bluuebunny/crossref_metadata_2025 huggingface dataset:
Sustainable Water Infrastructure Asset Management: A Gap Analysis of Customer and Service Provider Perspectives
Authors: Han Sangjong , Hwang Hwankook , Kim Seonghoon , Baek Gyu , Park Joonhong
Published: September 2015

The ultimate goal of urban water infrastructure asset management may be sustainable water supply with satisfaction for customers. In this work, we attempted to evaluate the gaps between the perspectives of customers and service providers in Korea’s water infrastructure asset management. To evaluate the customers’ perspective, a hierarchical questionnaire survey was conducted to estimate the weights of influence for six customer values and their attributes on Korean water utility management. To evaluate the service providers’ perspective, an AHP (Analytic Hierarchy Process) analysis was performed to estimate the weights of influence for the customer values and their PIs (performance indicators). The gap analysis results show that customers place higher value on customer service satisfaction (emotion and information) than do the service providers (managers), whereas the managers place more value on affordability than do the customers. The findings from this work imply that improving customer service is effective in satisfying the desirable water LOS (level of service) for customers. Recommendations have also been provided for administrators and engineers to develop integrated decision-making systems that can reflect customer needs regarding the improvement of their water infrastructure asset management. The findings from this work may be helpful for the Korean government and water supply utilities in improving the sustainability of their water infrastructure asset management.
Study of Adsorption and Flocculation Properties of Natural Clays to Remove Prorocentrum lima
Authors: Louzao Maria , Abal Paula , Fernández Diego , Vieytes Mercedes , Legido José , Gómez Carmen , Pais Jesus , Botana Luis
Published: September 2015

High accumulations of phytoplankton species that produce toxins are referred to as harmful algal blooms (HABs). HABs represent one of the most important sources of contamination in marine environments, as well as a serious threat to public health, fisheries, aquaculture-based industries, and tourism. Therefore, methods effectively controlling HABs with minimal impact on marine ecology are required. Marine dinoflagellates of the genera Dinophysis and Prorocentrum are representative producers of okadaic acid (OA) and dinophysistoxins responsible for the diarrhetic shellfish poisoning (DSP) which is a human intoxication caused by the consumption of shellfish that bioaccumulate those toxins. In this work we explore the use of natural clay for removing Prorocentrum lima. We evaluate the adsorption properties of clays in seawater containing the dinoflagellates. The experimental results confirmed the cell removal through the flocculation of algal and mineral particles leading to the formation of aggregates, which rapidly settle and further entrain cells during their descent. Moreover, the microscopy images of the samples enable one to observe the clays in aggregates of two or more cells where the mineral particles were bound to the outer membranes of the dinoflagellates. Therefore, this preliminary data offers promising results to use these clays for the mitigation of HABs.
Travel-acquired Japanese encephalitis and vaccination considerations
Authors: Pavli Androula , Maltezou Helena C
Published: September 2015

Japanese encephalitis (JE) is a serious arboviral disease caused by a virus of the genus Flavivirus. Japanese encephalitis is the most common vaccine-preventable virus causing encephalitis in Asia, affecting more than 50,000 persons and leading to 15,000 fatalities per year in endemic countries. For most travelers to Asia, the risk of Japanese encephalitis infection is extremely low and depends on destination, duration of travel, season, and activities. This article reviews travel-acquired Japanese encephalitis with a focus on epidemiology and prevention in the light of the newly available options for active immunization against Japanese encephalitis which have become available, and of the increasing popularity of travels to Japanese encephalitis endemic countries.
Synergy between antibiotics and natural agents results in increased antimicrobial activity against Staphylococcus epidermidis
Authors: Abidi Syed Hani , Ahmed Khalid , Sherwani Sikander Khan , Kazmi Shahana Urooj
Published: September 2015

Introduction: Staphylococcus epidermidis is one of the most frequent causes of biofilm-associated infections on indwelling medical devices. With the emergence of methicillin-resistant S. epidermidis (MRSE), there is an urgent need to discover novel active agents against a range of Gram-positive pathogens. We screened the clinical isolates of S. epidermidis for susceptibility/resistance against commonly prescribed antibiotics. Furthermore, we tested some natural agents alone and in combination with antibiotics to find possible synergistic antimicrobial effects. Methodology: S. epidermidis clinical isolates were screened for susceptibility/resistance against vancomycin, erythromycin, tetracycline, chloramphenicol, ampicillin, ofloxacin, cephalexin, and gentamicin using the Kirby-Bauer disk diffusion method. The antimicrobial potential of Camellia sinensis, Juglans regia, and Hippophae rhamnoides alone and in combination with antibiotics were examined using the disk diffusion method, where the antimicrobial potential activity was measured in terms of formation of zones of inhibition. Results: Most S. epidermidis isolates were found to be resistant to one or more antibiotics. Gentamycin and ofloxacin were found to be the most effective antibiotics against S. epidermidis isolates. Extracts of Hippophae rhamnoides, Juglans regia, and Camellia sinensis were found to be equally effective against S. epidermidis isolates. In combination with antibiotics, these extracts exhibited appreciable synergistic activity; the highest synergistic activity was observed with erythromycin and cephalexin. In the case of cephalexin, a reversion in resistance was observed. Conclusions: The plant extracts used in the study exhibited additive and synergistic antibacterial activity against S. epidermidis, hence providing an effective alternative to deal with the problem of multidrug resistance.
Characterization of epidemic clones of Listeria monocytogenes serotype 4b isolated from humans and meat products in Brazil
Authors: Barbosa André Victor , Cerqueira Aloysio de Mello Figueiredo , Rusak Leonardo Alves , Dos Reis Cristhiane Moura Falavina , Leal Nilma Cintra , Hofer Ernesto , Vallim Deyse Christina
Published: September 2015

