bluuebunny/crossref_metadata_2025 huggingface dataset:
Requirement of histone deacetylase activity for the expression of critical photoreceptor genes
Authors: Chen Bo , Cepko Constance L
Published: June 2007

Background

Histone deacetylases (HDACs) play a major role in the regulation of gene transcription, often leading to transcriptional repression, as well as other effects following deacetylation of non-histone proteins.

Results

To investigate the role of HDACs in the developing mammalian retina, a general inhibitor of HDACs, trichostatin-A (TSA), was used to treat newborn murine retinae in explant cultures. Inhibition of HDAC activity resulted in a reduction in RNA levels for genes that regulate retinal development, as well as cell cycle regulators. Several of the genes encode transcription factors essential for rod photoreceptor development, Otx2, Nrl, and Crx. Using luciferase reporter assays, the promoter activity of both Nrl and Crx was found to be compromised by HDAC inhibition. Furthermore, downregulation of gene expression by HDAC inhibition didn't require de novo protein synthesis, and was associated with hyperacetylation of histones and non-histone proteins. Finally, HDAC inhibition in retinal explant cultures resulted in increased cell death, reduction in proliferation, a complete loss of rod photoreceptors and Müller glial cells, and an increase in bipolar cells.

Conclusion

HDAC activity is required for the expression of critical pro-rod transcription factors and the development of rod photoreceptor cells.
Single fluorescent protein-based Ca2+sensors with increased dynamic range
Authors: Souslova Ekaterina A , Belousov Vsevolod V , Lock John G , Strömblad Staffan , Kasparov Sergey , Bolshakov Alexey P , Pinelis Vsevolod G , Labas Yulii A , Lukyanov Sergey , Mayr Lorenz M , Chudakov Dmitriy M
Published: June 2007

Background

Genetically encoded sensors developed on the basis of green fluorescent protein (GFP)-like proteins are becoming more and more popular instruments for monitoring cellular analytes and enzyme activities in living cells and transgenic organisms. In particular, a number of Ca2+ sensors have been developed, either based on FRET (Fluorescence Resonance Energy Transfer) changes between two GFP-mutants or on the change in fluorescence intensity of a single circularly permuted fluorescent protein (cpFP).

Results

Here we report significant progress on the development of the latter type of Ca2+ sensors. Derived from the knowledge of previously reported cpFP-based sensors, we generated a set of cpFP-based indicators with different spectral properties and fluorescent responses to changes in Ca2+ concentration. Two variants, named Case12 and Case16, were characterized by particular high brightness and superior dynamic range, up to 12-fold and 16.5-fold increase in green fluorescence between Ca2+-free and Ca2+-saturated forms. We demonstrated the high potential of these sensors on various examples, including monitoring of Ca2+ response to a prolonged glutamate treatment in cortical neurons.

Conclusion

We believe that expanded dynamic range, high brightness and relatively high pH-stability should make Case12 and Case16 popular research tools both in scientific studies and high throughput screening assays.
The revised international autoimmune hepatitis score in chronic liver diseases including autoimmune hepatitis/overlap syndromes and autoimmune hepatitis with concurrent other liver disorders
Authors: Papamichalis Panagiotis A , Zachou Kalliopi , Koukoulis George K , Veloni Aikaterini , Karacosta Efthimia G , Kypri Lampros , Mamaloudis Ioannis , Gabeta Stella , Rigopoulou Eirini I , Lohse Ansgar W , Dalekos George N
Published: June 2007

Background

We conducted a study in order to determine the usefulness and diagnostic value of International Autoimmune Hepatitis Group (IAHG) score in non-autoimmune hepatitis (AIH) hepatic disorders as well as in AIH/overlap syndromes and in cases with coexistence of AIH and other liver diseases.

Methods

We applied the IAHG score in 423 patients with liver diseases excluding patients with AIH, AIH/overlap syndromes and AIH with concurrent other liver disease namely, patients with chronic hepatitis B (n = 109), chronic hepatitis C (n = 95), chronic hepatitis D (n = 4), alchoholic liver disease (n = 28), non-alcoholic fatty liver disease (n = 55), autoimmune cholestatic liver diseases (n = 77), liver disorders of undefined origin (n = 32) and with miscellaneous hepatic disorders (n = 23). 24 patients with AIH associated with any kind of liver disorder including 10 patients with AIH/overlap syndromes and 14 AIH with concurrent other liver disease were also investigated. 43 patients with AIH consisted the control group.

Results

The specificity of the score was 98.1% while the sensitivity in unmasking AIH in patients with either AIH/overlap syndromes or AIH with concurrent other liver diseases was only 50% and 78.6%. In the binary logistic regression model, the presence of other autoimmune diseases (p < 0.001), the total histological score (p < 0.001) and positivity for autoantibodies (p < 0.05) were identified as independent predictors for the presnce of AIH/ovea syndromes o AI with concurren other liver diseass.

