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Biomedical subjects

David Goldberg

Publications and source records attributed to David Goldberg.

At least 19 recordsLinked to original sources
PubMed2026

Metabolic Dysfunction-Associated Steatotic Liver Disease Is Associated With Adverse Social Factors: An Analysis Using All of Us.

BACKGROUND AND AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) is progressive, with estimated global prevalence exceeding 30%. Social determinants of health (SDOH) may impact MASLD risk and progression. However, this has not been fully characterized. We harnessed the power of the All of Us Research Program (AoU) dataset to conduct a comprehensive analysis examining the association between various SDOH and MASLD. METHODS: We conducted a retrospective cross-sectional analysis of the AoU database. We identified participants with MASLD using ICD-9 and -10 codes and excluded individuals with other chronic liver diseases or self-reported heavy alcohol use. Healthy control participants were devoid of chronic liver diseases, heavy alcohol use, and comorbidities associated with MASLD if obese. We examined SDOH by combining relevant questions from various AoU surveys and conducted univariate and multivariate logistic regression to examine the association between various SDOH and MASLD. RESULTS: After matching cases to controls by age and race/ethnicity, the sample of 57,895 participants had a 1:3 case to control ratio; 16,666 had complete SDOH survey data (MASLD to controls, 1:3.4). Compared to controls, individuals with MASLD were more likely to have less than a high school education (10.7% vs 9.7%; P < .001) and annual income &#x2264;$35,000 (42.4% vs 34.3%; P < .001). Compared to controls, participants with MASLD had significantly higher levels of social isolation, neighborhood disorder, perceived stress, food insecurity, and transportation insecurity (P < .001 for all). CONCLUSION: The study identified significant associations between MASLD and multiple SDOH. Future studies should investigate how SDOH interact to drive MASLD risk and progression.

All of Us↗
PubMed2007

Generalized anxiety disorder and depression: childhood risk factors in a birth cohort followed to age 32.

BACKGROUND: The close association between generalized anxiety disorder (GAD) and major depressive disorder (MDD) prompts questions about how to characterize them in future diagnostic systems. We tested whether risk factors for MDD and GAD are similar or different. METHOD: The representative 1972-73 Dunedin birth cohort of 1037 males and females was followed to age 32 with 96% retention. Adult GAD and MDD were diagnosed at ages 18, 21, 26, and 32 years, and juvenile anxiety/depression were also taken into account. Thirteen prospective risk measures indexed domains of family history, adverse family environment, childhood behavior, and adolescent self-esteem and personality traits. RESULTS: Co-morbid MDD+GAD was antedated by highly elevated risk factors broadly across all domains. MDD+GAD was further characterized by the earliest onset, most recurrence, and greatest use of mental health services and medication. Pure GAD had levels of risk factors similar to the elevated levels for co-morbid MDD+GAD; generally, pure MDD did not. Pure GAD had risks during childhood not shared by pure MDD, in domains of adverse family environment (low SES, somewhat more maltreatment) and childhood behavior (internalizing problems, conduct problems, somewhat more inhibited temperament). Pure MDD had risks not shared by pure GAD, in domains of family history (of depression) and personality (low positive emotionality). CONCLUSIONS: Specific antecedent risk factors for pure adult MDD versus GAD may suggest partly different etiological pathways. That GAD and co-morbid MDD+GAD share many risk markers suggests that the presence of GAD may signal a pathway toward relatively more severe internalizing disorder.

Adolescent↗
PubMed2006

Data mining for proteins characteristic of clades.

A synapomorphy is a phylogenetic character that provides evidence of shared descent. Ideally a synapomorphy is ubiquitous within the clade of related organisms and nonexistent outside the clade, implying that it arose after divergence from other extant species and before the last common ancestor of the clade. With the recent proliferation of genetic sequence data, molecular synapomorphies have assumed great importance, yet there is no convenient means to search for them over entire genomes. We have developed a new program called Conserv, which can rapidly assemble orthologous sequences and rank them by various metrics, such as degree of conservation or divergence from out-group orthologs. We have used Conserv to conduct a largescale search for molecular synapomorphies for bacterial clades. The search discovered sequences unique to clades, such as Actinobacteria, Firmicutes and gamma-Proteobacteria, and shed light on several open questions, such as whether Symbiobacterium thermophilum belongs with Actinobacteria or Firmicutes. We conclude that Conserv can quickly marshall evidence relevant to evolutionary questions that would be much harder to assemble with other tools.

