bluuebunny/crossref_metadata_2025 huggingface dataset:
Unveiling the Unseen: Exploring the Lived Experiences of Family Caregivers of Young Adults with Chronic Mental Disorders: A Qualitative Phenomenological Study
Authors: Mathew Suja Chungathil , Mathias Thereza
Published: February 2024

Introduction: One of India’s most valuable resources is its young people, and this generation needs to be nurtured for the bright future of the nation. However, when the young generation is affected by chronic mental disorders, families find it difficult to take care of them and are burdened with the responsibility for several years. Aim: To explore the lived experiences of Family Caregivers (FCGs) of young adults with chronic mental disorders. Materials and Methods: This qualitative study was conducted at the selected mental inpatient and outpatient Department of a selected mental health facility in Urban Bangaluru, Karnataka, India from April 2021 to December 2021. The authors used a phenomenological qualitative study to explore the lived experiences of family caregivers of young adults with chronic mental disorders {mania, depression, Bipolar Affective Disorder (BPAD), schizophrenia} aged between 18-40 years. The Family Caregivers of young adults undergoing treatment were approached for written informed consent and recruited through purposive sampling. Data were collected using face-to-face, indepth, semi-structured interviews. Each interview lasted around 45 minutes to one hour, and data saturation was achieved with 15 samples. Interviews were conducted over a period of nine months. The audio-recorded interviews were transcribed, interpreted, and investigated using Colaizzi’s data analysis framework. Baseline variables were analysed using descriptive statistics. Results: In the present, the family caregivers’ ages ranged from 28 to 60 years, with the majority (67%) being females and employed. One of the family members was affected by a mental disorder. A rehabilitation facility was unavailable to the majority (67%) of them near their residence. Regarding the young adults with chronic mental disorders, the majority (74%) were unemployed and diagnosed with affective disorders. The maximum duration of illness was 20 years, with onset typically at the age of 17-21 years. From the analysis, six main themes and 36 subthemes emerged. The main themes were as follows: family caregivers experience difficulty in identifying the responsible person and support system, providing physical care, tackling emergencies, problems with medication and early identification of relapse, problems with indecent behaviour, and knowledge deficit related to mental disorders and their management. Conclusion: The study concludes that family caregivers of young adults with chronic mental disorders experience various psychosocial and economic issues and problems while caring for a young adult with chronic mental disorders. The knowledge generated from the present study can be utilised by mental health professionals to plan home-based care strategies to improve the quality of life and reduce the burden of care for FCGs.
Histopathological Spectrum of Central Nervous System Tumours in Adolescent and Young Adults: A Cross-sectional Study from Punjab, Northern India
Authors: Narang Vikram , Singh Gagandeep , Batta Gursheen Puri , Soni Ankita , Kaur Harpreet
Published: February 2024

Introduction: Central Nervous System (CNS) tumours are a common cause of cancer-related deaths in adolescents and young adults. The challenges in diagnosing and treating CNS tumours in this age group are unique and require special attention. Aim: To study the histopathological spectrum of CNS tumours in Adolescents and Young Adults (AYA). Materials and Methods: Present five-year cross-sectional study was conducted on CNS biopsies received in the Department of Pathology at Dayanand Medical College and Hospital, Ludhiana, Punjab, India, from July 1, 2016, to June 30, 2021, to analyse the histopathological spectrum of CNS tumours in the AYA group based on the site of the lesion, age, gender, and Isocitrate Dehydrogenase (IDH) status. Results: During the study period, a total of 215 cases of CNS tumours were identified, of which 52 (24.2%) belonged to the AYA group. Of these, 35 (67.3%) were males and 17 (32.7%) were females. The majority of the patients presented with complaints of headache (50/52, 96.1%), with the frontal lobe being the most common site of involvement (21/52, 40.4%). Diffuse astrocytic and oligodendroglial tumours were the most commonly observed (23/52, 44.2%). Conclusion: CNS tumours are one of the most common cancer diagnosis among the AYA group, and awareness should be enhanced among histopathologists and oncologists regarding these tumours based on the updated classification.
Asymptotic Theorems for Discrete Markov Chains
Authors: Halidias Nikolaos
Published: February 2024

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Edible Flowers: Super Foods with Potential Health Benefits
Authors: Sood Yachna , Lal Manmohan , Kalia Ayush , Verma Sakshi
Published: February 2024

Edible flowers have become popular in recent years as a unique and visually tempting addition to culinary creations. This review article explores the assorted world of edible flowers, focusing on their potential health benefits, bioactive compounds, and associated toxicological risks, with particular attention to the anti-nutritional compounds and toxic flowers. Edible flowers from different plant species provide a variety of bioactive compounds that contribute to their flavor, aroma, and potential health benefits. These bioactive compounds, including antioxidants, vitamins, minerals and phytochemicals, make edible flowers not only beautiful but also nutritious. Incorporating them into your diet can improve the overall nutritional content of your meals. However, consuming edible flowers is not without risks. Some flowers contain anti-nutrient compounds, such as oxalates and phytates, which can interfere with the absorption of essential minerals and lead to nutritional deficiencies over time. Therefore, it is important to practice moderation when consuming certain edible flowers, especially for those with pre-existing medical conditions or prone to mineral imbalances. However, it is essential to pay attention to anti-nutritional compounds that can affectmineral absorption and the potential toxicity of certain flowers. When used judiciously and safely, edible flowers can be a delicious and healthy addition to a balanced diet. Careful selection and proper preparation are essential to reap the benefits while minimizing the risks associated with these beautiful flowers. This review serves as a valuable resource for consumers, chefs and nutritionists, providing insight into the world of edible flowers and their bioactive compounds as well as considerations regarding anti-nutritional compounds and their toxicity.
Bio-Efficacy of New Herbicide Molecules for Weed Management in Grain Legumes
Authors: Kalyani, M. S. R.  , Ameena, M.  , Srinivas, Y.  , Shanavas Shifina , Susha, V. S.  , Sethulakshmi, V. S.
Published: February 2024