Introduction: Listeria monocytogenes is an important foodborne pathogen and the 4b serotype is responsible for many cases of human listeriosis reported in Brazil. Several listeriosis outbreaks worldwide have involved a small number of well-defined clonal groups, designated as epidemic clones (ECs). Methodology: We studied 71 strains of serotype 4b, including 25 isolates from human cases of listeriosis and 46 from meat-based foods, collected in Brazil between 1977 and 2010. The presence of ECs (I and II) markers and virulence genes (inlA, inlB, ilnC, inlJ and actA) were evaluated by PCR assay. The genetic relationship of ECs-positive strains was assessed by pulsed field gel electrophoresis. Results: ECI and ECII markers were found both in human and food strains, with 19.7% positive for the ECI marker and 40.8% for ECII. Most strains (97.2%) were positive for the virulence genes that were studied. Nevertheless, the actA gene amplicons showed two distinct sizes, with all ECI positive strains exhibiting a 105bp deletion. Pulsed field gel electrophoresis (PFGE) analysis allowed the recognition of highly related strains, particularly from two outbreaks of neonatal listeriosis in São Paulo State occurred in 1992 and 1997, both ECII-positive; and two ECI strains from a human case (1982) and from bovine meat (2009). Conclusions: The presence of ECs among clinical samples and beef isolates of serotype 4b from some regions of Brazil highlights the need for rigorous control of production procedures. Furthermore, the association of ECII with two nosocomial outbreaks suggests its ability to spread in these settings.
Comparison between potential risk factors for cardiovascular disease in people living with HIV/AIDS in areas of Brazil
Authors: Ximenes Ricardo AA , Lacerda Heloisa R , Miranda-Filho Democrito B , Albuquerque Maria de Fatima PM , Montarroyos Ulisses R , Turchi Marilia D , Nery Max W , Martelli Celina MT , Alencastro Paulo R , Ikeda Maria Leticia R , Wolff Fernando H , Brandao Ajacio BM , Barcellos Nemora T , Fuchs Sandra C
Published: September 2015

Introduction: Coronary heart disease and its risk factors depend on genetic characteristics, behaviors, and habits, all of which vary in different regions. The use of antiretroviral therapy (ARV) has increased the survival of people living with HIV/AIDS (PLWHA), who begin to present mortality indicators similar to the general population. This study aimed to compare the prevalence of factors potentially associated with coronary heart disease in three cohorts of PLWHA from three different regions of Brazil. Methodology: The study population was composed of participants of the cohorts of Pernambuco, Goiás, and Rio Grande do Sul states. In these sites, adult patients attending reference centers for treatment of HIV/AIDS were consecutively enrolled. Results: Pernambuco and Goiás had a higher proportion of males and of individuals with high-risk high-density lipoprotein (HDL). Pernambuco also had a greater proportion of individuals with hypertension, elevated triglycerides, and CD4 counts below 200 cells/mm3. Lower education was more frequent in Rio Grande do Sul, and the use of cocaine was higher in this state. Conclusions: The results confirm the importance of risk factors for coronary heart disease in PLHIV and highlight differences in the three cohorts. Specific measures against smoking and sedentary lifestyle, avoidance of advanced stages of immunosuppression, and appropriate treatment of dyslipidemia and dysglicemia are urgently needed to cope with the disease in Brazil.
Molecular identification of coagulase-negative staphylococci isolated from bovine mastitis and detection of β-lactam resistance
Authors: Srednik Mariela Elizabeth , Grieben Mario Andres , Bentancor Adriana , Gentilini Elida Raquel
Published: September 2015

Introduction: Bovine mastitis is a frequent cause of economic loss in dairy herds. Coagulase-negative staphylococci (CoNS) are increasing in importance as causeof bovine intramammary infection (IMI) throughout the world in recent years. CoNShave been isolated from milk samples collected from cows with clinical andsubclinical mastitis in several countries. Identification of mastitis pathogensis important when selection appropriate antimicrobial therapy.Methodology: A total of 93 strains of Staphylococcusspp isolated from bovine clinical andsubclinical mastitis in Argentina during 2010-2013 were identified by Restriction Fragment Length Polymorphism (RFLP)-PCR using the gap gene. The isolates were tested by PCR for the presence of blaZ gene and mecA gene and were tested by disk diffusion for the susceptibilityto penicillin and cefoxitin. Results: The most common CoNS species was S.chromogenes 46.2% (43/93), followed by S. devriesei 11.8% (11/93) and S. haemolyticus 9.7% (9/93). The blaZ gene was detected in 19 (20.4%) but only 16 (17.2%) isolates were resistant to penicillin; the mecA was detected in6 (6.5%) isolates but only 4 (4.3) were resistant to cefoxitin. The 6 mecA-positive isolates showed oxaxillinMICs ≥ 0.5 μg/ml. Discussion: CoNSare important minor mastitis pathogens and can be the cause of substantial economic losses. Despite the low resistance to PEN in Argentina, the presenceof MR isolates found in this study emphasize the importance of identificationof CoNS when an IMI is present because of the potentially risk of lateraltransfer of resistance genes between staphylococcal species.
Prevalence and antibiotic susceptibility of bacteria from acute and chronic wounds in Malaysian subjects
Authors: Wong Shin Yee , Manikam Rishya , Muniandy Sekaran
Published: September 2015

