bluuebunny/crossref_metadata_2025_split huggingface dataset:
HER-2/Neu Gene in Primary and Local Metastatic Axillary Lymph Nodes in Human Breast Tumors
Authors: Tommasi S. , Giannella C. , Paradiso A. , Barletta A. , Mangia A. , Simone G. , Primavera A.T. , Albarani V. , Schittulli F. , Longo S. , De Lena M. 
Published: March 2018

In order to verify whether the HER-2/neu gene is involved in the initial phases of neoplastic disease or in its progression, we evaluated the amplification and overexpression of this gene in the primary tumor and in synchronous metastatic axillary lymph nodes of 26 women with operable breast cancer. HER-2/neu was amplified in 35% and overexpressed in 33% of the primary sites; similar percentages were found in lymph nodes. The clear correlation between the two disease sites regarding gene, mRNA and protein levels, supports the hypothesis that this gene is involved in the initial and invasive phases of neoplasia. Its actual role with respect to other biological tumor characteristics during the metastatic process should be investigated further.
External Quality Assurance of the Carcinoembryonic Antigen (CEA) Assay: Main Findings in Six Years' Experience
Authors: Zucchelli G.C. , Ferdeghini M. , Pilo A. , Clerico A. , Masini S. , Prontera C. 
Published: March 2018

In 1984 we initiated a national external quality assessmnent (EQA) program (supported by the Italian National Research Council, CNR) for the CEA assay; at present, about 200 Italian laboratories are participating in the program. The laboratories assayed the quality control (QC) samples according to their routine procedures and returned the results together with the name of the method/kit they used. The collecterd results were computer-processed and reports were sent back to the participants. A significant reduction of the CVt (mean between-laboratory agreement) of the CEA assay was observed throughout the EQA survey (from 35% in 1985 to 20-25% in the last cycles). In order to better clarify the differences in variability observed in the first QC cycles against the last ones, we used the ANOVA technique to evaluate the components of variability. The improvement in between-laboratory agreement was mainly due to the reduction of the between-kit component (from 30.5% to 15.2%), rather than to the smaller decrease observed for the within-kit variability (from 18.4% to 14.0%). The results reported for QC samples from different materials showed differences in the between-lab variability and substantial changes of the kit biases, thus suggesting a different specificity of the antibodies used in the various method/kits against different families of CEA molecules. Considerable uncertainty was also encountered in the clinical classification of low pathological samples, which seems mainly due to the variability in cut-off values used by the laboratories for the clinical assessment of the same analytical results. Our data indicate a progressive increase in the reliability of CEA determination during our study and confirm that EQA has improved the reliability of analysis carried out by the participating laboratories, thus stimulating the kit manufacturers to provide more reliable products.
The Diagnostic Value of Mucinous Carcinoma-Associated Antigen (MCA) Tests in Breast Carcinomas
Authors: Günes I. , Miserez A.R. , Müller-Brand J. , Maecke H. 
Published: March 2018

MCA (Mucinous Carcinoma-Associated Antigen) levels of 176 breast carcinoma patients were tested postoperatively by serial determination. One hundred forty-one patients had nonprogressive disease (PD–) while 35 were in the progressive phase (PD +); in the latter the diagnosis was confirmed by means of current diagnostic procedures. One hundred seventeen of the 141 PD– patients showed MCA levels below cutoff whereas 27 of the 35 PD + cases showed high values. The difference in the incidence of elevated MCA levels between PD–and PD + groups was statistically significant (p < 0.05). The overall diagnostic efficacy of MCA assays showed 77% sensitivity and 82% specificity.
A New Approach to Tumour Marker Assessment by Perioperative Determination in Breast and Colorectal Cancer
Authors: Gion M. , Ruggeri G. , Mione R. , Marconato R. , Casella C. , Nosadini A. , Simoncini E. , Belloli S. , dal Zennaro E. , Bruscagnin G. 
Published: March 2018