Grain legumes including pigeon pea, chickpea, peanut, soybean, lentil, cowpea, common bean, faba bean, pea, and horse gram are extensively cultivated globally. Higher protein content, coupled with symbiotic nitrogen-fixing bacteria in root nodules enabling nitrogen fixation, highlights their importance in minimizing fertilizer use for agricultural production systems. Legume cultivation is limited by prolonged weed interference which is managed either through mechanical, cultural, chemical, or biological methods separately or in combinations. Nevertheless, herbicides remain and will persist as a crucial and economical element in global crop cultivation. While first-generation herbicides benefit agriculture, their long-term persistence and off-target toxicity have significant negative consequences, causing harm to both the environment and humans. Moreover, weed resistance and similar chemistry enforce the demand for new modes of action. Therefore, continuous research into new herbicides is important for combating herbicide resistance and ensuring crop output. In recent years, a few herbicides with novel mechanisms of action have occurred. Plants treated with new-generation herbicides resulted in increased WCE (weed control efficiency), decreased weed dry matter, and seed yield. There were no or minimal phytotoxicity symptoms observed on the existing and succeeding crops. This review emphasizes the importance of newly formulated herbicides signifying high selectivity, low toxicity, target specificity, and minimal application rates, contributing to an enhanced understanding of human and environmental health. Furthermore, it emphasizes the significance of economic viability and environmental friendliness in these formulations.
Metallo-Beta-Lactamase Producing Isolates of Escherichia coli and Klebsiella pneumoniae and their Resistance Profiles in Enugu, Nigeria: A Threat to Public Health
Authors: Maduakor Uzoamaka Charity , Eleazar Clara Idara , Mba Chidi George , Obodochukwu Chiamaka Cynthia , Eberechukwu Chioma Lily , Ogu Cornelius Osinachi
Published: February 2024

Background: A potential threat to public health is the rapidly spreading enterobacteriaceae, especially Escherichia coli and Klebsiella pneumoniae which produce metallo-beta-lactamases (MBL). This study evaluated the prevalence of metallo-beta-lactamase (MBL) from clinical and non-clinical sources in Enugu Metropolis.

Methodology: The study was conducted in the Microbiology Laboratory of the University of Nigeria Teaching Hospital, Ituku-Ozalla between October 2020 and July 2021. A total of 150 isolates including 85 and 65 isolates of Escherichia coli and Klebsiella pneumoniae respectively was recovered. Standard microbiology procedures were used to identify and characterize the isolates. Antimicrobial susceptibility was done using the Kirby-Bauer disc diffusion technique. Phenotypic detection of Metallo-beta-lactamase production was determined using Combined Disk Tests.

Results: Imipenem resistance was detected in 22 (25.9%) isolates of E. coli and 18 (27.7%) isolates of K. pneumoniae. Of the 22 strains of E. coli that were imipenem resistant, 8 (9.4%) and 14 (16.5%) were found to be MBL producers and non-MBL respectively. Of the 18 strains of Klebsiella pneumoniae that were imipenem resistant, 10 (15.4%) were MBL producers and 8 (12.3%) were non-MBL producers. The highest prevalence of MBL was recovered from urine sources in both E. coli and K. pneumonieae. All MBL-producing isolates were multidrug resistant.

Conclusion: The overall prevalence of MBL in this study was 12.0%. Public health is at risk due to the occurrence of metallo-beta-lactamase. Antimicrobial stewardship and the implementation of infection control strategies are required to halt the spread of these resistant bacteria in the environment. The use of antibiotics should be with utmost prudence.
The Effect of Extreme Temperature and Air Pollutant on Cardiovascular Disease in Ondo-State Nigeria
Authors: Danlami Babalola Abayomi , Esther Babalola Toju , Bello Aliyu Abdulaziz
Published: February 2024

This study investigates the relationship between extreme temperatures, air pollutants, and cardiovascular disease in Ondo State, Nigeria. Geographic Information System (GIS) satellite mapping techniques were utilized to analyze the spatial distribution of environmental parameters including methane, carbon monoxide, nitrogen dioxide, sulfur dioxide, and temperature across Ondo State. Data was obtained for the years 2020, 2021, and 2022 to allow for temporal analysis. The parameters exhibited some variations across different local government areas, indicating potential differences in exposure. 2020 data on cardiovascular disease and death cases revealed distinct spatial patterns, with northern regions showing higher disease burden compared to southern areas. The findings highlight the need for targeted public health interventions based on region-specific environmental and health profiles. Enhanced monitoring, continued research on emerging factors, and translation of evidence into policies and community initiatives is recommended to mitigate environmental risks and promote cardiovascular health across Ondo State. Overall, the study demonstrates the utility of GIS mapping for investigating complex connections between environmental factors and health outcomes to guide informed prevention strategies.
Computational study of a single‐phase flow in packed beds of spheres
Authors: Gunjal Prashant R. , Ranade Vivek V. , Chaudhari Raghunath V.
Published: January 2005