Conclusion

The IAHG scoring system has very good specificity for excluding AIH in patients with chronic liver diseases but not that sensitivity in order to unmask AIH/overlap syndromes or AIH with concurrent other liver diseases. The presence of other autoimmune diseases or autoantibody markers in the absence of hepatitis viral markers should alarm physicians for the possible presence of AIH either as "pure" AIH or in association with other liver disorders (AIH/overlap syndromes or AIH with concurrent other liver diseases). Under these conditions, liver histology seems essential and it must always be included in the work up of hepatic patients.
Endogenous hydrogen sulfide regulates leukocyte trafficking in cecal ligation and puncture-induced sepsis
Authors: Zhang Huili , Zhi Liang , Moochhala Shabbir M , Moore Philip Keith , Bhatia Madhav
Published: June 2007

Hydrogen sulfide (H2S) is recognized increasingly as a proinflammatory mediator in various inflammatory conditions. Here, we have investigated the role of H2S in regulating expression of some endothelial adhesion molecules and recruitment of leukocytes to inflamed sites in sepsis. Male Swiss mice were subjected to cecal ligation and puncture (CLP)-induced sepsis and treated with saline (i.p.), DL-propargylglycine (PAG; 50 mg/kg, i.p.), an inhibitor of H2S formation or NaHS (10 mg/kg, i.p.), an H2S donor. PAG was administered 1 h before or after the induction of sepsis, and NaHS was given at the same time of CLP. Using intravital microcopy, we found that in sepsis, prophylactic and therapeutic administration of PAG reduced leukocyte rolling and adherence significantly in mesenteric venules coupled with decreased mRNA and protein levels of adhesion molecules (ICAM-1, P-selectin, and E-selectin) in lung and liver. In contrast, injection of NaHS up-regulated leukocyte rolling and attachment significantly, as well as tissue levels of adhesion molecules in sepsis. Conversely, normal mice were given NaHS (10 mg/kg, i.p.) to induce lung inflammation, with or without NF-κB inhibitor BAY 11-7082 pretreatment. NaHS treatment enhanced the level of adhesion molecules and neutrophil infiltration in lung. These alterations were reversed by pretreatment with BAY 11-7082. Moreover, expression of CXCR2 in neutrophils obtained from H2S-treated mice was up-regulated significantly, leading to an obvious elevation in MIP-2-directed migration of neutrophils. Therefore, H2S acts as an important endogenous regulator of leukocyte activation and trafficking during an inflammatory response.
The risks of risk assessment
Authors: Undrill Guy
Published: June 2007

Risk assessment has become a large and anxiety-provoking part of the work of many psychiatrists. This article unpicks the different meanings of the word ‘risk’ to seek out the source of that anxiety, looking at both statistical and sociological ideas about risk. A risk assessment is often a subjective, plastic and context-dependent statement about a patient that carries strong moral overtones. Risk management is also highly anxiogenic for those charged with carrying it out, because uncertainty about the future is impossible to eliminate and the consequences of an adverse outcome in the patient may also carry hazards to the doctor making the risk assessment. This leads to behaviour change in people carrying out risk assessments as they attempt to minimise their anxiety in a rationally selfish way, often with unintended negative consequences for patients, doctors and health service providers generally. Some possible strategies for minimising this effect are considered.
Heroin-assisted treatment for opioid dependence
Authors: Haasen Christian , Verthein Uwe , Degkwitz Peter , Berger Juergen , Krausz Michael , Naber Dieter
Published: June 2007

Background

Heroin-assisted treatment has been found to be effective for people with severe opioid dependence who are not interested in or do poorly on methadone maintenance.

Aims

To study heroin-assisted treatment in people on methadone who continue intravenous heroin and in those who are heroin dependent but currently not in treatment.

Method

In an open-label multicentre randomised controlled trial, 1015 people with heroin dependence received a variable dose of injectable heroin (n=515) or oral methadone (n=500) for 12 months. Two response criteria, improvement of physical and/or mental health and decrease in illicit drug use, were evaluated in an intent-to-treat analysis.

Results

Retention was higher in the heroin (67.2%) than in the methadone group (40.0%) and the heroin group showed a significantly greater response on both primary outcome measures. More serious adverse events were found in the heroin group, and were mainly associated with intravenous use.

Conclusions

Heroin-assisted treatment is more effective for people with opioid dependence who continue intravenous heroin while on methadone maintenance or who are not enrolled in treatment. Despite a higher risk, it should be considered for treatment resistance under medical supervision.
Long-term outcomes after discharge from medium secure care: a cause for concern
Authors: Davies Steffan , Clarke Martin , Hollin Clive , Duggan Conor
Published: June 2007

Background

There are few long-term follow-up studies of patients discharged from medium secure units in the UK, even though these units were introduced over 20 years ago.

Aims

To describe mortality, rates of reconviction at different time periods; violent behaviour (not leading to conviction), readmission and employment, after discharge from a medium secure unit.

Method

Of 595 first admissions over a 20-year period, 550 discharged cases were followed-up. Multiple data sources were used.

Results

Fifty-seven (10%) patients had died, of whom 18 (32%) died by suicide, and the risk of death was six times greater than in the general population. Almost half (49%) of those discharged were reconvicted and almost two-fifths (38%) of patients were readmitted to secure care.

Conclusions

Community psychiatric services need to be aware that those discharged from medium secure care are a highly vulnerable group requiring careful follow-up if excess mortality high levels of psychiatric morbidity and further offending are to be prevented.
Young people who self-harm
Authors: Young Robert , van Beinum Michael , Sweeting Helen , West Patrick
Published: June 2007

Background

Self-harm among young people in the UK is possibly increasing but little is known about the reasons young people give for cessation and their link with gender or employment status.

Aims

To investigate self-harm in young people, prevalence, methods used, motivations for starting and ceasing, service use, and how these are related to gender, parental social class and current labour market position.

Method

Population-based survey of 1258 18-to 20-year-olds living in the Central Clydeside Conurbation, Scotland.

