Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic linkage and association between chromosome 1q and working memory function in schizophrenia

Schizophrenia is substantially heritable, but specific susceptibility genes remain to be identified. Progress in this endeavor has been hindered by non‐Mendelian transmission patterns, probable genetic heterogeneity, and an inability to detect premorbid and nonpenetrant carriers of predisposing genes. To circumvent these complexities, this study employed quantitative measures of liability, or “endophenotypes,” within a sample of twins discordant for schizophrenia, drawn from the relatively genetically isolated population of Finland. A region on the distal portion of chromosome 1 has shown evidence for linkage to schizophrenia in two prior studies using Finnish patient samples. To elucidate further the nature and location of this potential susceptibility gene, linkage and association analyses were carried out across the chromosome 1 region of interest using quantitative neuropsychological measures of liability. Analyses with a composite measure of liability yielded suggestive evidence for linkage at marker D1S2833 (P = 0.04). Follow‐up analyses of the individual trait measures showed that the Visual Span subtest of the Wechsler Memory Scale (WMS), an indicator of spatial working memory function, was uniquely sensitive to marker D1S2833 (P = 0.007). Association analysis confirmed that allelic variation in D1S2833 is associated with variation in spatial working memory performance as measured by the Visual Span subtest (P = 0.003), the significance of which was confirmed in an analysis of 10,000 Monte Carlo permutations. These data support the utility of this approach and provide evidence for a gene affecting spatial working memory function in schizophrenia patients and their unaffected co‐twins. © 2002 Wiley‐Liss, Inc.
Flow cytometric sperm sorting: Effects of varying laser power on embryo development in swine *

This study was conducted to determine fertilization rate and embryo development using the Beltsville Sperm Sexing Technology with two different laser power outputs, 25 and 125 milliwatts (mW). Freshly ejaculated boar semen was diluted; one aliquot was not stained or sorted (nonsort) and a second aliquot was stained with Hoechst 33342 and sorted as a complete population, not separated into X and Y populations (all‐sort). Ovulation controlled gilts were surgically inseminated with 2 × 105 spermatozoa (44–46 hr after human chorionic gonadotropin (hCG)) into the isthmus of each oviduct, one oviduct receiving nonsort and the other all‐sort at 25 or 125 mW. A total of 426 embryos were flushed from oviducts at slaughter 43 hr after laparotomy and prepared for determination of fertilization and cleavage rates using confocal laser microscopy for analysis of actin cytoskeleton and chromatin configuration. The percentage of fertilized eggs and embryos was less for the 25 mW all‐sort compared to nonsort or the 125 mW all‐sort (77.9 vs. 96.3 and 96.2%, P < 0.05). The percentage of fragmented embryos was greater for the 25 mW all‐sort than the nonsort (15.2 vs. 4.5%, P < 0.05), but did not differ significantly from 125 mW all‐sort mean (7.2%). The percentage of normal embryos (80.4% overall) did not differ (P > 0.05) among treatments. However, the rate of embryo development was slower (P < 0.05) after insemination with the 25 mW all‐sort spermatozoa compared to nonsort spermatozoa. Embryos in the 3–4 and 5–9 cell stages for the 25‐mW all‐sort and nonsort were 78 and 20% vs. 49 and 50%, respectively. The embryo percentages for the 125 mW (3–4 and 5–9 cell stages, 59 and 35%) did not differ significantly (P > 0.05) from the nonsort or 25 mW all‐sort. We conclude that the use of 125 mW laser power for sorting boar spermatozoa is advantageous to maintain high resolution separation and has no detrimental effect on embryo development compared to 25 mW. Mol. Reprod. Dev. 61: 87–92, 2002. © 2002 Wiley‐Liss, Inc.
Characteristics of elderly cancer patients' concerns and their quality of life in Japan: a Web-based survey.