Introduction: Chronic wounds represent a major health burden worldwide. It has been hypothesized that the polymicrobial nature of wounds plays an important role in their healing process. Thus, a review of pathogen frequency and susceptibility patterns in wounds is necessary to provide appropriate guidelines for antimicrobial usage. Methodology: In this study, microbiota and antimicrobial resistance in both acute and chronic wound patients treated at the University of Malaya Medical Centre, Malaysia, were compared. Wound swabs from 84 patients with acute wounds and 84 patients with chronic wounds were collected. The specimens were cultured using standard microbiological techniques. Isolates were then tested for antibiotic sensitivity with the broth microdilution method. Results: Of 210 pathogenic bacteria isolates, Staphylococcus aureus (49; 23.3%) and Pseudomonas aeruginosa (31; 14.8%) were the most prevalent bacteria found in wounds. Staphylococcus aureus was found significantly more often in patients with chronic wounds (41; 48.8%) than in patients with acute wounds (8; 9.5%), while Staphylococcus epidermidis was found predominantly in acute wounds (15; 17.9%). At the time of study, patients with chronic wounds (58.3%) had received more antibiotic treatments in the past previous 12 months compared with patients with acute wounds (16.7%). In the antibiotic susceptibility test, Staphylococcus spp. revealed highest resistance towards penicillin and ampicillin. Isolates showed no decrease in susceptibility against a number of newly developed antibiotics (linezolid, daptomycin, and tigecycline). Conclusions: Our finding showed that bacteria diversity and antimicrobial-resistant strains are more frequently found in chronic wounds than in acute wounds.
Comparison of cervico-vaginal colonization among sexually active women by intrauterine device use
Authors: Songur Dagli Selda , Demir Tülin
Published: September 2015

Introduction: In this study we aimed to evaluate the effect of intrauterine devices (IUDs) on cervico-vaginal colonization. Methodology: Cervico-vaginal samples of 96 patients with vaginal discharge were included in the study. Microscopic evaluation, bacteriological and fungal culture, and antigen testing for Chlamydia trachomatis using an immunochromatographic test method were performed. Results: Trichomonas vaginalis was not detected by wet mount examination. Gram smear revealed that seven patients (7.3%) had Candida spp. and five (5.2%) had clue cell. Of the 96 swabs tested for conventional culture, pathogenic microorganisms were isolated from 24 patients. While Neisseria gonorrhoeae was not found in any of the sample, five (5.2%) were positive for Gardnerella vaginalis. Five (5.2%) were positive for C. trachomatis antigen, while three positivity only for C. trachomatis antigen, one had G. vaginalis additionally, and the other had a mixed infection. Chlamydial antigen positivity was higher among women over 30 years of age (p = 0.157). Increase in polymorphonuclear leukocytes (PNL) was detected 40% and 35.2% of samples, positive and negative, for chlamydial antigen, respectively (p= 1.000). Among IUD+ cases, increase in PNL, fungal elements,  E. coli and Gram-positive bacteria and decrease in Lactobacillus spp. were observed, compared to IUD-cases. No statistically significant relationship was detected between IUD and chlamydial antigen with the reported rates of 4.8% and 5.6% for IUD+ or IUD-, respectively (p > 0.05). Conclusion: Statistically significant relationship was not detected between IUD and cervico-vaginal colonization. More comprehensive studies using specific test methods should be conducted to better understand the relationship.
Prevalence and risk factors of cytomegalovirus infection among HIV-infected and HIV-exposed uninfected infants in Nigeria
Authors: Anigilaje Emmanuel Ademola , Dabit Joseph Othniel , Nweke Nnamdi Okechukwu , Agbedeh Augustine Aondohemba
Published: September 2015

Introduction: Cytomegalovirus (CMV) co-infection increases morbidity and mortality in human immunodeficiency virus (HIV) disease. There has been no study on CMV infection and its risk factors among Nigerian HIV-infected and/or HIV-exposed uninfected infants. Methodology: This was a cross-sectional cohort study at the Federal Medical Center, Makurdi, between January 2012 and March 2013. Acute CMV infection among consecutive three-month- old HIV-infected and HIV-exposed uninfected infants was determined using the enzyme-linked immunosorbent assay of the CMV immunoglobulin M (IgM). The relationship between acute CMV infections in the infants and the potential risk factors was tested using logistic regression analyses. Results: The prevalence of acute CMV infection was 41.4% (91/220), including 12.1% (11/91) and 87.9% (80/91) among the HIV-infected and the HIV-exposed uninfected infants, respectively. In multivariate logistic regression analyses, oropharyngeal candidiasis in the infants, HIV co-infection in the infants, maternal mastitis during breastfeeding, and the absence of maternal chronic CMV infections significantly increased the risk of acute CMV in the young infants. Conclusions: In our setting, concerted efforts to prevent and/or promptly treat oropharyngeal candidiasis and mastitis during breastfeeding may reduce the burden of CMV among HIV-infected and HIV-exposed uninfected infants. Public enlightenment on the mode of CMV transmission and its prevention is also important.
Virulence genes in Moraxella spp. isolates from infectious bovine keratoconjunctivitis cases
Authors: Sosa Vanessa , Umpierrez Ana , Acquistapace Sofia , Zunino Pablo
Published: September 2015

