can play in recognition and management of sternal insufficiency fractures related to osteoporosis.

Research paper thumbnail of Autoantibody Signature for the Serologic Detection of Ovarian Cancer

Journal of proteome research, Jan 17, 2014

Sera from patients with ovarian cancer contain autoantibodies (AAb) to tumor-derived proteins tha... more Sera from patients with ovarian cancer contain autoantibodies (AAb) to tumor-derived proteins that are potential biomarkers for early detection. To detect AAb, we probed high-density programmable protein microarrays (NAPPA) expressing 5177 candidate tumor antigens with sera from patients with serous ovarian cancer (n = 34 cases/30 controls) and measured bound IgG. Of these, 741 antigens were selected and probed with an independent set of ovarian cancer sera (n = 60 cases/60 controls). Twelve potential autoantigens were identified with sensitivities ranging from 13 to 22% at >93% specificity. These were retested using a Luminex bead array using 60 cases and 60 controls, with sensitivities ranging from 0 to 31.7% at 95% specificity. Three AAb (p53, PTPRA, and PTGFR) had area under the curve (AUC) levels >60% (p < 0.01), with the partial AUC (SPAUC) over 5 times greater than for a nondiscriminating test (p…

Research paper thumbnail of Incidence of influenza virus infections in children in Hong Kong in a 3-year randomized placebo-controlled vaccine study, 2009-2012

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, Jan 15, 2014

School-aged children suffer high rates of influenza virus infections and associated illnesses eac... more School-aged children suffer high rates of influenza virus infections and associated illnesses each year, and are a major source of transmission in the community. However, information on the cumulative incidence of infection in specific epidemics is scarce, and there are limited studies with sufficient follow-up to identify the strength and duration of protection against reinfection. We randomly allocated children 5-17 years of age to receive trivalent inactivated influenza vaccine (TIV) or placebo from September 2009 through January 2010, and then conducted follow-up for 3 years including regular collection of sera, symptom diaries, and collection of nose and throat swabs during illness episodes in participants or their household members. Of 796 children initially randomized, 484 continued to participate for all 3 years. In unvaccinated children, cumulative incidence of infection was estimated to be 59% in the first wave of H1N1pdm09 in 2009-2010, and 7%, 14%, 20%, and 31% in subseq...

Research paper thumbnail of Somatic mutation as a mechanism of Wnt/β-catenin pathway activation in CLL

Blood, 2014

Key Points Wnt pathway is frequently mutated in CLL. Wnt pathway mutations can lead to pathway ac... more Key Points Wnt pathway is frequently mutated in CLL. Wnt pathway mutations can lead to pathway activation and enhanced CLL survival.

Research paper thumbnail of Interprofessional Teamwork for Health and Social Care

Research paper thumbnail of A scheme for improving ICT units with critically low student satisfaction

Proceedings of the 16th annual joint conference on Innovation and technology in computer science education, 2011

Abstract Unit evaluations across many Australian universities indicate that close to 10% of units... more Abstract Unit evaluations across many Australian universities indicate that close to 10% of units in Information and Communication Technology (ICT) and Engineering disciplines are flagged as needing critical attention, and as such these faculties often struggle to meet ...

Research paper thumbnail of Dr. Alexander Fleming and the discovery of penicillin

Primary Care Update for OB/GYNS, 2003

In our era of advanced medical technology, it is difficult to imagine a time when clinical treatm... more In our era of advanced medical technology, it is difficult to imagine a time when clinical treatment was absent or largely ineffective. Patients of the early 20th century had few options when it came to medical therapy. Many of the people admitted to hospitals at that time suffered from bacterial infections, which caused major morbidity and mortality, as antibiotics were not yet present. Dr. Alexander Fleming's discovery of penicillin and the subsequent development of antibiotics were the most significant advances that revolutionized the practice of medicine. The details of Fleming's life and work reveal a story combining his grand achievements with the accomplishments of others, intermixed with some measure of luck, arbitrariness, and serendipity.

