bluuebunny/crossref_metadata_2025_split huggingface dataset:
Variation in Institutional Review Board Responses to a Standard, Observational, Pediatric Research Protocol
Authors: Mansbach Jonathan , Acholonu Uchechi , Clark Sunday , Camargo Carlos A. 
Published: February 2007

Abstract
Background:
Multicenter studies are becoming more common, and variability in local institutional review board (IRB) assessments can be problematic.
Objective:
To investigate the variability of IRB responses to a multicenter observational study of children presenting to emergency departments.
Methods:
The authors collected the original IRB applications, subsequent correspondence, and a survey assessing submission timing and response and the nature of IRB queries. The study was conducted as part of the Emergency Medicine Network http://www.emnet‐usa.org
Results:
Of 37 sites initiating the IRB process, 34 (92%) participated in this IRB‐approved study. Institutional review boards returned initial applications in a median of 19 days (IQR, 11–34 d), and 91% considered the protocol to be minimal risk. Of 34 submissions, 13 required no changes, 18 received conditional approvals, and 3 were deferred. The median time from initial submission to final approval was 42 days (IQR, 27–61 d). Seven sites did not participate in patient recruitment: two had institutional issues, one obtained IRB approval too late for participation, and four sites (12%) reported that IRB hurdles contributed to their lack of participation. Nonetheless, 68% of sites that recruited patients reported that the overall experience made them more likely to participate in future multicenter research.
Conclusions:
There was substantial variation in IRB assessment of a standard protocol in this study. The burden of the application process contributed to some investigators not participating, but the majority of investigators remain enthusiastic about multicenter research. A national IRB may streamline the review process and facilitate multicenter clinical research.
Differential Gene Expression Patterns and Interaction Networks in BCR-ABL–Positive and –Negative Adult Acute Lymphoblastic Leukemias
Authors: Juric Dejan , Lacayo Norman J. , Ramsey Meghan C. , Racevskis Janis , Wiernik Peter H. , Rowe Jacob M. , Goldstone Anthony H. , O'Dwyer Peter J. , Paietta Elisabeth , Sikic Branimir I. 
Published: February 2007

Purpose To identify gene expression patterns and interaction networks related to BCR-ABL status and clinical outcome in adults with acute lymphoblastic leukemia (ALL). Patients and Methods DNA microarrays were used to profile a set of 54 adult ALL specimens from the Medical Research Council UKALL XII/Eastern Cooperative Oncology Group E2993 trial (21 p185BCR-ABL–positive, 16 p210BCR-ABL–positive and 17 BCR-ABL–negative specimens). Results Using supervised and unsupervised analysis tools, we detected significant transcriptomic changes in BCR-ABL–positive versus –negative specimens, and assessed their validity in an independent cohort of 128 adult ALL specimens. This set of 271 differentially expressed genes (including GAB1, CIITA, XBP1, CD83, SERPINB9, PTP4A3, NOV, LOX, CTNND1, BAALC, and RAB21) is enriched for genes involved in cell death, cellular growth and proliferation, and hematologic system development and function. Network analysis demonstrated complex interaction patterns of these genes, and identified FYN and IL15 as the hubs of the top-scoring network. Within the BCR-ABL–positive subgroups, we identified genes overexpressed (PILRB, STS-1, SPRY1) or underexpressed (TSPAN16, ADAMTSL4) in p185BCR-ABL–positive ALL relative to p210BCR-ABL–positive ALL. Finally, we constructed a gene expression- and interaction-based outcome predictor consisting of 27 genes (including GRB2, GAB1, GLI1, IRS1, RUNX2, and SPP1), which correlated with overall survival in BCR-ABL–positive adult ALL (P = .0001), independent of age (P = .25) and WBC count at presentation (P = .003). Conclusion We identified prominent molecular features of BCR-ABL–positive adult ALL, which may be useful for developing novel therapeutic targets and prognostic markers in this disease.
Phase I Study of Intraventricular Administration of Rituximab in Patients With Recurrent CNS and Intraocular Lymphoma
Authors: Rubenstein James L. , Fridlyand Jane , Abrey Lauren , Shen Arthur , Karch Jon , Wang Endi , Issa Samar , Damon Lloyd , Prados Michael , McDermott Michael , O'Brien Joan , Haqq Chris , Shuman Marc 
Published: February 2007