Results

Both past and current rates of self-harm were highest among those outside the labour market. This group was most likely to want to kill themselves and did not cite specialist mental health services as helpful in ceasing self-harm. Those in full-time education more often self-harmed for a brief time, mainly to reduce anxiety.

Conclusions

Current labour market position was a stronger predictor than parental social class or gender for self-harm, and was linked to level of severity, motivation for starting and ceasing, and service utilisation.
Feasibility and Efficacy of Molecular Analysis-Directed Individualized Therapy in Advanced Non–Small-Cell Lung Cancer
Authors: Simon George , Sharma Anupama , Li Xueli , Hazelton Todd , Walsh Frank , Williams Charles , Chiappori Alberto , Haura Eric , Tanvetyanon Tawee , Antonia Scott , Cantor Alan , Bepler Gerold
Published: June 2007

Purpose

The treatment of patients with advanced non–small-cell lung cancer (NSCLC) is based on clinical trials experience. Molecular characteristics that impact metabolism and efficacy of chemotherapeutic agents are not used for decision making. Ribonucleotide reductase subunit 1 (RRM1) is crucial for nucleotide metabolism, and it is the dominant molecular determinant of gemcitabine efficacy. Excision repair cross-complementing group 1 gene (ERCC1), a component of the nucleotide excision repair complex, is important for platinum-induced DNA adduct repair. We hypothesized that selection of double-agent chemotherapy based on tumoral RRM1 and ERCC1 expression would be feasible and beneficial for patients with advanced NSCLC.

Patients and Methods

We conducted a prospective phase II clinical trial in patients with advanced NSCLC. Patients were required to have a dedicated tumor biopsy for determination of RRM1 and ERCC1 gene expression by real-time quantitative reverse transcriptase polymerase chain reaction. Double-agent chemotherapy consisting of carboplatin, gemcitabine, docetaxel, and vinorelbine was selected based on gene expression. Disease response and patient survival were monitored.

Results

Eighty-five patients were registered, 75 had the required biopsy without significant complications, 60 fulfilled all eligibility criteria, and gene expression analysis was not feasible in five patients. RRM1 expression ranged from 0 to 1,637, ERCC1 expression ranged from 1 to 8,103, and their expression was correlated (Spearman's rho = 0.46; P < .01). Disease response was 44%. Overall survival was 59% and progression-free survival was 14% at 12 months, with a median of 13.3 and 6.6 months, respectively.

Conclusion

Therapeutic decision making based on RRM1 and ERCC1 gene expression for patients with advanced NSCLC is feasible and promising for improvement in patient outcome.
Plasma Lysophosphatidylcholine Levels: Potential Biomarkers for Colorectal Cancer
Authors: Zhao Zhenwen , Xiao Yijin , Elson Paul , Tan Haiyan , Plummer Sarah J. , Berk Michael , Aung Phyu P. , Lavery Ian C. , Achkar Jean P. , Li Li , Casey Graham , Xu Yan
Published: June 2007

Purpose

Plasma levels of lysophospholipids were evaluated as potential biomarkers for colorectal cancer (CRC), where a highly reliable and minimally invasive blood test is lacking.

Patients and Methods

Patients with CRC (n = 133) and control subjects (n = 125) were recruited through the Cleveland Clinic. Preoperative plasma samples were analyzed for lysophospholipid levels using liquid chromatography mass spectrometry in a blinded fashion. Participants were randomly divided in a 2:1 ratio into a “training set” (TS) and a “validation set” (VS). Logistic regression models were used in the TS to identify markers that best discriminated between CRC and controls. A cutoff point for the final discriminating model was developed using the receiver operating characteristic curve to achieve 95% specificity. All analyses were then independently validated in the VS.

Results

Plasma levels of several lysophosphatidylcholines (LPCs), including 18:1- and 18:2-LPC, were significantly decreased in CRC patients compared with controls (P < .001). A model based on total saturated LPC and the difference between the proportional amounts of 18:2-LPC and 18:1-LPC in the unsaturated LPC fraction was derived from the TS. This model achieved a sensitivity and specificity of 82% and 93%, respectively, in the VS. Overall, 118 (94%) of 125 control subjects and 113 (85%) of 133 CRC cases were correctly identified, including eight (89%) of nine CRC cases with stage T1 disease.

Conclusion

Percentage of 18:1-LPC or 18:2-LPC plasma levels compared with total saturated LPC levels, either individually or in combination, may represent potential biomarkers for CRC.
Randomized Phase III Trial of Gemcitabine Compared With Pegylated Liposomal Doxorubicin in Patients With Platinum-Resistant Ovarian Cancer
Authors: Mutch David G. , Orlando Mauro , Goss Tiana , Teneriello Michael G. , Gordon Alan N. , McMeekin Scott D. , Wang Yanping , Scribner Dennis R. , Marciniack Martin , Naumann R. Wendel , Secord Angeles Alvarez
Published: June 2007

Purpose

Ovarian cancer (OC) patients experiencing progressive disease (PD) within 6 months of platinum-based therapy in the primary setting are considered platinum resistant (Pt-R). Currently, pegylated liposomal doxorubicin (PLD) is a standard of care for treatment of recurrent Pt-R disease. On the basis of promising phase II results, gemcitabine was compared with PLD for efficacy and safety in taxane-pretreated Pt-R OC patients.

