bluuebunny/crossref_metadata_2025 huggingface dataset:
Quality Specifications for the Determination of Copper, Zinc, and Selenium in Human Serum or Plasma: Evaluation of an Approach Based on Biological and Analytical Variation
Authors: Arnaud Josiane , Weber Jean-Philippe , Weykamp Cas W , Parsons Patrick J , Angerer Jurgen , Mairiaux Eric , Mazarrasa Olav , Valkonen Sinikka , Menditto Antonio , Patriarca Marina , Taylor Andrew
Published: August 2008

Background: Trace element external quality assessment schemes monitor laboratory performance and provide a stimulus for improvement in accuracy. However, monitoring of participant performance varies according to the scheme and can lead to conflicting conclusions.

Methods: Quality specifications based on biological intra- and interindividual variability were calculated and compared to those currently used by various trace element external quality assessment schemes for plasma or serum copper, zinc, and selenium concentrations. For this purpose, we evaluated results reported by participating laboratories in different schemes, at key concentrations, using z scores.

Results: Minimal quality specifications developed from the biological intra- and interindividual variability were, for Cu, ±0.84 μmol/L or 12% of the assigned target concentration, whichever is greater; for Zn, ±1.20 μmol/L or 15% of the assigned target concentration, whichever is greater; and for Se, ±0.072 μmol/L or 12% of the assigned target concentration, whichever is greater. Reported performance of the participating laboratories depended on analyte, concentration, and the selected quality specification. In addition, the most commonly used methods for the determination of Cu, Zn, and Se may give different results.

Conclusions: The proposed minimal quality specifications based on biological variation are generally slightly less stringent than those currently in use, although they do not drastically change the performance evaluation in the different schemes. These specifications are a first step in the harmonization of practices among the schemes and remain to be evaluated.
Intraplatform Reproducibility and Technical Precision of Gene Expression Profiling in 4 Laboratories Investigating 160 Leukemia Samples: The DACH Study
Authors: Kohlmann Alexander , Haschke-Becher Elisabeth , Wimmer Barbara , Huber-Wechselberger Ariana , Meyer-Monard Sandrine , Huxol Heike , Siegler Uwe , Rossier Michel , Matthes Thomas , Rebsamen Michela , Chiappe Alberto , Diemand Adeline , Rauhut Sonja , Johnson Andrea , Liu Wei-min , Williams P Mickey , Wieczorek Lothar , Haferlach Torsten
Published: August 2008

Background: Gene expression profiling has the potential to offer consistent, objective diagnostic test results once a standardized protocol has been established. We investigated the robustness, precision, and reproducibility of microarray technology.

Methods: One hundred sixty individual patient samples representing 11 subtypes of acute and chronic leukemias, myelodysplastic syndromes, and nonleukemia as a control group were centrally collected and diagnosed as part of the daily routine in the Munich Leukemia Laboratory. The custom AmpliChip Leukemia research microarray was used for technical analyses of quadruplicate mononuclear cell lysates in 4 different laboratories in Germany (D), Austria (A), and Switzerland (CH) (the DACH study).

Results: Total-RNA preparations were successfully performed in 637 (99.5%) of 640 cases. Mean differences between pairs of laboratories in the total-RNA yield from the same sample ranged from 0.02 μg to 1.03 μg. Further processing produced 622 successful in vitro transcription reactions (97.6%); the mean differences between laboratories in the cRNA yield from the same sample ranged from 0.40 μg to 6.18 μg. After hybridization to microarrays, a mean of 47.6%, 46.5%, 46.2%, and 46.4% of probe sets were detected as present for the 4 laboratories, with mean signal-intensity scaling factors of 3.1, 3.7, 4.0, and 4.2, respectively. In unsupervised hierarchical cluster and principal component analyses, replicates from the same patient always clustered closely together, with no indications of any association between gene expression profiles due to different operators or laboratories.

Conclusions: Microarray analysis can be performed with high interlaboratory reproducibility and with comparable quality and high technical precision across laboratories.
„Qualis artifex pereo” – Neros letzte Reise (“Qualis artifex pereo” – Nero's Last Journey)
Authors: Meier Mischa
Published: August 2008

Nero bleibt ein Rätsel. Der römische Kaiser (54–68 n. Chr.), der seine Mutter ermordete, der angeblich Rom in Brand gesteckt hat, der zum ersten Mal in größerem Stile Christen verfolgte, der als Wagenlenker, Dichter und Bühnenschauspieler öffentlich auftrat und sich schließlich einsam das Leben nehmen mußte, bereitet der Forschung noch immer erhebliche Probleme. In der vorliegenden Studie soll ein neuer Zugang zu diesem Princeps eröffnet werden: Ausgehend von seiner Griechenlandreise im Jahr 66/67 werden die Zeugnisse für das Wirken Neros mit den Rahmenbedingungen und Handlungsspielräumen eines Princeps der frühen römischen Kaiserzeit in Relation gesetzt. Dabei werden insbesondere die vielfach belächelten (allerdings durch archäologisches und numismatisches Material bestätigten) Hinweise in der antiken Historiographie auf Neros singuläres Selbstverständnis als Künstler konsequent ausgewertet und weitergedacht. Das Ergebnis zeigt einen Herrscher, der sich weniger als Princeps denn als Künstler definierte, der in dieser Rolle eine geradezu mythische Qualität erstrebt und die Umsetzung dieses Vorhabens letztlich nur deshalb nicht erreicht hat, weil er am Ende seiner Herrschaft nicht mehr imstande war, mit der zunehmenden Eigendynamik der Entwicklungen um ihn herum mitzuhalten.
Kleinstaaten in der Frühen Neuzeit: Konturen eines Forschungsfeldes (Small States in Early Modern Times: Contours of a Field of Research)
Authors: Schnettger Matthias
Published: August 2008