Packed‐bed reactors are widely used in petrochemical, fine chemical, and pharmaceutical industries. Detailed knowledge of interstitial flow in the void space of such packed‐bed reactors is essential for understanding the heat and mass transfer characteristics. In this paper, fluid flow through the array of spheres was studied using the unit‐cell approach, in which different periodically repeating arrangements of particles such as simple cubical, 1‐D rhombohedral, 3‐D rhombohedral, and face‐centered cubical geometries were considered. Single‐phase flow through these geometries was simulated using computational fluid dynamics (CFD). The model was first validated by comparing predicted results with published experimental and computational results. The validated model was further used to study the effect of particle arrangement/orientation on velocity distribution and heat transfer characteristics. The simulated results were also used to understand and to quantify relative contributions of surface drag and form drag in overall resistance to the flow through packed‐bed reactors. The model and the results presented here would be useful in elucidating the role of microscopic flow structure on mixing and other transport processes occurring in packed‐bed reactors. © 2005 American Institute of Chemical Engineers AIChE J, 51: 365–378, 2005
Effect of internal and external resistances on the swelling of droplets
Authors: Phongikaroon Supathorn , Calabrese Richard V.
Published: January 2005

The diffusion equation is solved, subject to a quasi‐steady approximation, to determine the swelling rate of a spherical drop in an infinite medium. External convective mass transfer to the growing drop surface is accounted for as a boundary condition. Three cases are considered: the general case of finite Biot number (Bi), and the limiting cases of infinite Bi (negligible external convective resistance), and low Bi (negligible internal diffusion resistance). Analytical approximations and numerical solutions are developed and detailed results are presented. The dimensionless swelling rate is governed by a dimensionless mass driving force (), a dimensionless time (X), and the Biot number. The various models are compared over the range 0.001 < < 1.0; 10−5 < X < 500; and 0.01 < Bi < ∞ to determine when the more easily applied analytical approximations are valid, and to determine the critical Bi for which internal diffusion resistance or external convective resistance can be ignored. In these limits the simpler low Bi or infinite Bi models can be applied, respectively, in place of the finite Bi model. The results show that the analytical approximations are valid for ≤ 0.05. Furthermore, the infinite Bi numerical solution is accurate for Bi > 100, whereas the low Bi solution is valid for Bi < 1. © 2005 American Institute of Chemical Engineers AIChE J, 51: 379–391, 2005
Zur frühen Geschichte der Paläocheloniologie von Schaumburg‐Lippe. Die Rolle des Gymnasial‐Professors Max Ballerstedt in der Naturwissenschaft
Authors: Karl Hans‐Volker , Tichy Gottfried
Published: January 2005

A survey is given on some new aspects of the early history to the palaeochelonology in Schaumburg‐Lippe (Northern Germany). The very slow development of this is good reconstructable on base of authentic estates. It is the first time to made such a nearly complete reconstruction.
Das Förderprofil der Deutschen Forschungsgemeinschaft 1949 bis 1969
Authors: Orth Karin
Published: January 2005

The DFG, short for ‘Deutsche Forschungsgemeinschaft’ (German Research Foundation), was founded in 1920 and re‐founded after the 2. World War in 1949. This article concentrates on the activities of the DFG in the period between 1949 and the end of the sixties and on the two major programmes (the so‐called ‘Individual Grants Programme’ and the so‐called ‘Priority Programme’) because until now it has not been known, how many — and more importantly — which studies in which disciplines had been financed by the DFG.

All together almost 54.000 studies (36.500 in the ‘Individual Grants Programme’ and 17.400 in the ‘Priority Programmes’) were accomplished with the support of the DFG, whereas — in the ‘Individual Grants Programme’ — less than 3.000 proposals were declined (there are no figures for the ‘Priority Programmes’). Till the end of the seventies the whole amount of money allocated for the ‘Individual Grants Programme’ was not fixed for the different disciplines in advance. Consequently every proposal submitted in the ‘Individual Grants Programme’ had to compete against all others for the overall allocated funds. Who — in other words: which of the disciplines — won this competition? The analysis shows a clear result. With regard to both, the number of successful proposals and the money received, the winner was medical science (with 23 percent of all successful proposals in the ‘Individual Grants Programme’). Chemistry finished second with 15 percent and then biology a distant third (9 percent), followed by physics (8 percent) and agronomy (8 percent).