Patients and Methods

Patients (n = 195) with Pt-R OC were randomly assigned to either gemcitabine 1,000 mg/m2 (days 1 and 8; every 21 days) or PLD 50 mg/m2 (day 1; every 28 days) until PD or undue toxicity. Optional cross-over therapy was allowed at PD or at withdrawal because of toxicity. Primary end point was progression-free survival (PFS). Additional end points included tumor response, time to treatment failure, survival, and quality of life.

Results

In the gemcitabine and PLD groups, median PFS was 3.6 v 3.1 months; median overall survival was 12.7 v 13.5 months; overall response rate (ORR) was 6.1% v 8.3%; and in the subset of patients with measurable disease, ORR was 9.2% v 11.7%, respectively. None of the efficacy end points showed a statistically significant difference between treatment groups. The PLD group experienced significantly more hand-foot syndrome and mucositis; the gemcitabine group experienced significantly more constipation, nausea/vomiting, fatigue, and neutropenia but not febrile neutropenia.

Conclusion

Although this was not designed as an equivalency study, gemcitabine and PLD seem to have a comparable therapeutic index in this population of Pt-R taxane-pretreated OC patients. Single-agent gemcitabine may be an acceptable alternative to PLD for patients with Pt-R OC.
Effects of chronic exposure to dietary salicylate on elimination and renal excretion of salicylate byDrosophila melanogasterlarvae
Authors: Ruiz-Sanchez Esau , O'Donnell Michael J.
Published: June 2007

The effects of chronic exposure to dietary salicylate on elimination and renal excretion of salicylate by D. melanogaster larvae were evaluated using salicylate-selective microelectrodes. Larvae chronically exposed to dietary salicylate showed 25% less salicylate in the haemolymph compared to the control group after feeding on a salicylate-enriched diet. By 1 h after transfer to a salicylate-free diet the levels of salicylate in the haemolymph of larvae raised on dietary salicylate were 46% lower than in the control group. Salicylate flux increased dramatically across Malpighian tubules but not across midgut or hindgut isolated from larvae chronically exposed to dietary salicylate, relative to the control group. Malpighian tubules isolated from experimental larvae showed a 4.7-fold increase in Kt and a nearly 5-fold increase in Jmax relative to the control. These changes in salicylate transport were accompanied by a 3.2-fold increase in fluid secretion rate. Moreover, the high rates of fluid secretion by the Malpighian tubules isolated from experimental larvae were stimulated 2.1-fold and 2.8-fold when tubules were challenged with 1 mmol l–1 cAMP and 10 μmol l–1 leucokinin I, respectively. Taken together, these results indicate that chronic exposure of D. melanogaster larvae to dietary salicylate alters elimination of such toxins from the haemolymph and increases the basal rate of fluid secretion and excretion of salicylate by the Malpighian tubules.
Thermoregulation in pronghorn antelope (Antilocapra americanaOrd) in the summer
Authors: Lust A. , Fuller A. , Maloney S. K. , Mitchell D. , Mitchell G.
Published: June 2007

We have used thermistor/data logger assemblies to measure temperatures in the brain, carotid artery, jugular vein and abdominal cavity, and subcutaneously, in five pronghorn antelope over a summer in Wyoming. Globe and air temperature varied by up to ∼50°C daily during the summer and maximum solar radiation was ∼900 W m–2. Brain temperature(38.9±0.3°C) was consistently ∼0.2–0.5°C higher than carotid blood temperature (38.6±0.3°C), which was the same as abdominal temperature (38.8±0.4°C). Jugular blood temperature(38.0±0.4°C) varied, probably because of changes in Respiratory Evaporative Heat Loss (REHL), and was lower than other temperatures. Subcutaneous temperature (38.3±0.6°C) varied, probably because of peripheral vasoactivity, but on average was similar to other temperatures. Carotid blood temperature had a circadian/nycthemeral rhythm weakly but significantly (r=0.634) linked to the time of sunrise, of amplitude 0.8±0.1°C. There were daily variations of up to 2.3°C in carotid body temperature in individual animals. An average range of carotid blood temperature of 3.1±0.4°C over the study period was recorded for the group, which was significantly wider than the average variation in brain temperature (2.3±0.6°C). Minimum carotid temperature(36.4±0.8°C) was significantly lower than minimum brain temperature(37.7±0.5°C), but maximum brain and carotid temperatures were similar. Brain temperature was kept relatively constant by a combination of warming at low carotid temperatures and cooling at high carotid temperatures and so varied less than carotid temperature. This regulation of brain temperature may be the origin of the amplitude of the average variation in carotid temperature found, and may confer a survival advantage.
Adaptive Idea Screening Using Consumers
Authors: Toubia Olivier , Florès Laurent
Published: June 2007

Following a successful idea generation exercise, a company might easily be left with hundreds of ideas generated by experts, employees, or consumers. The next step is to screen these ideas and identify those with the highest potential. In this paper we propose a practical approach to involving consumers in idea screening.