Der Beitrag regt zur Beschäftigung mit Kleinstaaten als einer Sonderform frühmoderner Staatlichkeit an, die bislang nicht im Fokus des wissenschaftlichen Interesses gestanden hat. Charakteristisch für frühneuzeitliche Kleinstaaten war neben einer geringen territorialen Ausdehnung und begrenzten Ressourcen eine reduzierte Souveränität: Die deutschen Reichsstände verfügten über die bloße Landeshoheit und waren Kaiser und Reich unterstellt, und auch die italienischen Kleinstaaten waren zumeist in das Reichs- oder das päpstliche Lehnssystem eingebunden. Ausgehend von diesen Grundüberlegungen fragt der Beitrag nach dem Verhältnis der Kleinen zu den Großen, nach Vernetzungen und Abgrenzungen der Kleinstaaten und beleuchtet die innenpolitische Perspektive. Damit erörtert er die Möglichkeit, unter Berücksichtigung der politik-, sozial- und kulturgeschichtlichen Dimension für einzelne Fallbeispiele zu einer Art „microhistoire totale” vorzustoßen, als ein neuer, intensivierter und europäisch vergleichender Zugang zur Geschichte frühmoderner Staatlichkeit.
Elevated free IGF2 levels in localized, early-stage breast cancer in women
Authors: Espelund Ulrick , Cold Søren , Frystyk Jan , Ørskov Hans , Flyvbjerg Allan
Published: August 2008

Objective

Epidemiological studies imply an association between circulating IGF1 and breast cancer, whereas the role of IGF2, which also acts on the IGF1 receptor, is less settled. This study investigates the association between IGF2 and breast cancer in patients with localized disease.

Design

The participants were women with well-characterized, early stage, localized breast cancer (n=43) and matched healthy women (n=38), from whom fasting serum levels of IGF-related peptides were measured.

Results

In patients, mean free IGF2 was increased (+57%, P<0.001), in spite of reduced total IGF2 levels (−12%, P=0.003) when compared with controls. Similar changes were seen in free IGF1 (+28%, P=0.004) and total IGF1 (−16% P=NS). Pro-IGF2 and IGF-binding protein 1 (IGFBP1) were unchanged. IGFBP2 was reduced by 22% in the patients (P=0.004). The patients showed reduced IGFBP3 protease activity and accordingly increased levels of intact IGFBP3, whereas total IGFBP3 was unchanged.

Conclusion

Women with localized, early-stage breast cancer show elevated circulating free IGF1 and IGF2, reduced total IGF2 and alterations in IGFBPs. The changes observed despite minimal cancer disease suggest a role for the circulating IGF system in the progression of breast cancer in women.
Sleep and the epidemic of obesity in children and adults
Authors: Van Cauter Eve , Knutson Kristen L
Published: August 2008

Sleep is an important modulator of neuroendocrine function and glucose metabolism in children as well as in adults. In recent years, sleep curtailment has become a hallmark of modern society with both children and adults having shorter bedtimes than a few decades ago. This trend for shorter sleep duration has developed over the same time period as the dramatic increase in the prevalence of obesity. There is rapidly accumulating evidence from both laboratory and epidemiological studies to indicate that chronic partial sleep loss may increase the risk of obesity and weight gain. The present article reviews laboratory evidence indicating that sleep curtailment in young adults results in a constellation of metabolic and endocrine alterations, including decreased glucose tolerance, decreased insulin sensitivity, elevated sympathovagal balance, increased evening concentrations of cortisol, increased levels of ghrelin, decreased levels of leptin, and increased hunger and appetite. We also review cross-sectional epidemiological studies associating short sleep with increased body mass index and prospective epidemiological studies that have shown an increased risk of weight gain and obesity in children and young adults who are short sleepers. Altogether, the evidence points to a possible role of decreased sleep duration in the current epidemic of obesity.
Hitchhiking Both Ways: Effect of Two Interfering Selective Sweeps on Linked Neutral Variation
Authors: Chevin Luis-Miguel , Billiard Sylvain , Hospital Frédéric
Published: August 2008

The neutral polymorphism pattern in the vicinity of a selective sweep can be altered by both stochastic and deterministic factors. Here, we focus on the impact of another selective sweep in the region of influence of a first one. We study the signature left on neutral polymorphism by positive selection at two closely linked loci, when both beneficial mutations reach fixation. We show that, depending on the timing of selective sweeps and on their selection coefficients, the two hitchhiking effects can interfere with each other, leading to less reduction in heterozygosity than a single selective sweep of the same magnitude and more importantly to an excess of intermediate-frequency variants relative to neutrality under some parameter values. This pattern can be sustained and potentially alter the detection of positive selection, including by provoking spurious detection of balancing selection. In situations where positive selection is suspected a priori at several closely linked loci, the polymorphism pattern in the region may also be informative about their selective histories.
The Complementary Neighborhood Patterns and Methylation-to-Mutation Likelihood Structures of 15,110 Single-Nucleotide Polymorphisms in the Bovine Genome
Authors: Jiang Zhihua , Wu Xiao-Lin , Zhang Ming , Michal Jennifer J , Wright Raymond W
Published: August 2008