Coming to the ‘Priority Programmes’, which were instituted in the middle of the 1950s, it must first be stated that here the topic is fixed in advance. The broad issue of investigation is devised by the DFG itself or — to be more precise — by the Senate of the DFG. In contrast to the ‘Individual Grants Programme’ the ‘Priority Programme’ can therefore be seen as an important instrument of the politics of research support. This leads to the following question: Which programmes did the DFG establish between 1954 and 1969? In other words: Which research topics or fields were, in the view of the DFG, the most important ones? The database again shows a clear result. Almost 50 percent of the money distributed overall and more than 50 percent of all programmes were benefitted to natural science, another fifth part to engineering technology (which didn't play an important role in the ‘Individual Grants Programme’). Medical science which was the most successful discipline in the ‘Individual Grants Programme’ received 16 percent of the funds. With regard to — first — the number of successful proposals within a Programme, — second — to the money received and — third — to the duration there were three frontrunner programmes: nourishment research, research on water and hydraulic engineering, and aeronautical research. And the humanities? The DFG didn't grant much relief giving only 7 percent to these disciplines.
Human serum albumin complexes with chlorophyll and chlorophyllin
Authors: Ouameur A. Ahmed , Marty R. , Tajmir‐Riahi H.A.
Published: January 2005

Porphyrins and their metal derivatives are strong protein binders. Some of these compounds have been used for radiation sensitization therapy of cancer and are targeted to interact with cellular DNA and protein. The presence of several high‐affinity binding sites on human serum albumin (HSA) makes it possible target for many organic and inorganic molecules. Chlorophyll a and chlorophyllin (a food‐grade derivative of chlorophyll), the ubiquitous green plant pigment widely consumed by humans, are potent inhibitors of experimental carcinogenesis and interact with protein and DNA in many ways. This study was designed to examine the interaction of HSA with chlorophyll (Chl) and chlorophyllin (Chln) in aqueous solution at physiological conditions. Fourier transform infrared, UV‐visible, and CD spectroscopic methods were used to determine the pigment binding mode, the binding constant, and the effects of porphyrin complexation on protein secondary structure. Spectroscopic results showed that chlorophyll and chlorophyllin are located along the polypeptide chains with no specific interaction. Stronger protein association was observed for Chl than for Chln, with overall binding constants of KChl = 2.9 × 104M−1 and KChln = 7.0 × 103M−1. The protein conformation was altered (infrared data) with reduction of α‐helix from 55% (free HSA) to 41–40% and increase of β‐structure from 22% (free HSA) to 29–35% in the pigment–protein complexes. Using the CDSSTR program (CD data) also showed major reduction of α‐helix from 66% (free HSA) to 58 and 55% upon complexation with Chl and Chln, respectively. © 2005 Wiley Periodicals, Inc. Biopolymers, 2005
Interplay of charge distribution and conformation in peptides: Comparison of theory and experiment
Authors: Makowska Joanna , Bagińska Katarzyna , Kasprzykowski F. , Vila Jorge A. , Jagielska Anna , Liwo Adam , Chmurzyński Lech , Scheraga Harold A.
Published: January 2005

We assessed the correlation between charge distribution and conformation of flexible peptides by comparing the theoretically calculated potentiometric‐titration curves of two model peptides, Ac–Lys5–NHMe (a model of poly‐L‐lysine) and Ac–Lys–Ala11–Lys–Gly2–Tyr–NH2 (P1) in water and methanol, with the experimental curves. The calculation procedure consisted of three steps: (i) global conformational search of the peptide under study using the electrostatically driven Monte Carlo (EDMC) method with the empirical conformational energy program for peptides (ECEPP)/3 force field plus the surface‐hydration (SRFOPT) or the generalized Born surface area (GBSA) solvation model as well as a molecular dynamics method with the assisted model building and energy refinement (AMBER)99/GBSA force field; (ii) reevaluation of the energy in the pH range considered by using the modified Poisson–Boltzmann approach and taking into account all possible protonation microstates of each conformation, and (iii) calculation of the average degree of protonation of the peptide at a given pH value by Boltzmann averaging over conformations. For Ac–Lys5–NHMe, the computed titration curve agrees qualitatively with the experimental curve of poly‐L‐lysine in 95% methanol. The experimental titration curves of peptide P1 in water and methanol indicate a remarkable downshift of the first pKa value compared to the values for reference compounds (n‐butylamine and phenol, respectively), suggesting the presence of a hydrogen bond between the tyrosine hydroxyl oxygen and the Hϵ proton of a protonated lysine side chain. The theoretical titration curves agree well with the experimental curves, if conformations with such hydrogen bonds constitute a significant part of the ensemble; otherwise, the theory predicts too small a downward pH shift. © 2004 Wiley Periodicals, Inc. Biopolymers (Pept Sci), 2005
Electrophilic Attack on Sulfur–Sulfur Bonds: Coordination of Lithium Cations to Sulfur‐Rich Molecules Studied by Ab Initio MO Methods
Authors: Steudel Yana , Wong Ming Wah , Steudel Ralf
Published: January 2005

