bluuebunny/crossref_metadata_2025_split huggingface dataset:
Family functioning in depressed and non-clinical control families
Authors: Wang Jikun , Mansfield Abigail K , Zhao Xudong , Keitner Gabor 
Published: June 2012

Background: Existing studies of depression and family functioning have used western samples to examine how depression and impaired family functioning are related, and to explore levels of discrepancy between depressed patients and their family members. The purpose of the current study is to explore these questions in a Chinese sample. Method: This study examined the association between family functioning and depression in a Chinese sample of 60 depressed patients and their family members and 60 non-clinical controls and their family members. The study evaluated levels of agreement between family members on a self-report measure of family functioning (Family Assessment Device) using reliability statistics. It also compared families’ self-reported family functioning to that of a trained observer using an observational rating scale (McMaster Clinical Rating Scale). Results: Results indicate poorer family functioning among Chinese families with a depressed family member, high to moderate agreement between patients and family members, moderate to low agreement between non-clinical participants and their family members, and moderate correlations between subjective and objective ratings of family functioning in a mainland Chinese sample. Conclusions: As in other cultures, depression is associated with impaired family functioning in Chinese families. There is good agreement between family members and a trained evaluator about the family impairments. The Family Assessment Device and the McMaster Clinical Rating Scale are useful for assessing family functioning in Chinese families.
Extension traction treatment for patients with discogenic lumbosacral radiculopathy: a randomized controlled trial
Authors: Moustafa Ibrahim M , Diab Aliaa A 
Published: June 2012

Objective: To investigate the effects of lumbar extension traction in patients with unilateral lumbosacral radiculopathy due to L5–S1 disc herniation. Design: A randomized controlled study with six-month follow-up. Setting: University research laboratory. Subjects: Sixty-four patients with confirmed unilateral lumbosacral radiculopathy due to L5–S1 disc herniation and a lumbar lordotic angle less than 39°, randomly assigned to traction or control group. Interventions: The control group ( n = 32) received hot packs and interferential therapy, whereas the traction group ( n = 32) received lumbar extension traction in addition to hot packs and interferential therapy. Main outcome measures: Absolute rotatory angle, back and leg pain rating scale, Oswestry Disability Index, Modified Schober test, H-reflex (latency and amplitude) and intervertebral movements were measured for all patients three times (before treatment, after 10 weeks of treatment and at six-month follow-up). Results: There was a significant difference between the traction group and the control group adjusted to baseline values at 10 weeks post treatment with respect to: absolute rotatory angle ( P < 0.001), Oswestry Disability Index ( P = 0.002), back and leg pain ( P = 0.009, P = 0.005), Modified Schober test ( P = 0.002), latency and amplitude of H-reflex ( P = 0.01, P < 0.001), intervertebral movements ( P < 0.05). At six-month follow-up there were statistically significant differences between the study and control groups for all the previous variables ( P < 0.05). Conclusion: The traction group receiving lumbar extension traction in addition to hot packs and interferential therapy had better effects than the control group with regard to pain, disability, H-reflex parameters and segmental intervertebral movements.
In-Hospital Mortality and Unintentional Falls Among Older Adults in the United States
Authors: Moudouni Darcy K. McMaughan , Phillips Charles D. 
Published: June 2012

Purpose of the Study: To estimate the odds of death associated with documented unintentional falls and acute care hospitalization among older adults in the United States. Design and Method: Data were abstracted from the 2005 Nationwide Inpatient Sample (NIS) and odds of death were modeled using logistic regression. Results: The age 65 and older fall rate per 1,000 discharges was 53.0 while the mortality rate for those who fell was 33.2. Older-old (odds ration [ OR] = 2.93; confidence interval [CI] = [2.50, 3.43]), men ( OR = 1.64, CI = [1.54, 1.75]), and non-White ( OR = 1.09; CI = [1.01, 1.19]) had higher odds of death compared to younger-old, women, and Whites. Additional comorbidity ( OR = 3.41, CI = [3.05, 3.82]), dehydration ( OR = 1.14; CI = [1.05, 1.25]) and intracranial fractures ( OR = 4.46; CI = [4.02, 4.95]) resulted in greater odds of death. Implications: Among older adults who experienced a fall and hospitalization, odds of mortality appear influenced by factors beyond injury severity related to falling. Additional research is necessary to delineate the mechanisms behind these phenomena to inform the public about falls-prevention programs.
A statistical approach to central monitoring of data quality in clinical trials
Authors: Venet David , Doffagne Erik , Burzykowski Tomasz , Beckers François , Tellier Yves , Genevois-Marlin Eric , Becker Ursula , Bee Valerie , Wilson Veronique , Legrand Catherine , Buyse Marc 
Published: June 2012

