bluuebunny/crossref_metadata_2025 huggingface dataset:
Membrane Proteases and Aminoglycoside Antibiotic Resistance
Authors: Hinz Aaron , Lee Samuel , Jacoby Kyle , Manoil Colin
Published: July 2011

We present genetic studies that help define the functional network underlying intrinsic aminoglycoside resistance in
Pseudomonas aeruginosa
. Our analysis shows that proteolysis, particularly that controlled by the membrane protease FtsH, is a major determinant of resistance. First, we examined the consequences of inactivating genes controlled by AmgRS, a two-component regulator required for intrinsic tobramycin resistance. Three of the gene products account for resistance: a modulator of FtsH protease (YccA), a membrane protease (HtpX), and a membrane protein of unknown function (PA5528). Second, we screened mutations inactivating 66 predicted proteases and related functions. Insertions inactivating two FtsH protease accessory factors (HflK and HflC) and a cytoplasmic protease (HslUV) increased tobramycin sensitivity. Finally, we generated an
ftsH
deletion mutation. The mutation dramatically increased aminoglycoside sensitivity. Many of the functions whose inactivation increased sensitivity appeared to act independently, since multiple mutations led to additive or synergistic effects. Up to 500-fold increases in tobramycin sensitivity were observed. Most of the mutations also were highly pleiotropic, increasing sensitivity to a membrane protein hybrid, several classes of antibiotics, alkaline pH, NaCl, and other compounds. We propose that the network of proteases provides robust protection from aminoglycosides and other substances through the elimination of membrane-disruptive mistranslation products.
Rates of condom and non-condom-based anal intercourse practices among homosexually active men in Australia: deliberate HIV risk reduction?
Authors: Mao Limin , Kippax Susan C , Holt Martin , Prestage Garrett P , Zablotska Iryna B , de Wit John B F
Published: July 2011

Objective

Three decades into the HIV epidemic and with the advancement of HIV treatments, condom and non-condom-based anal intercourse among gay men in resource-rich countries needs to be re-assessed.

Methods

The proportions of men engaging in a range of anal intercourse practices were estimated from the ongoing cross-sectional Gay Community Periodic Surveys in six states in Australia from 2007 to 2009. Comparisons were made between HIV-negative men, HIV-positive men with an undetectable viral load and those with a detectable viral load.

Results

Condoms play a key role in gay men's anal intercourse practices: 33.8% of HIV-negative men, 25.1% of HIV-positive men with an undetectable viral load and 22.5% of those with a detectable viral load reported consistent condom use with all male partners in the 6 months before the survey. Among HIV-negative men, the second largest group were men who had unprotected anal intercourse (UAI) only in the context of HIV-negative seroconcordant regular relationships. Among HIV-positive men, the second largest group was men who had UAI in casual encounters preceded by HIV status disclosure to some, but not all, casual partners.

Conclusions

A minority, yet sizeable proportion, of men consistently engaged in a number of UAI practices in specific contexts, suggesting they have adopted deliberate HIV risk-reduction strategies. While it is important that HIV behavioural prevention continues to reinforce condom use, it needs to address both the challenges and opportunities of the substantial uptake of non-condom-based risk-reduction strategies.
Similarity of mouse perivascular and brown adipose tissues and their resistance to diet-induced inflammation
Authors: Fitzgibbons Timothy P. , Kogan Sophia , Aouadi Myriam , Hendricks Greg M. , Straubhaar Juerg , Czech Michael P.
Published: July 2011

Thoracic perivascular adipose tissue (PVAT) is a unique adipose depot that likely influences vascular function and susceptibility to pathogenesis in obesity and the metabolic syndrome. Surprisingly, PVAT has been reported to share characteristics of both brown and white adipose, but a detailed direct comparison to interscapular brown adipose tissue (BAT) has not been performed. Here we show by full genome DNA microarray analysis that global gene expression profiles of PVAT are virtually identical to BAT, with equally high expression of Ucp-1, Cidea, and other genes known to be uniquely or very highly expressed in BAT. PVAT and BAT also displayed nearly identical phenotypes upon immunohistochemical analysis, and electron microscopy confirmed that PVAT contained multilocular lipid droplets and abundant mitochondria. Compared with white adipose tissue (WAT), PVAT and BAT from C57BL6/J mice fed a high-fat diet for 13 wk had markedly lower expression of immune cell-enriched mRNAs, suggesting resistance to obesity-induced inflammation. Indeed, staining of BAT and PVAT for macrophage markers (F4/80 and CD68) in obese mice showed virtually no macrophage infiltration, and FACS analysis of BAT confirmed the presence of very few CD11b+/CD11c+macrophages in BAT (1.0%) compared with WAT (31%). In summary, murine PVAT from the thoracic aorta is virtually identical to interscapular BAT, is resistant to diet-induced macrophage infiltration, and thus may play an important role in protecting the vascular bed from inflammatory stress.
Identification of Fat4 and Tsc22d1 as Novel Candidate Genes for Spontaneous Pulmonary Adenomas
Authors: Berndt Annerose , Cario Clinton L. , Silva Kathleen A. , Kennedy Victoria E. , Harrison David E. , Paigen Beverly , Sundberg John P.
Published: July 2011