Research paper thumbnail of The course and prognostic factors of symptomatic cervical disc herniation with radiculopathy: a systematic review of the literature

The Spine Journal, 2014

BACKGROUND CONTEXT: Cervical spine disc herniation is a disabling source of cervical radiculopath... more BACKGROUND CONTEXT: Cervical spine disc herniation is a disabling source of cervical radiculopathy. However, little is known about its course and prognosis. Understanding the course and prognosis of symptomatic cervical disc herniation is necessary to guide patients' expectations and assist clinicians in managing patients. PURPOSE: To describe the natural history, clinical course, and prognostic factors of symptomatic cervical disc herniations with radiculopathy. STUDY DESIGN: Systematic review of the literature and best evidence synthesis. METHODS: A systematic search of MEDLINE, EMBASE, CINAHL, SportsDiscus, and the Cochrane Central Register of Controlled Trials from inception to 2013 was conducted to retrieve eligible articles. Eligible articles were critically appraised using the Scottish Intercollegiate Guidelines Network criteria. The results from articles with low risk of bias were analyzed using best evidence synthesis principles. RESULTS: We identified 1,221 articles. Of those, eight articles were eligible and three were accepted as having a low risk of bias. Two studies pertained to course and one study pertained to prognosis. Most patients with symptomatic cervical disc herniations with radiculopathy initially present with intense pain and moderate levels of disability. However, substantial improvements tend to occur within the first 4 to 6 months post-onset. Time to complete recovery ranged from 24 to 36 months in, approximately, 83% of patients. Patients with a workers' compensation claim appeared to have a poorer prognosis. CONCLUSIONS: Our best evidence synthesis describes the best available evidence on the course and prognosis of cervical disc herniations with radiculopathy. Most patients with symptomatic cervical spine disc herniation with radiculopathy recover. Possible recurrences and time to complete recovery need to be further studied. More studies are also needed to understand the prognostic factors for this condition.

Research paper thumbnail of Tracking humoral responses using self assembling protein microarrays

PROTEOMICS - CLINICAL APPLICATIONS, 2008

The humoral immune response is a highly specific and adaptive sensor for changes in the body's pr... more The humoral immune response is a highly specific and adaptive sensor for changes in the body's protein milieu, which responds to novel structures of both foreign and self antigens. Although immunoglobulins represent a major component of human serum and are vital to survival, little is known about the response specificity and determinants that govern the human immunome. Historically, antigen-specific humoral immunity has been investigated using individuallyproduced and purified target proteins, a labor-intensive process that has limited the number of antigens that have been studied. Here, we present the development of methods for applying selfassembling protein microarrays and a related method for producing 96-well formatted macroarrays for monitoring the humoral response at the proteome scale. Using plasmids encoding full-length cDNAs for over 850 human proteins and 1700 pathogen proteins, we demonstrate that these microarrays are highly sensitive, specific, reproducible, and can simultaneously measure immunity to thousands of proteins without a priori protein purification. Using this approach, we demonstrate the detection of humoral immunity to known and novel self-antigens, cancer antigens, autoimmune antigens, as well as pathogen-derived antigens. This represents a powerful and versatile tool for monitoring the immunome in health and disease.

Research paper thumbnail of Synthesis of sulfone-based nucleotide isosteres: identification of CMP-sialic acid synthetase inhibitors