Preoperative serum tumour markers are currently classified as positive or negative according to a predetermined cut-off point. In the present study we examined the dynamic variation of marker levels after radical surgery of breast and colorectal cancer. CEA and CA15.3 were measured in 93 patients with breast cancer, CEA and CA19.9 in 97 patients with colorectal carcinoma before and 30 days after radical surgery. Any variation higher than 3-fold the analytical coefficient of variation of the assay was considered significant. In patients with negative preoperative marker levels a significant decrease was noted after surgery in 15.6% of cases for CEA and 27.8% for CA15.3 in breast cancer and in 46.8% for CEA and 25.7% for CA19.9 in colorectal cancer. Using both cut-off-based and dynamic criteria, we found an overall positivity rate of 19.6% for CEA and 33.3% for CA15.3 in breast cancer; 60.0% for CEA and 37.1% for CA19.9 in colorectal cancer. From the present findings we conclude that the dynamic study of perioperative variations of tumour markers is a sensitive method additional to cut-off-based criteria for the assessment of the phenotypic expression of the marker by the tumour.
Serum levels of procollagen type I carboxyterminal extension peptide in cancer patients with bone metastases
Authors: Santi I. , Monti M. , Viganò A. , D'aprile E. , Rampoldi E. , Castellani L. , Accinni R. , Cunietti E. 
Published: March 2018

Serum levels of procollagen type I carboxy-terminal extension peptide (PICP) reflect the synthesis of type I collagen. As PICP is produced by osteoblasts and is not incorporated into bone matrix, serum PICP levels have been suggested as a marker of bone formation. In 37 cancer patients (21 men and 16 women; age: 72.4±8.6 (mean±SD) years) with bone metastases and 23 women (age: 77.3+6.64 years) as controls, the following biochemical variables were measured: serum PICP, calcium (Ca), phosphorus, alkaline phosphatase (AP) and tartrate-resistant acid phosphatase (TRAP), and urinary hydroxyproline and calcium corrected for creatinine excretion. Higher serum levels of PICP were observed in cancer patients than in controls (245±177 μg/l vs 121.7±36 μg/l, p<0.01). Cancer patients also had higher AP levels than controls (704±755 U/l vs 216.5±56 U/l, p<0.01). Abnormal PICP and AP serum concentrations (above the mean+2SD of controls) were found in 46% and 51% of patients, respectively. Moreover, patients showed significantly lower serum calcium concentrations (p<0.001), and higher TRAP and hydroxyproline levels although statistical significance was not reached. In the patients, PICP was correlated directly with AP (r=0.50, p<0.01) and TRAP (r=0.34, p<0.05). In conclusion, patients with bone metastases have increased bone turnover as shown by serum markers. Serum PICP may be used as an adjunctive, non-invasive index to assess bone metabolism. However, the clinical usefulness of PICP in cancer patients needs further evaluation.
Clinical utility of hyaluronic acid values in serum and bronchoalveolar lavage fluid as tumor marker for bronchogenic carcinoma
Authors: Hernández J.R. Hernández , García J.M. García , Muñíz M.A. Martínez , Monclus M.T. Allende , Morell A. Ruibal 
Published: March 2018