Genetic influences that underlie spontaneous lung oncogenesis are poorly understood. The objective of this study was to determine the genetic influences on spontaneous pulmonary adenoma frequency and severity in 28 strains of mice as part of a large-scale aging study conducted at the Jackson Aging Center (http://agingmice.jax.org/). Genome-wide association studies were conducted in these strains with both low-density (132,000) and high-density (4,000,000) panel of single-nucleotide polymorphisms (SNP). Our analysis revealed that adenomas were relatively less frequent and less severe in females than males, and that loci implicated in frequency and severity were often different between male and female mice. While some of the significant loci identified mapped to genomic locations known to be responsible for carcinogen-induced cancers (e.g., Pas1), others were unique to our study. In particular, Fat4 was influential in males and Tsc22d1 was influential in females. SNPs implicated were predicted to alter amino acid sequence and change protein function. In summary, our results suggested that genetic influences that underlie pulmonary adenoma frequency are dependent on gender, and that Fat4 and Tsc22d1 are likely candidate genes to influence formation of spontaneous pulmonary adenoma in aging male and female mice, respectively. Cancer Res; 71(17); 5779–91. ©2011 AACR.
Central and Peripheral Blood Flow During Exercise With a Continuous-Flow Left Ventricular Assist Device
Authors: Brassard Patrice , Jensen Annette S. , Nordsborg Nikolai , Gustafsson Finn , Møller Jacob E. , Hassager Christian , Boesgaard Søren , Hansen Peter Bo , Olsen Peter Skov , Sander Kåre , Secher Niels H. , Madsen Per Lav
Published: July 2011

Background—

End-stage heart failure is associated with impaired cardiac output (CO) and organ blood flow. We determined whether CO and peripheral perfusion are maintained during exercise in patients with an axial-flow left ventricular assist device (LVAD) and whether an increase in LVAD pump speed with work rate would increase organ blood flow.

Methods and Results—

Invasively determined CO and leg blood flow and Doppler-determined cerebral perfusion were measured during 2 incremental cycle exercise tests on the same day in 8 patients provided with a HeartMate II LVAD. In random order, patients exercised both with a constant (≈9775 rpm) and with an increasing pump speed (+400 rpm per exercise stage). At 60 W, the elevation in CO was more pronounced with increased pump speed (8.7±0.6 versus 8.1±1.1 L · min
−1
; mean±SD;
P
=0.05), but at maximal exercise increases in CO (from 7.0±0.9 to 13.6±2.5 L · min
−1
;
P
<0.01) and leg blood flow [0.7 (0.5 to 0.8) to 4.4 (3.9 to 4.8) L · min
−1
per leg; median (range);
P
<0.001] were similar with both pumping modes. Normally, middle cerebral artery mean flow velocity increases from ≈50 to ≈65 cm · s
−1
during exercise, but in LVAD patients with a constant pump speed it was low at rest (39±14 cm · s
−1
) and remained unchanged during exercise, whereas in patients with increasing pump speed, it increased by 5.2±2.8 cm · s
−1
at 60 W (
P
<0.01).

Conclusions—

With maximal exercise, the axial-flow LVAD supports near-normal increments in cardiac output and leg perfusion, but cerebral perfusion is poor. Increased pump speed augments cerebral perfusion during exercise.
Organizational Learning and Individual Values
Authors: Cohen Aaron , Rosenblatt Zehava , Buhadana Tali
Published: July 2011

This study examines the relationship between individual values and organizational learning among employees of an Israeli government ministry. The authors examined the predictive relationships between 10 individual values and organizational learning, focusing on four dimensions of organizational learning. The study sample consisted of 298 civil service employees working in one Israeli ministry. The findings showed that three values that reflect a focus on person–organization fit—namely, security, tradition, and universalism—were positively and consistently related to all dimensions of organizational learning. Other values representing a focus on the individual—power and self-direction—were negatively related to organizational learning.
Evaluation of Gastropexy and Stoma Tract Maturation Using a Novel Introducer Kit for Percutaneous Gastrostomy in a Porcine Model
Authors: Maxwell Christopher I. , Hilden Kristen , Glasgow Robert E. , Ollerenshaw Jeremy , Carlisle James G. , Fang John C.
Published: July 2011

Background: Fluoroscopic placement of percutaneous gastrostomy (PG) requires the use of T‐bar fasteners to affix the stomach to the anterior abdominal wall; the effect of T‐fasteners on stoma tract maturation is unknown. The authors studied PG stoma tract maturation, comparing PG + gastropexy with standard percutaneous endoscopic gastrostomy (PEG). Methods: Sixteen pigs underwent PG placement using a novel introducer kit. Three absorbable suture T‐fasteners were placed around the stoma site, and PG was placed using the Russell method. A standard PEG was then placed using the Ponsky pull method, allowing each animal to serve as its own control. Gross and histopathological integrity of stoma tract formation was assessed at 1–3 weeks. Results: At sacrifice, all PGs were intact with no evidence of infection, disruption, or significant leakage. Stoma tracts of all test and control sites were robust and histologically mature at all time points. Stoma tract diameters were also similar between test and control PGs (mean ± SEM: control 13.1 ± 0.7 mm, test 12.1 ± 0.4 mm; P = .2, n = 15). Histopathological evaluation demonstrated a generally comparable tissue response between test and control PGs, with slight decreases in fibrosis noted in test compared to control sites (P = .02, n = 15). Conclusions: Stoma tract maturation of PG with gastropexy provides similar results to standard PEG. Stoma tracts were mature at 1 week regardless of placement method. Placement and performance of PG using the new introducer kit with novel T‐fasteners and absorbable suture yields effective gastric anchoring and has similar ease of use as standard PEG placement.
Feature selection strategies for automated classification of digital media content
Authors: Rocha Rocío , Cobo Ángel
Published: July 2011