PurposeWe previously determined that intravenous administration of rituximab results in limited penetration of this agent into the leptomeningeal space. Systemic rituximab does not reduce the risk of CNS relapse or dissemination in patients with large cell lymphoma. We therefore conducted a phase I dose-escalation study of intrathecal rituximab monotherapy in patients with recurrent CNS non-Hodgkin's lymphoma (NHL).Patients and MethodsThe protocol planned nine injections of rituximab (10 mg, 25 mg, or 50 mg dose levels) through an Ommaya reservoir over 5 weeks. The safety profile of intraventricular rituximab was defined in 10 patients.ResultsThe maximum tolerated dose was determined to be 25 mg and rapid craniospinal axis distribution was demonstrated. Cytologic responses were detected in six patients; four patients exhibited complete response. Two patients experienced improvement in intraocular NHL and one exhibited resolution of parenchymal NHL. High RNA levels of Pim-2 and FoxP1 in meningeal lymphoma cells were associated with disease refractory to rituximab monotherapy.ConclusionThese results suggest that intrathecal rituximab (10 to 25 mg) is feasible and effective in NHL involving the CNS.
Antibodies to citrullinated peptides: a significant step forward in the early diagnosis of rheumatoid arthritis
Authors: Bizzaro Nicola 
Published: February 2007

AbstractThe early diagnosis of rheumatoid arthritis (RA) has become a priority owing to the availability of effective disease-modifying agents that can improve patient wellbeing and influence the clinical outcome. However, this represents a real challenge, as no clinical, radiological or immunological features are pathognomonic at the time of presentation. For this reason, development of the anti-cyclic citrullinated peptide (CCP) antibody assay, a highly disease-specific serological marker for RA, has been a great step forward for the rheumatologist and the clinical laboratory. Over recent years, this test has increased in popularity and many studies have been performed. This review briefly considers the most recent data on the diagnostic accuracy of the CCP test, the genetic background that predisposes to antibody production, the diagnostic, prognostic and predictive values, and the clinical use of the assay in patients with RA.Clin Chem Lab Med 2007;45:150–7.
Cardiac natriuretic peptides after myocardial infarction: relationship with infarct size, left ventricular function and remodelling assessed by 99mTc-sestamibi gated-single photon emission tomography
Authors: Ceriani Luca , Giovanella Luca 
Published: February 2007

Abstract: The aim of the study was to investigate the potential relationship between A-type (atrial) and B-type (brain) natriuretic peptides (ANP, BNP) and infarct size (IS), left ventricular (LV) function and remodelling as assessed by 99m technetium-hexakis-2-methoxy-isobutyl-isonitrile (99mTc-sestamibi) gated-single photon emission tomography (G-SPET).: Plasma concentrations of ANP and BNP in peripheral blood were measured in 54 patients with coronary artery disease (CAD) and previous myocardial infarction (MI). Of these, 25 subjects had a recent (<2 weeks) and 29 subjects an old (>6 months) MI. IS, left ventricular ejection fraction (LVEF) and end diastolic (EDV), end systolic (ESV) and stroke volume (SV) were quantitatively calculated from at-rest G-SPET.: In either univariate or multivariate regression analysis that included IS and the other G-SPET derived parameters as co-variables, both BNP and ANP showed a significant association with IS (BNP p<0.002; ANP p<0.01). No significant relationship was found between the two peptides and LVEF, EDV or ESV values. BNP, but not ANP concentrations, were significantly higher in patients with antero-septal vs. infero-lateral (p=0.01) and recent vs. old MI (p=0.003). In these two subgroups, univariate and multivariate analyses confirmed the correlation between BNP and IS, whereas ANP demonstrated a relationship with IS only in subjects with recent MI. CAD extent had no influence on BNP and ANP levels.: The present study showed a positive correlation between BNP and the perfusion defect measured by 99mTc-sestamibi G-SPET in patients with previous MI. Consequently, BNP may reflect the functional significance of myocardial damage and may be considered of prognostic value. ANP was also related to scintigraphic defects in the early phase after MI, but not in the chronic phase, confirming that ANP is a less sensitive marker of LV remodelling, depending also on atrial load conditions and dilatation. These preliminary data based on a small group of subjects need to be confirmed by prospective longitudinal studies involving larger populations.Clin Chem Lab Med 2007;45:226–31.
Amniotic fibronectin fragmentation and expression of its domains, sialyl and fucosyl glycotopes associated with pregnancy complicated by intrauterine infection
Authors: Hirnle Lidia , Kątnik-Prastowska Iwona 
Published: February 2007