Various authors have proposed the use of hyaluronic acid (HA) as a tumor marker. In order to analyze its usefulness as a marker in bronchogenic carcinoma, the most common carcinoma in men, we determined the HA values in serum and bronchoalveolar lavage fluid (BAL). We performed prospective studies on two groups of patients: 81 diagnosed as having bronchial carcinoma and 34 with benign respiratory diseases. HA values were higher in patients with cancer than in those with benign diseases (serum: 79.8 ng/ml vs 63.7 ng/ml; BAL: 927 ng/mg vs 522 ng/mg). Also, the percentage of patients with levels exceeding the established cutoff was greater in the group with cancer than in the group with benign diseases (serum: 24.6 vs 17.6; BAL: 25.3 vs 3). Statistically significant differences in these percentages were found in BAL (p<0.01). Patients with extended small cell carcinoma had higher HA values (p=0.04) than those with limited disease, and the percentage of patients with abnormal HA values was larger in the group with extended disease than in the group with limited disease (p=0.004). The serial determinations of HA values in serum reflected the clinical evolution after treatment in 73% of the small cell carcinomas. Most of the patients with benign diseases whose HA values exceeded the cutoff level suffered from acute infectious dis-eases. Once these cases were excluded, the specificity of HA value determination in the diagnosis of carcinoma was very high (serum 96%, BAL 100%). The determination of HA levels in serum or BAL did not have any prognostic value in this study. We conclude that the HA levels in serum and BAL could be of interest as a tumor marker, especially in patients with small cell carcinoma.
No evidence of disease activity (NEDA) analysis by epochs in patients with relapsing multiple sclerosis treated with ocrelizumab vs interferon beta-1a
Authors: Havrdová Eva , Arnold Douglas L , Bar-Or Amit , Comi Giancarlo , Hartung Hans-Peter , Kappos Ludwig , Lublin Fred , Selmaj Krzysztof , Traboulsee Anthony , Belachew Shibeshih , Bennett Iain , Buffels Regine , Garren Hideki , Han Jian , Julian Laura , Napieralski Julie , Hauser Stephen L , Giovannoni Gavin 
Published: March 2018

Background No evidence of disease activity (NEDA; defined as no 12-week confirmed disability progression, no protocol-defined relapses, no new/enlarging T2 lesions and no T1 gadolinium-enhancing lesions) using a fixed-study entry baseline is commonly used as a treatment outcome in multiple sclerosis (MS). Objective The objective of this paper is to assess the effect of ocrelizumab on NEDA using re-baselining analysis, and the predictive value of NEDA status. Methods NEDA was assessed in a modified intent-to-treat population ( n = 1520) from the pooled OPERA I and OPERA II studies over various epochs in patients with relapsing MS receiving ocrelizumab (600 mg) or interferon beta-1a (IFN β‐1a; 44 μg). Results NEDA was increased with ocrelizumab vs IFN β-1a over 96 weeks by 75% ( p < 0.001), from Week 0‒24 by 33% ( p < 0.001) and from Week 24‒96 by 72% ( p < 0.001). Among patients with disease activity during Weeks 0‒24, 66.4% vs 24.3% achieved NEDA during Weeks 24‒96 in the ocrelizumab and IFN β-1a groups (relative increase: 177%; p < 0.001). Conclusion Superior efficacy with ocrelizumab compared with IFN β-1a was consistently seen in maintaining NEDA status in all epochs evaluated. By contrast with IFN β-1a, the majority of patients with disease activity early in the study subsequently attained NEDA status with ocrelizumab.
Hand function and recurrence after limited fasciectomy for Dupuytren’s contracture: Long-term follow-up
Authors: Bergovec Marko , Jelicic Josko , Oljaca Ana , Bilic Ranko 
Published: March 2018

Purpose: The aim of this study was to analyze long-term results after limited fasciectomy for Dupuytren’s contracture. Methods: The study included 34 patients (52 rays), with an average follow-up of 9.5 years (range: 7–13 years). Range of motion, functional status, recurrence, and complications were recorded. Results: Preoperative metacarpophalangeal joint (MCPJ) contracture (median: 35°, range: 0–90°) improved postoperatively to full extension in all but one patient, with no recurrence at the most recent follow-up. Preoperative proximal interphalangeal joint (PIPJ) contractures (median: 52°, range: 5–100°) were initially corrected, but recurred with time (median: 25°, range 0°–80°). Hand function was assessed using the Disabilities of the Arm, Shoulder and Hand questionnaire. Postoperative hand function improved (median: 0, range: 0–27), compared to preoperative function (median: 20, range: 0–51). Hand function worsened with time (at most recent follow-up: median: 3, range: 0–40), mainly due to PIPJ contracture recurrence, but function remained better than before surgery. Conclusion: Limited fasciectomy is an effective treatment method for MCPJ, with full correction achievable in both the short and long term. Regarding the PIPJ, treatment outcomes seem to be multifactorial. Further clarification is required to distinguish between local recurrence and remaining contracture of the PIPJ.
T cell mediated immunity induced by the live-attenuated Shigella flexneri 2a vaccine candidate CVD 1208S in humans
Authors: Toapanta Franklin R. , Bernal Paula J. , Kotloff Karen L. , Levine Myron M. , Sztein Marcelo B. 
Published: March 2018