This paper proposes strategies for feature selection of digital news articles that allow an effective implementation of learning algorithms for the unsupervised classification of news articles. With the appropriate selection of a small subset of features a correct identification of related news can be achieved, thus enabling organizations and individual users to keep track of current events. The paper defines a quality measure of the discriminatory power of each feature and verifies that the selection of a feature subset with higher quality values allows obtaining good classification results. A Particle Swarm Optimization (PSO) based selection method is also proposed. Both proposals are validated on two collections of press clippings collated from news search services in digital media. Experimental results reveal that good classification accuracy can be achieved with small subsets of between 3 per cent and 6 per cent of the features.
The ‘hidden strength’ of active citizenship: The involvement of local residents in public safety projects
Authors: van Steden Ronald , van Caem Barbara , Boutellier Hans
Published: July 2011

The past two decades or so have seen a growing interest in ‘active’ (or ‘responsible’) citizenship within local public safety projects and programmes, but little is known about how such projects function in practice. Besides presenting theoretical debates on community safety projects, this article reports empirical insights into the wealth and variety of informal, citizen-based contributions, specifically to handling communal crime and disorder in Amsterdam, capital city of the Netherlands. Subsequently, it assesses the kind of lessons empirical studies provide about the importance of ‘social capital’ for public participation, the perils of social exclusion and the nature of relationships between citizens and professionals. It is argued that enthusiastic efforts of individual citizens are equally important, if not more so, than strong social ties. Moreover, in overall terms, active participation tends to have a significant bias in favour of the white, middle-aged, middle-class population. Finally, benevolent citizens regularly encounter professional barriers and bureaucratic ceilings that inhibit their desire to participate. All rhetoric to the contrary notwithstanding, promoting genuine active citizenship is easier said than done.
Oncogenic tyrosine kinase NPM-ALK induces expression of the growth-promoting receptor ICOS
Authors: Zhang Qian , Wang HongYi , Kantekure Kanchan , Paterson Jennifer C. , Liu Xiaobin , Schaffer Andras , Paulos Chrystal , Milone Michael C. , Odum Niels , Turner Suzanne , Marafioti Teresa , Wasik Mariusz A.
Published: July 2011

Here we report that T-cell lymphoma cells carrying the NPM-ALK fusion protein (ALK+ TCL) frequently express the cell-stimulatory receptor ICOS. ICOS expression in ALK+ TCL is moderate and strictly dependent on the expression and enzymatic activity of NPM-ALK. NPM-ALK induces ICOS expression via STAT3, which triggers the transcriptional activity of the ICOS gene promoter. In addition, STAT3 suppresses the expression of miR-219 that, in turn, selectively inhibits ICOS expression. ALK+ TCL cell lines display extensive DNA methylation of the CpG island located within intron 1, the putative enhancer region, of the ICOS gene, whereas cutaneous T-cell lymphoma cell lines, which strongly express ICOS, show no methylation of the island. Treatment of the ALK+ TCL cell lines with DNA methyltransferase inhibitor reversed the CpG island methylation and augmented the expression of ICOS mRNA and protein. Stimulation of the ICOS receptor with anti-ICOS antibody or ICOS ligand-expressing B cells markedly enhanced proliferation of the ALK+ TCL cells. These results demonstrate that NPM-ALK, acting through STAT3 as the gene transcriptional activator, induces the expression of ICOS, a cell growth promoting receptor. These data also show that the DNA methylation status of the intronic CpG island affects transcriptional activity of the ICOS gene and, consequently, modulates the concentration of the expressed ICOS protein.
Setting the pace: the 2011 Australasian Podiatry Council conference
Authors: Menz Hylton B , Firth Julia
Published: July 2011

The 2011 Australasian Podiatry Council conference was held from April 26 to 29 in Melbourne, Victoria, Australia. This commentary provides a brief overview of the conference, including the speakers and topic areas covered, selected original research highlights, and award winning presentations.
Marketing of Vice Goods: A Strategic Analysis of the Package Size Decision
Authors: Jain Sanjay
Published: July 2011

Consumers are often unable to resist the temptation of overconsuming certain products such as cookies, crackers, soft drinks, alcohol, etc. To control their consumption, some consumers buy small packages or abstain from purchasing the product altogether. Other consumers, however, still purchase large packages and overconsume. From a strategic perspective, firms have the option of introducing small packages or only offering large packages. We use the literature on hyperbolic discounting to model consumers' self-control problems and examine conditions under which firms will offer small packages to help consumers combat their self-control problem, and how this offering in turn affects prices, profits, consumer, and social welfare. Our results show that introducing small packages can increase firms' profits only when a small fraction of consumers have overconsumption problems or when small packages can bring in new customers. Additionally, we find that competition can sometimes reduce the incentives for firms to introduce small packages. This is particularly true when a large fraction of consumers is attracted to small packages. We also find that firms' profits can sometimes decrease if they produce healthier alternatives of their goods. Our analysis of consumer welfare reveals that small packages enhance consumer and social welfare, even though they sometimes increase the consumption of vice goods.
Intellectual Capital and Financing Decisions: Evidence from the U.S. Patent Data
Authors: Liu Qiao , Wong Kit Pong
Published: July 2011

This paper develops a real options model to understand two distinct roles played by intellectual capital in corporate financing decisions. Whereas limiting a firm's debt capacity because of its low liquidation value, intellectual capital enhances a firm's debt capacity through its positive impact on earnings. Our model shows that the former dominates or is dominated by the latter, depending on whether the rate of dissipation of intellectual capital upon default is larger or smaller than a critical level, respectively. Using patent-based and research-and-development-based variables as proxies for intellectual capital, we find robust evidence that the relation between intellectual capital and leverage is positive. Specifically, a one-standard-deviation increase in the level of a firm's intellectual capital is associated with an increase of 6.6% to 21.1% in its market leverage. We further find this positive relation to be stronger for biotechnology firms.