Background Classical monitoring approaches rely on extensive on-site visits and source data verification. These activities are associated with high cost and a limited contribution to data quality. Central statistical monitoring is of particular interest to address these shortcomings. Purpose This article outlines the principles of central statistical monitoring and the challenges of implementing it in actual trials. Methods A statistical approach to central monitoring is based on a large number of statistical tests performed on all variables collected in the database, in order to identify centers that differ from the others. The tests generate a high-dimensional matrix of p-values, which can be analyzed by statistical methods and bioinformatic tools to identify extreme centers. Results Results from actual trials are provided to illustrate typical findings that can be expected from a central statistical monitoring approach, which detects abnormal patterns that were not (or could not have been) detected by on-site monitoring. Limitations Central statistical monitoring can only address problems present in the data. Important aspects of trial conduct such as a lack of informed consent documentation, for instance, require other approaches. The results provided here are empirical examples from a limited number of studies. Conclusion Central statistical monitoring can both optimize on-site monitoring and improve data quality and as such provides a cost-effective way of meeting regulatory requirements for clinical trials.
Pivotal Advance: Protein synthesis modulates responsiveness of differentiating and malignant plasma cells to proteasome inhibitors
Authors: Cenci Simone , Oliva Laura , Cerruti Fulvia , Milan Enrico , Bianchi Giada , Raule Mary , Mezghrani Alexandre , Pasqualetto Elena , Sitia Roberto , Cascio Paolo 
Published: June 2012

AbstractProtein synthesis determines sensitivity of differentiating and malignant plasma cells to proteasome inhibitors by saturating cellular proteolytic capacity.A previously unsuspected, considerable proportion of newly synthesized polypeptides are hydrolyzed rapidly by proteasomes, possibly competing with endogenous substrates and altering proteostasis. In view of the anti-cancer effects of PIs, we set out to achieve a quantitative assessment of proteasome workload in cells hallmarked by different PI sensitivity, namely, a panel of MM cells, and in a dynamic model of plasma cell differentiation, a process that confers exquisite PI sensitivity. Our results suggest that protein synthesis is a key determinant of proteasomal proteolytic burden and PI sensitivity. In different MM cells and in differentiating plasma cells, the average proteolytic work accomplished per proteasome ranges over different orders of magnitude, an unexpected degree of variability, with increased workload invariably associated to increased PI sensitivity. The unfavorable load-versus-capacity balance found in highly PI-sensitive MM lines is accounted for by a decreased total number of immunoproteasomes/cell coupled to enhanced generation of RDPs. Moreover, indicative of cause-effect relationships, attenuating general protein synthesis by the otherwise toxic agent CHX reduces PI sensitivity in activated B and in MM cells. Our data support the view that in plasma cells protein synthesis contributes to determine PI sensitivity by saturating the proteasomal degradative capacity. Quantitating protein synthesis and proteasome workload may thus prove crucial to design novel negative proteostasis regulators against cancer.
Deletion of TGF-β signaling in myeloid cells enhances their anti-tumorigenic properties
Authors: Novitskiy Sergey V , Pickup Michael W , Chytil Anna , Polosukhina Dina , Owens Philip , Moses Harold L 
Published: June 2012

