Proteomics Mapping of Cord Blood Identifies Haptoglobin “Switch-On” Pattern as Biomarker of Early-Onset Neonatal Sepsis in Preterm Newborns

Intra-amniotic infection and/or inflammation (IAI) are important causes of preterm birth and early-onset neonatal sepsis (EONS). A prompt and accurate diagnosis of EONS is critical for improved neonatal outcomes. We sought to explore the cord blood proteome and identify biomarkers and functional protein networks characterizing EONS in preterm newborns.We studied a prospective cohort of 180 premature newborns delivered May 2004-September 2009. A proteomics discovery phase employing two-dimensional differential gel electrophoresis (2D-DIGE) and mass spectrometry identified 19 differentially-expressed proteins in cord blood of newborns with culture-confirmed EONS (n = 3) versus GA-matched controls (n = 3). Ontological classifications of the proteins included transfer/carrier, immunity/defense, protease/extracellular matrix. The 1(st)-level external validation conducted in the remaining 174 samples confirmed elevated haptoglobin and haptoglobin-related protein immunoreactivity (Hp&HpRP) in newborns with EONS (presumed and culture-confirmed) independent of GA at birth and birthweight (P<0.001). Western blot concurred in determining that EONS babies had conspicuous Hp&HpRP bands in cord blood ("switch-on pattern") as opposed to non-EONS newborns who had near-absent "switch-off pattern" (P<0.001). Fetal Hp phenotype independently impacted Hp&HpRP. A bayesian latent-class analysis (LCA) was further used for unbiased classification of all 180 cases based on probability of "antenatal IAI exposure" as latent variable. This was then subjected to 2(nd)-level validation against indicators of adverse short-term neonatal outcome. The optimal LCA algorithm combined Hp&HpRP switch pattern (most input), interleukin-6 and neonatal hematological indices yielding two non-overlapping newborn clusters with low (≤20%) versus high (≥70%) probability of IAI exposure. This approach reclassified ∼30% of clinical EONS diagnoses lowering the number needed to harm and increasing the odds ratios for several adverse outcomes including intra-ventricular hemorrhage.Antenatal exposure to IAI results in precocious switch-on of Hp&HpRP expression. As EONS biomarker, cord blood Hp&HpRP has potential to improve the selection of newborns for prompt and targeted treatment at birth

Strategies for a Successful Anatomic Pathology Subspecialty Workgroup: The 26-Year Collaboration of "The Elves''

From 1990 to present, 14 liver pathologists and 2 clinical hepatologists from 9 countries have met annually to hold thematic 2.5-day meetings centered on case-based discussion. The goal of these meetings has been to identify gaps in knowledge in our field and fuel scholarly effort to address these gaps. The founding principles were worldwide representation, good representation of women, compatibility of participants, commitment to stable membership and regular attendance, mutual education and friendship, and free exchange of ideas. A summary report of the 2.5-day meeting constituted an enduring document that captured the free flow of ideas discussed. These ideas were open to all participants for the pursuit of scholarship back at their home institutions. However, any idea borne out of an Elves meeting merits open invitation for other Elves to participate in, using established standards for meaningful coauthorship. Over 26 consecutive meetings (1990-2015), themes covered the breadth of liver pathology. With retirement of 2 individuals, resignation of 3, and death of 1, six new members were nominated and voted into membership. Over these same 26 years, active members published 2025 articles indexed in PubMEd Central under the topic "liver;" 3% of these articles represented collaborations between members. This international group represents a successful model in a subspecialty of anatomic pathology for open exchange of ideas, mutual education, and generation of topics worthy of scholarly investigation. We conclude that a self-selected group of subspecialty pathologists can meet successfully over 26 years, maintain a high state of engagement through each annual meeting, self-renew as a result of retirement or resignation, and provide a creative stimulus for highly productive academic careers

Identification of progressive mild cognitive impairment patients using incomplete longitudinal MRI scans

Distinguishing progressive mild cognitive impairment (pMCI) from stable mild cognitive impairment (sMCI) is critical for identification of patients who are at-risk for Alzheimer’s disease (AD), so that early treatment can be administered. In this paper, we propose a pMCI/sMCI classification framework that harnesses information available in longitudinal magnetic resonance imaging (MRI) data, which could be incomplete, to improve diagnostic accuracy. Volumetric features were first extracted from the baseline MRI scan and subsequent scans acquired after 6, 12, and 18 months. Dynamic features were then obtained by using the 18th-month scan as the reference and computing the ratios of feature differences for the earlier scans. Features that are linearly or non-linearly correlated with diagnostic labels are then selected using two elastic net sparse learning algorithms. Missing feature values due to the incomplete longitudinal data are imputed using a low-rank matrix completion method. Finally, based on the completed feature matrix, we build a multi-kernel support vector machine (mkSVM) to predict the diagnostic label of samples with unknown diagnostic statuses. Our evaluation indicates that a diagnosis accuracy as high as 78.2% can be achieved when information from the longitudinal scans is used – 6.6% higher than the case using only the reference time point image. In other words, information provided by the longitudinal history of the disease improves diagnosis accuracy

Manipulation of Ovarian Function Significantly Influenced Trabecular and Cortical Bone Volume, Architecture and Density in Mice at Death

<div><p>Previously, transplantation of ovaries from young, cycling mice into old, postreproductive-age mice increased life span and decreased cardiomyopathy at death. We anticipated that the same factors that increased life span and decreased cardiomyopathy could also influence the progression of orthopedic disease. At 11 months of age, prepubertally ovariectomized and ovary-intact mice (including reproductively cycling and acyclic mice) received new 60-day-old ovaries. At death, epiphyseal bone in the proximal tibia and the distal femur and mid-shaft tibial and femoral diaphyseal bone was analyzed with micro-computed tomography. For qualitative analysis of osteophytosis, we also included mineralized connective tissue within the stifle joint. Prepubertal ovariectomy had the greatest influence on bone volume, ovarian transplantation had the greatest influence on bone architecture and both treatments influenced bone density. Ovarian transplantation increased cortical, but not trabecular bone density and tended to increase osteophytosis and heterotopic mineralization, except in acyclic recipients. These effects may have been dictated by the timing of the treatments, with ovariectomy appearing to influence early development and ovarian transplantation limited to influencing only the postreproductive period. However, major differences observed between cycling, acyclic and ovariectomized recipients of new ovaries may have been, in part due to differences in the levels of hormone receptors present and the responsiveness of specific bone processes to hormone signaling. Changes that resulted from these treatments may represent a compensatory response to normal age-associated, negative, orthopedic changes. Alternatively, differences between treatments may simply be the 'preservation' of unblemished orthopedic conditions, prior to the influence of negative, age-associated effects. These findings may suggest that in women, tailoring hormone replacement therapy to the patient's current reproductive status may improve therapy effectiveness and that beginning therapy earlier may help preserve trabecular bone mineral density that would otherwise be lost during perimenopause.</p></div