Abstract
Background
Shigellosis persists as a public health problem worldwide causing ~ 165,000 deaths every year, of which ~ 55,000 are in children less than 5 years of age. No vaccine against shigellosis is currently licensed. The live-attenuated Shigella flexneri 2a vaccine candidate CVD 1208S (S. flexneri 2a; ΔguaBA, Δset, Δsen) demonstrated to be safe and immunogenic in phase 1 and 2 clinical trials. Earlier reports focused on humoral immunity. However, Shigella is an intracellular pathogen and therefore, T cell mediated immunity (T-CMI) is also expected to play an important role. T-CMI responses after CVD 1208S immunization are the focus of the current study.

Methods
Consenting volunteers were immunized orally (3 doses, 108 CFU/dose, 28 days apart) with CVD 1208S. T-CMI to IpaB was assessed using autologous EBV-transformed B-Lymphocytic cell lines as stimulator cells. T-CMI was assessed by the production of 4 cytokines (IFN-γ, IL-2, IL-17A and TNF-α) and/or expression of the degranulation marker CD107a in 14 volunteers (11 vaccine and 3 placebo recipients).

Results
Following the first immunization, T-CMI was detected in CD8 and CD4 T cells obtained from CVD 1208S recipients. Among CD8 T cells, the T effector memory (TEM) and central memory (TCM) subsets were the main cytokine/CD107a producers/expressors. Multifunctional (MF) cells were also detected in CD8 TEM cells. Cells with 2 and 3 functions were the most abundant. Interestingly, TNF-α appeared to be dominant in CD8 TEM MF cells. In CD4 T cells, TEM responses predominated. Following subsequent immunizations, no booster effect was detected. However, production of cytokines/expression of CD107a was detected in individuals who had previously not responded. After three doses, production of at least one cytokine/CD107a was detected in 8 vaccinees (73%) in CD8 TEM cells and in 10 vaccinees (90%) in CD4 TEM cells.

Conclusions
CVD 1208S induces diverse T-CMI responses, which likely complement the humoral responses in protection from disease.
Trial registration This study was approved by the Institutional Review Board and registered on ClinicalTrials.gov (identifier NCT01531530)
Occurrence of marked sepsis-induced immunosuppression in pediatric septic shock: a pilot study
Authors: Remy Solenn , Kolev-Descamps Karine , Gossez Morgane , Venet Fabienne , Demaret Julie , Javouhey Etienne , Monneret Guillaume 
Published: March 2018

Abstract
Background
While the process of sepsis-induced immunosuppression is now well described in adults, very little information is available on immune functions in pediatric sepsis. The current study investigated this in children with septic shock by performing immunomonitoring, including both innate (monocyte human leukocyte antigen-DR, mHLA-DR, expression) and adaptive immunity (lymphocyte subsets count), as well as cytokine concentrations (IL-6, IL-8, IL-10, IL-1Ra, TNF-α, IFN-γ). Subsequent objectives were to assess the associations between inflammatory response, potential immunosuppression and secondary acquired infection occurrence.