Amino Acid Sequence↗
PubMed2006

Activation of murine CD4+ and CD8+ T lymphocytes leads to dramatic remodeling of N-linked glycans.

Differentiation and activation of lymphocytes are documented to result in changes in glycosylation associated with biologically important consequences. In this report, we have systematically examined global changes in N-linked glycosylation following activation of murine CD4 T cells, CD8 T cells, and B cells by MALDI-TOF mass spectrometry profiling, and investigated the molecular basis for those changes by assessing alterations in the expression of glycan transferase genes. Surprisingly, the major change observed in activated CD4 and CD8 T cells was a dramatic reduction of sialylated biantennary N-glycans carrying the terminal NeuGcalpha2-6Gal sequence, and a corresponding increase in glycans carrying the Galalpha1-3Gal sequence. This change was accounted for by a decrease in the expression of the sialyltransferase ST6Gal I, and an increase in the expression of the galactosyltransferase, alpha1-3GalT. Conversely, in B cells no change in terminal sialylation of N-linked glycans was evident, and the expression of the same two glycosyltransferases was increased and decreased, respectively. The results have implications for differential recognition of activated and unactivated T cells by dendritic cells and B cells expressing glycan-binding proteins that recognize terminal sequences of N-linked glycans.

Animals↗
PubMed2006

Computer expert systems for African-American smokers in physicians offices: a feasibility study.

BACKGROUND: Stage-based computer expert systems (CES), delivered in physician offices, may offer unique opportunities to combine high participation and high efficacy, resulting in a high public health impact. Applying this technology in settings serving low-income African-American smokers, with the addition of practical tools for stress reduction, may help to reduce disparities in morbidity and mortality from smoking-related diseases. METHODS: Ninety-eight African-American smokers were recruited from a publicly funded, continuity care clinic waiting room to a study of computer interactive feedback and stress reduction audiotapes. The study was designed to assess: participation and retention rates; acceptability of both the computer expert system and the audiotapes; the fit of the transtheoretical model for the target population; and the 6-month shift in stages of change. RESULTS: Overall, 55.6% of invited smokers participated, 75.5% were seen at all three observation points. The CES and the audiotape were rated as highly interesting, relevant, and new, and most participants tried them. The predictable relationship between stage and decisional balance was reproduced in this low income African-American population. Significant stage progression occurred from baseline to 3 months (P = 0.011), from 3 to 6 months (P = 0.0001), and from baseline to 6 months (P = 0.0001). CONCLUSIONS: These data support the feasibility, acceptability and potential efficacy of stage-tailored computer interactive feedback plus stress reduction intervention delivered at the point of service to low-income African-Americans.

Black or African American↗
PubMed2006

The aetiology of depression.

This review will start by considering studies of the genetic contribution to the liability to depression, and go on to consider some of the ways in which environmental factors can modify gene expression. This will lead on to the pathways by which the genetic factors also appear to control stressful life events in adolescence and adult life, and then to a consideration of causes that are entirely environmental. We will conclude by considering the causes of the gender differences in the prevalence of depression during adult life.

Child↗
PubMed2006

Anonymous pilot study of hepatitis C virus prevalence in liver transplant surgeons.

The risk of hepatitis C virus (HCV) transmission to surgeons is related to the HCV prevalence in the surgical patient population. As HCV-related cirrhosis is the commonest indication for liver transplantation in Europe and North America, liver transplant surgeons are at particular risk. The prevalence of HCV infection in liver transplant surgeons is unknown. The aim of this study was to estimate the prevalence of HCV infection in liver transplant surgeons attending the 9th Congress of the International Liver Transplantation Society using unlinked anonymous testing for HCV. Surgeons attending the conference were invited to complete an anonymised questionnaire regarding their surgical and transplant practice and provide an unlinked anonymised blood spot sample by finger prick. Samples were screened for antibodies to HCV (enzyme-linked immunosorbent assay III, Ortho Diagnostics, Raritan, NJ). Polymerase chain reaction testing for HCV RNA was performed on reactive samples.A total of 117 liver transplant surgeons (79 European, 16 North American, 10 Asian, 9 South American, 3 Australasian) provided a blood spot sample. Two (1.7%) surgeons had antibodies to HCV, 1 (0.8%) had detectable HCV RNA (genotype 1a). Assuming that both infections were acquired during surgery, the estimated maximum rate of HCV transmission is 1 per 743 to 1,045 years of surgical (0.96 to 1.35 HCV transmissions per 1,000 years of general surgical practice) and 449 to 683 years of liver transplant practice (1.46 to 2.23 HCV transmissions per 1,000 years of liver transplantation practice). In conclusion, risk of HCV transmission to liver transplant surgeons appears to be low despite the particular risks associated with frequently operating on HCV infected patients.