Abstract: The presence of fibronectin fragments has been observed in some inflammatory diseases and is believed to reflect tissue breakdown. In this study, possible fibronectin fragmentation and alterations in its domain and sialyl and fucosyl glycotope expressions were analyzed in amniotic fluids in relation to intrauterine infection.: Samples of amniotic fluid were taken from normal pregnancies and pregnancies (28 and 42 weeks) complicated by intrauterine infection. Fibronectin fragmentation was analyzed by immunoblotting. The expression of cellular, fibrin, C-terminal and EDA fibronectin domains, as well as α2,3- and α2,6-linked sialic acids, and α1,6-, α1,3- and α1,2-linked fucoses, was determined by ELISA, using domain-specific monoclonal antibodies and specific lectins, respectively.: Amniotic fibronectin immunoblots from pregnancies with intrauterine infection revealed three groups of results. In group 1, with the native fibronectin band, and in group 2 with bands of native fibronectin and several fibronectin fragments, only higher α1,6-linked fucose expression was observed. In the infection group 3, characterized by profound fragmentation of fibronectin, lower expression of all fibronectin domains analyzed and of α1,6-linked sialic acid and α1,2-linked fucose was found.: Amniotic fibronectin status was found to be associated with pregnancy complicated by intrauterine infection. Such alterations could have a potential diagnostic value in the prevention of or intervention in fetal intrauterine infection.Clin Chem Lab Med 2007;45:208–14.
Determination of the hepatitis C virus subtype: comparison of sequencing and reverse hybridization assays
Authors: Stelzl Evelyn , Meer Carola van der , Gouw Remko , Beld Marcel , Grahovac Maja , Marth Egon , Kessler Harald H. 
Published: February 2007

AbstractHepatitis C virus (HCV) genotyping and accurate subtyping is becoming increasingly relevant to epidemiological studies, clinical management, pathogenicity, and vaccine development.The TRUGENEAll amplified samples from among the members of a HCV genotyping proficiency program panel that contained a single HCV genotype were subtyped correctly using all three HCV genotyping assays. With the TRUGENEThe two new methods show advantages over the routinely used TRUGENEClin Chem Lab Med 2007;45:167–70.
Prostataspezifisches Antigen: Bedeutung für die Diagnostik des Prostatakarzinoms bei geriatrischen Patienten / Prostate-specific antigen: significance for the diagnosis of prostate cancer in geriatric patients
Authors: Stachon Axel 
Published: February 2007

Zusammenfassung
Bei Männern der westlichen Welt ist das Prostatakarzinom die häufigste maligne Erkrankung. Für die frühzeitige Erkennung eines, möglichst noch auf das Organ begrenzten, bösartigen Wachstums der Prostata wird unter anderem die Bestimmung des prostataspezifischen Antigens (PSA) herangezogen. Sowohl benignes hyperplastisches als auch malignes Prostatagewebe sezernieren vermehrt PSA. Das führt, neben dem alterskorrelierenden Anstieg der PSA-Konzentration, zu einer geringen Spezifität der Gesamt-PSA-Bestimmung. Serielle PSA-Messungen, die Bestimmung von freiem oder komplexiertem PSA sowie die Berücksichtigung von klinischen Daten stellen diagnostische Strategien dar, um die Trennschärfe zwischen benigner Prostatahyperplasie und Prostatakarzinom zu erhöhen. Für aussagekräftige Messergebnisse sind neben den präanalytischen Bedingungen und den patientenspezifischen Einflussgrößen die Methodenwahl sowie die weitere Probenbehandlung von Bedeutung.
Schilddrüsenfunktion und -dysfunktion im Alter / Thyroid function and dysfunction in the elderly
Authors: Weissel Michael 
Published: February 2007