Although the number of ideas may potentially be very large, it would be unreasonable to ask each consumer to evaluate more than a few ideas. This raises the challenge of efficiently selecting the ideas to be evaluated by each consumer. We describe several idea-screening algorithms that perform this selection adaptively based on the evaluations made by previous consumers. We use simulations to compare and analyze the performance of the algorithms as well as to understand their behavior. The best-performing algorithm focuses on the ideas that are the most likely to have been misclassified (as “top” or “bottom” ideas) based on the previous evaluations, and avoids discarding ideas too fast by adding random perturbations to the misclassification probabilities. We demonstrate the convergent validity of this algorithm using a field experiment, which also confirms the convergence pattern predicted by simulations.
Globalization, Cosmopolitanism, and the Dönme in Ottoman Salonica and Turkish Istanbul
Authors: Baer Marc
Published: July 2007

This article provides a narrative of the rise and fall of two global cities, imperial Ottoman Salonica and nationalist Turkish Istanbul, as well as the experience of a marginal religious group known as the Dönme, descendants of seventeenth-century Jewish converts to Islam who formed a distinctive group of Muslims in both cities, and the interrupted trajectories of indigenous globalization. It argues that at the turn of the twentieth century, indigenous religious groups with transregional connections created alternate nodes of long-since forgotten globalization in marginal spaces at the fringes of empire, but that nation-states that replaced empire limited their abilities by controlling the flow of finance and people, making their resources useless in provincialized global cities. This article thus explains why the globalizing economic and cosmopolitan cultural role of the Dönme should have a place in debates on the global city.
Culture or Literature
Authors: Grabes Herbert
Published: July 2007

With the "cultural turn" English philology has changed in many places into a kind of super-discipline by taking over, at least in part, the work of sociology, history, psychology, and philosophy. The article argues that in order to avoid dilettantism, the excellent qualification for a semiotic or signifying approach to all aspects of culture should be made use of, especially since this approach goes well together with the more recent view of culture as an immaterial construct in terms of an ensemble, or rather a specific hierarchy, of values. In order to discuss the role of literature in and for the wider domain of culture it seems necessary to first delimit this textual corpus, and for that reason a number of recent attempts to define "literature" or "the literary" are considered \-\- including one of my own that sees its specificity in a validational modesty resulting from a focusing on the particular and the suspension of reference. Due to this modest confinement to the presentation of merely possible worlds, literature is granted a "free space" in culture where it can even intimate the limits of the culture of its origin. For this reason it deserves special attention even at a time when the study of culture and media studies are in vogue.
The Sexual Politics of Divine Femininity: Tārā in Transition in Gary Snyder's Poetry
Authors: Whalen-Bridge John
Published: July 2007

Gary Snyder has described his book-length poem Mountains and Rivers without End (1996) as a "mythic narrative of the female Buddha Tārā." Snyder's poem "An Offering for Tārā," like several other poems in his corpus, describes a sensual, forgiving feminine divinity of the sort that many literary scholars now find problematic. By considering two poems from the Sixties alongside one from the mid-Nineties, we can see the developments within Snyder's own myths and texts, but we also see how the images and ideas woven into discourses such as "Orientalism" or "the divine feminine" can undergo dramatic changes within the career of a single writer. Examining Snyder's early poems "For a Far-out Friend," and "Hymn to the Goddess San Francisco in Paradise" alongside Joanne Kyger's "Tapestry," the essay closely examines instances of divine femininity in Beat writing before returning to Snyder's mature work, "An Offering for Tārā," to show how Snyder fashions a postmodern American mode of tantric poetics that is politically progressive. His poetic approach has not been to repress the afflictive desires identified by feminist and anti-Orientalist critics but rather, in the manner of tantric Buddhist practice, to mindfully embrace and re-organize them.
An N-Terminal Molecular Form of Parathyroid Hormone (PTH) Distinct from hPTH(1–84) Is Overproduced in Parathyroid Carcinoma
Authors: Rubin Mishaela R , Silverberg Shonni J , D’Amour Pierre , Brossard Jean-Hugues , Rousseau Louise , Sliney James , Cantor Tom , Bilezikian John P
Published: June 2007

Background: A new parathyroid hormone (PTH) species, the N-terminal PTH form (N-PTH), is distinct from intact human PTH of 84 amino acid residues [hPTH(1–84)] and is recognized in a 3rd-generation assay of “whole” PTH (wPTH; the 1–2 epitope) but not in a 2nd-generation assay of “total” PTH (tPTH; the 12–18 epitope). N-PTH usually represents <15% of wPTH but can be overproduced in severe primary hyperparathyroidism (PHPT) and secondary hyperparathyroidism. We investigated whether N-PTH is also overproduced in parathyroid cancer and whether N-PTH concentration is influenced by calcimimetic therapy.

Methods: We studied 8 patients with parathyroid carcinoma before and at week 16 of cinacalcet therapy, 6 patients with PHPT, and 6 control individuals. We fractionated sera with HPLC and analyzed fractions with the 2 assays to quantify hPTH(1–84), N-PTH, and non-(1–84) PTH fragments.

Results: Half of parathyroid carcinoma patients had an increased wPTH:tPTH ratio [mean (SD), 1.35 (0.29)]; the others had a typical ratio [0.72 (0.12)]. HPLC fractionation of sera from 2 high-ratio patients confirmed N-PTH overproduction [65% (12%) of wPTH]. The N-PTH fraction was <15% of wPTH in PHPT and healthy individuals. Calcimimetic therapy appreciably reduced calcium concentrations in parathyroid carcinoma patients but had little influence on PTH concentration, the wPTH:tPTH ratio, or the PTH HPLC profile.

Conclusion: N-PTH is overproduced in some parathyroid cancer patients, but calcimimetic therapy does not influence its production. The clinical implications of this finding in parathyroid carcinoma await additional studies with an emphasis on N-PTH’s biological activity and with larger numbers of patients.
Quantitative Real-Time Reverse Transcription–PCR Study of the Expression of Vascular Endothelial Growth Factor (VEGF) Splice Variants and VEGF Receptors (VEGFR-1 and VEGFR-2) in Non–Small Cell Lung Cancer
Authors: Zygalaki Eleni , Tsaroucha Emily G , Kaklamanis Loukas , Lianidou Evi S
Published: June 2007

Background: Vascular endothelial growth factor (VEGF) is a major regulator of angiogenesis and its expression is increased in non–small cell lung cancer (NSCLC). We aimed to determine the expression pattern of VEGF splice variants in NSCLC and its correlation with the clinicopathological characteristics of tumors.