OBJECTIVE Cancer incidence and the number of cancer patients are increasing in today's aging society. The purpose of this study was to investigate the characteristics of elderly cancer patients' concerns and examine the association between their concerns and quality of life. METHODS This was a cross-sectional web-based survey completed by ambulatory cancer patients aged 20 years or older. The questionnaire on cancer patients' concerns, comprehensive concerns assessment tool and the European Organization for Research and Treatment of Cancer QLQ-C30 were distributed to the subjects. Multiple regression analysis was conducted to determine which patients' concerns significantly contributed to their quality of life. RESULTS The final study population consisted of 807 cancer patients, among whom 243 (30%) were elderly (65 years or older). Elderly cancer patients had particular difficulty with self-management, psychological symptoms and medical information, and the prevalence of their concerns was generally lower than that of younger patients, with the exception of physical symptoms. Multiple types of elderly patients' concerns were independently associated with quality of life. CONCLUSIONS We found that elderly cancer patients suffered from various concerns, thus multidisciplinary intervention is important for providing them with optimal care. The results of this study suggest that elderly cancer patients' quality of life will improve if their concerns are properly handled.
Increased Severe Trauma Patient Volume is Associated With Survival Benefit and Reduced Total Health Care Costs: A Retrospective Observational Study Using a Japanese Nationwide Administrative Database

Objective: The aim of this study was to evaluate the associations of severe trauma patient volume with survival benefit and health care costs. Background: The effect of trauma patient volume on survival benefit is inconclusive, and reports on its effects on health care costs are scarce. Methods: We conducted a retrospective observational study, including trauma patients who were transferred to government-approved tertiary emergency hospitals, or hospitals with an intensive care unit that provided an equivalent quality of care, using a Japanese nationwide administrative database. We categorized hospitals according to their annual severe trauma patient volumes [1 to 50 (reference), 51 to 100, 101 to 150, 151 to 200, and ≥201]. We evaluated the associations of volume categories with in-hospital survival and total cost per admission using a mixed-effects model adjusting for patient severity and hospital characteristics. Results: A total of 116,329 patients from 559 hospitals were analyzed. Significantly increased in-hospital survival rates were observed in the second, third, fourth, and highest volume categories compared with the reference category [94.2% in the highest volume category vs 88.8% in the reference category, adjusted odds ratio (95% confidence interval, 95% CI) = 1.75 (1.49–2.07)]. Furthermore, significantly lower costs (in US dollars) were observed in the second and fourth categories [mean (standard deviation) for fourth vs reference = $17,800 ($17,378) vs $20,540 ($32,412), adjusted difference (95% CI) = –$2559 (–$3896 to –$1221)]. Conclusions: Hospitals with high volumes of severe trauma patients were significantly associated with a survival benefit and lower total cost per admission.
Specific overexpression of OLFM4GW112/hGC−1 mRNA in colon, breast and lung cancer tissues detected using quantitative analysis

Overexpression of the olfactomedin 4 (OLFM4GW112,/hGC−1) gene was recently reported to inhibit various apoptotic pathways and promote proliferation of cancer cells, suggesting that OLFM4 might serve as a diagnostic marker for human cancers. Therefore, we examined cancer‐specific OLFM4 overexpression. OLFM4 mRNA was highly expressed in cancerous tissues obtained from the colon, breast and lung. Positivity for OLFM4 mRNA, defined as the mean + 2 SD in non‐cancerous colon and breast tissues, was observed in 68 and 50% of the studied colon and breast cancer tissues. OLFM4 mRNA expression was not detected in non‐cancerous lung tissues but was evident in 62% of the lung cancer tissues. On comparing paired samples, the expression of OLFM4 mRNA was observed to be elevated in 90, 69 and 85% of colon, breast and lung cancer tissues, respectively. OLFM4 mRNA expression was observed even in the early stages of each cancer type. The expression of OLFM4 mRNA did not correlate with that of the antiapoptotic molecule survivin, indicating that it can be used independently in cancer diagnosis. Combining OLFM4 and survivin resulted in higher positivity. Thus, OLFM4 mRNA might be a useful tool to support the diagnosis of cancer, irrespective of the clinical stages. (Cancer Sci 2007; 98: 315–320)
Disparities in data on Healthy People 2010 physical activity objectives collected by accelerometry and self-report.