Zusammenfassung
Die vorliegende Übersichtsarbeit gibt den momentanen Stand des Wissens über die Funktion und Dysfunktion der Schilddrüse im Alter wieder. Nach Besprechung der Epidemiologie und der Abhängigkeit der Funktionsstörungen von der Jodversorgung der Bevölkerung werden die physiologischen – also beim Gesunden auftretenden – Veränderungen des Schilddrüsen-Hypophysenregelkreises besprochen. Den Hauptteil der Arbeit stellt die Besprechung der Klinik, Labordiagnose und Therapie von Funktionsstörungen der Schilddrüse im Alter dar. Es wird auf die altersbedingte Symptomarmut und die daraus resultierende Schwierigkeit der klinischen Diagnose hingewiesen. Bei der Labordiagnose wird besonders auf die Interpretationsmöglichkeiten pathologischer Thyreotropin (TSH) Werte und ihrer therapeutischen und diagnostischen Konsequenzen beim alten Menschen eingegangen. Abschließend werden die Besonderheiten der Therapie vor allem der subklinischen Funktionsstörungen der Schilddrüse im Alter besprochen. Besonders hingewiesen wird darauf, dass latente Hypothyreosen beim betagten Patienten auf Grund des kardialen Risikos einer iatrogen induzierten Überfunktion nur im Einzelfall behandelt werden sollen. Es wird hervorgehoben, dass regelmäßige Laborkontrollen besonders beim alten Menschen unnötige Therapien vermeiden können.
Geriatrie: Was ist normal im Alter? Stehen wir vor einem Paradigmenwechsel in der Laboratoriumsmedizin? / Geriatrics: What is normal in the aged? Should we expect a paradigm shift in laboratory medicine?
Authors: Lapin Alexander 
Published: February 2007

Zusammenfassung
Die wachsende Bedeutung der Geriatrie stellt die Labordiagnostik vor neue Herausforderungen. Gleichzeitig besteht die Notwendigkeit grundlegende Prinzipien, wie das „Referenzintervallkonzept“ neu zu überdenken. Da in der Geriatrie die individuelle Lebensqualität vor dem allgemeinen Gesundheitsbegriff steht, soll die Befundbewertung nicht nur in Bezug auf das Gesundenkollektiv, sondern auch nach Vorwerten, im Sinne des individuellen Monitorings erfolgen. Daraus ergeben sich besondere Anforderungen an die Qualitätssicherung, Laborlogistik sowie Berücksichtigung der Präanalytik. Im Hinblick auf die jeweilige Lebenserwartungsprognose, können sich medizinische Aussagen von vielen Laborparametern im Alter verändern. Den Parametern, die Auskunft über die noch vorhandene physiologische Funktionsreserven geben, kommt aus klinischer Sicht eine besondere Bedeutung zu.
Validation of the Comprehensive International Classification of Functioning, Disability and Health Core Set for Rheumatoid Arthritis: The Perspective of Physical Therapists
Authors: Kirchberger Inge , Glaessel Andrea , Stucki Gerold , Cieza Alarcos 
Published: February 2007

Background and PurposeThe Comprehensive International Classification of Functioning, Disability and Health (ICF) Core Set for Rheumatoid Arthritis (RA) represents the typical spectrum of problems in the functioning of patients with RA. The objective of this study was to validate this ICF Core Set from the perspective of physical therapists.MethodsPhysical therapists were asked about their intervention goals in a 3-round Delphi survey. Intervention goals were compiled, and the physical therapists were asked whether they considered the goal classes to be relevant. The goal classes then were linked to the ICF.ResultsA total of 82 physical therapists in 12 countries named 562 intervention goals. A total of 45 goal classes covering all ICF components were identified. The goal classes addressing muscle tone, balance and coordination, and psychological distress were not represented in the ICF Core Set for RA.Discussion and ConclusionThe validity of the ICF Core Set for RA was largely supported. However, some categories currently not covered by the ICF Core Set for RA will need to be investigated further.
Primary Care Interventions to Prevent Child Maltreatment
Authors: Viswanathan Meera , Rains Caroline , Hart Laura C. , Doran Emma , Sathe Nila , Hudson Kesha , Ali Rania , Jonas Daniel E. , Chou Roger , Zolotor Adam J. 
Published: March 2024