This paper was accepted by Wei Xiong, finance.
Demand Forecasting Behavior: System Neglect and Change Detection
Authors: Kremer Mirko , Moritz Brent , Siemsen Enno
Published: July 2011

We analyze how individuals make forecasts based on time-series data. Using a controlled laboratory experiment, we find that forecasting behavior systematically deviates from normative predictions: Forecasters overreact to forecast errors in relatively stable environments, but underreact to errors in relatively unstable environments. The performance loss that is due to such systematic judgment biases is larger in stable than in unstable environments.

This paper was accepted by Martin Lariviere, operations management.
Sustainable development – the East Bali poverty project
Authors: Younger John Scott , Booth David John , Kurniawan Komang
Published: July 2011

Sustainable development is an essential objective for all governments, whether tasked with leading a fully industrialised country or grappling with the challenges faced by developing countries. Efforts to deal with some of the major issues of the world that have loomed over the past few decades such as water and sanitation and poverty, the scale of which has primarily resulted from very large population growth over the past half century, have generally failed. This is particularly noticeable in the fast industrialising countries of Asia and in parts of Africa. In more recent times, it has been recognised that resolution of poverty problems really only succeed if the people requiring assistance are directly and fully embraced in the solutions needed, along with the approaches and procedures adopted to tackle the problems. In this paper, details are presented of the approach taken to respond to the aspirations of a desperately poor community of 15 000 in a remote area of Bali, Indonesia, with difficult access, and raise it to a situation of sustainable development. In the beginning the elders of the community prioritised education for their children as a means of providing for a better future. Before the children could respond properly, serious health issues had to be addressed, and this meant taking a long-term and holistic view with a matching schedule of parallel infrastructure and social programmes, and full participation of the community. This privately funded integrated development is now in its eleventh year, and the many challenges and solutions to achieve sustainable development are described. The project provides many lessons for adaptation, and is already providing selective assistance elsewhere.
Does Product Market Competition Increase Credit Availability?
Authors: Cerasi Vittoria , Fedele Alessandro
Published: July 2011

With asymmetric information between investors and firms, credit availability is affected by the resale value of collateralized productive assets. If liquidation occurs, investors recover a greater value the higher the probability to find a buyer and the higher his willingness to pay to use the assets for production. We extend the idea of complementarities among firms in the same industry (as in Shleifer and Vishny, 1992) to study under which conditions credit availability is enhanced by competition in the product market when assets are industry specific.
Precursor Frequency and Competition Dictate the HLA-A2–Restricted CD8+ T Cell Responses to Influenza A Infection and Vaccination in HLA-A2.1 Transgenic Mice
Authors: Tan Amabel C. L. , La Gruta Nicole L. , Zeng Weiguang , Jackson David C.
Published: July 2011

The human HLA-A2–restricted CD8+ T cell response to influenza A virus (IAV) is largely directed against the matrix protein-derived M158–66 epitope and represents an archetypal example of CD8+ T cell immunodominance. In this study, we examined the CD8+ T cell hierarchy to M158–66 and two subdominant IAV-specific epitopes: NS1122–130 and PA46–55 in HLA-A2+ human subjects and HLA-A2.1 transgenic (HHD) mice. Using epitope-based lipopeptides, we show that the CD8+ T cell hierarchy induced by IAV infection could also be induced by lipopeptide vaccination in a context outside of viral infection when the Ag load is equalized. In the HHD HLA-A2.1 mouse model, we show that the naive T cell precursor frequencies, and competition at the Ag presentation level, can predict the IAV-specific CD8+ T cell hierarchy. Immunization of mice with subdominant epitopes alone was unable to overcome the dominance of the M158–66–specific response in the face of IAV challenge; however, a multiepitope vaccination strategy was most effective at generating a broad and multispecific response to infection.
Hypoxia-Inducible Factor-2α Regulates GM-CSF–Derived Soluble Vascular Endothelial Growth Factor Receptor 1 Production from Macrophages and Inhibits Tumor Growth and Angiogenesis
Authors: Roda Julie M. , Sumner Laura A. , Evans Randall , Phillips Gary S. , Marsh Clay B. , Eubank Timothy D.
Published: July 2011