OBJECTIVES We compared findings on physical activity from national accelerometry data and Healthy People 2010 self-report data to identify differences in disparities by sociodemographic characteristics, gender, age, race/ethnicity, education level, and disability status. METHODS Data were from the 2003 to 2004 National Health and Nutrition Examination Survey's accelerometry and the Healthy People 2010 Midcourse Review. We computed prevalence of inactivity and regular moderate- and vigorous-intensity movement according to Healthy People 2010 operational definitions. RESULTS Mexican American adults were more active than non-Hispanic Blacks and Whites, and groups defined by race/ethnicity and educational attainment were more similar in physical activity in accelerometer than in self-report data. Disparities by gender and disability status were consistent with Healthy People 2010. CONCLUSIONS Disparities in physical activity differ from previous findings. Increased understanding of these disparities should be used to design better and more cost-effective physical activity interventions. Physical activity surveillance methods should be revised to make use of data collection methods that are more valid than self-report.
TtsI regulates symbiotic genes in Rhizobium species NGR234 by binding to tts boxes

Infection of legumes by Rhizobium sp. NGR234 and subsequent development of nitrogen‐fixing nodules are dependent on the coordinated actions of Nod factors, proteins secreted by a type III secretion system (T3SS) and modifications to surface polysaccharides. The production of these signal molecules is dependent on plant flavonoids which trigger a regulatory cascade controlled by the transcriptional activators NodD1, NodD2, SyrM2 and TtsI. TtsI is known to control the genes responsible for T3SS function and synthesis of a symbiotically important rhamnose‐rich lipo‐polysaccharide, most probably by binding to cis elements termed tts boxes. Eleven tts boxes were identified in the promoter regions of target genes on the symbiotic plasmid of NGR234. Expression profiles of lacZ fusions to these tts boxes showed that they are part of a TtsI‐dependent regulon induced by plant‐derived flavonoids. TtsI was purified and demonstrated to bind directly to two of these tts boxes. DNase I footprinting revealed that TtsI occupied not only the tts box consensus sequence, but also upstream and downstream regions in a concentration‐dependent manner. Highly conserved bases of the consensus tts box were mutated and, although TtsI binding was still observed in vitro, gfp fusions were no longer transcribed in vivo. Random mutagenesis of a tts box‐containing promoter revealed more nucleotides critical for transcriptional activity outside of the consensus.
Benign hyperplastic nodules that originate in the peripheral zone of the prostate gland.

PURPOSE To describe a benign nodular lesion in the peripheral zone (PZ) of the prostate gland. MATERIALS AND METHODS In 1,087 patients, the features of 722 focal lesions in the PZ or central zone of the prostate on transrectal ultrasound (TRUS) scans were retrospectively compared with histologic findings in biopsy samples. RESULTS In 18 patients (5.5% of the 328 patients with benign lesions), benign hyperplasia was found in a focal, nodular lesion obviously located within the PZ. On TRUS scans, the nodules were well circumscribed, ovoid or round, and slightly hypoechoic (n = 11) or isoechoic (n = 7). The isoechoic lesions were surrounded by an anechoic halo. One nodule was an incidental sonographic finding; the 17 others were felt as firm (n = 11) or soft (n = 6) at digital rectal examination. The ratio of serum prostate-specific antigen (PSA) level to prostatic volume was low (< 0.1), except in one patient (0.24). CONCLUSION Some sonographic features and the normal PSA values might suggest a benign nodule in the PZ, but TRUS-guided biopsies and histologic correlation are necessary to confirm the diagnosis.
Lymphoid aggregates may contribute to the migration and epithelial commitment of bone marrow-derived cells in colonic mucosa

Aims Colonic inflammation is followed by regeneration supported by bone marrow-derived cells (BMDCs) including multipotent cells. They migrate to the colonic epithelial layer and may transdifferentiate into epithelial-like cells or keep their stem cell characteristics and produce progenies. The aim was to study the role of lymphoid aggregates in the migration and transition of BMDCs in both healthy colons and non-specific colitis (NSC). Methods Samples of normal colon (n=5) and NSC (n=5) from female patients who were initially transplanted with male bone marrow were studied. After detecting XY chromosomes using fluorescent in situ hybridisation, tissue sections were digitalised, the coverslips were eliminated and the samples were double stained for CD45 and cytokeratin with immunofluorescence. Then CDX2 expression, as a sign of intestinal epithelial commitment of Musashi-1+ stromal BMDCs, was also tested with both immunoperoxidase and parallel immunofluorescence stainings. The slides were digitalised again and analysed simultaneously. Results A significant increase in intraepithelial CD45–BMDCs was found in regions adjacent to lymphoid aggregates (median: 1.01) compared with healthy epithelial regions (median: 0.0175) or NSC (median: 0.04) samples. The stromal Musashi-1+ cells were positive for CDX2 as well, as a sign of epithelial differentiation. The CDX2+ cells bearing the Y chromosome proved the epithelial commitment of several stromal BMDCs. Conclusion Elevated number of intraepithelial CD45−BMDCs at lymphoid aggregates suggests that BMDCs play a role in epithelial regeneration and that lymphoid aggregates serve as their migration route.
Modification of lymphocyte migration by sulfated polysaccharides