Complex formation between gaseous Li+ions and sulfur‐containing neutral ligands, such as H2S, Me2Sn(n= 1–5; Me = CH3) and various isomers of hexasulfur (S6), has been studied by ab initio MO calculations at the G3X(MP2) level of theory. Generally, the formation of LiSnheterocycles and clusters is preferred in these reactions. The binding energies of the cation in the 29 complexes investigated range from −88 kJ mol−1for [H2SLi]+to −189 kJ mol−1for the most stable isomer of [Me2S5Li]+which contains three‐coordinate Li+. Of the various S6ligands (chair, boat, prism, branched ring, and triplet chain structures), two isomeric complexes containing the S5S ligand have the highest binding energies (−163±1 kJ mol−1). However, the global minimum structure of [LiS6]+is ofC3vsymmetry with the six‐membered S6homocycle in the well‐known chair conformation and three LiS bonds with a length of 256 pm (binding energy: −134 kJ mol−1). Relatively unstable isomers of S6are stabilized by complex formation with Li+. The interaction between the cation and the S6ligands is mainly attributed to ion–dipole attraction with a little charge transfer, except in cations containing the six sulfur atoms in the form of separated neutral S2, S3, or S4units, as in [Li(S3)2]+and [Li(S2)(S4)]+. In the two most stable isomers of the [LiS6]+complexes, the number of SS bonds is at maximum and the coordination number of Li+is either 3 or 4. A topological analysis of all investigated complexes revealed that the LiS bonds of lengths below 280 pm are characterized by a maximum electron‐density path and closed‐shell interaction.
Controlled Switchable Surface
Authors: Liu Ying , Mu Li , Liu Baohong , Kong Jilie
Published: January 2005

The macroscopic properties of a surface can be intelligently controlled by alternating the states of the modified molecules, such as polymers, metallic oxide, or self‐assembled monolayers (SAMs). This article reviews various approaches to create a switchable surface and different types of external stimuli used to switch the surface properties. This area is of potential benefit for biomaterials, biosensors, information storage, microfluidic systems, adhesive materials, nanolithography, and so on.
The Gas Phase Acidity of Oligofluorobenzenes and Oligochlorobenzenes: About the Additivity or Non‐Additivity of Substituent Effects
Authors: Hyla‐Kryspin Isabella , Grimme Stefan , Büker Heinz H. , Nibbering Nico M. M. , Cottet Fabrice , Schlosser Manfred
Published: January 2005

The deprotonation energies of benzene, fluorobenzene, all di‐, tri‐, and tetrafluorobenzenes, pentafluorobenzene, chlorobenzene, all di‐, tri‐, and tetrachlorobenzenes, and pentachlorobenzene have been calculated at various levels of second‐order Møller–Plesset and density functional theory. Taking the previously determined experimental data as a benchmark, good agreement was achieved in the chloro series even with moderate computational effort, whereas more extended basis sets have to be used to obtain meaningful numbers in the fluoro series. Apparently, most extensive electron correlation is required to avoid artifacts caused by the proximity of nonbonding lone pairs at the carbanionic center and at the fluorine atoms. When two or more fluorine substituents were introduced in the same aromatic ring, their individual effects (as defined by position‐dependent acidity increments) proved to be perfectly additive in the entire series. In contrast, the acidifying effect of chloro substituents was found to level off when the number of such halogens increases. Additivity or non‐additivity of element effects cannot be ascertained after having merely compared the acidity of mono‐ and disubstituted substrates, but only after having moved to higher degrees of substitution.
Radical cystectomy in the elderly
Authors: Clark Peter E. , Stein John P. , Groshen Susan G. , Cai Jie , Miranda Gus , Lieskovsky Gary , Skinner Donald G.
Published: January 2005

BACKGROUND

The authors reported their experience with radical cystectomy for transitional cell carcinoma (TCC) of the bladder. They compared pathologic features and survival rates between older and younger patients.

METHODS

The authors retrospectively reviewed the records of 1054 patients who underwent radical cystectomy for bladder TCC between 1971 and 1997. Four age groups were compared: < 60 years old at the time of cystectomy (n= 310), 60–69 years old (n= 381), 70–79 years old (n= 313), and ≥ 80 years old (n= 50).

RESULTS

There were no significant differences in pathologic features among the groups regarding frequency of carcinoma in situ, high‐grade disease, p53 status, and lymph node positivity. However, in the age groups < 60, 60–69, 70–79, and ≥ 80, 45%, 49%, 51%, and 72% of patients, respectively, had extravesical TCC (P=0.004). Significant differences also were seen in the proportion of patients who received adjuvant chemotherapy (26%, 26%, 15%, and 6%, respectively;P< 0.001). The 5‐year overall survival rates for patients < 60, 60–69, 70–79, and ≥ 80 years old were 72%, 58%, 54%, and 33%, respectively (P< 0.001). The 5‐year disease recurrence‐free survival rates were 75%, 65%, 68%, and 45%, respectively (P= 0.003). The elderly had a lower probability of receiving adjuvant chemotherapy.

CONCLUSIONS

Elderly patients undergoing cystectomy for TCC had similar pathologic features (except for disease stage) as younger patients. In the current series, elderly patients undergoing cystectomy had a higher pathologic stage and were less likely to receive adjuvant chemotherapy. The elderly hade worse disease recurrence‐free survival rates. Further work is needed to identify the causes for this and to develop strategies to improve cancer control in elderly patients. Cancer 2005. © 2005 American Cancer Society.
Detection of JC virus DNA sequences and expression of viral T antigen and agnoprotein in esophageal carcinoma
Authors: Del Valle Luis , White Martyn K. , Enam Sahnila , Oviedo Sergio Piña , Bromer Matthew Q. , Thomas Rebecca M. , Parkman Henry P. , Khalili Kamel
Published: January 2005

BACKGROUND

The human polyomavirus JC virus (JCV) causes progressive multifocal leukoencephalopathy. Subclinical infection with JCV occurs in 85–90% of the population worldwide. The virus usually remains latent but can reactivate under immunosuppressive conditions, resulting in progressive multifocal leukoencephalopathy. JCV is oncogenic in experimental animals and is associated with human brain tumors. JCV is found in normal mucosa of the gastrointestinal tract, and some colon carcinomas express the oncogenic JCV T‐antigen protein. The objective of this study was to examine the presence of JCV DNA sequences and JCV protein expression in normal and malignant human esophageal tissues.