Macrophage secretion of vascular endothelial growth factor (VEGF) in response to the hypoxic tumor microenvironment contributes to tumor growth, angiogenesis, and metastasis. We have recently demonstrated that macrophages stimulated with GM-CSF at low O2 secrete high levels of a soluble form of the VEGF receptor 1 (sVEGFR-1), which neutralizes VEGF and inhibits its biological activity. Using small interfering RNA targeting to deplete hypoxia-inducible factor (HIF)-1α or HIF-2α in murine macrophages, we found that macrophage production of sVEGFR-1 in response to low O2 was dependent on HIF-2α, whereas HIF-1α specifically regulated VEGF production. In our current report, we evaluated the growth of B16F10 malignant melanoma in mice with a monocyte/macrophage-selective deletion of HIF-1α or HIF-2α (HIF-1αflox/flox- or HIF-2αflox/+/LysMcre mice). GM-CSF treatment increased intratumoral VEGF and sVEGFR-1 in control mice, an effect that was associated with a decrease in microvessel density. GM-CSF treatment of HIF-1αflox/flox/LysMcre mice induced sVEGFR-1 but not VEGF, resulting in an overall greater reduction in tumor growth and angiogenesis compared with control mice. In addition, real-time PCR for melanoma-specific genes revealed a significantly reduced presence of lung micrometastases in HIF-1αflox/flox/LysMcre mice treated with GM-CSF. Conversely, GM-CSF treatment induced VEGF but not sVEGFR-1 in HIF-2αflox/+/LysMcre mice, and, correspondingly, GM-CSF did not decrease tumor growth, angiogenesis, or lung metastasis in these mice. This study reveals opposing roles for the HIFs in the regulation of angiogenesis by tumor-associated macrophages and suggests that administration of GM-CSF might be an effective means of inducing sVEGFR-1 and inhibiting tumor growth and angiogenesis in patients with melanoma.
Vitamin A Deficiency Impairs Vaccine-Elicited Gastrointestinal Immunity
Authors: Kaufman David R. , De Calisto Jaime , Simmons Nathaniel L. , Cruz Ashley N. , Villablanca Eduardo J. , Mora J. Rodrigo , Barouch Dan H.
Published: July 2011

Vitamin A deficiency is highly prevalent in much of the developing world, where vaccination programs are of paramount importance to public health. However, the impact of vitamin A deficiency on the immunogenicity and protective efficacy of vaccines has not been defined previously. In this article, we show that the vitamin A metabolite retinoic acid is critical for trafficking of vaccine-elicited T lymphocytes to the gastrointestinal mucosa and for vaccine protective efficacy in mice. Moderate vitamin A deficiency abrogated Ag-specific T lymphocyte trafficking to the gastrointestinal tract, gastrointestinal cellular immune responses, and protection against a mucosal challenge following immunization with a recombinant adenovirus vaccine vector. Oral vitamin A supplementation as well as retinoic acid administration fully restored the mucosal immune responses and vaccine protective efficacy. These data suggest that oral vitamin A supplementation may be important for optimizing the success of vaccines against HIV-1 and other mucosal pathogens in the developing world, highlighting a critical relationship between host nutritional status and vaccine efficacy.
Budget Impact Analysis of Circulating Tumor DNA Testing for Colon Cancer in Commercial Health and Medicare Advantage Plans
Authors: Li Yonghong , Heer Avneet K. , Sloane Hillary S. , Edelstein Daniel L. , Tie Jeanne , Gibbs Peter , Barzi Afsaneh
Published: May 2024

Importance

In a randomized clinical trial, treatment guided by tumor-informed circulating tumor (ct)DNA testing reduced adjuvant chemotherapy use without compromising recurrence-free survival in patients with stage II colon cancer. The potential budget impact of adopting ctDNA testing into routine patient care is unknown.

Objective

To compare the total cost of patient care scenarios with and without the adoption of ctDNA testing.

Design, Setting, and Participants

This budget impact analysis was conducted from the perspectives of US commercial health and Medicare Advantage payers. A decision-analytical model was populated with age-specific incidence of colon cancer, use of adjuvant chemotherapy, and use of single-agent or multiagent regimens. Total cost was estimated with the costs of ctDNA testing, drug acquisition, administration, surveillance, and adverse events. The analysis was conducted from September 2023 to January 2024.

Exposures

The adoption of ctDNA testing.

Main Outcomes and Measures

The incremental cost in the first year following the adoption of ctDNA testing, where testing will affect patient treatment and costs.

Results

In hypothetical plans with 1 million individuals covered, 35 commercial health plan members and 102 Medicare Advantage members aged 75 years and younger were eligible for ctDNA testing. In the base case with a 50% adoption rate, total cost savings were $221 684 (equivalent to $0.02 per member per month [PMPM]) for a commercial payer and $116 720 (equivalent to $0.01 PMPM) for a Medicare Advantage payer. Cost savings were robust to variations in assumptions of all parameters in the commercial population but sensitive to variations in assumptions of adjuvant chemotherapy use rates in the Medicare Advantage population. The number needed to test to avoid 1 patient receiving adjuvant chemotherapy was 4 in the commercial population and 10 in the Medicare Advantage population. The budget-neutral cost for ctDNA testing was $16 202 for a commercial payer and $5793 for a Medicare Advantage payer.

Conclusions and Relevance

Use of tumor-informed ctDNA testing to guide adjuvant chemotherapy in postsurgery patients with stage II colon cancer was projected to result in cost savings for both commercial and Medicare Advantage payers. Adoption of ctDNA testing is therefore advantageous from a budgetary perspective.
Hip Fracture Treatment and Outcomes Among Community-Dwelling People Living With Dementia
Authors: Adler Rachel R. , Xiang Lingwei , Shah Samir K. , Clark Clancy J. , Cooper Zara , Mitchell Susan L. , Kim Dae Hyun , Hsu John , Sepucha Karen , Chunga Richard E. , Lipsitz Stuart R. , Weissman Joel S. , Schoenfeld Andrew J.
Published: May 2024

Importance

The decision for surgical vs nonsurgical treatment for hip fracture can be complicated among community-dwelling people living with dementia.

