Miracle-dz/UniFAR-FTUs huggingface dataset:
Analysis of Expressed and Non-Expressed IGK Locus Rearrangements in Chronic Lymphocytic Leukemia

Immunoglobulin κ (IGK) locus rearrangements were analyzed in parallel on cDNA/genomic DNA in 188 κ- and 103 λ-chronic lymphocytic leukemia (CLL) cases. IGKV-KDE and IGKJ-C-intron-KDE rearrangements were also analyzed on genomic DNA. In κ-CLL, only 3 of 188 cases carried double in-frame IGKV-J transcripts: in such cases, the possibility that leukemic cells expressed more than one k chain cannot be excluded. Twenty-eight κ-CLL cases also carried nonexpressed (nontranscribed and/or out-of-frame) IGKV-J rearrangements. Taking IGKV-J, IGKV-KDE, and IGKJ-C-intron-KDE rearrangements together, 38% of κ-CLL cases carried biallelic IGK locus rearrangements. In λ-CLL, 69 IGKV-J rearrangements were detected in 64 of 103 cases (62%); 24 rearrangements (38.2%) were in-frame. Four cases carried in-frame IGKV-J transcripts but retained monotypic light-chain expression, suggesting posttranscriptional regulation of allelic exclusion. In all, taking IGKV-J, IGKV-KDE, and IGKJ-C-intron-KDE rearrangements together, 97% of λ-CLL cases had at least 1 rearranged IGK allele, in keeping with normal cells. IG repertoire comparisons in κ- versus λ-CLL revealed that CLL precursor cells tried many rearrangements on the same IGK allele before they became λ producers. Thirteen of 28 and 26 of 69 non-expressed sequences in, respectively, κ- or λ-CLL had < 100% homology to germline. This finding might be considered as evidence for secondary rearrangements occurring after the onset of somatic hypermutation, at least in some cases. The inactivation of potentially functional IGKV-J joints by secondary rearrangements indicates active receptor editing in CLL and provides further evidence for the role of antigen in CLL immunopathogenesis.
Insulin Resistance and Diabetes Mellitus Associated With Antiretroviral Use in HIV-Infected Patients: Pathogenesis, Prevention, and Treatment Options

The contribution of current antiretroviral treatment regimens to the long-term survival of HIV-infected individuals is accompanied by increased risk of glucose metabolism abnormalities in this patient population. The risk of insulin resistance and diabetes in HIV-infected patients receiving antiretroviral treatment stems from 2 sources: exposure to the same environmental factors that have led to an increased incidence of these conditions in the general population and the negative effects on glucose metabolism inherent to components of antiretroviral treatment regimens. This article reviews the pathogenesis and diagnosis of insulin resistance and diabetes and the contribution of components of antiretroviral therapy regimens to increased risk for these conditions. Optimization of antiretroviral treatment regimens for HIV-infected patients with or at increased risk for development of abnormalities in glucose metabolism is discussed.
Outcome Prediction of Third Ventriculostomy: A Proposed Hydrocephalus Grading System

An important factor in making a recommendation for different treatment modalities in hydrocephalus patients (VP shunt versus endoscopic third ventriculostomy) is the definition of the underlying pathology which determines the prognosis/outcome of the surgical procedure. Third ventriculostomies (3rd VS) are successful mainly in obstructive hydrocephalus but also in some subtypes of communicating hydrocephalus. A simple, easily applicable grading system that is designed to predict the outcome of 3rd VS is proposed. The hydrocephalus is graded on the basis of the extent of downward bulging of the floor of the third ventricle, which reflects the pressure gradient between the 3rd ventricle and the basal cisterns, presence of directly visualised CSF pathway obstruction in MRI, and the progression of the clinical symptoms resulting in five different grades. In this proposed grading system, grade 1 hydrocephalus subtype shows no downward bulged floor of the 3rd ventricle, no obstruction of the CSF pathway, and no progressive symptoms of hydrocephalus. There is no indication for 3rd VS. Grades 2 to 4 show different combinations of the described parameters. Grade 5 subtype shows a markedly downward bulged floor of the 3rd ventricle and direct detection of the CSF pathway obstruction (i.e., aqueductal stenosis) with progressive clinical deterioration. Retrospective application of this grading scheme to a series of 72 3rd VS has demonstrated a high correlation with the outcome: The success rate in grade 3 reached 40%, in grade 4: 58%, and in grade 5: 95%. This standardised grading system predicts the outcome of 3rd VS and helps in decision making for 3rd VS versus VP shunting.
Importance of Ribonucleotide Availability to Proliferating T-lymphocytes from Healthy Humans