Hepacivirus↗
PubMed2006

Glycomic profiling of cells and tissues by mass spectrometry: fingerprinting and sequencing methodologies.

Over the past decade, rapid, high-sensitivity mass spectrometric strat-egies have been developed and optimized for screening for the types of N- and O-glycans present in a diverse range of biological material, including secretions, cell lines, tissues, and organs. These glycomic strategies are based on matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass fingerprinting of permethylated derivatives, combined with electrospray (ES) or MALDI tandem mass spectrometry (MS/MS) sequencing and gas chromatography (GC)-MS linkage analysis, complemented by chemical and enzymatic degradations. Protocols for these methods are described in the first part of this chapter. Glycomic experiments yield large volumes of MS data, and interpretation of the resulting spectra remains a time-consuming bottleneck in the process. In the second part of this chapter, we describe the use and operation of a mass spectral viewer program capable of displaying and automatically labeling spectra arising from MALDI fingerprinting of N-glycans.

Amino Acid Sequence↗
PubMed2006

Automatic determination of O-glycan structure from fragmentation spectra.

Glycosylation is one of the most important classes of post-translational protein modifications, but the identification of glycans is difficult because of their branched structures and numerous isomers. We describe an algorithm called CartoonistTwo that proposes structures for O-linked glycans by automatically analyzing fragmentation mass spectra. CartoonistTwo improves upon previous glycan identification software primarily in its scoring function, which can more successfully distinguish among a number of similar structures. CartoonistTwo was designed and tested with FTICR mass spectra, and includes automatic recalibration and peak selection especially tuned for such data, yet it can be easily adapted to fragmentation spectra (MS2 or MSn) from other instrument types. On a validated test set of 34 SORI-CID MSn FTICR spectra from Xenopus egg jelly, CartoonistTwo gave the manually determined structural assignment either the first or second highest score over 90% of the time. And for over 50% of these spectra, CartoonistTwo selected a unique highest scoring structure that agreed with the manually determined one.

Algorithms↗
PubMed2006

Past, present, and future: vascular lasers/light devices.

Vascular lasers were among the first available cutaneous light-based technologies. The past 20 years has seen a variety of safe and effective laser and light-based vascular treatment devices. This article provides a review of the medical and scientific literature, which concludes that newer lasers have led to increasing success and safety in the treatment of cutaneous vascular lesions.

Forecasting↗
PubMed2006

De novo analysis of peptide tandem mass spectra by spectral graph partitioning.

We report on a new de novo peptide sequencing algorithm that uses spectral graph partitioning. In this approach, relationships between m/z peaks are represented by attractive and repulsive springs, and the vibrational modes of the spring system are used to infer information about the peaks (such as "likely b-ion" or "likely y-ion"). We demonstrate the effectiveness of this approach by comparison with other de novo sequencers on test sets of ion-trap and QTOF spectra, including spectra of mixtures of peptides. On all datasets, we outperform the other sequencers. Along with spectral graph theory techniques, the new de novo sequencer EigenMS incorporates another improvement of independent interest: robust statistical methods for recalibration of time-of-flight mass measurements. Robust recalibration greatly outperforms simple least-squares recalibration, achieving about three times the accuracy for one QTOF dataset.

Algorithms↗
PubMed2006

Treatment options in moderate and severe depression: decision analysis supporting a clinical guideline.