Org. Biomol. Chem., 2009

A modular replacement approach to the synthesis of sulfonucleotide analogs prepared from condensa... more A modular replacement approach to the synthesis of sulfonucleotide analogs prepared from condensation of nucleoside aldehydes with bis phosphonate Horner-Wadsworth-Emmons reagents is disclosed. These analogs were shown to be inhibitors of Neisseria meningitidis CSS (NmCSS), which is a key enzyme in the biosynthesis of the capsular polysaccharides required for bacterial infection. Neisseria meningitidis B is a leading cause of bacterial meningitis for which there is no available vaccine. These bacteria express a linear homopolymer of α-2,8-linked sialic acid (1) as part of their capsular polysaccharides. In humans, polysialic acid (1) expression occurs early in development and is down regulated by about two years of age suggesting that its functional role in bacteria may be related to host mimicry. 1-3 The bacteria may employ this polymer in cellular interactions that permit infection. Recently, we have focused our attention on developing methods for the synthesis of substrate-based inhibitors of enzymes involved in the biosynthesis of polysialic acids, which include CMP-sialic acid synthetases (CSS) and polysialyltransferases (PST). CSS is a bisubstrate enzyme that utilizes both sialic acid and cytidine triphosphate (CTP) as substrates in the production of CMP-sialic acid, which in turn is a substrate for PST, (Fig. 1). Activation of sialic acid to CMP-sialic acid is an essential step in the biosynthesis of sialoglyconjugates that is conserved from bacteria to humans: however, eukaryotic CSS are localized in the nuclear compartment whereas the bacterial enzymes are cytoplasmic. This fundamental difference offers the possibility of achieving selective inhibition as a function of nuclear transport. Presumably, inhibitors incapable of permeating the nuclear membrane would not inhibit mammalian enzymes. Development of substrate analogs of CSS enzymes as inhibitors and/or molecular probes represents an important area of investigation for potential drug development, as incorporation of sialic acid into capsular polysaccharides is required for the conversion of N. meningitidis to a serum resistant phenotype. 4-6 A number of CSS enzymes have been cloned from both bacterial and vertebrate sources. While several of these enzymes accept modified sialic acids as substrates, 7-12 less is known about their tolerance to CTP modifications. Various nucleotides including CTP, CDP, UTP † Electronic supplementary information (ESI) available: Experimental details of compound syntheses and NmCSS substrate and inhibition assays; NMR, HRMS, HPLC and CE spectra.

Research paper thumbnail of Up-to-date catalogues of yeast protein complexes

Nucleic Acids Research, 2008

Gold standard datasets on protein complexes are key to inferring and validating protein-protein i... more Gold standard datasets on protein complexes are key to inferring and validating protein-protein interactions. Despite much progress in characterizing protein complexes in the yeast Saccharomyces cerevisiae, numerous researchers still use as reference the manually curated complexes catalogued by the Munich Information Center of Protein Sequences database. Although this catalogue has served the community extremely well, it no longer reflects the current state of knowledge. Here, we report two catalogues of yeast protein complexes as results of systematic curation efforts. The first one, denoted as CYC2008, is a comprehensive catalogue of 408 manually curated heteromeric protein complexes reliably backed by small-scale experiments reported in the current literature. This catalogue represents an up-to-date reference set for biologists interested in discovering protein interactions and protein complexes. The second catalogue, denoted as YHTP2008, comprises 400 high-throughput complexes annotated with current literature evidence. Among them, 262 correspond, at least partially, to CYC2008 complexes. Evidence for interacting subunits is collected for 68 complexes that have only partial or no overlap with CYC2008 complexes, whereas no literature evidence was found for 100 complexes. Some of these partially supported and as yet unsupported complexes may be interesting candidates for experimental follow up. Both catalogues are freely

Research paper thumbnail of Treatment of Esophageal Cancer

New England Journal of Medicine, 1999

Abstrac

Research paper thumbnail of Effects of beta-alanine supplementation on performance and body composition in collegiate wrestlers and football players

Journal of the International Society of Sports Nutrition, 2009

Publish with Bio Med Central and every scientist can read your work free of charge "BioMed Centra... more Publish with Bio Med Central and every scientist can read your work free of charge "BioMed Central will be the most significant development for disseminating the results of biomedical researc h in our lifetime."