Objective

To compare outcomes of community-dwelling people living with dementia treated surgically and nonsurgically for hip fracture.

Design, Setting, and Participants

This retrospective cross-sectional study undertook a population-based analysis of national Medicare fee-for-service data. Participants included community-dwelling Medicare beneficiaries with dementia and an inpatient claim for hip fracture from January 1, 2017, to June 30, 2018. Analyses were conducted from November 10, 2022, to October 17, 2023.

Exposure

Surgical vs nonsurgical treatment for hip fracture.

Main Outcomes and Measures

The primary outcome was mortality within 30, 90, and 180 days. Secondary outcomes consisted of selected post–acute care services.

Results

Of 56 209 patients identified with hip fracture (73.0% women; mean [SD] age, 86.4 [7.0] years), 33 142 (59.0%) were treated surgically and 23 067 (41.0%) were treated nonsurgically. Among patients treated surgically, 73.3% had a fracture of the femoral head and neck and 40.2% had moderate to severe dementia (MSD). Among patients with MSD and femoral head and neck fracture, 180-day mortality was 31.8% (surgical treatment) vs 45.7% (nonsurgical treatment). For patients with MSD treated surgically vs nonsurgically, the unadjusted odds ratio (OR) of 180-day mortality was 0.56 (95% CI, 0.49-0.62; P < .001) and the adjusted OR was 0.59 (95% CI, 0.53-0.66; P < .001). Among patients with mild dementia and femoral head and neck fracture, 180-day mortality was 26.5% (surgical treatment) vs 34.9% (nonsurgical treatment). For patients with mild dementia who were treated surgically vs nonsurgically for femoral head and neck fracture, the unadjusted OR of 180-day mortality was 0.67 (95% CI, 0.60-0.76; P < .001) and the adjusted OR was 0.71 (95% CI, 0.63-0.79; P < .001). For patients with femoral head and neck fracture, there was no difference in admission to a nursing home within 180 days when treated surgically vs nonsurgically.

Conclusions and Relevance

In this cohort study of community-dwelling patients with dementia and fracture of the femoral head and neck, patients with MSD and mild dementia treated surgically experienced lower odds of death compared with patients treated nonsurgically. Although avoiding nursing home admission is important to persons living with dementia, being treated surgically for hip fracture did not necessarily confer a benefit in that regard. These data can help inform discussions around values and goals with patients and caregivers when determining the optimal treatment approach.
Laser‐Induced Porous Graphene/CuO Composite for Efficient Interfacial Solar Steam Generation
Authors: Wei Yujun , Li Weihong , Zhang Shaochong , Yu Jiadong , Tang Yong , Wu Jianing , Yu Shudong
Published: May 2024

Interfacial solar steam generation can produce clean water in an environmentally friendly and efficient way. The evaporator employing graphene as a photothermal conversion material represents an excellent paradigm within the realm of interfacial evaporators. However, existing graphene materials exhibit a certain degree of hydrophobicity and are associated with intricate manufacturing processes. Hence, the study proposes a hydrophilic composite graphene‐based material incorporating CuO, which is fabricated through a straightforward laser‐induced graphene synthesis method directly onto a polyimide film coated with CuCl2. Due to the fast capillary performance endowed by the enhanced hydrophilicity and hierarchical structural morphology, the assembled laser‐induced‐graphene evaporator achieves an evaporation rate of 2.54 kg m−2 h−1 under 1 sun irradiation with an evaporation efficiency of 91.1%, while also demonstrating excellent desalination capabilities. The as‐prepared graphene‐based evaporator has significant potential for desalination and wastewater treatment applications, offering an effective solution to address clean water challenges in remote areas.
Biomaterial‐Based Therapeutic Delivery of Immune Cells
Authors: Dravid Ameya A. , Singh Ankur , García Andrés J.
Published: May 2024

Immune cell therapy (ICT) is a transformative approach used to treat a wide range of diseases including type 1 diabetes, sickle cell disease, disorders of the hematopoietic system, and certain forms of cancers. Despite excellent clinical successes, the scope of adoptively transferred immune cells is limited because of toxicities like cytokine release syndrome and immune effector cell‐associated neurotoxicity in patients. Furthermore, reports suggest that such treatment can impact major organ systems including cardiac, renal, pulmonary, and hepatic systems in the long term. Additionally, adoptively transferred immune cells cannot achieve significant penetration into solid tissues, thus limiting their therapeutic potential. Recent studies suggest that biomaterial‐assisted delivery of immune cells can address these challenges by reducing toxicity, improving localization, and maintaining desired phenotypes to eventually regain tissue function. In this review, recent efforts in the field of biomaterial‐based immune cell delivery for the treatment of diseases, their pros and cons, and where these approaches stand in terms of clinical treatment are highlighted.
NIR‐II Absorption/Emission Dual Function Based 2D Targeted Nanotheranostics for Tunable Hydrogenothermal Therapy
Authors: Li Jinxuan , Gao Mengting , Wang Yuhang , Wang Wenxuan , Meng Shichao , Zhang Xin , Zhang Chongqing , Liu Pengmin , Zhang Xiaodong , Zheng Ziliang , Zhang Ruiping
Published: May 2024