Introduction: Infectious bovine keratoconjunctivitis (IBK) is an important ocular disease which affects cattle worldwide. To advance towards IBK effective prevention and treatment strategies, it is important to define the distribution and genetic diversity of potential virulence factors present in M. bovis and M. bovoculi. The objective of this work was to identify and to analyze Moraxella spp. potential virulence factor genes in a collection of clinical isolates. Methodology: The presence and diversity of virulence factors in a collection of Moraxella spp. strains isolated since 1983 to 2009 in Uruguay was analyzed by PCR using primers for partial amplification of tolC, omp79, plb, fur and mbxA. The selection criterion of these genes was based on the fact that they encode virulence factors which could be present and conserved within strains, an important issue for the development of vaccines. Results: Differences in PCR amplification were observed within tolC (84%), omp79 (80%), plb (76%) and fur (44%) in M. bovis strains, whereas mbxA was amplified in all M. bovis and M. bovoculi strains. Regarding genetic diversity, the tolC nucleotide sequences were the less diverse within all M. bovis and mbxA were the less diverse within all M. bovis and M. bovoculi strains. Conclusions: PCR amplifications suggest the occurrence of differences between both Moraxella species, related to evaluated genes within Moraxella spp. strains and suggests that both species may have different pathogenic attributes. MbxA and the outer membrane protein TolC might be considered for future studies to develop new vaccines against IBK.
Candida profiles and antifungal resistance evolution over a decade in Lebanon
Authors: Araj George Farah , Asmar Rima George , Avedissian Aline Zakaria
Published: September 2015

Introduction: Infection with and antifungal resistance of Candida species have been on the rise globally. Relevant data on these pathogens are relatively few in our region, including Lebanon, thus warranting this study. Methodology: This retrospective study of Candida spp. profiles and their in vitro antifungal susceptibility was based on analysis requests for 186 Candida non-albicans and 61 C. albicans during three periods (2005–2007, 2009–2011, and 2012–2014) over the span of the last 10 years at the American University of Beirut Medical Center (AUBMC), a major tertiary care center in Lebanon. Identification of Candida was done using the API 20C AUX system, and the E-test was used to determine the minimum inhibitory concentrations (MICs) of antifungal agents. Results: Among the 1,300–1,500 Candida isolates recovered yearly, C. albicans rates decreased from 86% in 2005 to around 60% in 2014. Simultaneously, the non-albicans rates increased from 14% in 2005 to around 40% in 2014, revealing 11 species, the most frequent of which were C. tropicalis, C. glabrata, and C. parapsilosis. All these demonstrated high resistance (35%–79%) against itraconazole, but remained uniformly susceptible (100%) to amphotericin B. Though C. albicans and the other species maintained high susceptibility against fluconazole and voriconazole, their MIC90 showed an elevated trend over time, and C. glabrata had the highest resistance rates. Conclusions: The observed rise in resistance among Candida spp. in Lebanon mandates the need for close surveillance and monitoring of antifungal drug resistance for both epidemiologic and treatment purposes.
Dissemination of extensively drug-resistant and KPC-2 producing Klebsiella pneumoniae isolated from bloodstream infections
Authors: Zhao Feng , Zhang Jun , Fu Ying , Ruan Zhi , Xie Xinyou
Published: September 2015

Introduction: Bloodstream infections (BSIs) are serious diseases associated with high mortality, especially when caused by extensively drug-resistant (XDR) Klebsiella pneumoniae. The prevalence and pandemic strains of extended-spectrum beta-lactamase (ESBL)-producing K. pneumoniae isolated from blood cultures of patients with BSIs were determined at Sir Run Run Shaw Hospital, China. Methodology: A total of 24 XDR K. pneumoniae were isolated from blood cultures, and the clinical data of the patients were analyzed retrospectively. Bacterial species identification and antimicrobial susceptibility testing were performed using VITEK2 and E-test methods, respectively. Common ESBL-resistant genes were amplified and sequenced after the validation of a modified Hodge test. Strain homology was also analyzed by pulsed-field gel electrophoresis (PFGE). Results: All of the isolates were resistant to 10 antimicrobial agents. Several strains showed partial sensitivity to aminoglycosides, but all showed sensitivity to polymyxin and tigecycline. All strains were Klebsiella pneumoniae carbapenemase (KPC-2) producing, and carried two or three ESBL-resistant genes, which belonged to 13 PFGE clones (A–M). The overall mortality rate in patients was as high as 29.2%. Conclusions: KPC-2-producing K. pneumoniae BSIs are associated with high mortality rates. Our observations suggest that KPC-2 and ESBL-producing K. pneumoniae might be responsible for the clonal dissemination of extensively drug-resistant isolates in our hospital.
Linguistics as a Theory of Knowledge
Authors: Castillo Jesus Martinez del
Published: September 2015

A theory of knowledge is the explanation of things in terms of the possibilities and capabilities of the human way of knowing. The human knowledge is the representation of the things apprehended sensitively either through the senses or intuition. A theory of knowledge concludes about the reality of the things studied. As such it is a priori speculation, based on synthetic a priori statements. Its conclusions constitute interpretation, that is, hermeneutics. Linguistics as the science studying real language, that is, the language spoken, reverts to human subjects in as much as they speak, say and know. Language thus must be studied as a theory of knowledge.This article deals with the study of language as the human activity of speaking, saying and knowing. It analyzes the possibilities of a scientific theory, its characteristics and pre-requisites to see if language can be studied. The fact of language reverting to the individual speaking subject makes linguists to consider the peculiarities of language study as a human science. Since human subjects are free, creative and absolute, human facts cannot be but interpreted. This article concludes about the character of linguistics and the key points it must study and be based on.
Does the Perception of Organizational Cronyism Leads to Career Satisfaction or Frustration with Work? The Mitigating Role of Organizational Commitment
Authors: Turan Aygul
Published: September 2015