Abstract
Specific deletion of TGF-β receptor II in macrophages, CD11b+Gr1+, and dendritic cells inhibit tumor growth by increasing efficiency of the immune system.
By crossing LysM-Cre and TGF-β type II receptor (Tgfbr2) floxed mice we achieved specific deletion of Tgfbr2 in myeloid cells (Tgfbr2MyeKO mice). S.c.-injected (LLC, EL4-OVA) and implanted (MMTV-PyMT) carcinoma cells grow slower in Tgfbr2MyeKO mice. The number of CD45+ cells in the tumor tissue was the same in both genotypes of mice, but upon analysis, the percentage of T cells (CD45+CD3+) in the KO mice was increased. By flow cytometry analysis, we did not detect any differences in the number and phenotype of TAMs, CD11b+Gr1+, and DCs in Tgfbr2MyeKO compared with Tgfbr2MyeWT mice. ELISA and qRT-PCR data showed differences in myeloid cell functions. In Tgfbr2MyeKO TAMs, TNF-α secretion was increased, basal IL-6 secretion was down-regulated, TGF-β did not induce any VEGF response, and there was decreased MMP9 and increased MMP2 and iNOS expression. TGF-β did not have any effect on CD11b+Gr1+ cells isolated from Tgfbr2MyeKO mice in the regulation of Arg, iNOS, VEGF, and CXCR4, and moreover, these cells have decreased suppressive activity relative to T cell proliferation. Also, we found that DCs from tumor tissue of Tgfbr2MyeKO mice have increased antigen-presented properties and an enhanced ability to stimulate antigen-specific T cell proliferation. We conclude that Tgfbr2 in myeloid cells has a negative role in the regulation of anti-tumorigenic functions of these cells, and deletion of this receptor decreases the suppressive function of CD11b+Gr1+ cells and increases antigen-presenting properties of DCs and anti-tumorigenic properties of TAMs.
Mechanisms for the Antihyperglycemic Effect of Sitagliptin in Patients with Type 2 Diabetes
Authors: Muscelli Elza , Casolaro Arturo , Gastaldelli Amalia , Mari Andrea , Seghieri Giuseppe , Astiarraga Brenno , Chen Yu , Alba Maria , Holst Jens , Ferrannini Ele 
Published: June 2012

AbstractContext:Dipeptidyl peptidase IV (DPP-4) inhibitors improve glycemic control in patients with type 2 diabetes. The underlying mechanisms (incretin effect, β-cell function, endogenous glucose production) are not well known.Objective:The aim of the study was to examine mechanisms of the antihyperglycemic effect of DPP-4 inhibitors.Design, Setting, and Patients:We administered a mixed meal with glucose tracers ([6,6-2H2]-glucose infused, [1-2H]-glucose ingested), and on a separate day, a glucose infusion matched the glucose responses to the meal (isoglycemic test) in 50 type 2 diabetes patients (hemoglobin A1c = 7.4 ± 0.8%) and seven controls; 47 diabetic completers were restudied after 6 wk. Glucose fluxes were calculated, and β-cell function was assessed by mathematical modeling. The incretin effect was calculated as the ratio of oral to iv insulin secretion.Intervention:We conducted a 6-wk, double-blind, randomized treatment with sitagliptin (100 mg/d; n = 25) or placebo (n = 22).Results:Relative to placebo, meal-induced changes in fasting glucose and glucose area under the curve (AUC) were greater with sitagliptin, in parallel with a lower appearance of oral glucose [difference (post-pre) AUC = −353 ± 915 vs. +146 ± 601 μmol · kg−1 · 5 h] and greater suppression of endogenous glucose production. Insulin sensitivity improved 10%, whereas total insulin secretion was unchanged. During the meal, β-cell glucose sensitivity improved (+19[29] vs. 5[21] pmol · min−1 · m−2 · mm−1; median [interquartile range]) and glucagon AUC decreased (19.6 ± 7.5 to 17.3 ± 7.1 ng · ml−1 · 5 h), whereas intact glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 AUC increased with sitagliptin vs. placebo. The incretin effect was unchanged because sitagliptin increased β-cell glucose sensitivity also during the isoglycemic test.Conclusions:Chronic sitagliptin treatment improves glycemic control by lowering the appearance of oral glucose, postprandial endogenous glucose release, and glucagon response, and by improving insulin sensitivity and β-cell glucose sensing in response to both oral and iv glucose.
The loss ofHoxa5function promotes Notch-dependent goblet cell metaplasia in lung airways
Authors: Boucherat Olivier , Chakir Jamila , Jeannotte Lucie 
Published: June 2012

SummaryHox genes encode transcription factors controlling complex developmental processes in various organs. Little is known, however, about how HOX proteins control cell fate. Herein, we demonstrate that the goblet cell metaplasia observed in lung airways from Hoxa5−/− mice originates from the transdifferentiation of Clara cells. Reduced CC10 expression in Hoxa5−/− embryos indicates that altered cell specification occurs prior to birth. The loss of Hoxa5 function does not preclude airway repair after naphthalene exposure, but the regenerated epithelium presents goblet cell metaplasia and less CC10-positive cells, demonstrating the essential role of Hoxa5 for correct differentiation. Goblet cell metaplasia in Hoxa5−/− mice is a FOXA2-independent process. However, it is associated with increased Notch signaling activity. Consistent with these findings, expression levels of activated NOTCH1 and the effector gene HEY2 are enhanced in patients with chronic obstructive pulmonary disease. In vivo administration of a γ-secretase inhibitor attenuates goblet cell metaplasia in Hoxa5−/− mice, highlighting the contribution of Notch signaling to the phenotype and suggesting a potential therapeutic strategy to inhibit goblet cell differentiation and mucus overproduction in airway diseases. In summary, the loss of Hoxa5 function in lung mesenchyme impacts on epithelial cell fate by modulating Notch signaling.
Adjunctive Treatment of Chronic Periodontitis With Systemic Low‐Dose Aspirin Therapy
Authors: Geisinger Maria L. , Holmes Carolyn M. , Vassilopoulos Philip J. , Geurs Nicolaas C. , Reddy Michael S. 
Published: June 2012