Methods: We used real-time reverse transcription PCR to quantify the mRNA expression of total VEGF, 4 VEGF splice variants (VEGF121, VEGF165, VEGF183, and VEGF189), and 2 VEGF receptors (VEGFR-1 and VEGFR-2) in 27 pairs of cancerous and adjacent noncancerous tissues originating from patients with NSCLC.

Results: Total VEGF, VEGF121, and VEGF165 were expressed in all specimens, whereas VEGF183 and VEGF189 were present in small amounts in certain samples. Total VEGF, VEGF121, and VEGF165 mRNA was upregulated in cancerous compared with healthy tissues, whereas VEGF183 and VEGF189 expression tended to be higher in healthy tissues. The expression of VEGFRs was similar between matched specimens. No correlation was found between the expression of total VEGF or VEGF splice variants and the clinicopathological characteristics of tumors. The expression patterns of VEGF splice variants differed between tissue pairs. VEGF121 was the major variant expressed in all samples; however, its relative expression was higher in cancerous tissues. The relative expression of VEGF183 and VEGF189 was upregulated in healthy lung tissues, whereas the ratio of VEGF165 to total VEGF was similar between matched specimens.

Conclusions: The expression pattern of certain VEGF splice variants is altered during tumorigenesis. Our data support the hypothesis that during malignant progression an angiogenic switch favoring the shorter diffusible isoforms occurs.
An Association Between RRM1 Haplotype and Gemcitabine-Induced Neutropenia in Breast Cancer Patients
Authors: Rha Sun Young , Jeung Hei Cheul , Choi Yeon Ho , Yang Woo Ick , Yoo Jin Ho , Kim Byung Soo , Roh Jae Kyung , Chung Hyun Cheol
Published: June 2007

Purpose.

We examined the pattern of single-nucleotide polymorphisms (SNPs) of gemcitabine metabolism-related and target genes in breast cancer patients and evaluated their association with drug response or toxicity.

Patients and Methods.

SNPs in deoxycytidine kinase (dCK), deoxycytidine monophosphate deaminase (DCTD), and ribonucleotide reductase M1 polypeptide (RRM1) were analyzed with genomic DNA of 10 breast cancer cell lines, 74 peripheral blood mononuclear cell (PBMC) samples from advanced breast cancer patients treated with gemcitabine, and 56 PBMC samples from healthy volunteers.

Results.

The incidences of SNPs of breast cancer patients were 1.4% in dCK (626 A>G), 10.8% in DCTD (315 T>C), 40.5% in the first RRM1 (1082 C>A), 44.6% in the second RRM1 (2455 A>G), 44.6% in the third RRM1 (2464 G>A), and 23% in two RRM1 sites (2455 A>G and 2464 G>A) that were similar to those of the normal control group. We found a double SNP of RRM1 (2455 A>G and 2464 G>A) to be the novel haplotype that was associated with a lower frequency of chemotherapy-induced toxicity, such as neutropenia (p < .01) and G-CSF requirement (p < .005).

Conclusion.

RRM1 haplotype showed an association with susceptibility to gemcitabine monotherapy in breast cancer patients.
The $5 Man: The Underground Economic Response to a Large Cigarette Tax Increase in New York City
Authors: Shelley Donna , Cantrell M. Jennifer , Moon-Howard Joyce , Ramjohn Destiny Q. , VanDevanter Nancy
Published: June 2007

Objectives. We examined the mechanisms by which living in a disadvantaged minority community influences smoking and illegal cigarette sale and purchasing behaviors after a large cigarette tax increase.

Methods. Data were collected from 14 focus groups (n=104) that were conducted during the spring of 2003 among Blacks aged 18 years and older living in New York City.

Results. A large tax increase led to what focus group participants described as a pervasive illegal cigarette market in a low-income minority community. Perceived pro-smoking community norms, a stressful social and economic environment, and the availability of illegal cigarettes worked together to reinforce smoking and undermine cessation.

Conclusions. Although interest in quitting was high, bootleggers created an environment in which reduced-price cigarettes were easier to access than cessation services. This activity continues to undermine the public health goals of the tax increase.
Attempts to Undermine Tobacco Control
Authors: Sebrié Ernesto M. , Glantz Stanton A.
Published: June 2007

We sought to understand how the tobacco industry uses “youth smoking prevention” programs in Latin America. We analyzed tobacco industry documents, so-called “social reports,” media reports, and material provided by Latin American public health advocates.

Since the early 1990s, multinational tobacco companies have promoted “youth smoking prevention” programs as part of their “Corporate Social Responsibility” campaigns. The companies also partnered with third-party allies in Latin America, most notably nonprofit educational organizations and education and health ministries.

