bluuebunny/crossref_metadata_2025 huggingface dataset:
Grau de internacionalização de empresas brasileiras de manufaturados e a influência de fatores organizacionais e estratégicos
Authors: Honório Luiz Carlos
Published: August 2010

O artigo tem por objetivo identificar quais os fatores organizacionais influenciam o processo estratégico internacional. Pretende, também, analisar a influência dos fatores organizacionais e estratégicos sobre o grau de internacionalização da firma em termos de indicadores financeiros e não financeiros de desempenho, respectivamente, volume de vendas e dispersão geográfica. Realizou-se uma survey com 73 empresas brasileiras do setor de manufatura que desenvolvem negócios internacionais por meio de diferentes modalidades, desde a exportação até o investimento direto no estrangeiro. Os resultados encontrados evidenciam que fatores organizacionais associados ao tamanho da firma influenciam fundamentalmente o processo estratégico internacional das empresas pesquisadas, cujo desenrolar é demarcado por elementos centralizadores e racionais. O grau de internacionalização das empresas pesquisadas mostra-se influenciado pelo fator organizacional associado à experiência internacional e pelos fatores estratégicos associados ao modo deliberado de formação estratégica (top-down) e à escolha de parcerias internacionais.
Staphylococcus Coagulase-Positive Skin Inflammation Associated with Epidermal Growth Factor Receptor-Targeted Therapy: An Early and a Late Phase of Papulopustular Eruptions
Authors: Amitay-Laish Iris , David Michael , Stemmer Salomon M.
Published: August 2010

Objective.

Cutaneous eruptions, mainly papulopustular, are the most common associated side effects of epidermal growth factor receptor inhibitors (EGFRIs).

This study investigated the possible role of bacterial infection in EGFRI-induced eruptions and its relation to clinical morphology.

Patients and Methods.

The study group consisted of all 29 patients referred for dermatologic evaluation of side effects of cetuximab or erlotinib from March 2008 to November 2009. Specimens were taken for bacterial culture from pustules in patients with grade >1 papulopustular rash and from periungual secretions in patients with paronychia.

Results.

Twenty-four of 29 patients had a papulopustular reaction; five of 29 had paronychia/xerosis. Of the papulopustular eruption patients, time to rash appearance yielded two distinct groups: early-phase, median 8 days after drug initiation, located mainly on the face (n = 17) and late-phase, median ∼200 days after drug initiation, located mainly on the trunk (n = 7). Bacterial culture grew Staphylococcus aureus (SA) in seven of 13 early-phase patients tested and in all late-phase patients. Treatment consisted of topical steroids with or without topical/systemic antibiotics. All patients had a clear improvement in their cutaneous symptoms within a few days. Dose reduction or temporary discontinuation of the EGFRI was necessary in only four of 29 patients.

Conclusions.

As described in the literature, EGFRI-induced papulopustular eruption may appear early and probably is an inflammatory process with or without SA secondary infection. The papulopustular eruption may also appear as a late phase, described here for the first time, which is an infectious process with all patients being SA+.

The >50% overall incidence of SA infection in our study highlights the need for routine bacterial cultures from EGFRI-induced eruption.
Patient-Centered Mental Health Care: Encouraging Caregiver Participation
Authors: Buila Sarah Melinda Dobie , Swanke Jayme R.
Published: August 2010

Caregivers of patients with mental illness play a vital role caring for their loved ones, yet they may not always be fully included in the process of assessment and treatment. A patient-centered approach to treating persons with mental illness views caregivers as partners in providing care for the patient. This study sought to explore perceptions of caregivers of persons with mental illness regarding the care their loved ones receive and to illicit specific issues caregivers wish to communicate with professionals that could improve patient care. A modified nominal group technique exercise was conducted as part of a suicide prevention workshop. Participants completed a four-item questionnaire. Five main themes emerged: the caregivers’ perception that they need to be included in the mental health care of their loved one; concerns about the diagnosing process; communication with professionals; a desire for individualized, holistic treatment; and the need for information about services and resources for the caregiver and the patient. Findings are similar to studies that also sought to understand the perspectives of caregivers. Caregivers provide an invaluable resource for the patient with mental illness. Efforts to include caregivers would enhance the overall care provided to patients with mental illness.
Irony and the Sociocultural Construction of Old Age in South Korea: Perspectives From Government, the Medical Profession, and the Aged
Authors: Kim Heekyoung , Traphagan John W.
Published: August 2010

This article explores the intersection between discourses with multiple meanings that relate to the cultural construction of elder identities in South Korea. The authors explore the experiences of elder patients at a free clinic to consider how government policy, attitudes among biomedical professionals, and elders themselves come into contact and influence the experiences of older Koreans within the national health care system. The study is ethnographic, using interview data to examine how the identities of elder Koreans are being shifted from “weak and in need of care” to “potentially problematic consumer” and how governmental policies both stimulate and respond to that shift. By focusing on the situational status of the elderly, this article is intended to represent the voices of some elderly, voices that can be submerged within the process of decision making related to public policy.
General Assistance Recipients and Welfare‐To‐Work Programs: Evidence from New York City
Authors: Ifcher John
Published: August 2010

General Assistance (GA) programs are virtually unstudied. Yet, GA programs serve an economically vulnerable, non‐trivial population that should be of interest. To begin to address this shortcoming, two welfare‐to‐work programs, in which GA recipients participated, are studied. Using a quasi‐experimental approach, the effect of each program on welfare use and employment is estimated. The results indicate that each program significantly increased welfare exits and that the second program significantly increased employment (employment data was unavailable for the first program).
Does Low Inequality Cause Low Poverty? Evidence from High‐Income and Developing Countries
Authors: Wagle Udaya R
Published: August 2010

