bluuebunny/crossref_metadata_2025 huggingface dataset:
Antibacterial Agents
Authors: Lewis James S. , Bush Karen
Published: January 2025

Antimicrobial chemotherapy has played a vital role in the treatment of human infectious diseases since the discovery of penicillin in the 1920s. This chapter provides an overview of the antibacterial agents currently marketed in the United States, with major emphasis on their mechanisms of action, spectra of activity, important pharmacologic parameters, and toxicities. The major antibacterial action of penicillins is derived from their ability to inhibit multiple bacterial enzymes, namely, penicillin‐binding proteins (PBPs), that catalyze the last steps of peptidoglycan synthesis. The penicillins have antibacterial activity against most Gram‐positive and many Gram‐negative and anaerobic organisms. Like the penicillins, cephalosporins act by binding to PBPs of susceptible organisms, thereby interfering with the synthesis of peptidoglycan of the bacterial cell wall. Clavulanic acid is a naturally occurring weak antimicrobial agent found initially in cultures of
Streptomyces clavuligerus
. Streptomycin, neomycin, kanamycin, tobramycin, and gentamicin are naturally occurring aminoglycosides.
Antimicrobial Susceptibility Testing Systems
Authors: Karlowsky James A. , Richter Sandra S. , Patel Jean B.
Published: January 2025

This chapter focuses primarily on commercial Antimicrobial Susceptibility Testing (AST) systems currently available in the United States. Only one semiautomated system for disk diffusion testing is marketed in the United States; additional systems are available in other countries. AST systems include data management software that may be interfaced with a laboratory information system and offer various levels of expert system and epidemiological analyses. The manual broth microdilution systems facilitate the visual reading and recording of minimal inhibitory concentrations. The semiautomated broth microdilution systems use automated devices to read susceptibility and identification tests after offline incubation. New technology provided by the Accelerate Pheno system generates AST results directly from positive blood cultures in less time than testing performed on isolates. In the future, the time required to complete AST testing may also be reduced with the application of molecular techniques.
Susceptibility Test Methods: Anaerobic Bacteria
Authors: Schuetz Audrey N. , Carpenter Darcie E.
Published: January 2025

Anaerobic bacterial pathogens cause serious infections, particularly in the hospital environment. Antimicrobials are a mainstay of treatment, and as with aerobic pathogens, resistance in anaerobic bacteria is increasingly becoming problematic. This chapter covers resistance in specific anaerobe‐antimicrobial agent combinations. It outlines susceptibility testing methods and emphasizes the advantages and disadvantages of each approach. The chapter summarizes susceptibility data for major antimicrobials within four groups of anaerobic pathogens (Gram‐negative bacilli, Gram‐positive spore‐forming bacilli, Gram‐positive non‐spore‐forming bacilli, and cocci). It presents pertinent trends of increasing resistance for each group, and reviews specific recommendations for testing and reporting. A quality control program is designed to monitor the accuracy and precision of the susceptibility testing process being performed. Clinical laboratories should provide susceptibility testing of anaerobes to optimize patient care. More frequent susceptibility testing of anaerobes will lead to a better understanding of the epidemiology of resistance.
Human T‐Cell Lymphotropic Viruses
Authors: Switzer William M. , Heneine Walid , Owen S. Michele
Published: January 2025

Human T‐cell lymphotropic virus types 1 and 2 (HTLV‐1 and HTLV‐2) are members of the
Deltaretrovirus
genus in the
Retroviridae
family. Classification of HTLV groups using Roman numerals was replaced over a decade ago with Arabic numerals, following the guidelines of the International Committee on Taxonomy of Viruses. Many molecular epidemiologic studies have shown HTLV proviruses to be remarkably stable genetically, which has allowed strong resolution of HTLV phylogenies and molecular dating of these viruses. Serum or plasma is suitable for use in serologic assays for HTLV detection and can be drawn at the time of presentation. Isolation of HTLV has been difficult since these viruses are cell associated. Testing for antibodies to HTLV‐1 and HTLV‐2 should be performed for all blood donors and patients presenting with relevant clinical signs and symptoms.
Parainfluenza and Mumps Viruses
Authors: Relich Ryan F.
Published: January 2025

The human parainfluenza viruses (HPIVs) and mumps virus (MuV) are currently classified among the genera
Respirovirus
and
Orthorubulavirus
within the family
Paramyxoviridae
, order
Mononegavirales
. All the viruses described in this chapter are enveloped and possess helical nucleocapsids. Virus isolation and RNA detection have also been recommended for mumps diagnosis in individuals with a documented immunization history. Diagnosis of mumps does not typically involve direct microscopic examination of clinical specimens. However, microscopic examination of affected salivary glands reveals an edematous interstitium diffusely infiltrated by macrophages, lymphocytes, and plasma cells, which compress acini and ducts. The accepted laboratory criteria for the diagnosis of MuV infection are isolation of the virus from clinical specimens, detection of MuV RNA via molecular methods, a significant rise between acute‐ and convalescent‐phase antibody titers in serum, or a positive IgM result for mumps.
Measles and Rubella Viruses
Authors: Crooke Stephen N. , Coughlin Melissa M. , Perelygina Ludmila M.
Published: January 2025