Even though there is no evidence that these programs reduce smoking among youths, they have met the industry’s goal of portraying the companies as concerned corporate citizens and undermining effective tobacco control interventions that are required by the World Health Organization Framework Convention on Tobacco Control.
Effect of Smoke-Free Laws on Bar Value and Profits
Authors: Alamar Benjamin , Glantz Stanton A.
Published: June 2007

The tobacco industry has claimed that smoke-free bar laws caused bar revenues to decline by 30%. After we controlled for economic variables, we found that bars located in areas with smoke-free laws sold for prices that were comparable to prices for similar bars in areas with no smoking restrictions. Other studies have reported that sales did not decline, and we also found that neither price nor sales declined. Therefore, bar owners’ concerns that smoke-free laws will reduce the value of their bars are unfounded.
The Rise and Fall of Tobacco Control Media Campaigns, 1967–2006
Authors: Ibrahim Jennifer K. , Glantz Stanton A.
Published: June 2007

Extensive research has demonstrated that public education through media campaigns is an effective means to reduce smoking prevalence and tobacco consumption. Aggressive media campaigns that confront the tobacco industry’s deceptive practices are most effective and are therefore a prime target for attack. The tobacco industry has attacked public tobacco control media campaigns since 1967, when the first public tobacco control media advertisements ran.

Through studying tobacco control media campaigns in Arizona, California, Florida, Massachusetts, Minnesota, and Oregon, and of the American Legacy Foundation, we identified industry strategies to prevent a campaign’s creation, limit the target audience and the content of the messages, limit or eliminate the campaign’s funding, and pursue litigation against the campaigns.

Tobacco control advocates must learn from the past and continue to confront the tobacco industry and its third-party allies to defend antitobacco media campaigns or, despite evidence of their effectiveness, they will be eliminated.
A Closer Look at Smoking Among Young Adults: Where Tobacco Control Should Focus Its Attention
Authors: Green Molly P. , McCausland Kristen L. , Xiao Haijun , Duke Jennifer C. , Vallone Donna M. , Healton Cheryl G.
Published: June 2007

Objectives. We sought to fill gaps in knowledge of smoking behaviors among college-educated and non–college-educated young adults.

Methods. We used data from the 2003 Tobacco Use Supplement of the Current Population Survey to analyze smoking behaviors among young adults aged 18–24 years and older young adults aged 25–34 years by college status (enrolled, or with a degree, but not enrolled) and other measures of socioeconomic position.

Results. Current smoking prevalence among US young adults aged 18–24 years who are not enrolled in college or who do not have a college degree was 30%. This was more than twice the current smoking prevalence among college-educated young adults (14%). Non–college-educated young adults were more likely than were college-educated young adults to start smoking at a younger age and were less likely to have made a quit attempt, although no differences were found in their intentions to quit. Higher rates of smoking in the non–college-educated population were also evident in the slightly older age group.

Conclusions. Non–college-educated young adults smoke at more than twice the rate of their college-educated counterparts. Targeted prevention and cessation efforts are needed for non–college-educated young adults to prevent excess morbidity and mortality in later years.
Differences in Donor Heart Acceptance by Race and Gender of Patients on the Transplant Waiting List
Authors: Breathett Khadijah , Knapp Shannon M. , Lewsey Sabra C. , Mohammed Selma F. , Mazimba Sula , Dunlay Shannon M. , Hicks Albert , Ilonze Onyedika J. , Morris Alanna A. , Tedford Ryan J. , Colvin Monica M. , Daly Richard C.
Published: March 2024

Importance

Barriers to heart transplant must be overcome prior to listing. It is unclear why Black men and women remain less likely to receive a heart transplant after listing than White men and women.

Objective

To evaluate whether race or gender of a heart transplant candidate (ie, patient on the transplant waiting list) is associated with the probability of a donor heart being accepted by the transplant center team with each offer.

Design, Setting, and Participants

This cohort study used the United Network for Organ Sharing datasets to identify organ acceptance with each offer for US non-Hispanic Black (hereafter, Black) and non-Hispanic White (hereafter, White) adults listed for heart transplant from October 18, 2018, through March 31, 2023.

Exposures

Black or White race and gender (men, women) of a heart transplant candidate.

Main Outcomes and Measures

The main outcome was heart offer acceptance by the transplant center team. The number of offers to acceptance was assessed using discrete time-to-event analyses, nonparametrically (stratified by race and gender) and parametrically. The hazard probability of offer acceptance for each offer was modeled using generalized linear mixed models adjusted for candidate-, donor-, and offer-level variables.

Results

Among 159 177 heart offers with 13 760 donors, there were 14 890 candidates listed for heart transplant; 30.9% were Black, 69.1% were White, 73.6% were men, and 26.4% were women. The cumulative incidence of offer acceptance was highest for White women followed by Black women, White men, and Black men (P < .001). Odds of acceptance were less for Black candidates than for White candidates for the first offer (odds ratio [OR], 0.76; 95% CI, 0.69-0.84) through the 16th offer. Odds of acceptance were higher for women than for men for the first offer (OR, 1.53; 95% CI, 1.39-1.68) through the sixth offer and were lower for the 10th through 31st offers.