This paper examines the role of economic inequality in determining poverty globally. Although the immediate observation from the cross‐national data covering 1980 to 2005 suggests the relationship to be strong and positive for high‐income countries and unpredictable for developing countries, more comprehensive analyses detect it to be consistently positive. While high‐income and developing countries typically apply different poverty measurement methodologies with the former using relative and the latter using absolute poverty thresholds, variations in poverty outcomes go beyond these methodological differences. Rejecting any systematic role of economic growth, especially in cases of developing countries, these findings reaffirm the pivotal role that reduction in inequality can play in effectively curbing poverty, with important implications for redistributive policies.
Review of To Right These Wrongs: The North Carolina Fund and the Battle to End Poverty and Inequality in 1960s America
Authors: Seroka Jim
Published: August 2010

Jim Seroka, a professor at Auburn University and a member of the Poverty & Public Policy editorial board, examines and offers his thoughts regarding To Right These Wrongs.
The People, the Economy, and the Issues: A Participant Reports on National “Town Hall” Meetings on the Deficit
Authors: Skidmore Max J.
Published: August 2010

On June 26, 2010, the organization “AmericaSpeaks” sponsored “town hall meetings” in various cities around the United States, built around the theme “Our Budget, Our Economy.” The sessions purported to aim at determining the degree of support from citizens for various ways to reduce the country's budget deficit. Editor Max J. Skidmore applied to attend one of these meetings, and was accepted. He reports on his experiences as a participant, and also examines the validity of the overall activity, one that its organizers describe as an objective effort to assess public opinion. He concludes that such efforts are no substitute for scientific polling, that they are more effective as public relations exercises than opinion assessment, and that activities such as “Our Budget, Our Economy,” if effective, could potentially affect poverty adversely.
A Tale of Three Commissions: The Good, the Bad, and the Ugly
Authors: Kingson Eric R.
Published: August 2010

Eric Kingson was an advisor to the 1982 National Commission on Social Security Reform and to the 1994 Bipartisan Commission on Entitlements and Tax Reform. Drawing on the experience of 1982 (the “Good”) and 1994 (the “Bad”) commissions, he concludes that the fast‐track debt commission as proposed by Senators Kent Conrad and Judd Gregg would result in an unprecedented and deleterious approach to Social Security policy‐making. The structure and functioning of the 1994 commission provides insight into likely goals and functioning of the Conrad‐Gregg Commission, a commission Kingson suggests would be akin to the 1994 entitlement commission “on steroids.” Noting the disregard for traditional congressional processes and the mischaracterization of Social Security as part of a unified “entitlements” problem, Kingson concludes that Senator Max Baucus is not exaggerating when he warned on the Senate floor that “Senators Conrad and Gregg have painted a big red target on Social Security and Medicare. That's what this commission is all about.”
Effect of colostral volume, interval between calving and first milking, and photoperiod on colostral IgG concentrations in dairy cows
Authors: Morin Dawn E. , Nelson Stephanie V. , Reid Eric D. , Nagy Dusty W. , Dahl Geoffrey E. , Constable Peter D.
Published: August 2010

Objective—To identify cow and management factors associated with colostral IgG concentration in dairy cows.

Design—Prospective observational study.

Animals—81 multiparous Holstein-Friesian cows from a single herd.

Procedures—Serum was obtained at the start of the nonlactating period, and cows were assigned to 1 of 4 photoperiod groups: natural day length (n = 22 cows), long days (16 h of light/d [21]) or short days (8 h of light/d [20]) for the entire nonlactating period, or natural day length followed by short days for the last 21 days of the nonlactating period (18). Serum and colostrum were collected at the first milking after calving. Regression analysis was used to investigate associations between colostral IgG concentration and the interval between calving and first milking, colostral volume, photoperiod, length of the nonlactating period, and season of calving.

Results—Colostral IgG concentration decreased by 3.7% during each subsequent hour after calving because of postparturient secretion by the mammary glands. The interval between calving and first milking and the colostral volume were significantly and negatively associated with colostral IgG concentration, with the former effect predominating. Photoperiod had no effect on colostral IgG concentration or volume. Serum protein concentration at calving correlated poorly with colostral IgG concentration.

Conclusions and Clinical Relevance—Dairy producers should harvest colostrum as soon as possible after calving to optimize transfer of passive immunity in neonatal calves. Photoperiod can be manipulated without adversely affecting colostral IgG concentration.
The molecular cloning of glial fibrillary acidic protein in Gekko japonicus and its expression changes after spinal cord transection
Authors: Gao Dehong , Wang Yongjun , Liu Yan , Ding Fei , Gu Xiaosong , Li Zhengli
Published: August 2010

The glial fibrillary acidic protein (GFAP) is an astrocyte-specific member of the class III intermediate filament proteins. It is generally used as a specific marker of astrocytes in the central nervous system (CNS). We isolated a GFAP cDNA from the brain and spinal cord cDNA library of Gekko japonicus, and prepared polyclonal antibodies against gecko GFAP to provide useful tools for further immunochemistry studies. Both the real-time quantitative PCR and western blot results revealed that the expression of GFAP in the spinal cord after transection increased, reaching its maximum level after 3 days, and then gradually decreased over the rest of the 2 weeks of the experiment. Immunohistochemical analyses demonstrated that the increase in GFAP-positive labeling was restricted to the white matter rather than the gray matter. In particular, a slight increase in the number of GFAP positive star-shaped astrocytes was detected in the ventral and lateral regions of the white matter. Our results indicate that reactive astrogliosis in the gecko spinal cord took place primarily in the white matter during a short time interval, suggesting that the specific astrogliosis evaluated by GFAP expression might be advantageous in spinal cord regeneration.
Can We Enhance Durable Resistance Against Plasmopara Halstedii (Sunflower Downy Mildew)?
Authors: Sakr Nachaat
Published: August 2010

Can We Enhance Durable Resistance AgainstPlasmopara Halstedii(Sunflower Downy Mildew)?