Methods
Single-center prospective observational study, including children aged between 1 month and 18 years admitted to pediatric intensive care unit (PICU) for septic shock. Age-matched controls were children hospitalized for elective surgery without any infectious criteria. Blood was sampled at day 1–2, 3–5, and 7–9 after sepsis onset. mHLA-DR and lymphocyte subsets count were measured by flow cytometry and cytokine concentrations by Luminex technology.

Results
A total of 26 children and 30 controls were included. Patients had lymphopenia, and mHLA-DR levels were significantly lower than controls at each time point (p < 0.0001). All cytokines peaked at day 1–2. Children with secondary acquired infection had lower day 3–5 mHLA-DR and higher pro-inflammatory cytokine concentrations (IL-6, IL-8 and TNF-α) at day 1–2 compared to children without secondary acquired infection.

Conclusions
The higher initial inflammatory cytokine production was, the more innate immunity was altered, while evaluated by low mHLA-DR expression. Children with decreased mHLA-DR expression developed more secondary acquired infections. Upon confirmation in multicenter cohorts, these results pave the way for immunostimulation for the most immunosuppressed children in order to prevent nosocomial infections in PICU.
Trial registration PedIRIS study NCT02848144. Retrospectively registered 28 July 2016
Palliative Care Program Development in a Low- to Middle-Income Country: Delivery of Care by a Nongovernmental Organization in India
Authors: Krishnan Anjali , Rajagopal M.R. , Karim Safiya , Sullivan Richard , Booth Christopher M. 
Published: March 2018

Purpose Limited data describe the delivery of palliative care services in low- and middle-income countries. We describe delivery of care by the Trivandrum Institute of Palliative Sciences (TIPS) in Trivandrum, India. Methods Administrative records were used to describe case volumes, setting of care, and organizational expenditures. An estimate of cost per clinical encounter was derived by dividing 2016 monthly clinical expenditures by the number of patient visits. Costs are reported in US dollars and are corrected for Organization for Economic Co-operation and Development purchasing power parity (PPP). Results A total of 11,620 new patients were seen at TIPS during 2007 to 2016; 59% had cancer. The average annual growth rate in case volumes was 18% (480 new patients in 2007 and 1,882 in 2016). The proportion of patients with cancer increased over time from 56% in 2014 to 66% in 2016 ( P < .001). During 2014 to 2016, outpatient visits increased 26% (from 8,524 to 10,732), inpatient days increased 49% (from 1,763 to 2,625), inpatient visits at other hospitals increased 41% (from 248 to 417), and home visits increased 57% (from 3,951 to 6,186). Total clinical expenditures in 2016 were $288,489 (PPP corrected, $5.1 million). Between 2014 and 2016, the cost of delivering care increased by 74%. The mean cost per clinical encounter in 2016 was $15 (PPP corrected, $263). Conclusion Demand for palliative care services has increased substantially, with an increasing proportion related to cancer. The organization of clinical services by TIPS may serve as a model for the development of other palliative care programs in low- and middle-income countries.
Generation of Mouse for Conditional Expression of Forkhead Box A2
Authors: Wang Peng , Wu San-Pin , Brooks Kelsey E , Kelleher Andrew M , Milano-Foster Jessica J , DeMayo Francesco J , Spencer Thomas E 
Published: March 2018