Bayesian analysis was performed to examine the single-nucleotide polymorphism (SNPs) neighborhood patterns in cattle using 15,110 SNPs, each with a flanking sequence of 500 bp. Our analysis confirmed three well-known features reported in plants and/or other animals: (1) the transition is the most abundant type of SNPs, accounting for 69.8% in cattle; (2) the transversion occurs most frequently (38.56%) in cattle when the A + T content equals two at their immediate adjacent sites; and (3) C ↔ T and A ↔ G transitions have reverse complementary neighborhood patterns and so do A ↔ C and G ↔ T transversions. Our study also revealed several novel SNP neighborhood patterns that have not been reported previously. First, cattle and humans share an overall SNP pattern, indicating a common mutation system in mammals. Second, unlike C ↔ T/A ↔ G and A ↔ C/G ↔ T, the true neighborhood patterns for A ↔ T and C ↔ G might remain mysterious because the sense and antisense sequences flanking these mutations are not actually recognizable. Third, among the reclassified four types of SNPs, the neighborhood ratio between A + T and G + C was quite different. The ratio was lowest for C ↔ G, but increased for C ↔ T/A ↔ G, further for A ↔ C/G ↔ T, and the most for A ↔ T. Fourth, when two immediate adjacent sites provide structures for CpG, it significantly increased transitions compared to the structures without the CpG. Finally, unequal occurrence between A ↔ G and C ↔ T in five paired neighboring structures indicates that the methylation-induced deamination reactions were responsible for ∼20% of total transitions. In addition, conversion can occur at both CpG sites and non-CpG sites. Our study provides new insights into understanding molecular mechanisms of mutations and genome evolution.
Sister Chromatid Cohesion Role for CDC28-CDK in Saccharomyces cerevisiae
Authors: Brands Alex , Skibbens Robert V
Published: August 2008

High-fidelity chromosome segregation requires that the sister chromatids produced during S phase also become paired during S phase. Ctf7p (Eco1p) is required to establish sister chromatid pairing specifically during DNA replication. However, Ctf7p also becomes active during G2/M in response to DNA damage. Ctf7p is a phosphoprotein and an in vitro target of Cdc28p cyclin-dependent kinase (CDK), suggesting one possible mechanism for regulating the essential function of Ctf7p. Here, we report a novel synthetic lethal interaction between ctf7 and cdc28. However, neither elevated CDC28 levels nor CDC28 Cak1p-bypass alleles rescue ctf7 cell phenotypes. Moreover, cells expressing Ctf7p mutated at all full- and partial-consensus CDK-phosphorylation sites exhibit robust cell growth. These and other results reveal that Ctf7p regulation is more complicated than previously envisioned and suggest that CDK acts in sister chromatid cohesion parallel to Ctf7p reactions.
Spermatogonial Stem Cell Self-Renewal Requires OCT4, a Factor Downregulated During Retinoic Acid-Induced Differentiation
Authors: Dann Christina Tenenhaus , Alvarado Alma L. , Molyneux Laura A. , Denard Bray S. , Garbers David L. , Porteus Matthew H.
Published: August 2008

The long-term production of billions of spermatozoa relies on the regulated proliferation and differentiation of spermatogonial stem cells (SSCs). To date only a few factors are known to function in SSCs to provide this regulation. Octamer-4 (OCT4) plays a critical role in pluripotency and cell survival of embryonic stem cells and primordial germ cells; however, it is not known whether it plays a similar function in SSCs. Here, we show that OCT4 is required for SSC maintenance in culture and for colonization activity following cell transplantation, using lentiviral-mediated short hairpin RNA expression to knock down OCT4 in an in vitro model for SSCs (“germline stem” [GS] cells). Expression of promyelocytic leukemia zinc-finger (PLZF), a factor known to be required for SSC self-renewal, was not affected by OCT4 knockdown, suggesting that OCT4 does not function upstream of PLZF. In addition to developing a method to test specific gene function in GS cells, we demonstrate that retinoic acid (RA) triggers GS cells to shift to a differentiated, premeiotic state lacking OCT4 and PLZF expression and colonization activity. Our data support a model in which OCT4 and PLZF maintain SSCs in an undifferentiated state and RA triggers spermatogonial differentiation through the direct or indirect downregulation of OCT4 and PLZF. The current study has important implications for the future use of GS cells as an in vitro model for spermatogonial stem cell biology or as a source of embryonic stem-like cells.

Disclosure of potential conflicts of interest is found at the end of this article.
Estrogen treatment up-regulates female genes but does not suppress all early testicular markers during rainbow trout male-to-female gonadal transdifferentiation
Authors: Vizziano-Cantonnet Denise , Baron Daniel , Mahè Sophie , Cauty Chantal , Fostier Alexis , Guiguen Yann
Published: August 2008