The role of sulfated polysaccharides in lymphocyte migration has been analyzed in vivo using lymphocytes labeled with an intracellular DNA‐binding fluorochrome Hoechst 33342. The influence of a panel of sulfated polysaccharides on entry (by injecting the sulfated polysaccharide prior to the labeled cells) and displacement from lymphoid organs (by injecting the sulfated polysaccharide after the labeled cells have localized) indicated that different sulfated polysaccharides have selective effects on entry and displacement, and furthermore positioning of subpopulations within organs. Additional experiments suggested that receptors for sulfated polysaccharides on high endothelial venules may interact with complementary structures on lymphocytes. The data supporting this conclusion were: (a) the normal localization behavior of lymphocytes preincubated with sulfated polysaccharides; (b) an inverse relationship between the expression of lymphocyte surface receptors for sulfated polysaccharides and the ability of the lymphocytes to enter lymphoid organs and (c) the selective binding of sulfated polysaccharide‐coupled fluoresceinated beads to high endothelial venules. In this case only the beads coupled with the sulfated polysaccharides that inhibited entry bound to the high endothelial venules. These findings are discussed in terms of a fundamental cellular recognition system utilizing sulfated polysaccharides.
Statistical Fluctuations in HfOx Resistive-Switching Memory: Part I - Set/Reset Variability

Resistive switching memory (RRAM) relies on the voltage-driven formation/disruption of a conductive filament (CF) across a thin insulating layer. Due to the 1-D structure of the CF and discrete nature of defects, the set and reset states of the memory device generally display statistical variability from cycle to cycle. For projecting cell downscaling and designing improved programming operations, the variability as a function of the operation parameters, such as the maximum current in the set process and maximum voltage in the reset process, need to be evaluated and understood. This paper addresses set/reset variability, presenting statistical data for HfOx-based RRAM and introducing a physics-based Monte Carlo model for switching statistics. The model can predict the distribution of the set state as a function of the compliance (maximum) current during set and distribution of the reset state as a function of the stop (maximum) voltage during reset. Numerical modeling results are finally presented to provide additional insight into discrete fluctuation events.
The der(21)t(12;21) chromosome is always formed in a 12;21 translocation associated with childhood acute lymphoblastic leukaemia

We studied 116 patients (93 children and 23 adults) with acute lymphoblastic leukaemia (ALL) using fluorescence in situ hybridization (FISH) with the yeast artificial chromosome (YAC) clone, 964c10, which includes the recently described ETS‐like gene, TEL, on 12p13. FISH revealed that nine of the patients had a t(12;21), which had not been previously detected. The nine patients were all children, seven boys and two girls, aged 1–10 years (median 3 years), had an early B immunophenotype, and achieved complete remission, although two of them experienced haematological relapse. In addition to the t(12;21), FISH also revealed that three of the nine had a del(12p) in the other homolog of chromosome 12 or in the der(12) chromosome itself, and that two others had 12p translocations in the other chromosome 12 homolog. Although chromosomal rearrangements associated with the t(12;21) were heterogenous and complex, fusion of the sequences from chromosomes 12 and 21 on the der(21)t(12;21) chromosomes was consistent, suggesting that the TEL‐AML1 gene fusion on the der(21) chromosome may be critical in leukaemogenesis and that FISH or reverse transcriptase‐polymerase chain reaction (RT‐PCR) targeted to the chimaeric sequences on the der(21) will be most useful in detecting the t(12:21) or following a patient with the t(12;21), which is one of the most frequent chromosomal rearrangements in both Caucasian and Asian childhood ALL.
Protecting Participants of Clinical Trials Conducted in the Intensive Care Unit