Conclusions and Relevance

The cumulative incidence of heart offer acceptance by a transplant center team was consistently lower for Black candidates than for White candidates of the same gender and higher for women than for men. These disparities persisted after adjusting for candidate-, donor-, and offer-level variables, possibly suggesting racial and gender bias in the decision-making process. Further investigation of site-level decision-making may reveal strategies for equitable donor heart acceptance.
Understanding the Impacts of the Supreme Court Case FDA v Alliance for Hippocratic Medicine
Authors: Espey Eve , Hailstorks Tiffany , Hofler Lisa
Published: March 2024

This Viewpoint outlines the potential effects of the Supreme Court case regarding mifepristone restrictions: a decision for the FDA would allow current dispensing, while ruling against the FDA would severely curtail access to reproductive health options.
Eating Family Meals Together at Home
Authors: Brown Callie L. , Kay Melissa C. , Thompson Lindsay A.
Published: March 2024

This JAMA Pediatrics Patient Page describes the benefits of eating family meals together at home.
Transport Geography
Authors: Rodrigue Jean‐Paul
Published: March 2024

Transport geography is a subdiscipline of geography concerned with the mobility of freight, people, and information. It seeks to understand the spatial organization of mobility by considering its attributes and constraints as they relate to the origin, destination, extent, nature, and purpose of movements. The subject covers the main principles of transport geography, how relevant transportation is at different scales, and how transport geography has emerged to address contemporary mobility challenges.
Economic Geography
Authors: Barnes Trevor J. , Sheppard Eric
Published: March 2024

Anglophone economic geography has played a central role in the evolution of human geography. That includes economic geography's various philosophical and theoretical shifts as it moved from an imperialist commercial geography, through to regional economic geography, spatial science and location theory, Marxism, feminism, and poststructuralism. The discipline is now inordinately diverse, reflecting an enormous breadth of interests and approaches including the use of various quantitative and qualitative methodologies. Such diversity is a strength not a weakness given the disciplinary spirit of engaged pluralism. The field's unifying theme now is some form of geographical political economy – the idea that capitalism is an unstable, conflict‐ridden political economic system characterized by geographical uneven development, with its spatiotemporal evolution shaped by reciprocal relations between political–economic, cultural, and biophysical processes. Major current areas of research in anglophone economic geography include geographies of production and consumption, work and the body, high‐tech and the platform economy, governance and regulation, financialization, environment and economy, globalization and development, and diverse (more‐than‐capitalist) economies.
Gut‐Derived Exosomes Mediate the Microbiota Dysbiosis‐Induced Spermatogenesis Impairment by Targeting Meioc in Mice
Authors: Chen Tong , Zhang Boqi , He Guitian , Wang Nan , Cao Maosheng , Shen Caomeihui , Chen Xue , Chen Lu , Liu Kening , Luo Yuxin , huang Yiqiu , Yuan Chenfeng , Zhou Xu , Li Chunjin
Published: March 2024

Diseases like obesity and intestinal inflammation diseases are accompanied by dysbiosis of the gut microbiota (DSGM), which leads to various complications, including systemic metabolic disorders. DSGM reportedly impairs the fertility of male mice; however, the regulatory mechanism is unclear. Exosomes are molecular mediators of intercellular communication, but the regulation of spermatogenesis by non‐reproductive tissue‐originated exosomes remains unknown. The present study shows that DSGM altered the miRNA expression profile of mouse circulating exosomes and impaired spermatogenesis. Moreover, the single‐cell sequencing results indicate that circulating exosomes from mice with DSGM impaired spermatogenesis, while circulating exosomes from wild mice improved spermatogenesis by promoting meiosis. Further study demonstrates that DSGM leads to abnormal upregulation of miR‐211‐5p in gut‐derived circulating exosomes, which inhibited the expression of meiosis‐specific with coiled‐coil domain (Meioc) in the testes and impaired spermatogenesis by disturbing meiosis process. In summary, this study defines the important role of gut‐derived exosomes in connecting the “gut‐testis” axis.
Does fall manure injection cause differential growth and forage nutritive value in small grains?
Authors: Hilfiker Derek R. , Maguire Rory O. , Ferreira Gonzalo , Thomason Wade E. , Stewart Ryan D.
Published: March 2024

Producers utilizing fall manure injection have reported increased growth and greenness in small grains growing on the injection band compared to small grains growing between injection bands. To determine how producers utilizing fall manure injection in small grains should manage potential differential growth, 24 sites under fall manure injection were established. Soil samples were taken in‐band and between‐band 1 month after manure application and at silage harvest for soil NO3‐N. Small grain growth stage was assessed 1 month after planting and at silage harvest, while dry matter (DM) yield and forage nutritive value parameters were assessed at silage harvest. Soil NO3‐N was elevated in‐band compared to between‐band 1 month after manure application (p < 0.05); however, this did not persist until silage harvest. No differences in growth stage were observed 1 month after planting in 2021; however, growth stage means were consistently elevated in‐band in 2022, likely due to earlier planting dates in 2022 compared to 2021. Growth stage at harvest was the same in‐band and between‐band at each site. Small grain DM yield was only increased in‐band compared to between‐band in three of 24 sites. Two of the three sites planted with wheat (Triticum aestivum L.) showed significantly increased DM yield in‐band, suggesting DM yield response could be species dependent. No consistent differences in forage nutritive value parameters were observed. As no consistent differences in small grain DM yield and forage nutritive value were found at harvest, we recommend no changes to management practices for producers utilizing fall manure injection in small grains.
Detection of plagiarism among rhinology scientific journals
Authors: Benaim Ezer H. , Wase Saima , Zaidi Saif , Monk Aurelia , Klatt‐Cromwell Cristine , Thorp Brian D. , Ebert Charles S. , Kimple Adam J. , Senior Brent A.
Published: March 2024

Key points

Automated plagiarism‐checking software can be a valuable tool for detecting plagiarism in manuscripts.

Twenty‐five of 60 articles (42%) had at least one incidence of plagiarism, predominately text recycling.

A “similarity score” ranging from 22% to 35% could be a potential cut‐off value when screening submitted manuscripts.