In non-mammalian vertebrates, estrogens are key players in ovarian differentiation, but the mechanisms by which they act remain poorly understood. The present study on rainbow trout was designed to investigate whether estrogens trigger the female pathway by activating a group of early female genes (i.e. cyp19a1, foxl2a, foxl2b, fst, bmp4, and fshb) and by repressing early testicular markers (i.e. dmrt1, nr0b1, sox9a1 and sox9a2). Feminization was induced in genetically all-male populations using 17α-ethynylestradiol (EE2, 20 mg/kg of food during 2 months). The expression profiles of 100 candidate genes were obtained by real-time RT-PCR and 45 expression profiles displayed a significant differential expression between control populations (males and females) and EE2-treated populations. These expression profiles were grouped in five temporally correlated expression clusters. The estrogen treatment induced most of the early ovarian differentiation genes (foxl2a, foxl2b, fst, bmp4, and fshb) and in particular foxl2a, which was strongly and quickly up-regulated. Simultaneously, Leydig cell genes, involved in androgen synthesis, as well as some Sertoli cell markers (amh, sox9a2) were strongly repressed. However, in contrast to our initial hypothesis, some genes considered as essential for mammalian and fish testis differentiation were not suppressed during the early process of estrogen-induced feminization (dmrt1, nr0b1, sox9a1 and pax2a) and some were even strongly up-regulated (nr0b1, sox9a1and pax2a). In conclusion, estrogens trigger male-to-female transdifferentiation by up-regulating most ovarian specific genes and this up-regulation appears to be crucial for an effective feminization, but estrogens do not concomitantly down-regulate all the testicular differentiation markers.
Identification of the invariant chain (CD74) as an angiotensin AGTR1-interacting protein
Authors: Szaszák Márta , Chen Hung-Dar , Chen Hao-Chia , Baukal Albert , Hunyady László , Catt Kevin J
Published: August 2008

Little is known about the protein–protein interactions that regulate the trafficking of the angiotensin II type I receptor (AGTR1) through the biosynthetic pathway. The membrane-proximal region of the cytoplasmic tail of the AGTR1 has been identified by site-directed mutagenesis studies as an essential site for normal AGTR1 folding and surface expression. Based on yeast two-hybrid screening of a human kidney cDNA library with the AGTR1 carboxyl-terminal tail as a bait, we identified the invariant chain (CD74) as a novel interacting protein. This association was confirmed by co-immunoprecipitation and co-localization studies. The binding site for CD74 on the AGTR1 carboxyl-terminal tail was localized to a site previously identified as important for the exit of the AGTR1 from the endoplasmic reticulum (ER), and conserved in many G protein-coupled receptors. Transient co-expression of CD74 with the AGTR1 in CHO-K1 cells consistently reduced the AGTR1 density at the cell surface. Furthermore, the interaction of CD74 with the carboxyl-terminal tail of the AGTR1 caused its retention in the ER and promoted its proteasomal degradation. These observations indicate that CD74 and the AGTR1 become associated in the early biosynthetic pathway, and that CD74 is a negative regulator of AGTR1 expression.
The Importance of Diversity to Public Health
Authors: Satcher David
Published: August 2008

This commentary first appeared in Public Health Reports 123:263, 2008.
Prevention and Preparedness: Working Together to Improve Public Health
Authors: Moritsugu Kenneth
Published: August 2008

This commentary first appeared in Public Health Reports 123:262, 2008.
A Flexible Approach to Training Veterinarians in Public Health: An Overview and Early Assessment of the DVM/MPH Dual-Degree Program at the University of Minnesota
Authors: Minicucci Larissa A. , Hanson Kate A. , Olson Debra K. , Hueston William D.
Published: August 2008

As a result of the growing need for public-health veterinarians, novel educational programs are essential to train future public-health professionals. The University of Minnesota School of Public Health, in collaboration with the College of Veterinary Medicine, initiated a dual DVM/MPH program in 2002. This program provides flexibility by combining distance learning and on-campus courses offered through a summer public-health institute. MPH requirements are completed through core courses, elective courses in a focus area, and an MPH project and field experience. Currently, more than 100 students representing 13 veterinary schools are enrolled in the program. The majority of initial program graduates have pursued public-practice careers upon completion of the program. Strengths of the Minnesota program design include accessibility and an environment to support multidisciplinary training. Continued assessment of program graduates will allow for evaluation and adjustment of the program in the coming years.
The Combined Master of Public Health Program at Tufts University
Authors: Lindenmayer Joann M. , Schlaff Anthony L.
Published: August 2008

The Combined Master of Public Health program at Tufts University unites medical and veterinary medical students in a four-year curriculum that integrates students’ clinical studies with simultaneous studies on population health. Thirty years ago, Tufts University adopted a “One Medicine” approach to teaching health professionals. That perspective has been updated as “One Health” and is now being applied in a university environment that emphasizes interdisciplinary education, a global outlook, and civic engagement.
One Medicine, One University: The DVM/MPH Program at the University of Illinois
Authors: Herrmann John A. , Hershow Ronald C.
Published: August 2008

The University of Illinois at Urbana-Champaign College of Veterinary Medicine (UIUC-CVM) and the University of Illinois-Chicago School of Public Health (UIC-SPH) are in the fourth year of a collaborative Doctor of Veterinary Medicine and Master of Public Health dual-degree program. The two campuses, one urban and one rural, are 150 miles apart but are sister schools within the University of Illinois system. This article describes the origin of the program, how the program functions across two campuses, its academic focus, required coursework, and research projects designed to fulfill the program's capstone requirements. The article shows how two campuses can be linked through a combination of online and on-site didactic coursework, briefly describes innovative proposals for projects within the United States and abroad, and highlights faculty committed to educating cross-trained public-health professionals while addressing the national need for veterinarians trained in public health. The authors also discuss how the dual-degree program has led to the formation of the Illinois Center for One Medicine, One Health (ICOMOH), an intra-university collaboration focusing on the interface of human, animal, and ecosystem health.
Public Health Education at Michigan State University
Authors: Funk Julie A. , Bartlett Paul C.
Published: August 2008