METHODS

The authors examined the presence of JCV DNA sequences and protein expression in normal and malignant human esophageal tissues. Seventy well characterized biopsy specimens from patients with a spectrum of esophageal disorders were studied by immunohistochemistry, and 18 specimens were analyzed further by polymerase chain reaction amplification.

RESULTS

JC viral DNA was isolated from 11 of 13 normal esophageal biopsy specimens (85%) and from 5 of 5 esophageal carcinomas (100%). Using immunohistochemistry, JCV T antigen was detected in 10 of 19 carcinomas (53%), agnoprotein was detected in 8 carcinomas (42%), p53 tumor suppressor was detected in 11 carcinomas (58%), and β‐catenin was detected in 4 carcinomas (21%). Zero of 51 normal, benign, and premalignant esophageal samples expressed viral proteins. Laser‐capture microdissection verified the presence and specificity of JCV DNA sequences. β‐Catenin and p53 were colocalized with JCV T‐antigen in the nuclei of neoplastic cells.

CONCLUSIONS

The results provide evidence for infection of gastrointestinal tract cells by JCV and suggest a potential role of JCV in the development of upper digestive tract carcinomas. Cancer 2005. © 2005 American Cancer Society.
Repeat needle biopsies combined with clinical observation are safe and accurate in the management of a solitary pulmonary nodule
Authors: Welker James A. , Alattar Mohammed , Gautam Sandeep
Published: January 2005

BACKGROUND

Sixty percent of removed solitary pulmonary nodules (SPNs) are benign. An approach that reduces the unnecessary excision of benign nodules is consistent with the oncologic objective of organ preservation.

METHODS

A prospective observational study was performed at a lung cancer referral center in which consecutive patients were evaluated who presented with SPNs measuring < 4 cm on computed tomography (CT) scans. Patients underwent transbronchial biopsy (TBB), percutaneous needle aspiration (PCNA), clinical observation, repeat CT scans, and repeat biopsies. Patients were observed clinically and underwent repeat biopsies in an effort to reduce unnecessary surgical intervention.

RESULTS

One hundred eighteen patients underwent 194 biopsy sessions, including 137 TBB sessions and 57 PCNA sessions. The mean follow‐up was 4 years. The shortest follow‐up of a benign lesion was 3 years. The incidence of malignancy was 61%. The positive predictive value, negative predictive value, sensitivity, specificity, and accuracy all were 100%. Five patients had a delayed change in diagnosis from benign to malignant. This delay in diagnosis neither resulted in a change in tumor stage nor had an impact on patient management or survival.

CONCLUSIONS

Repeat needle biopsies combined with clinical observation and repeat CT scans can classify an SPN as benign versus malignant with 100% accuracy (95% confidence interval, 96.1–100.0%). An SPN diagnostic approach that includes a TBB, then PCNA, clinical observation, repeat CT scans, and repeat biopsies for continued suspicion of malignancy appears to reduce the unnecessary surgical excision of benign nodules from the current rate of 60% to 5% of SPN resections without affecting the survival of patients who have malignant SPNs. Cancer 2005. © 2005 American Cancer Society.
Development of prognostic factors and survival in cutaneous melanoma over 25 years
Authors: Buettner Petra G. , Leiter Ulrike , Eigentler Thomas K. , Garbe Claus
Published: January 2005

BACKGROUND

Recent studies revealed that incidence rates of cutaneous melanoma (CM) were leveling off predominantly among younger people and patterns suggested birth‐cohort effects. The current study analyzed the development of prognostic factors and survival in incident CM over 25 years.

METHODS

All 45,483 patients with incident CM diagnosed between 1976 and 2000 recorded by the German Central Malignant Melanoma Registry were considered. Linear and logistic regression analyses were used to judge time trends. Trends of survival rates were tested with the multivariate Cox model.

RESULTS

Median tumor thickness decreased from 1.81 mm in 1976 to 0.53 mm in 2000 (P < 0.0001). The percentages of in situ and level II CM increased, respectively (P < 0.0001). The percentage of ulcerated CM decreased (P < 0.0001). The percentage of superficial spreading melanoma increased, whereas the percentage of nodular melanoma decreased (P < 0.0001). These time trends were all significant in the strata of gender, however, male patients presented in general with more advanced disease. Between 1976 and 2000, the average patient got older (P < 0.0001). The percentage of patients diagnosed with the primary tumor alone increased (P < 0.0001). Across the 25 years of observation, adjusted survival rates did not increase for females (P = 0.1561) but they increased for males (P < 0.0001).