ImportanceChild maltreatment is associated with serious negative physical, psychological, and behavioral consequences.ObjectiveTo review the evidence on primary care–feasible or referable interventions to prevent child maltreatment to inform the US Preventive Services Task Force.Data SourcesPubMed, Cochrane Library, and trial registries through February 2, 2023; references, experts, and surveillance through December 6, 2023.Study SelectionEnglish-language, randomized clinical trials of youth through age 18 years (or their caregivers) with no known exposure or signs or symptoms of current or past maltreatment.Data Extraction and SynthesisTwo reviewers assessed titles/abstracts, full-text articles, and study quality, and extracted data; when at least 3 similar studies were available, meta-analyses were conducted.Main Outcomes and MeasuresDirectly measured reports of child abuse or neglect (reports to Child Protective Services or removal of the child from the home); proxy measures of abuse or neglect (injury, visits to the emergency department, hospitalization); behavioral, developmental, emotional, mental, or physical health and well-being; mortality; harms.ResultsTwenty-five trials (N = 14 355 participants) were included; 23 included home visits. Evidence from 11 studies (5311 participants) indicated no differences in likelihood of reports to Child Protective Services within 1 year of intervention completion (pooled odds ratio, 1.03 [95% CI, 0.84-1.27]). Five studies (3336 participants) found no differences in removal of the child from the home within 1 to 3 years of follow-up (pooled risk ratio, 1.06 [95% CI, 0.37-2.99]). The evidence suggested no benefit for emergency department visits in the short term (&amp;lt;2 years) and hospitalizations. The evidence was inconclusive for all other outcomes because of the limited number of trials on each outcome and imprecise results. Among 2 trials reporting harms, neither reported statistically significant differences. Contextual evidence indicated (1) widely varying practices when screening, identifying, and reporting child maltreatment to Child Protective Services, including variations by race or ethnicity; (2) widely varying accuracy of screening instruments; and (3) evidence that child maltreatment interventions may be associated with improvements in some social determinants of health.Conclusion and RelevanceThe evidence base on interventions feasible in or referable from primary care settings to prevent child maltreatment suggested no benefit or insufficient evidence for direct or proxy measures of child maltreatment. Little information was available about possible harms. Contextual evidence pointed to the potential for bias or inaccuracy in screening, identification, and reporting of child maltreatment but also highlighted the importance of addressing social determinants when intervening to prevent child maltreatment.
Primary Care Interventions to Prevent Child Maltreatment
Authors:   US Preventive Services Task Force, Barry Michael J. , Nicholson Wanda K. , Silverstein Michael , Chelmow David , Coker Tumaini Rucker , Davis Esa M. , Jaén Carlos Roberto , Krousel-Wood M. (Tonette) , Lee Sei , Li Li , Rao Goutham , Ruiz John M. , Stevermer James J. , Tsevat Joel , Underwood Sandra Millon , Wiehe Sarah 
Published: March 2024

ImportanceChild maltreatment, which includes child abuse and neglect, can have profound effects on health, development, survival, and well-being throughout childhood and adulthood. The prevalence of child maltreatment in the US is uncertain and likely underestimated. In 2021, an estimated 600 000 children were identified by Child Protective Services as experiencing abuse or neglect and an estimated 1820 children died of abuse and neglect.ObjectiveThe US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate benefits and harms of primary care–feasible or referable behavioral counseling interventions to prevent child maltreatment in children and adolescents younger than 18 years without signs or symptoms of maltreatment.PopulationChildren and adolescents younger than 18 years who do not have signs or symptoms of or known exposure to maltreatment.Evidence AssessmentThe USPSTF concludes that the evidence is insufficient to determine the balance of benefits and harms of primary care interventions to prevent child maltreatment in children and adolescents younger than 18 years without signs or symptoms of or known exposure to maltreatment.RecommendationThe USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of primary care interventions to prevent child maltreatment. (I statement)
Bacterial Infections
Authors: Wootton Catriona , Elliott Ivo 
Published: March 2024

Abstract
The skin provides a barrier between the body and the external environment and it is colonised by the bacteria and other microorganisms that make up the skin microbiome. Bacterial infections occur when bacteria invade through damage to the skin barrier, via trauma or pre‐existing skin conditions, or through inoculation or inhalation; bacterial skin infections can range from minor irritations to life‐threatening conditions. This chapter explores bacterial infections which can affect the skin, from the common to the rare, describing the epidemiology, presentation and management of each condition.
Mycobacterial Infections
Authors: Walker Stephen L. , Phillips Richard O. 
Published: March 2024

Abstract

The genus
Mycobacterium
contains more than 190 species of which over 25 are pathogenic in humans and other vertebrates. The most important obligate human pathogens are
M. tuberculosis
and
M. leprae
, but others such as
M. avium
complex (
M. avium
and
M. intracellulare
) and
M. ulcerans
are also significant. Disease‐causing mycobacteria other than those of the
M. tuberculosis
complex (including
M. tuberculosis
,
M. bovis
,
M. bovis
bacillus Calmette–Guérin (BCG) and related species) and
M. leprae
are referred to as non‐tuberculous mycobacteria (NTM), although the terms atypical, environmental or opportunistic mycobacteria are also used. This chapter will deal first with the general properties and characteristics of the mycobacteria, before discussing tuberculosis and highlighting aspects such as lupus vulgaris and tuberculids. Due to emergence and interest in NTMs, this section is substantially updated.