Many reports have highlighted the need for the veterinary profession to fill critical shortages of veterinarians in public health and food safety. Michigan State University's College of Veterinary Medicine offers educational programs within the professional veterinary curriculum, as well as graduate degree programs, to meet these societal needs. Within the scope of the professional veterinary curriculum, educational opportunities in public health include clerkships in veterinary public health and an innovative Web-based curriculum on judicious use of antimicrobials. For graduate degree programs, Michigan State University has a memorandum of understanding with the University of Minnesota for the Master of Public Health degree and an innovative Online Professional Master of Science in Food Safety degree program. A new option available is the opportunity for veterinary students to pursue the Master of Science in Food Safety concurrently with the DVM (DVM/MS in Food Safety). These educational programs will prepare graduates to meet societal needs in public health and food safety.
Reviewing the Undergraduate Veterinary Curriculum in Finland for Control Tasks in Veterinary Public Health
Authors: Maijala Riitta , Korkeala Hannu
Published: August 2008

To review and develop the undergraduate veterinary curriculum on official control in veterinary public health, an electronic survey was sent to 204 Finnish veterinarians employed in the field of food hygiene in 2005. The response rate was 44%. Most frequently cited as strengths of the current curriculum were extensive education and good knowledge. Respondents considered the main challenges in their work to be a wide field of activity, organizational changes, financial resources, organization of substitutes, and collaboration with decision makers. Of the 23 items to be included in the undergraduate curriculum, therefore, respondents prioritized state and local decision making, the role of the public servant, and leadership and management in the area of social factors; in the field of practical control work, in-house control systems, organizations and responsibilities, control techniques, and planning and targeting of controls were prioritized. Of areas traditionally covered in the undergraduate curriculum, legislation; legal proceedings and implications of controls; risks to human, animal, and plant health; and hazards in feed, animal, and food production were stated to be the most important. Although respondents were generally content with their career choice, veterinary public health tasks were not their first choice of career path immediately after graduation. Based on these findings, more attention should be focused on social aspects and practical training in official control in the undergraduate veterinary curriculum. The survey results also highlight the contrasts between society's needs and veterinarians’ motivations and career-path expectations, which pose a significant challenge for future curricula.
Teaching Nutrition to the Left and Right Brain: An Overview of Learning Styles
Authors: Churchill Julie A.
Published: August 2008

Functioning effectively as a veterinarian requires proficiency in multiple learning styles. Whether the goal is to design a nutrition course, plan a veterinary curriculum, or help students develop interpersonal, communication, and leadership skills, students benefit when content, design, and delivery are balanced to meet their learning-style preferences. An overview of four different learning style models is presented: the Myers-Briggs Type Indicator (MBTI), Kolb's Learning Style Model, the Felder-Silverman Learning Style Model, and the Herrmann Brain Dominance Instrument (HBDI). A whole-brain approach (HBDI) was used in the development and implementation of the small-animal clinical nutrition course at the University of Minnesota College of Veterinary Medicine. One educational objective of this course is to help students develop mental dexterity, increasing their proficiency in both their preferred and their less preferred modes of learning. The instructional goals are to deliver the content of the small-animal clinical nutrition course through exercises that meet the needs of learners in each thinking quadrant (left and right, cerebral and limbic) at least part of the time. Examples of exercises are presented to portray a balanced or whole-brain approach to teaching clinical nutrition.
Resident and Graduate Training in Veterinary Nutrition
Authors: Fascetti Andrea J.
Published: August 2008

Training programs for veterinarians seeking board certification by the American College of Veterinary Nutrition (ACVN) are structured in one of two ways: (1) as programs similar to specialty training in other clinical disciplines or (2) as graduate programs leading to advanced degrees combined with clinical training. Residency training occurs through a variety of approaches, including didactic coursework, case-based and applied learning, clinical training, teaching, research, and self-study. Challenges to successful residency and graduate training include low numbers of diplomates, particularly at veterinary schools; low numbers of applicants; small numbers of funded programs; and faculty promotion systems that do not reward residency or graduate training and program development. The mentoring of individuals seeking both board certification and a graduate degree presents additional considerations, including recruitment of individuals motivated in research and structuring a combined program that facilitates completion of both tasks in a timely fashion.
Medicare Transitional Care Management Program and Changes in Timely Postdischarge Follow-Up
Authors: Anderson Timothy S. , Herzig Shoshana J. , Marcantonio Edward R. , Yeh Robert W. , Souza Jeffrey , Landon Bruce E.
Published: April 2024

Importance

In 2013, Medicare implemented payments for transitional care management (TCM) services, which provide increased reimbursement to clinicians providing ambulatory care to patients after discharge from medical facilities to the community.

Objective

To determine whether the introduction of TCM payments was associated with an increase in timely postdischarge follow-up.

Design, Setting, and Participants

This cross-sectional interrupted time-series study assessed quarterly postdischarge visit rates before (2010-2012) and after (2013-2019) TCM implementation 100% sample of Medicare fee-for-service beneficiaries discharged to the community after a hospital or skilled nursing facility stay. Data analyses were performed February 1 to December 15, 2023.

Exposure

Implementation of payments for TCM.

Main Outcomes and Measures

Timely postdischarge primary care follow-up, defined as receipt of a primary care ambulatory visit within 14 days of discharge. Secondary outcomes included receipt of a TCM visit and specialty care follow-up.