Research paper thumbnail of Protein Microarray Signature of Autoantibody Biomarkers for the Early Detection of Breast Cancer

Journal of Proteome Research, 2011

Cancer patients spontaneously generate autoantibodies (AAb) to tumor-derived proteins.. To detect... more Cancer patients spontaneously generate autoantibodies (AAb) to tumor-derived proteins.. To detect AAb, we have probed novel high-density custom protein microarrays (NAPPA) expressing 4,988 candidate tumor antigens with sera from patients with early stage breast cancer (IBC), and bound IgG was measured. We used a three-phase serial screening approach. First, a pre-screen was performed to eliminate uninformative antigens. Sera from stage I-III IBC (n=53) and healthy women (n=53) were screened for AAb to all 4,988 protein antigens. Antigens were selected if the 95 th percentile of signal of cases and controls were significantly different (p<0.05) and if the number of cases with signals above the 95 th percentile of controls was significant (p<0.05). These 761 antigens were screened using an independent set of IBC sera (n=51) and sera from women with benign breast disease (BBD) (n=39). From these, 119 antigens had a partial area under the ROC curve (p<0.05), with sensitivities ranging from 9-40% at >91% specificity. 28 of these antigens were confirmed using an independent serum cohort (n=51 cases/38 controls, p<0.05). Using all 28 AAb, a classifier was identified with a sensitivity of 80.8% and a specificity of 61.6% (AUC=0.756). These are potential biomarkers for the early detection of breast cancer.

Research paper thumbnail of Tumors of the esophagus

Research paper thumbnail of SF3B1 Mutation Alters The Selection Of 3' RNA Splice Sites In Chronic Lymphocytic Leukemia

Blood, 2013

Large-scale cancer sequencing efforts have enabled the discovery of previously unknown paths to c... more Large-scale cancer sequencing efforts have enabled the discovery of previously unknown paths to carcinogenesis. In chronic lymphocytic leukemia (CLL), these initiatives have identified highly recurrent mutations in the core spliceosome component SF3B1 at restricted sites (i.e. 50% at K700E), implicating a role of altered RNA splicing in CLL. Mutated SF3B1 has been associated with adverse clinical outcome in CLL and a higher incidence in refractory/relapsed CLL. However, mechanistic insights into downstream paths affected by mutated SF3B1 and its role in the oncogenic phenotype are still lacking. To this end, we first examined if mutated SF3B1 alters known disrupted pathways in CLL. We tested the effect of expressing constructs encoding full-length mutated vs. wild-type SF3B1 into hematopoietic cell lines on established pathway readout assays but observed no discernible changes in cell cycle, Notch or Wnt signaling. On the other hand, given the key role of SF3B1 in pre-mRNA splicing,...

Research paper thumbnail of Carcinoma of the esophagus

Research paper thumbnail of Is exercise effective for the management of subacromial impingement syndrome and other soft tissue injuries of the shoulder? A systematic review by the Ontario Protocol for Traffic Injury Management (OPTIMa) Collaboration

Manual Therapy, 2015

Is exercise effective for the management of subacromial impingement syndrome and other soft tissu... more Is exercise effective for the management of subacromial impingement syndrome and other soft tissue injuries of the shoulder? A systematic review by the Ontario Protocol for Traffic Injury Management (OPTIMa) Collaboration,

Research paper thumbnail of Are non-steroidal anti-inflammatory drugs effective for the management of neck pain and associated disorders, whiplash-associated disorders, or non-specific low back pain? A systematic review of systematic reviews by the Ontario Protocol for Traffic Injury Management (OPTIMa) Collaboration