CONCLUSIONS

The data demonstrated a strong trend towards prognostically more favorable CM most likely due to earlier diagnosis. Men and older people should be the focus of health promotion activities as they presented with more advanced disease. Cancer 2005. © 2005 American Cancer Society.
The MHC class II transactivator (CIITA) mRNA stability is critical for the HLA class II gene expression in myelomonocytic cells
Authors: De Lerma Barbaro Andrea , Procopio Francesco A. , Mortara Lorenzo , Tosi Giovanna , Accolla Roberto S.
Published: January 2005

The human promyelocytic U937 cells express detectable levels of MHC class II (MHC‐II) molecules. Treatment with 12‐o‐‐tetradecanoyl phorbol 13‐acetate (TPA), inducing macrophage‐like differentiation, produces a dramatic decrease of MHC‐II expression as result of down‐modulation of the activation of immune response gene 1 (AIR‐1)‐encoded MHC‐II transactivator (CIITA). This event is specific, as MHC class I remains unaffected. Similar results are observed with U937 cells expressing an exogenous full‐length CIITA. Molecular studies demonstrate that TPA treatment affects the stability of CIITA mRNA rather than CIITA transcription. Importantly, cis‐acting elements within the distal 650 bp of the 1035‐bp 3′ untranslated region (3′UTR, nucleotides 3509–4543) are associated to transcript instability. Transcription inhibitors actinomycin D and 5,6‐dichlororibofuranosyl benzimidazole, and the translation inhibitor cycloheximide significantly rescue the accumulation of CIITA mRNA in TPA‐treated cells. A similar effect is also observed after treatment with staurosporine and the PKC‐specific inhibitor GF109203X. The instability of CIITA mRNA produced by TPA in U937 cells is not seen in B cells. These results demonstrate the presence of an additional level of control of MHC‐II expression in the macrophage cell lineage depending upon the control of CIITA mRNA stability, most likely mediated by differentiation‐induced, 3′UTR‐interacting factors which require kinase activity for their destabilizing function.
Single nucleotide polymorphisms as a prerequisite for autoantigens
Authors: Stadler Michael B. , Arnold Diana , Frieden Sara , Luginbühl Sarah , Stadler Beda M.
Published: January 2005

It is still elusive why certain self proteins induce an autoimmune response. One immunological hypothesis is that only modified or altered self‐proteins may become a target. Thus, we asked whether such alterations may actually be genetic polymorphisms that can be revealed by analyzing sequence variability in the known human autoantigens. Indeed, we found autoantigens to contain significantly more single nucleotide polymorphisms (SNP) than other human genes do. Our finding may offer an explanation for autoimmune responses through allogeneic exposure. Besides other contributing factors in autoimmunity, SNP may represent an essential prerequisite for the primary induction of an autoimmune response.

See accompanying Commentary: http://dx.doi.org/10.1002/eji.200425888
Critical role of the liver CD8+ CD122+ T cells in the generalized Shwartzman reaction of mice
Authors: Sato Kengo , Kinoshita Manabu , Motegi Akira , Habu Yoshiko , Takayama Eiji , Nonoyama Shigeaki , Hiraide Hoshio , Seki Shuhji
Published: January 2005

We examined the role of mouse CD8+ CD122+ T cells, which increase in number with age, in the generalized Shwartzman reaction. This reaction was induced by IL‐12 priming and subsequent LPS challenge (after 24 h) in mice of various ages (4–50 weeks of age). Although most young mice (4 or 6 weeks of age) survived, mortality essentially increased with increasing age of the mice, and all mice of 20 weeks of age or older died within 48 h. Serum TNF‐α levels after LPS challenge also increased age dependently. The neutralization of either IL‐12‐induced IFN‐γ or LPS‐induced TNF‐α improved the survival of middle‐aged (25‐week‐old) mice. Both IFN‐γ production after IL‐12 priming and TNF‐α production from the liver mononuclear cells after LPS challenge were also prominent in the middle‐aged mice. CD8+CD122+ T cells cultured with IL‐12 produced a much larger amount of IFN‐γ than CD8+CD122– T cells. Although the depletion of NK/NK T cells did not decrease the IFN‐γ or TNF‐α production in the Shwartzman reaction of the middle‐aged mice, an additional depletion of CD8+CD122+ T cells did decrease such production and also improved mouse survival. Furthermore, young mice transferred with CD8+CD122+ T cells from aged B6 nude mice showed an enhanced Shwartzman reaction.
Isolation of potent human Fab fragments against a novel highly immunogenic region on human muscle acetylcholine receptor which protect the receptor from myasthenic autoantibodies
Authors: Fostieri Efrosini , Tzartos Socrates J. , Berrih‐Aknin Sonia , Beeson David , Mamalaki Avgi
Published: January 2005

In the autoimmune disease myasthenia gravis (MG), antibodies against the muscle nicotinic acetylcholine receptor (AChR) cause loss of functional AChR in the neuromuscular junction. To isolate AChR‐specific human antibody fragments (Fab), a phage‐display library was constructed from an MG patient's thymic B lymphocytes. The first Fab isolated had a low affinity for human AChR, but two sequential antibody chain shufflings using the MG donor heavy and light chain gene repertoires resulted in isolating two new Fab with an approximately 30‐fold higher binding ability. The selected Fab contained extensively mutated heavy and light chains and probably represent intraclonal variants of a common progenitor having diverged in vivo by somatic hypermutation. Interestingly, the isolated Fab bound to an extracellular highly immunogenic region located either on an α‐subunit site affected by the γ/ϵ‐subunits or on the interface between α‐ and γ/ϵ‐subunits. This region is not the previously described "main immunogenic region" (MIR), although it seems to be close to it, as one improved Fab and an anti‐MIR mAb competed for AChR binding with distinctly different subpopulations of MG sera. Furthermore, this Fab protected surface AChR in cell cultures against MG autoantibody‐induced antigenic modulation, suggesting a potential therapeutic use in MG, especially in combination with a human anti‐MIR Fab.
High epitope density in a single protein molecule significantly enhances antigenicity as well as immunogenicity: a novel strategy for modern vaccine development and a preliminary investigation about B cell discrimination of monomeric proteins
Authors: Liu Wanli , Chen Ying‐Hua
Published: January 2005