Sunflower downy mildew caused byPlasmopara halstediiis one of the most potentially important diseases. So far, a complete, major gene resistance (Pl) has been used successfully, but with the appearance of eight races in France since 2000, research on more durable resistance was undertaken. In this study, we present new results concerning the evolution of pathogenicity ofP. halstediiunder conditions of re-enforced infection and differentPlgene selection pressures. Moreover, we imagine the evolution of virulence and aggressiveness ofP. halstediiunder a mixture model of sunflower inbred lines carrying the two types of resistance which may enhance durable resistance against it. Examples of host-parasite interactions including the influence of plant mixture models against pathogens are equally presented to understand how the pathogen develops its pathogenicicity.
Efficacy of Some Bioinsecticides Against Bruchidius Incarnatus (Boh.) (Coleoptera: Bruchidae) Infestation During Storage
Authors: Sabbour Magda , E-Abd-El-Aziz Shadia
Published: August 2010

Efficacy of Some Bioinsecticides AgainstBruchidius Incarnatus(Boh.) (Coleoptera: Bruchidae) Infestation During Storage

Potential activities of three essential oils (cumin, clove and mustard) and of microbial agents (Paecilomyces fumosoroseus, Nomuraea rileyi, Lecanicillium (Verticillium) lecaniiand their combinations againstBruchidius incarnatus(Boh.) were evaluated. In choice test, mustard and clove oils revealed a strong repellent activity after 7 days (89% and 71%, respectively) againstB. incarnatusbeetles. Cumin oil showed the lowest repellency (47%). Accumulative mortality of beetles increased gradually with the increase of exposure intervals. Mustard oil treatment gave the highest mortality percentage of 76% after 168 h from treatment followed by clove treatment which amounted to 63% and the lowest percentage of 42.8% was recorded in case of cumin oil. Mustard oil was the most effective in enhancing the potency ofP. fumosoroseusandN. rileyiand decreased LC50of the target insect (100 and 102×107, respectively). The persistent effect of formulated mustard oil with eitherP. fumosoroseusorN. rileyifungi on foam covering gunny bags displayed several different modes of action, by reducing oviposition and adult emergence (F1) ofB. incarnatus.The oviposition was completely inhibited when stored broad bean seeds were treated with mustard oil +P. fumosoroseusduring 20, 40 and 60 days of storage. Application of mustard oil combined withP. fumosoroseuson foam covering gunny bags provided promising oviposition deterrency, toxicity and suppressingB. incarnatusinfestation, persistence and protecting broad bean seeds from beetles' infestation for 120 days during storage.
Comparison of monoclonal antibody performance characteristics for the detection of two representatives of A- and B-trichothecenes: T-2 toxin and deoxynivalenol
Authors: Baumgartner S. , Führer M. , Krska R.
Published: August 2010

Mycotoxins are secondary metabolites produced by fungi belonging mainly to the Aspergillus, Penicillium and
Fusarium genera. They represent a relevant source of danger to human and animal health causing food- and feedborne
intoxication. One group, produced by Fusarium spp., are the trichothecenes, of which T-2 toxin belongs to
the type-A trichothecenes and deoxynivalenol to the type-B trichothecenes. As these mycotoxins are ubiquitous,
the testing of products is required to keep our food and feed safe. For this purpose, sensitive and reliable tests
are needed to detect contaminations. One detection possibility is an immunoanalytical based test which needs
antibodies as reagents. Cell culture facilities allow cell line selection and production of monoclonal antibodies
for further immunological test development. Especially for mycotoxins antibody development for further use in
immunoassays is a crucial task. T-2 toxin and deoxynivalenol specific monoclonal antibodies were developed and
further characterised to test stability and solvent resistance properties. Especially cross-reactivities were determined
to related mycotoxins also belonging to the trichothecene family, e.g. HT-2 toxin or 3-acetyldeoxynivalenol.
Neisseria lactamicaSelectively Induces Mitogenic Proliferation of the Naive B Cell Pool via Cell Surface Ig
Authors: Vaughan Andrew T. , Brackenbury Louise S. , Massari Paola , Davenport Victoria , Gorringe Andrew , Heyderman Robert S. , Williams Neil A.
Published: August 2010

Neisseria lactamica is a commensal bacteria that colonizes the human upper respiratory tract mucosa during early childhood. In contrast to the closely related opportunistic pathogen Neisseria meningitidis, there is an absence of adaptive cell-mediated immunity to N. lactamica during the peak age of carriage. Instead, outer membrane vesicles derived from N. lactamica mediate a B cell-dependent proliferative response in mucosal mononuclear cells that is associated with the production of polyclonal IgM. We demonstrate in this study that this is a mitogenic human B cell response that occurs independently of T cell help and any other accessory cell population. The ability to drive B cell proliferation is a highly conserved property and is present in N. lactamica strains derived from diverse clonal complexes. CFSE staining of purified human tonsillar B cells demonstrated that naive IgD+ and CD27− B cells are selectively induced to proliferate by outer membrane vesicles, including the innate CD5+ subset. Neither purified lipooligosaccharide nor PorB from N. lactamica is likely to be responsible for this activity. Prior treatment of B cells with pronase to remove cell-surface Ig or treatment with BCR-specific Abs abrogated the proliferative response to N. lactamica outer membrane vesicles, suggesting that this mitogenic response is dependent upon the BCR.
A Complementary Role for the Tetraspanins CD37 and Tssc6 in Cellular Immunity
Authors: Gartlan Kate H. , Belz Gabrielle T. , Tarrant Jacqueline M. , Minigo Gabriela , Katsara Maria , Sheng Kuo-Ching , Sofi Mariam , van Spriel Annemiek B. , Apostolopoulos Vasso , Plebanski Magdalena , Robb Lorraine , Wright Mark D.
Published: August 2010