Results

The study sample comprised 79 125 965 eligible discharges. Of these, 55.4% were female; 1.5% were Asian, 12.1% Black, 5.6% Hispanic, and 79.0% were White individuals; and 79.6% were beneficiaries aged 65 years and older. Timely primary care follow-up increased from 31.5% in 2010 to 38.8% in 2019 (absolute increase 7.3%), whereas specialist follow-up increased from 27.6% to 30.8% (absolute increase 3.2%). By 2019, 11.3% of eligible patients received TCM services. Interrupted time-series analyses demonstrated an increased slope of timely primary care follow-up after the introduction of TCM services (pre-TCM slope, 0.12% per quarter vs post-TCM slope, 0.29% per quarter; difference, 0.13%; 95% CI, 0.02% to 0.22%). Receipt of timely follow-up increased for all demographic groups; however, Black, Hispanic, and Medicaid dual-eligible patients and patients residing in urban areas and counties with high-level social deprivation were less likely to receive follow-up during the study period. These disparities widened for Black patients (difference-in-differences in pre-TCM vs post-TCM slope, −0.14%; 95% CI, −0.25% to −0.2%) and patients who were Medicaid dual-eligible (difference-in-differences pre-TCM vs post-TCM slope, −0.21%; 95% CI, −0.35% to −0.07%).

Conclusions

These findings indicate that Medicare’s introduction of payments for TCM services was associated with a persistent increase in the rate of timely postdischarge primary care but did not narrow demographic or socioeconomic disparities. Most beneficiaries did not receive timely primary care follow-up.
Depression Onset After a Spouse’s Cardiovascular Event
Authors: Komura Toshiaki , Tsugawa Yusuke , Kondo Naoki , Inoue Kosuke
Published: April 2024

Importance

Although cardiovascular disease (CVD) is a known risk factor for depression, evidence is lacking regarding whether and to what extent a spouse’s CVD is associated with the subsequent mental health of individuals.

Objective

To examine the association between CVD onset in spouses and subsequent depression.

Design, Setting, and Participants

This cohort study examined 277 142 matched married couples enrolled in the Japan Health Insurance Association health insurance program between April 2015 and March 2022, covering approximately 40% of the working-age population in Japan. Index individuals (primary insured) whose spouses (dependent) experienced incident CVD between April 2016 and March 2022 were 1:1 matched to controls whose spouses did not experience CVD. Matching was based on age, sex, income, or the onset date of the spouses’ CVD. Data analysis was conducted from April 2016 to March 2022.

Exposure

Spousal onset of CVD between fiscal years 2016 and 2021. The International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes were used to identify the composite CVD outcomes (stroke, heart failure, and myocardial infarction).

Main Outcomes and Measures

Multivariate Cox proportional hazards models were used to investigate the association between spouses’ new-onset CVD and individuals’ depression, adjusting for sociodemographic characteristics and comorbidities of index individuals (diabetes, hypertension, and CVD) and spouses (diabetes, hypertension, and depression). Subgroup analyses were conducted according to sex, age, income levels, and history of CVD.

Results

Among 277 142 matched pairs of married couples, 263 610 (95.1%) had a male index individual; the mean (SD) age of index individuals was 58.2 (10.2) years. A new onset of depression was observed in 4876 individuals (1.8%). In multivariable Cox models, there was an association between the spouse’s CVD and the individuals’ depression (hazard ratio, 1.13 [95% CI, 1.07-1.20]). The subgroup analysis found no evidence of heterogeneity in sex, age, income level, or CVD history. The results were consistent when additionally adjusted for health behaviors (smoking, alcohol consumption, physical activity, and use of antihypertensive drugs) and objectively measured physical health conditions (body mass index, blood pressure, cholesterol levels, glucose levels, and estimated glomerular filtration rate) (hazard ratio, 1.16 [95% CI, 1.06-1.28]).

Conclusions and Relevance

In this nationwide cohort study of matched couples, a spouse’s onset of CVD was associated with an increased risk of an individual’s depression. These findings highlight the importance of preventive care for mental health disorders in individuals whose spouses experience incident CVD.
The lipid droplet lipidome
Authors: Wölk Michele , Fedorova Maria
Published: April 2024

Lipid droplets (LDs) are intracellular organelles with a hydrophobic core formed by neutral lipids surrounded by a phospholipid monolayer harboring a variety of regulatory and enzymatically active proteins. Over the last few decades, our understanding of LD biology has evolved significantly. Nowadays, LDs are appreciated not just as passive energy storage units, but rather as active players in the regulation of lipid metabolism and quality control machineries. To fulfill their functions in controlling cellular metabolic states, LDs need to be highly dynamic and responsive organelles. A large body of evidence supports a dynamic nature of the LD proteome and its contact sites with other organelles. However, much less is known about the lipidome of LDs. Numerous examples clearly indicate the intrinsic link between LD lipids and proteins, calling for a deeper characterization of the LD lipidome in various physiological and pathological settings. Here, we reviewed the current state of knowledge in the field of the LD lipidome, providing a brief overview of the lipid classes and their molecular species present within the neutral core and phospholipid monolayer.
Glycyrrhiza polysaccharides may have an antitumor effect in γδT cells through gut microbiota and TLRs/NF‐κB pathway in mice
Authors: Chen Yinxiao , Li Zhaodong , Bai Liding , Lu Bin , Peng Yanfei , Xu Pengjuan , Song Xinbo , Bian Yuhong , Wang Xiangling , Zhao Shuwu
Published: April 2024