Photothermal therapy (PTT) is a promising approach for treating tumors that offers multiple advantages. Nevertheless, its practical use in clinical settings faces several limitations, such as suboptimal delivery efficiency, uneven heat distribution, and challenges in predicting optimal treatment duration. In addition, the localized hyperthermia generated by the PTT method to induce cell apoptosis can result in the production of excessive reactive oxygen species (ROS) and the release of inflammatory cytokines, which can pose a threat to the healthy tissues surrounding the tumor. To address the above challenges, this work designs an integrated H2 delivery nanoplatform for multimodal imaging H2 thermal therapy. The combination of the second near‐infrared window (NIR‐II) fluorescence imaging (FL) agent (CQ4T) and the photothermal and photoacoustic (PA) properties of Ti3C2 (TC) enables real‐time monitoring of the tumor area and guides photothermal treatment. Simultaneously, due to the acid‐responsive H2 release characteristics of the nanoplatform, H2 can be utilized for synergistic photothermal therapy to eradicate tumor cells effectively. Significantly, acting as an antioxidant and anti‐inflammatory agent, Ti3C2‐BSA‐CQ4T‐H2 (TCBCH) protects peritumoral normal cells from damage. The proposed technique utilizing H2 gas for combination therapies and multimodal imaging integration exhibits prospects for effective and secure treatment of tumors in future clinical applications.
Optically Actuated Soft Microrobot Family for Single‐Cell Manipulation
Authors: Iványi Gergely T. , Nemes Botond , Gróf Ilona , Fekete Tamás , Kubacková Jana , Tomori Zoltán , Bánó Gregor , Vizsnyiczai Gaszton , Kelemen Lóránd
Published: May 2024

Precisely controlled manipulation of nonadherent single cells is often a pre‐requisite for their detailed investigation. Optical trapping provides a versatile means for positioning cells with submicrometer precision or measuring forces with femto‐Newton resolution. A variant of the technique, called indirect optical trapping, enables single‐cell manipulation with no photodamage and superior spatial control and stability by relying on optically trapped microtools biochemically bound to the cell. High‐resolution 3D lithography enables to prepare such cell manipulators with any predefined shape, greatly extending the number of achievable manipulation tasks. Here, it is presented for the first time a novel family of cell manipulators that are deformable by optical tweezers and rely on their elasticity to hold cells. This provides a more straightforward approach to indirect optical trapping by avoiding biochemical functionalization for cell attachment, and consequently by enabling the manipulated cells to be released at any time. Using the photoresist Ormocomp, the deformations achievable with optical forces in the tens of pN range and present three modes of single‐cell manipulation as examples to showcase the possible applications such soft microrobotic tools can offer are characterized. The applications describe here include cell collection, 3D cell imaging, and spatially and temporally controlled cell–cell interaction.
Carbon‐based Flame Retardants for Polymers: A Bottom‐up Review
Authors: Yeoh Guan Heng , De Cachinho Cordeiro Ivan Miguel , Wang Wei , Wang Cheng , Yuen Anthony Chun Yin , Chen Timothy Bo Yuan , Vargas Juan Baena , Mao Guangzhao , Garbe Ulf , Chua Hui Tong
Published: May 2024

This state‐of‐the‐art review is geared toward elucidating the molecular understanding of the carbon‐based flame‐retardant mechanisms for polymers via holistic characterization combining detailed analytical assessments and computational material science. The use of carbon‐based flame retardants, which include graphite, graphene, carbon nanotubes (CNTs), carbon dots (CDs), and fullerenes, in their pure and functionalized forms are initially reviewed to evaluate their flame retardancy performance and to determine their elevation of the flammability resistance on various types of polymers. The early transition metal carbides such as MXenes, regarded as next‐generation carbon‐based flame retardants, are discussed with respect to their superior flame retardancy and multifunctional applications. At the core of this review is the utilization of cutting‐edge molecular dynamics (MD) simulations which sets a precedence of an alternative bottom‐up approach to fill the knowledge gap through insights into the thermal resisting process of the carbon‐based flame retardants, such as the formation of carbonaceous char and intermediate chemical reactions offered by the unique carbon bonding arrangements and microscopic in‐situ architectures. Combining MD simulations with detailed experimental assessments and characterization, a more targeted development as well as a systematic material synthesis framework can be realized for the future development of advanced flame‐retardant polymers.
Dual‐Adaptive Heterojunction Synaptic Transistors for Efficient Machine Vision in Harsh Lighting Conditions
Authors: Wang Yiru , Nie Shimiao , Liu Shanshuo , Hu Yunfei , Fu Jingwei , Ming Jianyu , Liu Jing , Li Yueqing , He Xiang , Wang Le , Li Wen , Yi Mingdong , Ling Haifeng , Xie Linghai , Huang Wei
Published: May 2024