The concept of organizational cronyism has been investigated to explain different concepts in
the literature. In this study, we aim at researching the influence of organizational cronyism on
organizational commitment of individuals and explain how the influence differentiates their
career satisfaction or frustration with work perception of individuals. Therefore, we focused
on government officials working in a public institution and examine their perception of
cronyism in the organization. Having gathered the data from 193 government officials,
confirmatory as well as explanatory factor analyses initially was initially conducted on the
scales of organizational cronyism, organizational commitment, career satisfaction and
frustration with work. After controlling the validity and reliability of the scales, measurement
model and structural model testing were carried out. Results indicated that organizational
commitment partially mediated the relationship between organizational cronyism and career
satisfaction. In addition, organizational commitment partially mediated the relationship
between organizational cronyism and frustration with work.
Numerical Modeling, Simulation and Validation of Hybrid Solar Photovoltaic, Wind Turbine and Fuel Cell Power System
Authors: Sami S. , Icaza D.
Published: September 2015

The energy conversion equations describing the total power generated by a hybrid system of solar photovoltaic, wind turbine, fuel cell as well as hydrogen storage were presented, and integrated simultaneously. For the purpose of validating, this simulation model, the aforementioned equations were coded with MATLAB V13.2 and used for optimization and design purposes. A block diagram approach was used during the simulation with MATLAB. In order to validate and tune up the predicted output results, on-site data was used to validate the simulation program under various conditions. Comparison between the data and predicted results showed a fair agreement.
A Plea for Design: Historians, Digital Platforms, and the Mindful Dissemination of Content and Concepts
Authors: Bonnett John
Published: September 2015

One of the most significant attributes of digital computation is that it has disrupted extant work practices in multiple disciplines, including history. In this contribution, I argue that far from being a trend that should be resisted, it in fact should be encouraged. Computation is presenting historians with novel opportunities to express, analyze, and teach the past, but that potential will only be realized if scholars assume a new research mandate, that of design. For many historians, such a research agenda is likely to seem strange, if not beyond the pale. There are tasks that fall properly within the domain of the Historian’s Craft and the design of workflows for digital platforms and expressive forms for digital narratives are not among them. In Section One, via the writings of Harold Innis, I make the case that a preoccupation with design is in fact very much part of Canada’s historiographic tradition. In Section Two, I present an environmental scan of emerging technologies, and suggest that now is an opportune time to revive Innis’ preoccupation with design. In the following two sections, I present the StructureMorph Project, a case study showing how historians can leverage the properties of digital form to realize their expressive, narrative, and attestive needs in the digital, virtual worlds that will become increasingly important platforms for representing, disseminating, and interpreting the past.
Highs and Lows
Authors: Durkin Claire
Published: August 2024

In this narrative medicine essay, a transplant hepatology fellow whose gestational diabetes progressed to type 1 diabetes finds robust online support groups that have helped her navigate her new reality.
What Is Pertussis?
Authors: Scruggs-Wodkowski Elizabeth , Malani Preeti
Published: August 2024

This JAMA Patient Page describes pertussis illness, its signs and symptoms, and its diagnosis, treatment, and prevention measures.
Caring for Your Heart During Cancer Treatment
Authors: Mysore Manu , Singhi Dylan , Singhi Eric K.
Published: August 2024

This JAMA Oncology Patient Page describes cardio-oncology, a relatively new area in medicine that focuses on taking care of the heart while going through cancer treatments.
Externally Controlled Studies Using Real-World Data in Patients With Hematological Cancers
Authors: Hermans Sjoerd J. F. , van der Maas Niek G. , van Norden Yvette , Dinmohamed Avinash G. , Berkx Elizabeth , Huijgens Peter C. , Rivera Donna R. , de Claro R. Angelo , Pignatti Francesco , Versluis Jurjen , Cornelissen Jan J.
Published: August 2024

Importance

The use of real-world data (RWD) external control arms in prospective studies is increasing. The advantages, including the immediate availability of a control population, must be balanced with the requirements of meeting evidentiary standards.

Objective

To address the question of whether and to what extent the methods of RWD studies compare to standard methods used in randomized clinical trials.

Evidence Review

A systematic search across 4 electronic databases and Google Scholar was conducted from January 1, 2000, to October 23, 2023. Studies were included in the systematic review if they compared an intervention arm in a clinical trial to an RWD control arm in patients with hematological cancers and if they were published between 2000 and 2023.

Findings

Thirty-two prospective intervention studies incorporating external control data from RWD sources of patients with hematological cancers were identified. A total of 4306 patients from intervention arms and 10 594 from RWD control arms were included across all studies. Only 2 studies (6%) included prospectively collected RWD. The complete trial inclusion criteria were applied to the RWD cohort in 7 studies (22%). Four studies (13%) published the statistical analysis plan and prespecified use of RWD. A total of 23 studies (72%) applied matching algorithms for trial and RWD cohorts, including matching for demographic, disease, and/or therapy-related characteristics. The end point criteria were the same as the trial in 8 studies (25%). In contrast, 12 studies (38%) used different end points, and 12 (38%) did not provide an end point definition for the RWD. Twelve studies (38%) had a median follow-up difference of less than a year between arms. Eight studies (25%) reported toxic effect data for the trial arm, of which 5 studies reported toxic effect data for the RWD arm.