The cooperative nature of tetraspanin–tetraspanin interactions in membrane organization suggests functional overlap is likely to be important in tetraspanin biology. Previous functional studies of the tetraspanins CD37 and Tssc6 in the immune system found that both CD37 and Tssc6 regulate T cell proliferative responses in vitro. CD37−/− mice also displayed a hyper-stimulatory dendritic cell phenotype and dysregulated humoral responses. In this study, we characterize “double knockout” mice (CD37−/−Tssc6−/−) generated to investigate functional overlap between these tetraspanins. Strong evidence for a cooperative role for these two proteins was identified in cellular immunity, where both in vitro T cell proliferative responses and dendritic cell stimulation capacity are significantly exaggerated in CD37−/−Tssc6−/− mice when compared with single knockout counterparts. Despite these exaggerated cellular responses in vitro, CD37−/−Tssc6−/− mice are not more susceptible to autoimmune induction. However, in vivo responses to pathogens appear poor in CD37−/−Tssc6−/− mice, which showed a reduced ability to produce influenza-specific T cells and displayed a rapid onset hyper-parasitemia when infected with Plasmodium yoelii. Therefore, in the absence of both CD37 and Tssc6, immune function is further altered when compared with CD37−/− or Tssc6−/− mice, demonstrating a complementary role for these two molecules in cellular immunity.
Position-Dependent Silencing of Germline Vβ Segments on TCRβ Alleles Containing Preassembled VβDJβCβ1 Genes
Authors: Brady Brenna L. , Oropallo Michael A. , Yang-Iott Katherine S. , Serwold Thomas , Hochedlinger Konrad , Jaenisch Rudolf , Weissman Irving L. , Bassing Craig H.
Published: August 2010

The genomic organization of TCRβ loci enables Vβ-to-DJβ2 rearrangements on alleles with assembled VβDJβCβ1 genes, which could have deleterious physiologic consequences. To determine whether such Vβ rearrangements occur and, if so, how they might be regulated, we analyzed mice with TCRβ alleles containing preassembled functional VβDJβCβ1 genes. Vβ10 segments were transcribed, rearranged, and expressed in thymocytes when located immediately upstream of a Vβ1DJβCβ1 gene, but not on alleles with a Vβ14DJβCβ1 gene. Germline Vβ10 transcription was silenced in mature αβ T cells. This allele-dependent and developmental stage-specific silencing of Vβ10 correlated with increased CpG methylation and decreased histone acetylation over the Vβ10 promoter and coding region. Transcription, rearrangement, and expression of the Vβ4 and Vβ16 segments located upstream of Vβ10 were silenced on alleles containing either VβDJβCβ1 gene; sequences within Vβ4, Vβ16, and the Vβ4/Vβ16-Vβ10 intergenic region exhibited constitutive high CpG methylation and low histone acetylation. Collectively, our data indicate that the position of Vβ segments relative to assembled VβDJβCβ1 genes influences their rearrangement and suggest that DNA sequences between Vβ segments may form boundaries between active and inactive Vβ chromatin domains upstream of VβDJβCβ genes.
Trans- but Not Cis-Resveratrol Impairs Angiotensin-II–Mediated Vascular Inflammation through Inhibition of NF-κB Activation and Peroxisome Proliferator-Activated Receptor-γ Upregulation
Authors: Rius Cristina , Abu-Taha May , Hermenegildo Carlos , Piqueras Laura , Cerda-Nicolas Jose-Miguel , Issekutz Andrew C. , Estañ Luís , Cortijo Julio , Morcillo Esteban J. , Orallo Francisco , Sanz Maria-Jesus
Published: August 2010

Angiotensin II (Ang-II) displays inflammatory activity and is implicated in several cardiovascular disorders. This study evaluates the effect of cis- and trans (t)-resveratrol (RESV) in two in vivo models of vascular inflammation and identifies the cardioprotective mechanisms that underlie them. In vivo, Ang-II–induced arteriolar leukocyte adhesion was inhibited by 71% by t-RESV (2.1 mg/kg, i.v.), but was not affected by cis-RESV. Because estrogens influence the rennin-angiotensin system, chronic treatment with t-RESV (15 mg/kg/day, orally) inhibited ovariectomy-induced arteriolar leukocyte adhesion by 81%, partly through a reduction of cell adhesion molecule (CAM) expression and circulating levels of cytokine-induced neutrophil chemoattractant, MCP-1, and MIP-1α. In an in vitro flow chamber system, t-RESV (1–10 μM) undermined the adhesion of human leukocytes under physiological flow to Ang-II–activated human endothelial cells. These effects were accompanied by reductions in monocyte and endothelial CAM expression, chemokine release, phosphorylation of p38 MAPK, and phosphorylation of the p65 subunit of NF-κB. Interestingly, t-RESV increased the expression of peroxisome proliferator-activated receptor-γ in human endothelial and mononuclear cells. These results demonstrate for the first time that the in vivo anti-inflammatory activity of RESV is produced by its t-RESV, which possibly interferes with signaling pathways that cause the upregulation of CAMs and chemokine release. Upregulation of proliferator-activated receptor-γ also appears to be involved in the cardioprotective effects of t-RESV. In this way, chronic administration of t-RESV may reduce the systemic inflammatory response associated with the activation of the rennin-angiotensin system, thereby decreasing the risk of further cardiovascular disease.
Alport Alloantibodies but Not Goodpasture Autoantibodies Induce Murine Glomerulonephritis: Protection by Quinary Crosslinks Locking Cryptic α3(IV) Collagen Autoepitopes In Vivo
Authors: Luo Wentian , Wang Xu-Ping , Kashtan Clifford E. , Borza Dorin-Bogdan
Published: August 2010