European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society, 2015

To evaluate the effectiveness of non-steroidal anti-inflammatory drugs (NSAIDs) for the managemen... more To evaluate the effectiveness of non-steroidal anti-inflammatory drugs (NSAIDs) for the management of neck pain and associated disorders (NAD), whiplash-associated disorders, and non-specific low back pain (LBP) with or without radiculopathy. We systematically searched six databases from 2000 to 2014. Random pairs of independent reviewers critically appraised eligible systematic reviews using the Scottish Intercollegiate Guidelines Network criteria. We included systematic reviews with a low risk of bias in our best evidence synthesis. We screened 706 citations and 14 systematic reviews were eligible for critical appraisal. Eight systematic reviews had a low risk of bias. For recent-onset NAD, evidence suggests that intramuscular NSAIDs lead to similar outcomes as combined manipulation and soft tissue therapy. For NAD (duration not specified), oral NSAIDs may be more effective than placebo. For recent-onset LBP, evidence suggests that: (1) oral NSAIDs lead to similar outcomes to plac...

Research paper thumbnail of Spontaneous conus medullaris infarction in a 79 year-old female with cardiovascular risk factors: a case report

The Journal of the Canadian Chiropractic Association, 2012

To detail the case of a 79 year-old female who presented with sudden bilateral neurological defic... more To detail the case of a 79 year-old female who presented with sudden bilateral neurological deficits of the lower extremities and was later diagnosed with non-traumatic conus medullaris infarction. The purpose of this case report is to inform primary contact practitioners of the presentation, diagnosis and the associated risk factors of this condition in order to facilitate prompt management. Spinal cord infarction presenting as low back pain with a high degree of bilateral loss of motor strength, sensation and reflexes in the lower extremities and bowel/bladder dysfunction, in a patient with previous coronary artery bypass graft surgery and renal insufficiency. Referral to emergency within hours of symptom onset allowed for immediate assessment, management and relatively favourable partial recovery. Although rare, conus medullaris infarction is potentially devastating and requires an appropriate clinical index of suspicion for timely diagnosis, treatment and optimal neurological re...

Research paper thumbnail of Sternal insufficiency fracture related to steroid-induced osteoporosis: A case report

The Journal of the Canadian Chiropractic Association, 2013

Osteoporosis often results in fractures, deformity and disability. A rare but potentially challen... more Osteoporosis often results in fractures, deformity and disability. A rare but potentially challenging complication of osteoporosis is a sternal insufficiency fracture. This case report details a steroid-induced osteoporotic male who suffered a sternal insufficiency fracture after minimal trauma. Prompt diagnosis and appropriate management resulted in favourable outcome for the fracture, though a sequalae involving a myocardial infarction ensued with his osteoporosis and complex health history. The purpose of this case report is to heighten awareness around distinct characteristics of sternal fractures in osteoporotic patients. Discussion focuses on the incidence, mechanism, associated factors and diagnostic challenge of sternal insufficiency fractures. This case report highlights the role primary contact practitioners can play in recognition and management of sternal insufficiency fractures related to osteoporosis.

Research paper thumbnail of Autoantibody Signature for the Serologic Detection of Ovarian Cancer

Journal of proteome research, Jan 17, 2014

Sera from patients with ovarian cancer contain autoantibodies (AAb) to tumor-derived proteins tha... more Sera from patients with ovarian cancer contain autoantibodies (AAb) to tumor-derived proteins that are potential biomarkers for early detection. To detect AAb, we probed high-density programmable protein microarrays (NAPPA) expressing 5177 candidate tumor antigens with sera from patients with serous ovarian cancer (n = 34 cases/30 controls) and measured bound IgG. Of these, 741 antigens were selected and probed with an independent set of ovarian cancer sera (n = 60 cases/60 controls). Twelve potential autoantigens were identified with sensitivities ranging from 13 to 22% at >93% specificity. These were retested using a Luminex bead array using 60 cases and 60 controls, with sensitivities ranging from 0 to 31.7% at 95% specificity. Three AAb (p53, PTPRA, and PTGFR) had area under the curve (AUC) levels >60% (p < 0.01), with the partial AUC (SPAUC) over 5 times greater than for a nondiscriminating test (p…

Research paper thumbnail of Incidence of influenza virus infections in children in Hong Kong in a 3-year randomized placebo-controlled vaccine study, 2009-2012