BACKGROUND: Treatment options for depression include antidepressants, psychological therapy and a combination of the two. AIMS: To develop cost-effective clinical guidelines. METHOD: Systematic literature reviews were used to identify clinical, utility and cost data. A decision analysis was then conducted to compare the benefits and costs of antidepressants with combination therapy for moderate and severe depression in secondary care in the UK. RESULTS: Over the 15-month analysis period, combination therapy resulted in higher costs and an expected 0.16 increase per person in the probability of remission and no relapse compared with antidepressants. The cost per additional successfully treated patient was 4056 UK pounds (95% CI1400-18300); the cost per quality-adjusted life year gained was 5777 UK pounds (95% CI1900-33 800) for severe depression and 14 540 UK pounds (95% CI 4800-79 400) for moderate depression. CONCLUSIONS: Combination therapy is likely to be a cost-effective first-line secondary care treatment for severe depression. Its cost-effectiveness for moderate depression is more uncertain from current evidence. Targeted combination therapy could improve resource utilisation.

Antidepressive Agents↗
PubMed2005

Mental distress and quality of life in a deaf population.

BACKGROUND: High risks of mental illness within the deaf community are reported. The assessment of the level of mental distress and quality of life in the deaf community is difficult due to communication problems in spoken and written language. The deaf community is characterized by the use of sign language. METHODS: A new measure of acceptable reliability using sign language is described. The interactive computerised package including special versions of the World Health Organisation's Brief Quality of Life questionnaire (WHOQOL-BREF), the 12-Item General Health Questionnaire (GHQ-12) and five subscales of the Brief Symptom Inventory (BSI) was administered to a large community sample of deaf people (n = 236), and results were compared with normative data for German-speaking hearing people. RESULTS: The deaf sample has a significantly poorer quality of life than the general population for the physical and psychological domains (p < 0.01) as measured by the WHOQOL-BREF. However, in the domain of social relationships, no significant difference (p = 0.19) was demonstrated. All findings with the GHQ-12 and the BSI show much higher levels (p = 0.01) of emotional distress among the deaf. CONCLUSION: Although a poorer quality of life and a higher level of mental distress are demonstrated, the similarity to the general population in the domain social relationships shows that this does not affect all domains. These findings show the need for easily accessible health services for the deaf which offer sensitive communication with them.

Deafness↗
PubMed2005

Automatic selection of representative proteins for bacterial phylogeny.

BACKGROUND: Although there are now about 200 complete bacterial genomes in GenBank, deep bacterial phylogeny remains a difficult problem, due to confounding horizontal gene transfers and other phylogenetic "noise". Previous methods have relied primarily upon biological intuition or manual curation for choosing genomic sequences unlikely to be horizontally transferred, and have given inconsistent phylogenies with poor bootstrap confidence. RESULTS: We describe an algorithm that automatically picks "representative" protein families from entire genomes for use as phylogenetic characters. A representative protein family is one that, taken alone, gives an organismal distance matrix in good agreement with a distance matrix computed from all sufficiently conserved proteins. We then use maximum-likelihood methods to compute phylogenetic trees from a concatenation of representative sequences. We validate the use of representative proteins on a number of small phylogenetic questions with accepted answers. We then use our methodology to compute a robust and well-resolved phylogenetic tree for a diverse set of sequenced bacteria. The tree agrees closely with a recently published tree computed using manually curated proteins, and supports two proposed high-level clades: one containing Actinobacteria, Deinococcus, and Cyanobacteria ("Terrabacteria"), and another containing Planctomycetes and Chlamydiales. CONCLUSION: Representative proteins provide an effective solution to the problem of selecting phylogenetic characters.

Algorithms↗
PubMed2005

Automatic annotation of matrix-assisted laser desorption/ionization N-glycan spectra.

Matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS) is the pre-eminent technique for mass mapping of glycans. In order to make this technique practical for high-throughput screening, reliable automatic methods of annotating peaks must be devised. We describe an algorithm called Cartoonist that labels peaks in MALDI spectra of permethylated N-glycans with cartoons which represent the most plausible glycans consistent with the peak masses and the types of glycans being analyzed. There are three main parts to Cartoonist. (i) It selects annotations from a library of biosynthetically plausible cartoons. The library we currently use has about 2800 cartoons, but was constructed using only about 300 archetype cartoons entered by hand. (ii) It determines the precision and calibration of the machine used to generate the spectrum. It does this automatically based on the spectrum itself. (iii) It assigns a confidence score to each annotation. In particular, rather than making a binary yes/no decision when annotating a peak, it makes all plausible annotations and associates them with scores indicating the probability that they are correct.

Algorithms↗