Focused Clinical QuestionIn patients presenting with generalized moderate‐to‐severe chronic periodontitis (CP), does adjunctive use of systemic low‐dose aspirin therapy with non‐surgical periodontal therapy improve the maintenance of alveolar bone support and/or clinical attachment level?Clinical ScenarioA 55‐year‐old male presents for a periodontal evaluation after deep pockets were noted at a periodontal maintenance visit. The patient reports a dental history significant for non‐surgical periodontal therapy and resective osseous surgery ≈18 years before the current evaluation, and has been seeing a general dentist for periodontal maintenance every 6 months since his surgical treatment. The patient also reports a medical history significant for hypertension and a recent transient ischemic attack (TIA). After the TIA, the patient was placed on 325 mg acetylsalicylic acid daily to reduce his risk of cardiovascular and cerebrovascular events. The treatment plan includes non‐surgical periodontal therapy followed by resective and regenerative surgeries. During medical consultation, the patient's physician states a preference that the patient continue taking aspirin therapy throughout periodontal treatment. The patient is concerned about disease progression after the previous surgical therapy and inquires about the advantages and disadvantages of low‐dose aspirin therapy use in patients with CP. See Figures 1 through 3 for the intraoral presentation of the patient.
A Longitudinal Study of Listening Perception in Adult Learners of English: Implications for Teachers
Authors: Derwing Tracey M. , Thomson Ron I. , Foote Jennifer A. , Munro Murray J. 
Published: June 2012

Abstract: This study is intended to help ESL (English as a second language) instructors make evidence-based decisions based on second language (L2) listening-development findings when selecting features for pronunciation instruction. In a longitudinal study of listening perception, we examined five common problems to determine which were most likely to improve in the absence of explicit instruction and which ones did not improve over time. Twenty Mandarin and 20 Slavic language speakers completed 5 tasks at 2-month intervals over a period of 10 months; we measured their listening perception of word stress, sentence stress, intonation, can/can’t, and -teen/-ty number distinctions. We also compared the participants’ scores at the final testing time to native speaker scores on the same tests. The L2 learners’ perceptions of sentence stress, intonation, and -teen/-ty number distinctions improved while their perceptions of word stress and can/can’t did not. When the L2 speakers’ performance on the tests at the 10-month point was compared to that of the native speakers, there were no significant differences for word stress, intonation, and -teen/-ty number distinctions. However, the native speakers significantly outperformed the Slavic speakers on sentence stress and outperformed both the Slavic and Mandarin speakers on can/can’t distinctions. Implications for pronunciation teaching within general adult ESL classes are discussed.
Chronique commentée des décisions de l'Organe de Règlement des Différends (juin 2010-novembre 2011)
Authors: Busseuil Guillaume , Garinot Jean-Marie , Grayot-Dirx Stéphanie , Jourdain-Fortier Clotilde , Moine-Dupuis Isabelle 
Published: June 2012

Cette année de décisions de l’Organe de Règlement des Différends (ORD) nous permet, à la suite des précédentes, d’observer, et aussi de tenter d’évaluer, les rapports entre la libéralisation du commerce international et les valeurs non marchandes. Valeurs non marchandes ou intérêts économiques ? Les plaignants qui mettent en avant ces valeurs (santé publique, environnement...) sont fréquemment suspectés – parfois à juste titre – de ne les utiliser que comme prétexte à des attitudes protectionnistes (voir notamment affaires Chine – Matières premières, États-Unis – Cigarettes aux clous de girofle ). Réussir à convaincre est d’une importance primordiale, d’où une importance croissante des questions procédurales, ou liées à l’office du juge de l’ORD, qui tiennent une part non négligeable dans la présente chronique. Plusieurs Accords étaient invoqués par les plaignants : le GATT de 1994, le plus fréquemment, mais aussi l’Accord OTC, l’Accord SMC. Enfin, nous noterons la longueur de certains litiges (l’affaire Pommes – commencée en 2007, qui semble avoir trouvé son épilogue – ou l’affaire Aéronefs gros porteurs – la plainte contre Airbus datant de 2004).
Breakdown in Repression of IFN-γ mRNA Leads to Accumulation of Self-Reactive Effector CD8+ T Cells
Authors: Chang Pheh-Ping , Lee Sau K. , Hu Xin , Davey Gayle , Duan Guowen , Cho Jae-Ho , Karupiah Guna , Sprent Jonathan , Heath William R. , Bertram Edward M. , Vinuesa Carola G. 
Published: June 2012