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, Jan 15, 2014

School-aged children suffer high rates of influenza virus infections and associated illnesses eac... more School-aged children suffer high rates of influenza virus infections and associated illnesses each year, and are a major source of transmission in the community. However, information on the cumulative incidence of infection in specific epidemics is scarce, and there are limited studies with sufficient follow-up to identify the strength and duration of protection against reinfection. We randomly allocated children 5-17 years of age to receive trivalent inactivated influenza vaccine (TIV) or placebo from September 2009 through January 2010, and then conducted follow-up for 3 years including regular collection of sera, symptom diaries, and collection of nose and throat swabs during illness episodes in participants or their household members. Of 796 children initially randomized, 484 continued to participate for all 3 years. In unvaccinated children, cumulative incidence of infection was estimated to be 59% in the first wave of H1N1pdm09 in 2009-2010, and 7%, 14%, 20%, and 31% in subseq...

Research paper thumbnail of Somatic mutation as a mechanism of Wnt/β-catenin pathway activation in CLL

Blood, 2014

Key Points Wnt pathway is frequently mutated in CLL. Wnt pathway mutations can lead to pathway ac... more Key Points Wnt pathway is frequently mutated in CLL. Wnt pathway mutations can lead to pathway activation and enhanced CLL survival.

Research paper thumbnail of Interprofessional Teamwork for Health and Social Care

Research paper thumbnail of A scheme for improving ICT units with critically low student satisfaction

Proceedings of the 16th annual joint conference on Innovation and technology in computer science education, 2011

Abstract Unit evaluations across many Australian universities indicate that close to 10% of units... more Abstract Unit evaluations across many Australian universities indicate that close to 10% of units in Information and Communication Technology (ICT) and Engineering disciplines are flagged as needing critical attention, and as such these faculties often struggle to meet ...

Research paper thumbnail of Dr. Alexander Fleming and the discovery of penicillin

Primary Care Update for OB/GYNS, 2003

In our era of advanced medical technology, it is difficult to imagine a time when clinical treatm... more In our era of advanced medical technology, it is difficult to imagine a time when clinical treatment was absent or largely ineffective. Patients of the early 20th century had few options when it came to medical therapy. Many of the people admitted to hospitals at that time suffered from bacterial infections, which caused major morbidity and mortality, as antibiotics were not yet present. Dr. Alexander Fleming's discovery of penicillin and the subsequent development of antibiotics were the most significant advances that revolutionized the practice of medicine. The details of Fleming's life and work reveal a story combining his grand achievements with the accomplishments of others, intermixed with some measure of luck, arbitrariness, and serendipity.

Research paper thumbnail of The course and prognostic factors of symptomatic cervical disc herniation with radiculopathy: a systematic review of the literature

The Spine Journal, 2014

BACKGROUND CONTEXT: Cervical spine disc herniation is a disabling source of cervical radiculopath... more BACKGROUND CONTEXT: Cervical spine disc herniation is a disabling source of cervical radiculopathy. However, little is known about its course and prognosis. Understanding the course and prognosis of symptomatic cervical disc herniation is necessary to guide patients' expectations and assist clinicians in managing patients. PURPOSE: To describe the natural history, clinical course, and prognostic factors of symptomatic cervical disc herniations with radiculopathy. STUDY DESIGN: Systematic review of the literature and best evidence synthesis. METHODS: A systematic search of MEDLINE, EMBASE, CINAHL, SportsDiscus, and the Cochrane Central Register of Controlled Trials from inception to 2013 was conducted to retrieve eligible articles. Eligible articles were critically appraised using the Scottish Intercollegiate Guidelines Network criteria. The results from articles with low risk of bias were analyzed using best evidence synthesis principles. RESULTS: We identified 1,221 articles. Of those, eight articles were eligible and three were accepted as having a low risk of bias. Two studies pertained to course and one study pertained to prognosis. Most patients with symptomatic cervical disc herniations with radiculopathy initially present with intense pain and moderate levels of disability. However, substantial improvements tend to occur within the first 4 to 6 months post-onset. Time to complete recovery ranged from 24 to 36 months in, approximately, 83% of patients. Patients with a workers' compensation claim appeared to have a poorer prognosis. CONCLUSIONS: Our best evidence synthesis describes the best available evidence on the course and prognosis of cervical disc herniations with radiculopathy. Most patients with symptomatic cervical spine disc herniation with radiculopathy recover. Possible recurrences and time to complete recovery need to be further studied. More studies are also needed to understand the prognostic factors for this condition.