Abstract
Forkhead box A2 (FOXA2) is a pioneer transcription factor involved in organ development, function, and cancer. In the uterus, FOXA2 is essential for pregnancy and expressed specifically in the glands of the endometrium. Loss of FOXA2 function occurs during development of endometrial cancer in humans. The current study describes the development of a mouse model for conditional expression of mouse FOXA2. Using a system consisting of a minigene located at the Rosa26 locus, we generated a CAG-S-mFOXA2 allele in embryonic stem cells and subsequently in mice; before activation, the minigene is silent because of a floxed stop cassette inserted between the promoter and the transgene. To validate functionality, mice with the CAG-S-mFOXA2 allele were crossed with progesterone receptor (Pgr)–Cre mice and lactotransferrin (Ltf)-iCre mice that express Cre in the immature and adult uterus, respectively. In immature Pgr-Cre-CAG-S-mFoxa2 mice, FOXA2 protein was expressed in the luminal epithelium (LE), glandular epithelium (GE), stroma, and inner layer of the myometrium. Interestingly, FOXA2 protein was not observed in most of the LE of uteri from adult Pgr-Cre-CAG-S-mFoxa2 mice, although FOXA2 was maintained in the stroma, GE, and myometrium. The adult Pgr-Cre-CAG-S-mFoxa2 females were completely infertile. In contrast, Ltf-iCre-CAG-S-mFoxa2 mice were fertile with no detectable histological differences in the uterus. The adult uterus of Pgr-Cre-CAG-S-mFoxa2 mice was smaller, contained few endometrial glands, and displayed areas of partially stratified LE and GE. This transgenic mouse line is a valuable resource to elucidating and exploring FOXA2 function.
Metabolomics Identifies Distinctive Metabolite Signatures for Measures of Glucose Homeostasis: The Insulin Resistance Atherosclerosis Family Study (IRAS-FS)
Authors: Palmer Nicholette D , Okut Hayrettin , Hsu Fang-Chi , Ng Maggie C Y , Chen Yii-Der Ida , Goodarzi Mark O , Taylor Kent D , Norris Jill M , Lorenzo Carlos , Rotter Jerome I , Bergman Richard N , Langefeld Carl D , Wagenknecht Lynne E , Bowden Donald W 
Published: March 2018

Abstract

Context
Metabolomics provides a biochemical fingerprint that, when coupled with clinical phenotypes, can provide insight into physiological processes.

Objective
Survey metabolites associated with dynamic and basal measures of glucose homeostasis.

Design
Analysis of 733 plasma metabolites from the Insulin Resistance Atherosclerosis Family Study.

Setting
Community based.

Participants
One thousand one hundred eleven Mexican Americans.

Main Outcome
Dynamic measures were obtained from the frequently sampled intravenous glucose tolerance test and included insulin sensitivity and acute insulin response to glucose. Basal measures included homeostatic model assessment of insulin resistance and β-cell function.

Results
Insulin sensitivity was associated with 99 metabolites (P &lt; 6.82 × 10−5) explaining 28% of the variance (R2adj) beyond 28% by body mass index. Beyond branched chain amino acids (BCAAs; P = 1.85 × 10−18 to 1.70 × 10−5, R2adj = 8.1%) and phospholipids (P = 3.51 × 10−17 to 3.00 × 10−5, R2adj = 14%), novel signatures of long-chain fatty acids (LCFAs; P = 4.49 × 10−23 to 4.14 × 10−7, R2adj = 11%) were observed. Conditional analysis suggested that BCAA and LCFA signatures were independent. LCFAs were not associated with homeostatic model assessment of insulin resistance (P &gt; 0.024). Acute insulin response to glucose was associated with six metabolites; glucose had the strongest association (P = 5.68 × 10−16). Homeostatic model assessment of β-cell function had significant signatures from the urea cycle (P = 9.64 × 10−14 to 7.27 × 10−6, R2adj = 11%). Novel associations of polyunsaturated fatty acids (P = 2.58 × 10−13 to 6.70 × 10−5, R2adj = 10%) and LCFAs (P = 9.06 × 10−15 to 3.93 × 10−7, R2adj = 10%) were observed with glucose effectiveness. Assessment of the hyperbolic relationship between insulin sensitivity and secretion through the disposition index revealed a distinctive signature of polyunsaturated fatty acids (P = 1.55 × 10−12 to 5.81 × 10−6; R2adj = 3.8%) beyond that of its component measures.

Conclusions
Metabolomics reveals distinct signatures that differentiate dynamic and basal measures of glucose homeostasis and further identifies new metabolite classes associated with dynamic measures, providing expanded insight into the metabolic basis of insulin resistance.