Conclusions and Relevance

In this systematic review, limitations were observed in the application of clinical trial eligibility criteria to RWD, statistical rigor and application of matching methods, the definition of end points, follow-up, and reporting of adverse events, which may challenge the conclusions reported in studies using RWD.
Pharyngeal Manometry and Upper Airway Collapse During Drug-Induced Sleep Endoscopy
Authors: Harkins Tice , Tangutur Akshay , Keenan Brendan T. , Seay Everett G. , Thuler Eric , Dedhia Raj C. , Schwartz Alan R.
Published: August 2024

Importance

Drug-induced sleep endoscopy (DISE) is used to guide therapeutic management of obstructive sleep apnea (OSA), depending on the levels and patterns of pharyngeal collapse. However, the collapsibility of specific pharyngeal sites remains unknown.

Objective

To assess collapse sites in patients with OSA undergoing DISE and whether number and location are associated with differences in airway collapsibility; and to quantify differences in collapsibility between primary and secondary sites in multilevel collapse.

Design, Setting, and Participants

This cohort study assessed adult patients (≥18 years) with OSA undergoing DISE with manometry and positive airway pressure (PAP) titration at a tertiary care center from November 2021 to November 2023. Patients with an AHI score greater than 5 were included; those with less than 1 apnea event during DISE or incorrect catheter placement were excluded. Data were analyzed from September 28, 2022, to March 31, 2024.

Exposure

DISE with manometry and PAP titration.

Main Outcomes and Measures

Active pharyngeal critical pressure (Pcrit-A) and pharyngeal opening pressure (PhOP) were used to quantify airway collapsibility, adjusted for covariates (age, sex, race, and body mass index [BMI]).

Results

Of 94 screened, 66 patients (mean [SD] age, 57.4 [14.3] years; BMI, 29.2 [3.9]; 51 [77.3%] males) with a mean (SD) apnea-hypopnea index (AHI) of 31.6 (19.0) were included in the analysis. Forty-seven patients (71.2%) had multilevel collapse, 10 (15.2%) had single-level nasopalatal collapse, and 9 (13.6%) had single-level infrapalatal collapse. Groups did not differ in demographic characteristics or established measures of OSA severity. The single-level nasopalatal group had substantially elevated levels of airway collapsibility (Pcrit-A and PhOP covariate adjusted mean, 2.4; 95% CI, 1.1 to 3.8; and 8.2; 95% CI, 6.4 to 9.9 cmH2O) compared to the single-level infrapalatal group (−0.9; 95% CI, −2.4 to 0.5 cmH2O; and 4.9; 95% CI, 3.0 to 6.8 cmH2O, respectively) and similar to the level among the multilevel group (1.3; 95% CI, 0.7 to 2.0; and 8.5; 95% CI, 7.7 to 9.3 cmH2O). The multilevel group had more negative inspiratory pressure (−24.2; 95% CI, −28.1 to −20.2 cmH2O) compared to the single-level nasopalatal group (−9.8; 95% CI, −18.3 to −1.28 cmH2O). In patients with multilevel collapse, airway collapsibility was significantly higher at the primary nasopalatal compared to secondary infrapalatal site (mean difference, 13.7; 95% CI, 11.3 to 16.1 cmH2O).

Conclusions and Relevance

The findings of this cohort study suggest that intervention should target the primary site of pharyngeal collapse, and secondary sites only if they are nearly as collapsible as the primary site. Future work is needed to precisely define the difference in primary and secondary collapsibility that necessitates multilevel treatment.
Safety and Postoperative Outcomes of Transoral Surgery for Oropharyngeal Carcinoma in Older Adults
Authors: Costantino Andrea , Haughey Bruce , Alamoudi Uthman , Biskup Mathew , Magnuson Jeffery Scott
Published: August 2024

Importance

Transoral surgery (TOS) has become the primary surgical treatment for oropharyngeal squamous cell carcinoma (OPSCC). However, despite the increasing incidence of OPSCC in older patients, data regarding the safety and postoperative outcomes of TOS in this subgroup are lacking.

Objective

This study aimed to evaluate the safety and postoperative outcomes of TOS in patients with OPSCC aged 70 years or older compared with younger individuals.

Design, Setting, and Participants

This retrospective cohort study included patients with microscopic diagnostic confirmation of invasive OPSCC diagnosed between 2010 and 2021. Data were obtained from the US National Cancer Database. Data were analyzed in March 2024.

Exposure

Minimally invasive TOS not converted to an open approach.

Main Outcomes and Measures

Multivariable logistic and linear regression models were constructed to compare postoperative outcomes, adjusting for baseline patient and tumor characteristics. The results are reported as odds ratios (ORs) or mean differences with corresponding 95% CI, as appropriate.

Results

A total of 10 430 patients (mean [SD] age, 60.7 [9.6] years; 8744 [83.8%] male) were included, with 1808 patients (17.3%) aged at least 70 years. No clinically meaningful difference was observed in terms of postoperative mortality at 30 days (adjusted OR, 1.24; 95% CI, 0.65-2.33) or 90 days (adjusted OR, 1.11; 95% CI, 0.65-1.87). Patients aged 70 years or older were less likely to undergo adjuvant radiotherapy (adjusted OR, 0.69; 95% CI, 0.57-0.83) and chemotherapy (adjusted OR, 0.63; 95% CI, 0.51-0.77). In addition, the adjuvant treatment was more frequently not administered in the older population due to patient refusal or comorbidities, despite being clinically indicated (radiotherapy: adjusted OR, 1.36; 95% CI, 1.05-1.77; chemotherapy: adjusted OR, 1.70; 95% CI, 1.17-2.45). No meaningful differences were observed regarding the remaining study outcomes, apart from a slightly longer hospitalization time for older patients, with an adjusted mean difference of 0.39 (95% CI, 0.05-0.74) days.