The noncollagenous (NC1) domains of α3α4α5(IV) collagen in the glomerular basement membrane (GBM) are targets of Goodpasture autoantibodies or Alport posttransplant nephritis alloantibodies mediating rapidly progressive glomerulonephritis. Because the autoepitopes but not the alloepitopes become cryptic upon assembly of α3α4α5NC1 hexamers, we investigated how the accessibility of B cell epitopes in vivo influences the development of glomerulonephritis in mice passively immunized with human anti-GBM Abs. Alport alloantibodies, which bound to native murine α3α4α5NC1 hexamers in vitro, deposited linearly along the mouse GBM in vivo, eliciting crescentic glomerulonephritis in Fcgr2b−/− mice susceptible to Ab-mediated inflammation. Goodpasture autoantibodies, which bound to murine α3NC1 monomer and dimer subunits but not to native α3α4α5NC1 hexamers in vitro, neither bound to the mouse GBM in vivo nor induced experimental glomerulonephritis. This was due to quinary NC1 crosslinks, recently identified as sulfilimine bonds, which comprehensively locked the cryptic Goodpasture autoepitopes in the mouse GBM. In contrast, non-crosslinked α3NC1 subunits were identified as a native target of Goodpasture autoantibodies in the GBM of squirrel monkeys, a species susceptible to Goodpasture autoantibody-mediated nephritis. Thus, crypticity of B cell autoepitopes in tissues uncouples potentially pathogenic autoantibodies from autoimmune disease. Crosslinking of α3α4α5NC1 hexamers represents a novel mechanism averting autoantibody binding and subsequent tissue injury by posttranslational modifications of an autoantigen.
The MAPK/ERK and PI(3)K Pathways Additively Coordinate the Transcription of Recombination-Activating Genes in B Lineage Cells
Authors: Novak Rostislav , Jacob Eyal , Haimovich Joseph , Avni Orly , Melamed Doron
Published: August 2010

Rag-1 and Rag-2 are essential for the construction of the BCR repertoire. Regulation of Rag gene expression is tightly linked with BCR expression and signaling during B cell development. Earlier studies have shown a major role of the PI(3)K/Akt pathway in regulating the transcription of Rag genes. In this study, by using the 38c13 murine B cell lymphoma we show that transcription of Rag genes is also regulated by the MEK/ERK pathways, and that both pathways additively coordinate in this regulation. The additive effect is observed for both ligand-dependent (upon BCR ligation) and ligand independent (tonic) signals. However, whereas the PI(3)K/Akt regulation of Rag transcription is mediated by Foxo1, we show in this study that the MEK/ERK pathway coordinates with the regulation of Rag by controlling the phosphorylation and turnover of E47 and its consequential binding to the Rag enhancer regions. Our results suggest that the PI(3)K and MEK/ERK pathways additively coordinate in the regulation of Rag transcription in an independent manner.
Blood Testing for Phosphatidylethanol
Authors: Mazhar Areej , Cheung Amanda
Published: May 2024

A 36-year-old man with obesity and dyslipidemia presented with elevated liver enzymes following a liver transplant to treat acute-on-chronic liver failure due to alcohol-associated hepatitis. What would you do next?
Fosamax Fractures—Justice Has Not Been Served
Authors: Curfman Gregory
Published: May 2024

This Viewpoint discusses the ongoing lawsuit between plaintiffs who had been affected by atypical femoral fractures while receiving alendronate and the drug manufacturer.
Sociopolitical Factors and Mental Health Following the Turkey-Syria Earthquake
Authors: Hou Wai Kai , Tao Tiffany Junchen , Li Crystal Jingru , Wong Evon Lam , Saral Aysuhan Tuba , Liu Huinan , Galea Sandro
Published: May 2024

This survey study evaluates the association between sociopolitical factors and mental health following the 2023 Turkey-Syria earthquake.
Patient Preferences for Telemedicine Video Backgrounds
Authors: Houchens Nathan , Saint Sanjay , Kuhn Latoya , Ratz David , Engle Jason M. , Meddings Jennifer
Published: May 2024

This cross-sectional study assesses patient preferences for various visual backgrounds during telemedicine video visits.
Upadacitinib in Active Non‐radiographic Axial Spondyloarthritis: 1‐Year Data From a Double‐Blind, Randomized, Placebo‐Controlled, Phase 3 Trial
Authors: Van den Bosch Filip , Deodhar Atul , Poddubnyy Denis , Maksymowych Walter P. , van der Heijde Désirée , Kim Tae‐Hwan , Kishimoto Mitsumasa , Baraliakos Xenofon , Li Yihan , D'Silva Kristin , Wung Peter , Song In‐Ho
Published: May 2024

Objective

Upadacitinib improved the signs and symptoms of non‐radiographic axial spondyloarthritis (nr‐axSpA) versus placebo over 14 weeks in the primary analysis of the SELECT‐AXIS 2 nr‐axSpA study. Here, we evaluated the efficacy and safety of upadacitinib through 1 year in patients with nr‐axSpA in SELECT‐AXIS 2.