Research paper thumbnail of Tracking humoral responses using self assembling protein microarrays

PROTEOMICS - CLINICAL APPLICATIONS, 2008

The humoral immune response is a highly specific and adaptive sensor for changes in the body's pr... more The humoral immune response is a highly specific and adaptive sensor for changes in the body's protein milieu, which responds to novel structures of both foreign and self antigens. Although immunoglobulins represent a major component of human serum and are vital to survival, little is known about the response specificity and determinants that govern the human immunome. Historically, antigen-specific humoral immunity has been investigated using individuallyproduced and purified target proteins, a labor-intensive process that has limited the number of antigens that have been studied. Here, we present the development of methods for applying selfassembling protein microarrays and a related method for producing 96-well formatted macroarrays for monitoring the humoral response at the proteome scale. Using plasmids encoding full-length cDNAs for over 850 human proteins and 1700 pathogen proteins, we demonstrate that these microarrays are highly sensitive, specific, reproducible, and can simultaneously measure immunity to thousands of proteins without a priori protein purification. Using this approach, we demonstrate the detection of humoral immunity to known and novel self-antigens, cancer antigens, autoimmune antigens, as well as pathogen-derived antigens. This represents a powerful and versatile tool for monitoring the immunome in health and disease.

Research paper thumbnail of Synthesis of sulfone-based nucleotide isosteres: identification of CMP-sialic acid synthetase inhibitors

Org. Biomol. Chem., 2009

A modular replacement approach to the synthesis of sulfonucleotide analogs prepared from condensa... more A modular replacement approach to the synthesis of sulfonucleotide analogs prepared from condensation of nucleoside aldehydes with bis phosphonate Horner-Wadsworth-Emmons reagents is disclosed. These analogs were shown to be inhibitors of Neisseria meningitidis CSS (NmCSS), which is a key enzyme in the biosynthesis of the capsular polysaccharides required for bacterial infection. Neisseria meningitidis B is a leading cause of bacterial meningitis for which there is no available vaccine. These bacteria express a linear homopolymer of α-2,8-linked sialic acid (1) as part of their capsular polysaccharides. In humans, polysialic acid (1) expression occurs early in development and is down regulated by about two years of age suggesting that its functional role in bacteria may be related to host mimicry. 1-3 The bacteria may employ this polymer in cellular interactions that permit infection. Recently, we have focused our attention on developing methods for the synthesis of substrate-based inhibitors of enzymes involved in the biosynthesis of polysialic acids, which include CMP-sialic acid synthetases (CSS) and polysialyltransferases (PST). CSS is a bisubstrate enzyme that utilizes both sialic acid and cytidine triphosphate (CTP) as substrates in the production of CMP-sialic acid, which in turn is a substrate for PST, (Fig. 1). Activation of sialic acid to CMP-sialic acid is an essential step in the biosynthesis of sialoglyconjugates that is conserved from bacteria to humans: however, eukaryotic CSS are localized in the nuclear compartment whereas the bacterial enzymes are cytoplasmic. This fundamental difference offers the possibility of achieving selective inhibition as a function of nuclear transport. Presumably, inhibitors incapable of permeating the nuclear membrane would not inhibit mammalian enzymes. Development of substrate analogs of CSS enzymes as inhibitors and/or molecular probes represents an important area of investigation for potential drug development, as incorporation of sialic acid into capsular polysaccharides is required for the conversion of N. meningitidis to a serum resistant phenotype. 4-6 A number of CSS enzymes have been cloned from both bacterial and vertebrate sources. While several of these enzymes accept modified sialic acids as substrates, 7-12 less is known about their tolerance to CTP modifications. Various nucleotides including CTP, CDP, UTP † Electronic supplementary information (ESI) available: Experimental details of compound syntheses and NmCSS substrate and inhibition assays; NMR, HRMS, HPLC and CE spectra.