Tumor immunotherapy can be a suitable cancer treatment option in certain instances. Here we investigated the potential immunomodulatory effect of oral glycyrrhiza polysaccharides (GCP) on the antitumor function of γδT cells in intestinal epithelial cells in mice. We found that GCP can inhibit tumor growth and was involved in the regulation of systemic immunosuppression. GCP administration also promoted the differentiation of gut epithelia γδT cells into IFN‐γ‐producing subtype through regulation of local cytokines in gut mucosa. GCP administration increased local cytokine levels through gut microbiota and the gut mucosa Toll‐like receptors / nuclear factor kappa‐B pathway. Taken together, our results suggest that GCP might be a suitable candidate for tumor immunotherapy, although further clinical research, including clinical trials, are required to validate these results.
Conditional deficiency of Rho‐associated kinases disrupts endothelial cell junctions and impairs respiratory function in adult mice
Authors: Akamine Takahiro , Terabayashi Takeshi , Sasaki Takako , Hayashi Riku , Abe Ichitaro , Hirayama Fumihiro , Nureki Shin‐ichi , Ikawa Masahito , Miyata Haruhiko , Tokunaga Akinori , Kobayashi Takashi , Hanada Katsuhiro , Thumkeo Dean , Narumiya Shuh , Ishizaki Toshimasa
Published: April 2024

The Ras homology (Rho) family of GTPases serves various functions, including promotion of cell migration, adhesion, and transcription, through activation of effector molecule targets. One such pair of effectors, the Rho‐associated coiled‐coil kinases (ROCK1 and ROCK2), induce reorganization of actin cytoskeleton and focal adhesion through substrate phosphorylation. Studies on ROCK knockout mice have confirmed that ROCK proteins are essential for embryonic development, but their physiological functions in adult mice remain unknown. In this study, we aimed to examine the roles of ROCK1 and ROCK2 proteins in normal adult mice. Tamoxifen (TAM)‐inducible ROCK1 and ROCK2 single and double knockout mice (ROCK1flox/flox and/or ROCK2flox/flox;Ubc‐CreERT2) were generated and administered a 5‐day course of TAM. No deaths occurred in either of the single knockout strains, whereas all of the ROCK1/ROCK2 double conditional knockout mice (DcKO) had died by Day 11 following the TAM course. DcKO mice exhibited increased lung tissue vascular permeability, thickening of alveolar walls, and a decrease in percutaneous oxygen saturation compared with noninducible ROCK1/ROCK2 double‐floxed control mice. On Day 3 post‐TAM, there was a decrease in phalloidin staining in the lungs in DcKO mice. On Day 5 post‐TAM, immunohistochemical analysis also revealed reduced staining for vascular endothelial (VE)‐cadherin, β‐catenin, and p120‐catenin at cell–cell contact sites in vascular endothelial cells in DcKO mice. Additionally, VE‐cadherin/β‐catenin complexes were decreased in DcKO mice, indicating that ROCK proteins play a crucial role in maintaining lung function by regulating cell–cell adhesion.
A multi‐omics study to monitor senescence‐associated secretory phenotypes of Alzheimer's disease
Authors: Yang Jingzhi , Zhou Yinge , Wang Tianjiao , Li Na , Chao Yufan , Gao Songyan , Zhang Qun , Wu Shuo , Zhao Liang , Dong Xin
Published: April 2024

Objective

Alzheimer's disease (AD) is characterized by the progressive degeneration and damage of neurons in the brain. However, developing an accurate diagnostic assay using blood samples remains a challenge in clinic practice. The aim of this study was to explore senescence‐associated secretory phenotypes (SASPs) in peripheral blood using mass spectrometry based multi‐omics approach and to establish diagnostic assays for AD.

Methods

This retrospective study included 88 participants, consisting of 29 AD patients and 59 cognitively normal (CN) individuals. Plasma and serum samples were examined using high‐resolution mass spectrometry to identify proteomic and metabolomic profiles. Receiver operating characteristic (ROC) analysis was employed to screen biomarkers with diagnostic potential. K‐nearest neighbors (KNN) algorithm was utilized to construct a multi‐dimensional model for distinguishing AD from CN.

Results

Proteomics analysis revealed upregulation of five plasma proteins in AD, including RNA helicase aquarius (AQR), zinc finger protein 587B (ZNF587B), C‐reactive protein (CRP), fibronectin (FN1), and serum amyloid A‐1 protein (SAA1), indicating their potential for AD classification. Interestingly, KNN‐based three‐dimensional model, comprising AQR, ZNF587B, and CRP, demonstrated its high accuracy in AD recognition, with evaluation possibilities of 0.941, 1.000, and 1.000 for the training, testing, and validation datasets, respectively. Besides, metabolomics analysis suggested elevated levels of serum phenylacetylglutamine (PAGIn) in AD.