Conclusions and Relevance

Findings from this study suggest that age was not independently associated with postoperative mortality in older patients undergoing TOS for OPSCC. However, older patients less frequently received adjuvant radiotherapy and chemotherapy compared with younger patients, and future studies should be conducted to examine the impact on long-term survival.
Enhancement of Microwave Absorption Properties of Crystal‐Engineered Perovskite Oxide Using Cobalt Ferrite
Authors: Gorai Anupam , Dutta Alo , Mandal Kalyan
Published: August 2024

A multiferroic composite that comprises of a non‐ferromagnetic ferroelectric material with a high dielectric constant and a non‐ferroelectric ferromagnetic material with a high magnetostriction is of tremendous interest as microwave absorption material due to its applicability in tunable microwave phase shifters, resonators, filters, absorbers, etc. In the previous work, the solid solution of strontium titanate and sodium bismuth titanate (Sr0.5(Na0.5Bi0.5)0.5TiO3, SNBT50), which is observed to possess a very high dielectric constant at room temperature (Ferroelectrics, Vol 583, 252–263 [2021]), is successfully reported. Thus, in this work, a core–shell magnetoelectric composite is prepared by coating highly ferromagnetic and magnetostrictive cobalt ferrite onto a diamagnetic but strongly ferroelectric SNBT50 to enhance its magnetic properties and to investigate the modification in microwave absorption. Detailed characterization of electric and magnetic parameters in microwave frequency range (1–20 GHz) reports substantial enhancement in the magnetic permeabilities as well as the magnetic loss of the composite system, as opposed to bare SNBT50. This results in improved impedance matching in the system and enhanced microwave absorption, with a minimum reflection loss (RL) of −20.19 dB and an increased effective absorption bandwidth of 4.56 GHz at a mere 2.7 mm absorber length. Consequently, in this investigation, a promising pathway is established for the development of multiferroic composites with favorable magnetoelectric coupling at room temperature that possesses wide absorption bandwidth and suitable RL, making them highly suitable for use in multiferroic‐based microwave components.
Transparent Cellulose Aerogels from Concentrated Salt Solutions: Synthesis and Characterization
Authors: Schroeter Baldur , Holst Sven , Jung Isabella , Gibowsky Lara , Subrahmanyam Raman , Gurikov Pavel , Smirnova Irina
Published: August 2024

In this work, nanostructured and transparent cellulose aerogels are synthesized via a purely salt induced approach from non‐modified microcrystalline cellulose type II. The production process requires in contrast to state of the art methods no pretreatment of cellulose or use of expensive cellulose‐solvents: it consists of hydrogel formation via cross‐linking of cellulose with calcium ions, a solvent exchange and a supercritical drying step. A systematic multiparameter study reveals that a high level of structural control is achievable: ratios of macro‐ to mesoporosity and the size of mesopores can be tailored by adjustment of the calcium ion content, while keeping a high overall porosity in the range of 92% – 96 %. The build‐up of homogeneous, fine pore structures results in a significant increase of the specific surface area as compared to conventional calcium‐free aerogels (684 vs. 300 m2 g−1). Remarkably, the Ca2+‐cross‐linking renders aerogels transparent, with Rayleigh scattering being the dominant scattering mechanism. Additional ion exchange to Ca2+ in the hydrogel‐state leads to further reduction of the pore size and to products with optimized optical properties, e.g., light transmission of 91% at an incidents light wavelength of 800 nm and a substrate thickness of 1.5 mm.
2D Ruddlesden‐Popper versus 2D Dion‐Jacobson Perovskites: Of the Importance of Determining the “True” Average n‐Value of Annealed Layers
Authors: Cresp Marie , Liu Min , Rager Marie‐Noelle , Zheng Daming , Pauporté Thierry
Published: August 2024

2D Ruddlesden‐Popper (RP) and Dion‐Jacobson (DJ) halide perovskite structures are characterized by the n parameter that represents the number of PbI6 layers in the spacer‐separated perovskite slabs. In most of the literature, n is referred to the initial composition of the precursor solution and, then, to the initial spacer content. In this approach, the fact that the spacer can be partially lost upon annealing is not considered. Here, the chemical processes occurring upon the preparation of reduced‐dimensional halide perovskite thin films of both families are investigated with a special focus on the organic cations composition and, especially, the evolution of n values. For each family, several spacers are investigated. It is shown that a large amount of monoammonium spacer cations is progressively eliminated upon annealing for the 2D‐RP perovskites, while, on the contrary, the final composition is close to the initial one in the case of the diammonium spacer cations of the 2D‐DJ perovskites. The elimination is related to the volatilization of the species after their deprotonation and the phenomenon can be regulated by halide additives. This work provides an important insight into the chemistry of the 2D perovskite layers and shows the importance of determining their “true” n value.
Selenium Nanoparticles Synergize with a KRAS Nanovaccine against Breast Cancer
Authors: Ferro Cláudio , Matos Ana I. , Serpico Luigia , Fontana Flavia , Chiaro Jacopo , D'Amico Carmine , Correia Alexandra , Koivula Risto , Kemell Marianna , Gaspar Maria Manuela , Acúrcio Rita C. , Cerullo Vincenzo , Santos Hélder A. , Florindo Helena F.
Published: August 2024