Sensitive high performance liquid chromatography techniques, which differentiate between purine and pyrimidine ribonucleoside and deoxyribonucleoside triphosphates, were used to quantify pools in phytohemagglutinin-stimulated T-lymphocytes (98% CD4 and CD8) from healthy volunteers. The importance of de novo synthesis and salvage was evaluated by incubating the cells with C-radiolabeled precursors (40 μM), azaserine (20 μM; a glutamine antagonist), and ribavirin (50 μM; an IMP dehydrogenase inhibitor). We confirmed that resting T-lymphocytes meet their metabolic requirements by salvage. Noteworthy observations were as follows. First, nucleotide pool expansion over 72 h is disproportionate, with that for purines (ATP and GTP) being 2-fold compared with up to 8-fold for pyridine (NAD) or pyrimidine (UTP, UDP-Glc, and CTP) pools. This supports an additional role for the latter in membrane lipid biosynthesis, protein glycosylation, and strand break repair. Second, intact de novo pathways are essential for such expansion. Azaserine not only inhibited purine synthesis (confirmed by N-formylglycinamide polyphosphate accumulation), but also reduced expansion of pyrimidine and NAD pools by 70%. Ribavirin depleted GTP pools by 40% and reduced pyrimidine pool expansion by 40% at 72 h. These findings underline the importance of pyrimidine ribonucleotide availability as well as GTP synthesis de novo to proliferating T-lymphocytes. They also demonstrate an absence of coordinate regulation between de novo purine and pyrimidine biosynthesis.
Effects of experimentally elevated traffic noise on nestling white-crowned sparrow stress physiology, immune function and life history

SUMMARY Roads have been associated with behavioral and physiological changes in wildlife. In birds, roads decrease reproductive success and biodiversity and increase physiological stress. Although the consequences of roads on individuals and communities have been well described, the mechanisms through which roads affect birds remain largely unexplored. Here, we examine one mechanism through which roads could affect birds: traffic noise. We exposed nestling mountain white-crowned sparrows (Zonotrichia leucophrys oriantha) to experimentally elevated traffic noise for 5 days during the nestling period. Following exposure to traffic noise we measured nestling stress physiology, immune function, body size, condition and survival. Based on prior studies, we expected the traffic noise treatment to result in elevated stress hormones (glucocorticoids), and declines in immune function, body size, condition and survival. Surprisingly, nestlings exposed to traffic noise had lower glucocorticoid levels and improved condition relative to control nests. These results indicate that traffic noise does affect physiology and development in white-crowned sparrows, but not at all as predicted. Therefore, when evaluating the mechanisms through which roads affect avian populations, other factors (e.g. edge effects, pollution and mechanical vibration) may be more important than traffic noise in explaining elevated nestling stress responses in this species.
Biobanks and the search for predictive biomarkers of local and systemic outcome in atherosclerotic disease

Summary Multiple risk factors have been associated with progression of atherosclerosis. To identify the individual patient who is at risk for disruption of a vulnerable plaque, leading to a cardiovascular event, remains a major challenge. Current screening methods, based on traditional risk factors, do not allow risk stratification on an individual level. The discovery of new biomarkers would aid in identifying specific patient groups at risk for adverse cardiovascular events due to atherosclerotic disease progression. The current definition of the vulnerable plaque, e.g. atheromatous inflammatory plaque with a thin fibrous cap, has been based on cross-sectional post-mortem studies. The predictive value of these histological characteristics of the vulnerable plaque is likely to be low, because they are also frequently observed at multiple locations in symptomatic and asymptomatic patients. The Athero-express study follows a new concept to search for the atherosclerotic patient who may suffer from adverse events. In this study, we investigate the predictive value of local plaque composition for adverse events in other vascular territories, regarding the plaque as a concentrated expression of this systemic disease. First results from this longitudinal biobank study show that the local plaque hides strong predictive value for cardiovascular events elsewhere in the vascular tree. Longitudinal biobank studies will facilitate the identification of novel local plaque markers. The search for the plaque protein signature that is predictive for adverse events might enable patient stratification that will allow individualized tailor made medicine and subsequently guide the choice for therapeutic interventions.
Opportunity lost: end-of-life discussions in cancer patients who die in the hospital.