Interpretation

The multi‐omics outcomes highlighted the significance of the SASPs, specifically AQR, ZNF587B, CRP, and PAGIn, in terms of their potential for diagnosing AD and suggested neuronal aging‐associated pathophysiology.
High‐Strength Wear‐Resistant Cu/Tungsten Carbide/Diamond Composites Fabricated by Powder Metallurgy
Authors: Zhang Xiaoyan , Lei Qian , Gao Yang , Zhou Shijie , Qiu Wenting
Published: April 2024

Copper‐based diamond composites are widely used for thermal management and wear‐resistant materials. In this work, Cu/diamond, Cu/tungsten carbide (WC)/diamond, and Cu–0.92Cr/WC/diamond composites are fabricated by high‐energy ball milling and rapid hot‐pressing sintering. Physical characteristics, compressive strength, and tribological properties of the studied composites are investigated. The compressive strength of Cu/7wt%WC/diamond composites is 102% higher than the Cu/diamond composites, reaching 415 MPa. Compression fractures extend from the interface due to compression cracks, consistent with the compression curves from molecular dynamics (MD) simulations. The crack propagates from the interface during the compression experiment, which is consistent with the result of MD simulation. The Cu/7wt%WC/diamond composites exhibit a wear rate of 0.6 × 10−6 mm3 (N m)−1 and a friction coefficient of 0.37 at 50 N. The addition of WC and diamond improves the compressive strength and wear resistance. These findings are helpful in the development of copper composites with high compression strength and wear resistance.
Influence of Metal Surface Structures on Composite Formation during Polymer–Metal Joining Based on Reactive Al/Ni Multilayer Foil
Authors: Glaser Marcus , Ehlich Kai , Matthes Sebastian , Hildebrand Jörg , Schaaf Peter , Bergmann Jean Pierre
Published: April 2024

Progressive developments in the field of lightweight construction and engineering demand continuous substitution of metals with suitable polymers. However, the combination of dissimilar materials results in a multitude of challenges based on different chemical and physical material properties. Reactive multilayer systems offer a promising joining method for flexible and low‐distortion joining of dissimilar joining partners with an energy source introduced directly into the joining zone. Within this publication, hybrid lap joints between semicrystalline polyamide 6 and surface‐structured austenitic steel X5CrNi18–10 (EN 1.4301) are joined using reactive Al/Ni multilayer foils of the type Indium–NanoFoil. The main objective is to examine possibilities of influencing crack initiation in the foil plane by variation of joining pressure and different metal surface structures with regard to geometry, density, and orientation. Thus, the position of foil cracks is superimposed onto the metal structure and associated filling with molten plastic is improved. Consequently, characterization of occurring crack positions as a function of joining pressure and metal structure, analysis of the composite in terms of structural filling and joint strength, as well as possible causes of crack initiation are evaluated.
Evaluation of Interface and Residual Strain of NiTi Layer Deposited on NiTiX Substrate by Laser Powder Bed Fusion
Authors: Memarian Mahshid , Mohri Maryam , Golrang Mahbod , Leinenbach Christian , Ferretto Irene , Ghafoori Elyas , Nili‐Ahmadabadi Mahmoud
Published: April 2024

This study investigates the microstructure and properties of functionally graded NiTi alloy bilayers. The NiTi layer is printed by laser powder bed fusion on a NiTiX (where X is Hf or Cu) substrate prepared by vacuum arc remelting. Specimens produced with different thicknesses of layers, but constant thickness ratio, are examined by optical and scanning electron microscopy prior to and postannealing process at 1000 °C for 16 h. Scanning electron microscopy– energy‐dispersive X‐ray spectroscopy and transmission electron microscopy studies reveal the presence of Ti2Ni and Ni4Ti3 precipitates in the as‐printed NiTi/NiTiCu samples and Ti2Ni type precipitates in as‐printed NiTi/NiTiHf. Digital image correlation quantifies residual strain in the as‐printed bilayer and enables strain relief to be monitored during heating. It has been shown that microcracks occurring along interfacial zones during the laser powder bed fusion are diminished after annealing heat treatment. The microcrack closure occurs by diffusion of third elements to the open microcracks, leading to precipitation and accumulation of third elements in the interfaces. Eventually, the as‐printed NiTi/NiTiCu sample displays two‐way shape memory effects with about 24.5% shape recovery. This work enhances understanding of controlling fabrication to yield tailored properties in additively manufactured functionally graded NiTi‐based materials.
The Effect of the Iso‐Thermal Heat Treatment on the Microstructure and Properties of Powder Bed Fusion–Laser Beam AlSi10Mg Alloy
Authors: Katti Indrajeet , Zhang Duyao , Qiu Dong , Weiss Matthias , Forsmark Joy H. , Easton Mark
Published: April 2024

The effect of iso‐thermal heat treatments on powder bed fusion–laser beam (PBF–LB) AlSi10Mg alloy has been studied; however, an extensive process–property relationship evaluation has not yet been undertaken. In addition, the coarsening of eutectic Si from low‐to‐high (200–500 °C) temperature heat treatment has not been investigated systematically. Therefore, AlSi10Mg alloy is heat‐treated at 200, 300, 400, and 500 °C for holding times ranging from 0.5 to 32 h. Uniaxial tensile and hardness tests are conducted, and the microstructure is characterized. A unique approach is adopted for estimating Si solubility where 200 °C heat‐treated microstructure data to estimate solute trapping due to the high cooling rate in the as‐fabricated state. It is observed that increasing the heat‐treatment temperature and time reduces the strength and strain‐hardening rate but increases the tensile elongation up to 400 °C heat treatment. At 500 °C, the yield strength increases, and the elongation reduces compared with the 400 °C heat treatment owing to the refined Fe containing dispersoid formation at 500 °C. The important outcome of this study is heat‐treatment process–property contour maps that are useful for fine‐tuning the mechanical properties of PBF–LB AlSi10Mg alloy for industrial prototyping application.