Methods

Patients aged at least 18 years diagnosed with nr‐axSpA who fulfilled the 2009 Assessment of SpondyloArthritis International Society (ASAS) classification criteria and were receiving stable background therapy were randomized to upadacitinib 15 mg once daily or placebo for the 52‐week double‐blind period. Efficacy was assessed using non‐responder imputation incorporating multiple imputation (NRI‐MI) and as‐observed analyses for binary endpoints, and mixed‐effects model repeated measures for continuous endpoints.

Results

Of 314 randomized patients, 259 (upadacitinib, n = 129; placebo, n = 130) completed 52 weeks of treatment. More patients receiving upadacitinib versus placebo achieved ≥40% improvement in ASAS at week 52 (63% vs 43%, NRI‐MI; nominal P < 0.001). Similar treatment effects were observed for the achievement of axSpA Disease Activity Score inactive disease (33% v 11%, NRI‐MI; nominal P < 0.001). Overall, patients receiving upadacitinib versus placebo showed greater improvement in disease activity, inflammation, pain, function, enthesitis, and quality of life through 52 weeks. Adverse events were generally comparable between the treatment groups. No opportunistic infections, malignancies, major adverse cardiovascular events, venous thromboembolic events, inflammatory bowel disease, or deaths were reported in those receiving upadacitinib.

Conclusion

Treatment with upadacitinib showed sustained efficacy versus placebo with no new safety findings identified through 1 year. These results support the continued favorable benefit–risk profile of upadacitinib treatment for nr‐axSpA.
Bioabsorbable Composite Laminates of Poly‐Lactic Acid Reinforced with Surface‐Modified Mg Wires for Orthopedic Implant Applications
Authors: Ali Wahaaj , González Carlos , Kopp Alexander , LLorca Javier
Published: May 2024

Unidirectional and multidirectional laminates of Mg‐wire‐reinforced poly‐lactic‐acid–matrix composites are manufactured by an improved compression molding strategy that allows excellent control on the position and orientation of the wires. Two different types of Mg wires, with and without surface modification by continuous plasma electrolytic oxidation, are used, the former to improve the interfacial strength and to reduce the degradation rate of Mg wires in biological environments. The mechanical properties of the constituents as well as of composites are measured before and after in vitro degradation by immersion in simulated body fluids and the corresponding deformation, fracture, and degradation mechanisms are analyzed in detail. It is found that the presence of the Mg wires improves the mechanical behavior in tension and compression of unidirectional composites in the longitudinal direction (close to cortical bone) and that quasi‐isotropic laminates with tailored properties can be designed from the data of unidirectional composites.
Intrabacterial Nitroreductase‐Activated Imaging and Persistently Illuminated Photodynamic Therapy for Intracellular Infection Theranostics
Authors: Ran Pan , Cao Wenxiong , Zheng Huan , Xie Shuang , Zhang Guiyuan , Liu Yuan , Li Xiaohong
Published: May 2024

Intracellular bacterial (ICB) infection is one of the most life‐threatening cases of drug resistance, and photodynamic therapy (PDT) is challenged by limited light penetration into tissues and unspecific toxicity to host cells. Herein, theranostic nanoparticles (NPs) are developed to facilitate on‐demand activation of photosensitizers inside ICBs and persistent PDT of deep‐tissue ICB infections. Mechanoluminescent SrAl2O4:Eu2+ and persistence luminescent CaS:Eu2+ are sequentially deposited on mesoporous silica to prepare mSC, followed by encapsulation by bacterial membranes with loaded nitroreductase (NTR)‐activatable methylene blue (nMB) to obtain mSC‐nMB@BM NPs. The fluorescence quenching of nMB with mSC offers few cytotoxicities even under ultrasonication, and bacterial membrane coatings mediate the specific NP internalization into ICB‐infected macrophages. Bacterial pore‐forming toxins trigger nMB release from NPs, and intrabacterial NTR rejuvenates methylene blue probes from nMB for real‐time imaging of ICB infections. Ultrasonication of NPs continuously excites the rejuvenated methylene blue to generate reactive oxidative species and reduce viable ICBs by 3.54 log magnitude folds. NP treatment on ICB‐infected mice exhibits full survival and restores viscera functions without any pathological abnormality. Therefore, this concise NP design demonstrates capabilities of bacterial membrane‐mediated specific internalization, bacterial toxin‐triggered release and intrabacterial NTR‐rejuvenation of fluorescent probes, and persistent internal light‐illumination for ICB theranostics.
A Simple In Situ Marker Guiding Shape‐Controlled Synthesis of Iron Oxide Nanoparticles
Authors: Llacer‐Wintle Joaquin , Hertle Lukas , Ziegler Salomon , Pellicer Eva , Roca Alejandro G. , Nogués Josep , Puigmartí‐Luis Josep , Nelson Bradley J. , Chen Xiang‐Zhong , Pané Salvador
Published: May 2024