Selenium (Se) is an element crucial for human health, known for its anticancer properties. Although selenium nanoparticles (SeNPs) have shown lower toxicity and higher biocompatibility than other Se compounds, bare SeNPs are unstable in aqueous solutions. In this study, several materials, including bovine serum albumin (BSA), chitosan, polymethyl vinyl ether‐alt‐maleic anhydride, and tocopherol polyethylene glycol succinate, are explored to develop stable SeNPs and further evaluate their potential as candidates for cancer treatment. All optimized SeNP are spherical, <100 nm, and with a narrow size distribution. BSA‐stabilized SeNPs produced under acidic conditions present the highest stability in medium, plasma, and at physiological pH, maintaining their size ≈50–60 nm for an extended period. SeNPs demonstrate enhanced toxicity in cancer cell lines while sparing primary human dermal fibroblasts, underscoring their potential as effective anticancer agents. Moreover, the combination of BSA‐SeNPs with a nanovaccine results in a strong tumor growth reduction in an EO771 breast cancer mouse model, demonstrating a three‐fold decrease in tumor size. This synergistic anticancer effect not only highlights the role of SeNPs as effective anticancer agents but also offers valuable insights for developing innovative combinatorial approaches using SeNPs to improve the outcomes of cancer immunotherapy.
Palladium‐Catalyzed Directing‐Group‐Mediated γ‐C(sp3)−H Glycosylation for Synthesis of C‐Alkyl Glycosides
Authors: Zhong Qiuyu , Yu Changyue , Wang Jinlin , Wang Jiang , Chen Kaixian , Liu Hong , Dai Wenhao
Published: August 2024

C‐alkyl glycosides play a crucial role in various bioactive compounds. However, the synthesis of C‐alkyl glycosides poses significant challenges, particularly through C(sp3)−H glycosylation. Here, we report a set of reactions for constructing C‐alkyl glycosides through directing‐group‐mediated functionalization of unactivated γ‐C(sp3)−H bonds under mild conditions. These reactions not only achieve high regioselectivity and stereoselectivity in glycosylation, but also exhibit a wide substrate scope. They are compatible with both arene and alkane substrates, as well as natural and unnatural amino acid substrates. Mechanistic studies have shown that the directing‐group 8‐aminoquinoline (AQ) and picolinamide (PA) may affect the chirality of the β‐carbon of L‐valine through a sterically favorable trans‐palladacycle intermediate, resulting in (R) or (S) configuration of glycosylated amino acid, respectively. These reactions are promising to provide a convenient and powerful tool for constructing C‐alkyl glycosides and carbohydrate‐based drugs in the future.
Genome‐Wide Association Analysis Identifies LILRB2 Gene for Pathological Myopia
Authors: Jiang Lingxi , Huang Lulin , Dai Chao , Zheng Rui , Miyake Masahiro , Mori Yuki , Nakao Shin‐ya , Morino Kazuya , Ymashiro Kenji , Miao Yang‐Bao , Li Qi , Ren Weiming , Ye Zimeng , Li Hongjing , Yang Zhenglin , Shi Yi
Published: August 2024

Pathological myopia (PM) is one of the leading causes of blindness, especially in Asia. To identify the genetic risk factors of PM, a two‐stage genome‐wide association study (GWAS) and replication analysis in East Asian populations is conducted. The analysis identified LILRB2 in 19q13.42 as a new candidate locus for PM. The increased protein expression of LILRB2/Pirb (mouse orthologous protein) in PM patients and myopia mouse models is validated. It is further revealed that the increase in LILRB2/Pirb promoted fatty acid synthesis and lipid accumulation, leading to the destruction of choroidal function and the development of PM. This study revealed the association between LILRB2 and PM, uncovering the molecular mechanism of lipid metabolism disorders leading to the pathogenesis of PM due to LILRB2 upregulation.
Highly‐Strong and Highly‐Tough Alginate Fibers with Photo‐Modulating Mechanical Properties
Authors: Zhang Lei , Du Qianyao , Chen Jia , Liu Yun , Chang Jiahao , Wu Zhongtao , Luo Xiliang
Published: August 2024

The good combination of high strength and high toughness is a long‐standing challenge in the design of robust biomaterials. Meanwhile, robust biomaterials hardly perform fast and significant mechanical property changes under the trigger of light at room temperature. These limit the application of biomaterials in some specific areas. Here, photoresponsive alginate fibers are fabricated by using the designed azobenzene‐containing surfactant as flexible contact point for cross‐linking polysaccharide chains of alginate, which gain high mechanics through reinforced plastic strain and photo‐modulating mechanics through isomerization of azobenzene. By transferring molecular motion into macro‐scale mechanical property changes, such alginate fibers achieve reversible photo‐modulations on the mechanics. Their breaking strength and toughness can be photo‐modulated from 732 MPa and 112 MJ m−3 to 299 MPa and 27 MJ m−3, respectively, leading to record high mechanical changes among the developed smart biomaterials. With merits of good tolerance to pH and temperature, fast response to light, and good biocompatibility, the reported fibers will be suitable for working in various application scenarios as new smart biomaterials. This study provides a new design strategy for gaining highly‐strong and highly‐tough photoresponsive biomaterials.