Research paper thumbnail of Up-to-date catalogues of yeast protein complexes

Nucleic Acids Research, 2008

Gold standard datasets on protein complexes are key to inferring and validating protein-protein i... more Gold standard datasets on protein complexes are key to inferring and validating protein-protein interactions. Despite much progress in characterizing protein complexes in the yeast Saccharomyces cerevisiae, numerous researchers still use as reference the manually curated complexes catalogued by the Munich Information Center of Protein Sequences database. Although this catalogue has served the community extremely well, it no longer reflects the current state of knowledge. Here, we report two catalogues of yeast protein complexes as results of systematic curation efforts. The first one, denoted as CYC2008, is a comprehensive catalogue of 408 manually curated heteromeric protein complexes reliably backed by small-scale experiments reported in the current literature. This catalogue represents an up-to-date reference set for biologists interested in discovering protein interactions and protein complexes. The second catalogue, denoted as YHTP2008, comprises 400 high-throughput complexes annotated with current literature evidence. Among them, 262 correspond, at least partially, to CYC2008 complexes. Evidence for interacting subunits is collected for 68 complexes that have only partial or no overlap with CYC2008 complexes, whereas no literature evidence was found for 100 complexes. Some of these partially supported and as yet unsupported complexes may be interesting candidates for experimental follow up. Both catalogues are freely

Research paper thumbnail of Treatment of Esophageal Cancer

New England Journal of Medicine, 1999

Abstrac

Research paper thumbnail of Effects of beta-alanine supplementation on performance and body composition in collegiate wrestlers and football players

Journal of the International Society of Sports Nutrition, 2009

Publish with Bio Med Central and every scientist can read your work free of charge "BioMed Centra... more Publish with Bio Med Central and every scientist can read your work free of charge "BioMed Central will be the most significant development for disseminating the results of biomedical researc h in our lifetime."

Research paper thumbnail of Protein Microarray Signature of Autoantibody Biomarkers for the Early Detection of Breast Cancer

Journal of Proteome Research, 2011

Cancer patients spontaneously generate autoantibodies (AAb) to tumor-derived proteins.. To detect... more Cancer patients spontaneously generate autoantibodies (AAb) to tumor-derived proteins.. To detect AAb, we have probed novel high-density custom protein microarrays (NAPPA) expressing 4,988 candidate tumor antigens with sera from patients with early stage breast cancer (IBC), and bound IgG was measured. We used a three-phase serial screening approach. First, a pre-screen was performed to eliminate uninformative antigens. Sera from stage I-III IBC (n=53) and healthy women (n=53) were screened for AAb to all 4,988 protein antigens. Antigens were selected if the 95 th percentile of signal of cases and controls were significantly different (p<0.05) and if the number of cases with signals above the 95 th percentile of controls was significant (p<0.05). These 761 antigens were screened using an independent set of IBC sera (n=51) and sera from women with benign breast disease (BBD) (n=39). From these, 119 antigens had a partial area under the ROC curve (p<0.05), with sensitivities ranging from 9-40% at >91% specificity. 28 of these antigens were confirmed using an independent serum cohort (n=51 cases/38 controls, p<0.05). Using all 28 AAb, a classifier was identified with a sensitivity of 80.8% and a specificity of 61.6% (AUC=0.756). These are potential biomarkers for the early detection of breast cancer.