BACKGROUND End-of-life discussions are associated with decreased use of life-sustaining treatments in patients dying of cancer in the outpatient setting, but little is known about discussions that take place during terminal hospitalizations. OBJECTIVES To determine the proportion of patients assessed by the clinical team to have decisional capacity on admission, how many of these patients participated or had a surrogate participate in a discussion about end-of-life care, and whether patient participation was associated with treatments received. DESIGN Retrospective review. SETTING Inpatient. PATIENTS Adult patients with advanced cancer who died in the hospital between January 1, 2004 and December 31, 2007. RESULTS Of the 145 inpatients meeting inclusion criteria, 115 patients (79%) were documented to have decisional capacity on admission. Among these patients, 46 (40%) were documented to lose decisional capacity prior to an end-of-life discussion and had the discussion held instead by a surrogate. Patients who had surrogate participation in the end-of-life discussions were more likely to receive mechanical ventilation (56.5% vs 23.2%, P < 0.01), artificial nutrition (45.7% vs 25.0%, P = 0.03), chemotherapy (39.1% vs 5.4%, P <0.01), and intensive care unit (ICU) treatment (56.5% vs 23.2%, P <0.01) compared to patients who participated in discussions. There was no difference between palliative treatments received. CONCLUSION The majority of patients with advanced cancer are considered to have decisional capacity at the time of their terminal hospitalization. Many lose decisional capacity before having an end-of-life discussion and have surrogate decision-makers participate in these discussions. These patients received more aggressive life-sustaining treatments prior to death and represent a missed opportunity to improve end-of-life care.
Management of acute bacterial rhinosinusitis

Acute bacterial rhinosinusitis is an infection of the nasal epithelium and paranasal sinus mucosa, usually caused in children by Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and, less frequently, group A Streptococcus species. The clinical diagnosis is based on daytime cough that may be worse at night or purulent rhinorrhea, or both, lasting at least 10 days, often worsening after a period of initial improvement after initial symptoms of the common cold, and often associated with facial or dental pain, facial fullness, or swelling, headache, and fever. Sinusitis is diagnosed clinically; radiographic evaluation is not indicated for diagnosis. When the disease persists despite treatment, or is complicated by potential intracranial or orbital extension, CT is the preferred imaging modality. Initial therapy should be amoxicillin in a high dosage (80–90 mg/kg/day). Treatment is generally for 10 to 14 days and for at least 7 days beyond the time of substantial improvement in symptoms. Complications of acute bacterial rhinosinusitis in children are rare.
Engineered zinc‐binding sites confirm proximity and orientation of transmembrane helices I and III in the human serotonin transporter

The human serotonin transporter (hSERT) regulates neurotransmission by removing released serotonin (5‐HT) from the synapse. Previous studies identified residues in SERT transmembrane helices (TMHs) I and III as interaction sites for substrates and antagonists. Despite an abundance of data supporting a 12‐TMH topology, the arrangement of the TMHs in SERT and other biogenic amine transporters remains undetermined. A high‐resolution structure of a bacterial leucine transporter that demonstrates homology with SERT has been reported, thus providing the basis for the development of a SERT model. Zn2+‐binding sites have been utilized in transporters and receptors to define experimentally TMH proximity. Focusing on residues near the extracellular ends of hSERT TMHs I and III, we engineered potential Zn2+‐binding sites between V102 or W103 (TMH I) and I179–L184 (TMH III). Residues were mutated to either histidine or cysteine. TMH I/III double mutants were constructed from functional TMH I mutants, and Zn2+ sensitivity was assessed. Dose‐response assays suggest an approximately twofold increase in sensitivity to Zn2+ inhibition at the hSERT V102C/M180C and approximately fourfold at the V102C/I179C mutant compared to the hSERT V102C single mutant. We propose that the increased sensitivity to Zn2+ confirms the proximity and the orientation of TMHs I and III in the membrane. Homology modeling of the proposed Zn2+‐binding sites using the coordinates of the Aquifex aeolicus leucine transporter structure provided a structural basis for interpreting the results and developing conclusions.
Effects of a Smoke-Free Law on Hair Nicotine and Respiratory Symptoms of Restaurant and Bar Workers