Abstract
Tight regulation of virus-induced cytotoxic effector CD8+ T cells is essential to prevent immunopathology. Naturally occurring effector CD8+ T cells, with a KLRG1hi CD62Llo phenotype typical of short-lived effector CD8+ T cells (SLECs), can be found in increased numbers in autoimmune-prone mice, most notably in mice homozygous for the san allele of Roquin. These SLEC-like cells were able to trigger autoimmune diabetes in a susceptible background. When Roquin is mutated (Roquinsan), effector CD8+ T cells accumulate in a cell-autonomous manner, most prominently as SLEC-like effectors. Excessive IFN-γ promotes the accumulation of SLEC-like cells, increases their T-bet expression, and enhances their granzyme B production in vivo. We show that overexpression of IFN-γ was caused by failed posttranscriptional repression of Ifng mRNA. This study identifies a novel mechanism that prevents accumulation of self-reactive cytotoxic effectors, highlighting the importance of regulating Ifng mRNA stability to maintain CD8+ T cell homeostasis and prevent CD8-mediated autoimmunity.
A Role for the NF-κB Pathway in Cell Protection from Complement-Dependent Cytotoxicity
Authors: Gancz Dana , Lusthaus Michal , Fishelson Zvi 
Published: June 2012

Abstract
Nucleated cells are equipped with several mechanisms that support their resistance to complement-dependent cytotoxicity (CDC). The role of the NF-κB pathway in cell protection from CDC was examined. Elevated sensitivity to CDC was demonstrated in cells lacking the p65 subunit of NF-κB or the IκB kinases IKKα or IKKβ, and in cells treated with p65 small interfering RNA. Pretreatment with the IKK inhibitor PS-1145 also enhanced CDC of wild-type cells (WT) but not of p65−/− cells. Furthermore, reconstitution of p65 into p65−/− cells and overexpression of p65 in WT cells lowered their sensitivity to CDC. The postulated effect of p65 on the JNK-mediated death-signaling pathway activated by complement was examined. p65 small interfering RNA enhanced CDC in WT cells but not in cells lacking JNK. JNK phosphorylation induced by complement was more pronounced in p65−/− cells than in WT cells. The results indicate that the NF-κB pathway mediates cell resistance to CDC, possibly by suppressing JNK-dependent programmed necrotic cell death.
Activation of Invariant NKT Cells in Early Phase of Experimental Autoimmune Encephalomyelitis Results in Differentiation of Ly6Chi Inflammatory Monocyte to M2 Macrophages and Improved Outcome
Authors: Denney Laura , Kok Wai Ling , Cole Suzanne L. , Sanderson Sharon , McMichael Andrew J. , Ho Ling-Pei 
Published: June 2012

Abstract
Neuropathology in multiple sclerosis is closely linked to presence of macrophages in the CNS. Both M1 (inflammatory) and M2 (alternatively activated, noninflammatory) macrophages are found in the inflamed CNS and thought to differentiate from infiltrating monocytes. It is unclear whether the balance of M1 and M2 macrophages can be altered and whether this affects disease outcome. We show in this article that Ly6Chi inflammatory monocytes are the early and dominant infiltrating cells in the CNS during experimental autoimmune encephalomyelitis, a model for the acute phase of multiple sclerosis. Activation of invariant NKT (iNKT) cells reduced the frequency of Ly6Chi monocytes and increased the proportion of M2 macrophages in the CNS with associated improvement in neurologic impairment. In contrast, iNKT-deficient mice showed higher numbers of Ly6Chi monocytes, reduced M2, and much more severe disease. Adoptive transfer of M2-enriched cells to iNKT-deficient mice markedly improved neurologic impairment. In vitro and in vivo experiments showed that iNKT cells promote differentiation of monocytes to M2 macrophages in an IL-4 and CD1d-dependent process. These findings indicate that infiltrating Ly6Chi inflammatory monocytes are early players in acute neuroinflammation and that their frequency and differentiation can be influenced by activation of iNKT cells with resultant improvement in disease outcome.