Research in the intensive care unit (ICU) raises a number of scientific and ethical challenges. Potential participants in critical care studies are likely to be considered particularly vulnerable—they may lack sufficient capacity to make informed decisions about trial participation, their health care proxies may lack legal authority to enroll them in research trials or may not know their true intent, and the life-threatening nature of the illness may make them or their surrogates more susceptible to therapeutic misconception. Because of this, critical care investigators must exercise extreme caution when designing and conducting studies in the ICU. In this article, we review the key literature addressing the various scientific and ethical issues raised by critical care research, including questions of equipoise and the selection of control groups, informed consent, therapeutic misconception, conflict of interest, and quality improvement projects. We also describe the current status of key policy or regulatory initiatives designed to address these issues, particularly in light of recent controversies involving critical care studies like the ARDSNet trial.
Determinants of urinary 8‐hydroxy‐2′‐deoxyguanosine in Chinese children with acute leukemia

The 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG), an oxidized nucleoside of DNA, not only is a widely used biomarker for the measurement of endogenous oxidative DNA damage, but might also be a risk factor for many diseases including cancer. Elevated level of urinary 8‐OHdG has been detected in patients with various malignancies. In the present study, the level of urinary 8‐OHdG was examined in 116 Chinese children with acute leukemia (94 acute lymphoid leukemia, ALL, 22 acute myeloid leukemia, AML), and its correlation with urinary metal elements was investigated. Our result showed that the level of urinary 8‐OHdG in children with acute leukemia before treatment was significantly elevated compared with that in normal controls (11.92 ± 15.42 vs. 4.03 ± 4.70 ng/mg creatinine, P < 0.05). In particular, urinary 8‐OHdG was higher in children with acute leukemia aged under 3 years (20.86 ± 21.75 ng/mg creatinine) than in those aged 3–15 years (8.09 ± 9.65 ng/mg creatinine), whereas no differences were shown in terms of gender, parental smoking and education, household income, place of residence, and use of paracetamol. In addition, urinary 8‐OHdG levels were similar among different subtypes of acute lymphoid leukemia (ALL) patients. Furthermore, linear regression analysis revealed a significant correlation between urinary 8‐OHdG and urinary Cr, but not Fe or As, in group aged <3 years compared with group aged 3–15 years (P = 0.041), indicating that the metal elements may be involved in increasing urinary 8‐OHdG level in younger children with acute leukemia. Our results suggest that children with acute leukemia undergo an increased risk of oxidative DNA damage, which may be correlated with high level of Cr exposure in Chinese children with acute leukemia. © 2008 Wiley Periodicals, Inc. Environ Toxicol, 2009.
Mutations in HlyD, Part of the Type 1 Translocator for Hemolysin Secretion, Affect the Folding of the Secreted Toxin

ABSTRACT HlyD, a member of the membrane fusion protein family, is essential for the secretion of the RTX hemolytic toxin HlyA from Escherichia coli. Random point mutations affecting HlyA secretion were obtained, distributed in most periplasmic regions of the HlyD molecule. Analysis of the secretion phenotypes of different mutants allowed the identification of regions in HlyD involved in different steps of HlyA translocation. Four mutants, V349-I, T85-I, V334-I and L165-Q, were conditionally defective, a phenotype shown to be linked to the presence of inhibitory concentrations of Ca2+ in extracellular medium. Hly mutant T85-I was defective at an early stage in secretion, while mutants V334-I and L165-Q appeared to accumulate HlyA in the cell envelope, indicating a block at an intermediate step. Mutants V349-I, V334-I, and L165-Q were only partially defective in secretion, allowing significant levels of HlyA to be transported, but in the case of V349-I and L165-Q the HlyA molecules secreted showed greatly reduced hemolytic activity. Hemolysin molecules secreted from V349-I and V334-I are defective in normal folding and can be reactivated in vitro to the same levels as HlyA secreted from the wild-type translocator. Both V349-I and V334-I mutations mapped to the C-terminal lipoyl repeat motif, involved in the switching from the helical hairpin to the extended form of HlyD during assembly of the functional transport channel. These results suggest that HlyD is an integral component of the transport pathway, whose integrity is essential for the final folding of secreted HlyA into its active form.