Thermal decomposition of iron oleate is a simple and widespread method for synthesizing monodispersed iron oxide nanoparticles (IONPs) with well‐defined morphology. However, the complexity of the underlying mechanism makes this method rather sensitive to variations in experimental conditions, and the lack of simple techniques to monitor the reaction progress in situ usually results in poor reproducibility and time‐consuming optimizations. Here, a simple, robust, and versatile in situ marker to monitor particle formation based on a sudden change in the temperature during reflux is reported. A linear relationship between the onset of particle formation and the concentration of surfactants is unveiled, corroborating a ‘chemically activated’ burst nucleation mechanism. Using this linear relationship as a guide, highly uniform spherical, cubic, and star‐shaped particles between 12 and 30 nm can be obtained. This temperature marker and the derived linear relationship not only deepen the understanding of the reaction process, but also provide a powerful tool for the straightforward optimization of IONPs.
Fillable Magnetic Microrobots for Drug Delivery to Cardiac Tissues In Vitro
Authors: Chen Maggie S. , Sun Rujie , Wang Richard , Zuo Yuyang , Zhou Kun , Kim Junyoung , Stevens Molly M.
Published: May 2024

Many cardiac diseases, such as arrhythmia or cardiogenic shock, cause irregular beating patterns that must be regulated to prevent disease progression toward heart failure. Treatments can include invasive surgery or high systemic drug dosages, which lack precision, localization, and control. Drug delivery systems (DDSs) that can deliver cargo to the cardiac injury site could address these unmet clinical challenges. Here, a microrobotic DDS that can be mobilized to specific sites via magnetic control is presented. This DDS incorporates an internal chamber that can protect drug cargo. Furthermore, the DDS contains a tunable thermosensitive sealing layer that gradually degrades upon exposure to body temperature, enabling prolonged drug release. Once loaded with the small molecule drug norepinephrine, this microrobotic DDS modulated beating frequency in induced pluripotent stem‐cell derived cardiomyocytes (iPSC‐CMs) in a dose‐dependent manner, thus simulating drug delivery to cardiac cells in vitro. The DDS also navigates several maze‐like structures seeded with cardiomyocytes to demonstrate precise locomotion under a rotating low‐intensity magnetic field and on‐site drug delivery. This work demonstrates the utility of a magnetically actuating DDS for precise, localized, and controlled drug delivery which is of interest for a myriad of future opportunities such as in treating cardiac diseases.
Sustained‐Release Hydrogen‐Powered Bilateral Microneedles Integrating CD‐MOFs for In Situ Treating Allergic Rhinitis
Authors: Ruan Hang , Long Meng , Li Jiaqi , Zhang Di , Feng Nianping , Zhang Yongtai
Published: May 2024

Glucocorticoids are widely used for treating allergic rhinitis, but conventional intranasal administration encounters unfavorable nasal cilia clearance and nasal mucosal barrier. Herein, a bilateral microneedle patch is fabricated for delivering cyclodextrin‐based metal–organic frameworks (CD‐MOF) encapsulating dexamethasone (DXMS) and paeonol (Pae), while NaH particles are mounted on the basal part of each microneedle. By intranasal administration, the microneedles are propelled into the nasal mucosa by NaH‐generated hydrogen and then swell to form a hydrogel for sustainedly releasing drugs. The DXMS/Pae combination is demonstrated to be superior to more than the twofold dose of DXMS alone for improving allergic rhinitis in rats. It involves reducing mast cell degranulation and modulating Treg/Th17 cell homeostasis, whereas inhibiting Th1 to Th2 differentiation is associated with regulating the GATA3/T‐bet pathway, as well as repairing epithelial barrier function by increasing MUC1 and downregulating periostin. In addition, this delivery system modulates the lipid metabolism of the nasal mucosa. Notably, the newly designed device significantly enhances the drug's therapeutic effect, and NaH‐generated hydrogen may have the potential adjunctive therapeutic effect. Collectively, such an emerging microneedle‐mediated nasal drug delivery creates a new form for alleviating immune inflammation and contributes a promising solution to reduce clinical glucocorticoid abuse.
Investigation of the Single‐Particle Scale Structure–Activity Relationship Providing New Insights for the Development of High‐Performance Batteries
Authors: Wang Fei , Zhang Chong , Wu Fan , He Zhichao , Huang Yudong
Published: May 2024

As electric vehicles, portable electronic devices, and tools have increasingly high requirements for battery energy density and power density, constantly improving battery performance is a research focus. Accurate measurement of the structure–activity relationship of active materials is key to advancing the research of high‐performance batteries. However, conventional performance tests of active materials are based on the electrochemical measurement of porous composite electrodes containing active materials, polymer binders, and conductive carbon additives, which cannot establish an accurate structure–activity relationship with the physical characterization of microregions. In this review, in order to promote the accurate measurement and understanding of the structure–activity relationship of materials, the electrochemical measurement and physical characterization of energy storage materials at single‐particle scale are reviewed. The potential problems and possible improvement schemes of the single particle electrochemical measurement and physical characterization are proposed. Their potential applications in single particle electrochemical simulation and machine learning are prospected. This review aims to promote the further application of single particle electrochemical measurement and physical characterization in energy storage materials, hoping to achieve 3D unified evaluation of physical characterization, electrochemical measurement, and theoretical simulation at the single particle scale to provide new inspiration for the development of high‐performance batteries.
Entanglement Added to Cross‐Linked Chains Enables Tough Gelatin‐Based Hydrogel for Zn Metal Batteries
Authors: Kumankuma‐Sarpong James , Chang Caiyun , Hao Jing , Li Titi , Deng Xianming , Han Cuiping , Li Baohua
Published: May 2024