Photoadaptive synaptic devices enable in‐sensor processing of complex illumination scenes, while second‐order adaptive synaptic plasticity improves learning efficiency by modifying the learning rate in a given environment. The integration of above adaptations in one phototransistor device will provide opportunities for developing high‐efficient machine vision system. Here, a dually adaptable organic heterojunction transistor as a working unit in the system, which facilitates precise contrast enhancement and improves convergence rate under harsh lighting conditions, is reported. The photoadaptive threshold sliding originates from the bidirectional photoconductivity caused by the light intensity‐dependent photogating effect. Metaplasticity is successfully implemented owing to the combination of ambipolar behavior and charge trapping effect. By utilizing the transistor array in a machine vision system, the details and edges can be highlighted in the 0.4% low‐contrast images, and a high recognition accuracy of 93.8% with a significantly promoted convergence rate by about 5 times are also achieved. These results open a strategy to fully implement metaplasticity in optoelectronic devices and suggest their vision processing applications in complex lighting scenes.
Diastereoselective Synthesis of CF3‐Pyrano[3,4‐c]quinolones from Hetero‐Dendralenes and Aldehydes
Authors: Nagababu Chavakula , Sainadh Srirangam , Desagoni Madhu , Nanubolu Jagadeesh Babu , Punna Nagender
Published: May 2024

Herein, we demonstrate an Oxa‐Diels‐Alder reaction of 3‐trifluoroacetyl‐4‐methyl‐quinolin‐2(1H)‐one with aldehydes in the presence of a base to engineer the functionalized pyrano[3,4‐c]quinolones. This reaction proceeds through an in‐situ generated hetero dendralene intermediate and features perfect stereoselectivity on a wide range of substrates with excellent atom economy. The high electron‐withdrawing nature of CF3‐group is responsible for making the methyl group present in quinolone moiety more acidic to furnish the corresponding hetero dendralene intermediate.
Two Catalytic Protocols for the Synthesis of CF2‐Containing Quinazolinones via Domino Reaction
Authors: Wei Congyin , Yu Zhiyou , Shi Lei
Published: May 2024

Copper‐catalyzed and visible‐light catalytic difluoroalkylation reactions of N‐cyanamide alkenes have been developed. Various α‐bromodifluoromethyl substituted esters, amides and heterocycles were employed as the CF2 source. Both protocols are characterized by medium to high yields, good functional group compatibility, and applicable to gram‐scale synthesis. Comparable studies of copper catalysis and photoredox catalysis demonstrate minimal differences between the two protocols. Preliminary mechanism suggest that both transformations involve tandem radical cyclization process.
Characteristics of MAPbI3 Stacked on the GaN Nanowires‐On‐Glass
Authors: Lee Kwang Jae , Kim Yeong Jae , Min Jung‐Hong , Kang Chun Hong , Subedi Ram Chandra , Zhang Huafan , Al‐Maghrabi Latifah , Park Kwangwook , Ahn Dante , Pak Yusin , Ng Tien Khee , Song Young Min , Ooi Boon S. , Bakr Osman M. , Min Jungwook
Published: May 2024

When implementing optoelectronic devices through the stacking of heterogeneous materials, considering the bandgap offset is crucial for achieving efficient carrier dynamics. In this study, the bandgap offset characteristics are investigated when n‐type gallium nitride nanowires (n‐GaN NWs) are used as electron transport layers in methylammonium lead iodide (MAPbI3)‐based optoelectronic devices. n‐GaN NWs are grown on indium‐tin‐oxide (ITO)‐coated glass via the plasma‐assisted molecular beam epitaxy (PA‐MBE) process to form the “GaN NWs‐on‐glass” platform. A MAPbI3 thin film is then spin‐coated on the GaN NWs‐on‐glass. X‐ray photoelectron spectroscopy (XPS) shows that the valence and conduction band offsets in the MAPbI3/n‐GaN heterostructure are 2.19 and 0.40 eV, respectively, indicating a type‐II band alignment ideal for optoelectronic applications. Prototype photovoltaic devices stacking perovskite on GaN NWs‐on‐glass show excellent interfacial charge‐transfer ability, photon recycling, and carrier extraction efficiency. As a pioneering step in exploiting the diverse potential of the GaN‐on‐glass, it is demonstrated that the junction characteristics of MAPbI3/n‐GaN NW heterostructures can lead to a variety of optoelectronic device applications.
Silver Single Atoms Combined with Clusters on Carbon Nanotubes Mediates Exclusive Electrochemical CO2‐to‐CO Conversion
Authors: Xu Yanzhi , Zhang Xu , Yang Chenyu , Gong Chen , Qin Xupeng , Sun Haixin , Chen Honglei , Soldatov Mikhail A. , Zheng Kun , Li Changli , Gan Tao , Li Jiong , He Jingfu , Liu Qinghua
Published: May 2024

The electrochemical reduction of CO2 (eCO2RR) that exclusively produces one product at industrial current density is crucial for the substantial storage of renewable energy. Modulating the electronic structure of atomically dispersed catalysts can effectively regulate the adsorption of rate‐determining‐step intermediates to achieve the desired products. Here, the study constructs a hybrid catalyst consisting of single Ag atoms and Ag atomic clusters supported on nitrogen‐doped multi‐walled carbon nanotubes that can effectively regulate the important intermediate structure of *COOH. The X‐ray photoelectron and X‐ray absorption near‐edge spectroscopies demonstrate that turning Ag single atoms into Ag clusters can weaken the electron transfer between Ag–N and present a relatively rich electron state. Thus, the rate‐determining step of *COOH massive formation is significantly accelerated, as proven by in situ synchrotron infrared spectroscopy and density functional theory calculations. Using this strategy, a CO Faradaic efficiency outperforming 99% from −0.3 to −0.8 V (vs reversible hydrogen electrode) with current densities above 200 mA cm−2 and a half‐cell energetic efficiency of 86% is achieved. This work highlights a promising approach to advancing synergistic catalysts for achieving more controllable and efficient eCO2RR.