Objective: Bar and restaurant workers’ exposure to secondhand smoke (SHS) was compared before and 3 and 6 months after implementation of a smoke-free ordinance. Methods: Hair nicotine, self-reported exposure to SHS, and respiratory symptoms were assessed on 105 smoking and nonsmoking workers from randomly selected establishments in Lexington, Kentucky. Thirty-eight percent were current smokers with more than half smoking 10 or fewer cigarettes per day. Workers provided a hair sample at baseline and at the 3-month interview. Results: There was a significant decline in hair nicotine 3 months postlaw when controlling for cigarettes smoked per day. Bar workers showed a significantly larger decline in hair nicotine compared with restaurant workers. The only significant decline in SHS exposure was in the workplace and other public places. Regardless of smoking status, respiratory symptoms declined significantly postlaw. Conclusions: Hospitality workers demonstrated significant declines in hair nicotine and respiratory symptoms after the law. Comprehensive smoke-free laws can provide the greatest protection to bar workers who are the most vulnerable to SHS exposure at work.
Characterization of non-extractable 14C- and 13C-sulfadiazine residues in soil including simultaneous amendment of pig manure

Recently, we reported on soil fate of SDZ residues amended with pig manure treated with 14C-labeled sulfadiazine (14C-SDZ). The first objective of the present study was to determine whether this strategy can be substituted by application of 14C-SDZ to soil. The second objective was to characterize non-extractable SDZ residues by fractionation, size exclusion chromatography (SEC) and solid state 13C-NMR. The fate of 14C-SDZ was examined for 28 d, using two soils with and without amendment of pig manure. Mineralization of 14C-SDZ was low; extractable residues decreased to 7–30%. Compared to the previous study, results were similar. 14C-SDZ derived bound radioactivity was found in HCl-washings, fulvic, humic acids and humin. According to SEC, one bound 14C portion (70%) co-eluted with fulvic acids (above 910 g mol−1); the other consisted of adsorbed/entrapped 14C-SDZ. The 13C-SDZ study was performed for 30 d; humic acids were examined by 13C-NMR. A signal (100–150 ppm) was referred to 13C-SDZ. SEC and 13C-NMR demonstrated rapid integration of SDZ into humics.
Inductance characterization of high-leakage transformers

In this paper the inductances of high-leakage transformers are investigated by analysis, measurement, and finite-element simulation. Series-coupling tests, featuring differential coupling (series opposing) and cumulative coupling (series aiding), are conducted in addition to the standard open-circuit and short-circuit tests. This paper initially reviews and discusses the various test approach featuring the open-circuit, short-circuit and series-coupling tests. Two very different types of high-leakage transformers are then characterized based on these tests. The short-circuit and series-coupling tests performed comparably for investigating the spatial variations of the primary and secondary leakage inductances of the high-power, high-leakage transformer first investigated. For the second low-power, high-leakage, high-resistance planar transformer the differential-coupling test proves to be a more useful, accurate, and insightful test than the short-circuit test.
Title Parental migration and the mental health of those who staybehind to care for children in South-East Asia

The international migration of parents from the global south raises questions about the health impacts of family separation on those who stay behind. This paper uses data collected in 2008 and 2009 for a project on Child Health and Migrant Parents in South-East Asia (CHAMPSEA) to address a largely neglected research area by investigating the mental health of those who stay behind in Indonesia, Philippines and Vietnam to care for the children of overseas migrants. A mixed-methods research design is employed to answer two questions. First, whether carers in transnational (migrant) households are more likely to suffer mental health problems than those in non-migrant households; and secondly, whether transnational family practices and characteristics of migration are associated with mental health outcomes for stay-behind carers. The Self-Reporting Questionnaire (SRQ-20) was completed by carers in selected communities (N 1⁄4 3026) and used to identify likely cases of common mental disorders (CMD). Multivariate logistic regression and thematic analysis of qualitative interviews (N 1⁄4 149) reveal a nuanced picture. All stay-behind carers in the Indonesian sample are more likely than carers in nonmigrant households to suffer CMD. Across the three study countries, however, it is stay-behind mothers with husbands working overseas who are most likely to experience poor mental health. Moreover, infrequent contact with the migrant, not receiving remittances and migrant destinations in the Middle East are all positively associated with carer CMD, whereas greater educational attainment and greater wealth are protective factors. These findings add new evidence on the ‘costs’ of international labour migration and point to the role of gendered expectations and wider geopolitical structures. Governments and international policy makers need to intervene to encourage transnational family practices that are less detrimental to the mental health of those who stay behind to care for the next
Soluble glypican 3 inhibits the growth of hepatocellular carcinoma in vitro and in vivo