Currently, it is still challenging to develop a hydrogel electrolyte matrix that can successfully achieve a harmonious combination of mechanical strength, ionic conductivity, and interfacial adaptability. Herein, a multi‐networked hydrogel electrolyte with a high entanglement effect based on gelatin/oxidized dextran/methacrylic anhydride, denoted as ODGelMA is constructed. Attribute to the Schiff base network formulation of ─RC═N─, oxidized dextran integrated gelatin chains induce a dense hydrophilic conformation group. Furthermore, addition of methacrylic anhydride through a grafting process, the entangled hydrogel achieves impressive mechanical features (6.8 MPa tensile strength) and high ionic conductivity (3.68 mS cm−1 at 20 °C). The ODGelMA electrolyte regulates the zinc electrode by circumventing dendrite growth, and showcases an adaptable framework reservoir to accelerate the Zn2+ desolvation process. Benefiting from the entanglement effect, the Zn anode achieves an outstanding average Coulombic efficiency (CE) of 99.8% over 500 cycles and cycling stability of 900 h at 5 mA cm−2 and 2.5 mAh cm−2. The Zn||I2 full cell yields an ultra‐long cycling stability of 10 000 cycles with a capacity retention of 92.4% at 5 C. Furthermore, a 60 mAh single‐layer pouch cell maintains a stable work of 350 cycles.
General Fabrication of Robust Alloyed Metal Anodes for High‐Performance Metal Batteries
Authors: Yin Qingyang , Liu Qian , Liu Yatao , Qu Zhibin , Sun Fei , Wang Chongzhen , Yuan Xintong , Li Yuzhang , Shen Li , Zhang Chi , Lu Yunfeng
Published: May 2024

Revitalizing metal anodes for rechargeable batteries confronts challenges such as dendrite formation, limited cyclicity, and suboptimal energy density. Despite various efforts, a practical fabrication method for dendrite‐free metal anodes remains unavailable. Herein, focusing on Li as exemplar, a general strategy is reported to enhance reversibility of the metal anodes by forming alloyed metals, which is achieved by induction heating of 3D substrate, lithiophilic metals, and Li within tens of seconds. It is demonstrated that preferred alloying interactions between substrates and lithiophilic metals created a lithiophilic metal‐rich region adjacent to the substrate, serving as ultrastable lithiophilic host to guide dendrite‐free deposition, particularly during prolonged high‐capacity cycling. Simultaneously, an alloying between lithiophilic metals and Li creates a Li‐rich region adjacent to electrolyte that reduces nucleation overpotential and constitutes favorable electrolyte‐Li interface. The resultant composite Li anodes paired with high areal loading LiNi0.8Co0.1Mn0.1O2 cathodes achieve superior cycling stability and remarkable energy density above 1200 Wh L−1 (excluding packaging). Furthermore, this approach shows broader applicability to other metal anodes plagued by dendrite‐related challenges, such as Na and Zn. Overall, this work paves the way for development of commercially viable metal‐based batteries that offer a combination of safety, high energy density, and durability.
Unlocking the Potential and Versatility of Quantum Dots: from Biomedical to Environmental Applications and Smart Micro/Nanorobots
Authors: Ussia Martina , Privitera Vittorio , Scalese Silvia
Published: May 2024

Quantum dots (QDs) are recognized as the most promising functional nanotechnology, for which its discoverers are awarded the Nobel Prize in 2023. Their remarkable tunability of optoelectronic properties has attracted significant interest from both researchers and industries, placing QDs at the forefront of developing cutting‐edge technologies. This comprehensive review aims to explore the exciting results in terms of fundamental science, present and forthcoming applications. Beyond their contributions to biomedicine, energy, environmental science, quantum sensing, and quantum information processing, QDs have brought important results due to their integration into micro/nanorobotic systems, self‐propelled materials representing the state of the art research at the micro and nanoscale. These hybrid systems have demonstrated noteworthy outcomes, unlocking novel possibilities in biomedicine, quantum sensing, and environmental science, accurately reviewed in this article. In conclusion, this review addresses current challenges, offering insights to facilitate further research, stimulate new developments, and enhance the comprehension of the full potential of QDs.
Quercetin‐Loaded Bioglass Injectable Hydrogel Promotes m6A Alteration of Per1 to Alleviate Oxidative Stress for Periodontal Bone Defects
Authors: Zhu Huimin , Cai Chao , Yu Yeke , Zhou Yuning , Yang Shiyuan , Hu Yue , Zhu Yan , Zhou Jia , Zhao Jieyun , Ma Hailong , Chen Yujie , Xu Yuanjin
Published: May 2024

Periodontal disease ranks third among noncommunicable illnesses, behind cancer and cardiovascular disease, and is closely related to the occurrence and progression of various systemic diseases. However, elucidating the processes of periodontal disease and promoting periodontal bone regeneration remains a challenge. Here, quercetin is demonstrated to reduce the oxidative stress state of orofacial mesenchymal stem cells (OMSCs) in vitro and to affect the osteogenic growth of OMSCs through molecular mechanisms that mediate the m6A change in Per1. Nevertheless, the limited therapeutic efficacy of systemic medication and the limitations of local medication resulting from the small, moist, and highly dynamic periodontal environment make it challenging to treat periodontal tissues with medication. Herein, a biosafe injectable hydrogel drug‐controlled delivery system is constructed as a bone‐enhancing factory and loaded with quercetin to treat oxidative stress injury in periodontal tissues. This drug‐carrying system made up of nanoscale bioglass microspheres and a light‐cured injectable hydrogel, allows effective drug particle loading and cementation in the dynamic and moist periodontal environment. Furthermore, the system demonstrates the ability to stimulate OMSCs osteogenic differentiation in a Per1‐dependent manner, which ultimately promotes periodontal bone repair, suggesting that this system has potential for clinical periodontal therapy.