Although early studies have shown a close correlation between epitope density and epitope‐specific humoral immune responses, few attempts have been made to quantitatively compare the antigenic and immunogenic differences between protein molecules bearing low or high degrees of epitope density, nor have studies quantitatively investigated the mechanism of B cell discrimination of monomeric antigens. In this study, we prepared glutathione S‐transferase (GST) fusion proteins bearing various copies of the M2e epitope from the influenza virus M2 protein [GST‐(M2e)8, GST‐(M2e)4 and GST‐(M2e)1], which were used to detect and compare the real‐time kinetic binding with M2e‐specific mAb by surface plasma resonance. Our data show clearly that fusion proteins bearing higher M2e epitope density resulted in higher average avidity for M2e‐specific mAb. Furthermore, it was observed that fusion proteins bearing high M2e epitope density could induce polyclonal antibodies (pAb) with enhanced an average affinity constant (KA) for M2e epitope peptide compared to fusion proteins bearing low epitope density. The average KA of pAb induced by GST‐(M2e)8 (3.08 × 108 M–1 or 9.96 × 108 M–1) was up to two orders of magnitude greater than the average KA of pAb induced by GST‐(M2e)1 (2.00 × 106 M–1 or 3.43 × 106 M–1). Thus, the data presented here demonstrate that high epitope density in a single protein molecule significantly enhances antigenicity and immunogenicity. These findings enrich our knowledge of how epitope density might relate to the recognition, activation and antibody production processes of epitope‐specific immature B cells.
Do autoantigens define autoimmunity or vice versa?
Authors: Eisenberg Robert
Published: January 2005

The basic function of the adaptive immune system is to distinguish self from foreign. The failure of self tolerance can result in autoimmunity, which comes in many forms but still targets a limited selection of the total available autologous determinants. This selectivity must reflect the underlying mechanisms of the autoimmune reaction, as well as the particular features of the autoantigens that are targeted. Here I discuss the overall paradigm of autoimmunity, and what kinds of mechanisms might play a role. It is likely that multiple different pathways are critical in various diseases, and even in a single condition.

See accompanying article: http://dx.doi.org/10.1002/eji.200425481
Syntheses, Structures and Magnetic Properties of Layered Metal(II) Mandelates
Authors: Beghidja Adel , Hallynck Sylvain , Welter Richard , Rabu Pierre
Published: January 2005

A series of MnII, FeII, CoII, NiII and CuII layered mandelates has been synthesised in the form of crystalline powders by a hydrothermal route. The five compounds are isostructural with the copper analogue, also obtained in a single crystal form, except that the latter shows a strong Jahn−Teller distortion of the coordination spheres around the CuII centres. The complexes crystallise in the monoclinic centrosymmetric space group P21/a and their structures consist of layers of six‐coordinate metal(II) ions interconnected through carboxylato bridges in a diamond‐like network. The magnetic data indicate very small antiferromagnetic in‐plane couplings for 1, 2, 3 and 5, with J/kB = −0.122 K for 1. The NiII compound 4 exhibits ferromagnetic coupling within the layers (J/kB = +1.213 K) and ferromagnetic 3D ordering can be observed at TC = 2.7 K. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Polarized fluorescence correlation spectroscopy of DNA‐DAPI complexes
Authors: Barcellona Maria Luisa , Gammon Seth , Hazlett Theodore , Digman Michelle A. , Gratton Enrico
Published: January 2005

We discuss the use of fluorescence correlation spectroscopy for the measurement of relatively slow rotations of large macromolecules in solution or attached to other macromolecular structures. We present simulations and experimental results to illustrate the range of rotational correlation times and diffusion times that the technique can analyze. In particular, we examine various methods to analyze the polarization fluctuation data. We have found that by first constructing the polarization function and then calculating the autocorrelation function, we can obtain the rotational motion of the molecule with very little interference from the lateral diffusion of the macromolecule, as long as the rotational diffusion is significantly faster than the lateral diffusion. Surprisingly, for common fluorophores the autocorrelation of the polarization function is relatively unaffected by the photon statistics. In our instrument, two‐photon excitation is used to define a small volume of illumination where a few molecules are present at any instant of time. The measurements of long DNA molecules labeled with the fluorescent probe DAPI show local rotational motions of the polymers in addition to translation motions of the entire polymer. For smaller molecules such as EGFP, the viscosity of the solution must be increased to bring the relaxation due to rotational motion into the measurable range. Overall, our results show that polarized fluorescence correlation spectroscopy can be used to detect fast and slow rotational motion in the time scale from microsecond to second, a range that cannot be easily reached by conventional fluorescence anisotropy decay methods. Microsc. Res. Tech. 65:205–217, 2004. © 2005 Wiley‐Liss, Inc.