The heterogeneity of the molecular pathology of HCC poses a formidable obstacle to the development of non‐cytotoxic therapies. Several pro‐tumorigenic signaling pathways can be aberrantly activated in HCC, including those triggered by Wnts. Glypican‐3 (GPC3), a membrane‐bound heparan sulfate proteoglycan that is overexpressed in most HCCs, promotes the growth of these tumors by stimulating Wnt signaling. Because GPC3 binds with high affinity to Wnts, and its growth‐promoting activity requires attachment to the cell membrane, we have hypothesized that a mutated GPC3 lacking the GPI anchoring domain (sGPC3) will block Wnt signaling and inhibit the growth of Wnt‐dependent tumors. In addition, because sGPC3 displays heparan sulfate chains, this secreted glypican could also inhibit HCC growth by blocking the activity of other heparin‐binding growth factors. To test this hypothesis, HCC cell lines were infected with an sGPC3‐expressing lentivirus or virus control, and the effect of sGPC3 on the in vitro and in vivo growth was investigated. In addition, the signaling pathways targeted by sGPC3 were identified. We observed that sGPC3‐expressing cells had lower proliferation rate. In addition, sGPC3 significantly inhibited the in vivo growth of the Huh6, HepG2 and Huh7 HCC cell lines. sGPC3 blocked Wnt signaling in Huh6‐ and Huh7‐derived tumors and Erk1/2 and Akt phosphorylation in tumors generated by Huh7 and HepG2 cells, respectively. An anti‐angiogenic effect in Huh7 and HepG2‐derived tumors was also observed. We conclude that sGPC3 can inhibit HCC tumorigenicity by blocking the activity of several pro‐tumorigenic growth factors.
A high carbohydrate diet induces the beneficial effect of the CC genotype of hepatic lipase C-514T polymorphism on the apoB100/apoAI ratio only in young Chinese males

Both diet and genetic background have profound effects on plasma lipid profiles. It was hypothesized that a high carbohydrate (high-CHO) diet could affect the ratios of serum lipids and apolipoproteins (apo) differently in subjects with different genotypes of the C-514T hepatic lipase rs1800588 polymorphism. Fifty-six healthy university students were given a stabilization diet of 54.1% carbohydrate for 7 days, followed with a high-CHO diet of 70.1% carbohydrate for 6 days. Body composition, serum lipids, apolipoproteins and the hepatic lipase C-514T rs1800588 polymorphism were analyzed. The ratios of serum lipids and apolipoproteins were calculated afterwards. At baseline, females have significantly lower waist circumference (WC) (CC genotype: p = 0.049; T carriers: p = 0.015) and waist-to-hip ratio (WHR) (CC genotype: p = 0.019; T carriers: p = 0.000) than males. When compared with those before the high-CHO diet, the body mass index (BMI) (p = 0.043) and WC (p = 0.048) were significantly decreased in the male T carriers, the TG/HDL-C ratios were significantly increased in females (CC genotype: p = 0.047; T carriers: p = 0.003). The TC/HDL-C ratios were significantly decreased in males (CC genotype: p = 0.000; T carriers: p = 0.003). And the LDL-C/HDL-C ratios were significantly decreased in all subjects (males with the CC genotype: p = 0.001; male T carriers: p = 0.000; females with the CC genotype: p = 0.018; female T carriers: p = 0.006). However, the apoB100/apoAI ratio was only significantly decreased in male CC genotype after the high-CHO diet (p = 0.005).