Measles virus is the prototypic member of the genus
Morbillivirus
in the family
Paramyxoviridae
, and it is the only member of the genus that causes human disease. Characteristic cytopathic effects of measles virus infection include giant multinucleated cells (Warthin‐Finkeldey giant cells) as well as intracytoplasmic and intranuclear cellular inclusions. Rubella virus was historically classified in the family
Togaviridae
as the sole member of the genus
Rubivirus
; however, in 2018, rubella virus (and the genus
Rubivirus
) was reclassified as the sole member the new family
Matonaviridae
. The present description of laboratory testing for rubella emphasizes identification of postnatal and congenital rubella cases. However, in the United States, much of the testing is for assessing immunity to rubella, since health care providers should test all pregnant women for immunity by a serum IgG test at the earliest prenatal visit.
Arenaviruses and Filoviruses
Authors: Raabe Vanessa N. , Gilchrist Alison , Kraft Colleen
Published: January 2025

This chapter focuses on the viruses capable of causing viral hemorrhagic fever (VHF) from two taxa, the families
Arenaviridae
and
Filoviridae
. Some members of these virus families can cause severe VHF with high mortality in localized areas of the world. Continuing detection and isolation of new arenavirus and filovirus species from new geographic locations remains important for public health. Human infection with filoviruses and arenaviruses can cause a wide spectrum of illness. For virus isolation, antigen detection, and RT‐PCR, serum, heparinized plasma, or whole blood should be collected during the acute, febrile stages of illness and frozen on dry ice or in liquid nitrogen vapor. Most arenavirus and filovirus species grow well in cell culture. Early diagnosis of arenavirus and filovirus infections is desirable since specific monoclonal antibody treatments and appropriately selected antiviral drugs are, in certain cases, effective when treatment is initiated soon after onset.
Human Cytomegalovirus
Authors: Hodinka Richard L.
Published: January 2025

This chapter emphasizes the fundamental characteristics and clinical importance of cytomegalovirus (CMV) and focuses on the laboratory tests that can be used to identify the virus and to monitor and predict disease and susceptibility to antiviral therapy, and on the philosophy behind the interpretation and reporting of test results in various defined patient populations. Molecular and immunologic techniques, including whole‐genome sequencing directly from clinical specimens, have been used to study variation among CMV strains. CMV infections are common and usually asymptomatic in otherwise healthy children and adults; however, the incidence and spectrum of disease in newborns and in immunocompromised hosts establish this virus as an important human pathogen. Histopathologic testing, antigenemia assays, and qualitative and quantitative molecular methods have been routinely used for the direct detection of CMV from clinical samples. In the immunocompromised host, the use of direct detection methods to diagnose CMV disease is most beneficial for patient care.
Human Polyomaviruses
Authors: Leuzinger Karoline , Hirsch Hans H.
Published: January 2025

Polyomaviruses (PyVs) were discovered in the 1950s as infectious agents that pass bacterium‐tight filters and form different tumors in rodents, hence their name. The multifunctional large tumor antigen protein successfully maintained the bidirectional gene expression, which is a hallmark of the circular PyV genomes. Biopsy‐proven BK polyomavirus nephropathy is characterized by cytopathic changes in renal tubular epithelial cells, showing enlarged nuclei with intranuclear inclusions, rounding up, and cell detachment. Nucleic acid testing (NAT) is the most widely used diagnostic approach to detect viral DNA genomes in specimens from patients with suspected human polyomavirus (HPyV) infection. The diagnostic value of qualitative NATs in the clinical routine resides primarily in the analysis of sterile or NAT‐negative human materials, which must be obtained by clean invasive procedures. The assessment of HPyV‐specific immune responses is of increasing interest for evaluating the risk of primary infection or reactivation as well as identifying predictors of insufficient or reconstituted immune control.
Pneumocystis Jirovecii
Authors: Cushion Melanie T. , Smulian A. George , Powers‐Fletcher Margaret V.
Published: January 2025

Fungi in the genus
Pneumocystis
are extracellular, hostobligate, mostly host‐specific, and typically restricted to the lung tissues of mammals, although extrapulmonary manifestations have been reported.
Pneumocystis
species all appear to contain similar life cycle stages, although the clusters of organisms removed from the lungs of the different host species can vary in presentation and size. There is no consensus for a typing system for
P. jirovecii
. Serological assays to detect anti‐
P. jirovecii
antibodies are useful for epidemiological studies, but not for diagnosis of
Pneumocystis pneumonia
. The microscopic demonstration of
P. jirovecii
in tissue and fluids by staining with Gomori methenamine silver or a rapid variant of the Wright‐Giemsa stain, by immunofluorescent assay, or by other stains such as Papanicolaou stain should be considered sufficient for diagnosis.
Histoplasma
,
Blastomyces
,
Coccidioides
,
Paracoccidioides
and Other Dimorphic Fungi Causing Systemic Mycoses
Authors: Thompson George R. , Gomez Beatriz L.
Published: January 2025

The dimorphic fungi causing systemic disease belong to the class
Eurotiomycetes
, order
Onygenales
. This chapter covers the dimorphic members of the families
Onygenaceae
and
Ajellomycetaceae
.
Ajellomycetaceae
contains the species
Ajellomyces dermatitidis
,
A. capsulatum
,
A. duboisii
, and
A. crescens
, the anamorphs of which have been placed in the genera
Blastomyces
and
Histoplasma
. DNA sequence data place
Paracoccidioides
in the family
Ajellomycetaceae
as well. However, it is important to appreciate that tissue‐form cells of
Histoplasma
and
Blastomyces
can appear similar to each other as well as to yeast cells of various Candida species,
Cryptococcus neoformans
,
Cryptococcus gattii
, and
Talaromyces marneffei
and to endospores of
Coccidioides
species.
Lagenidium
,
Paralagenidium
,
Pythium
,
Rhinosporidium
, and Uncultivated
Paracoccidioides
Species (Formerly
Lacazia loboi
)
Authors: Vilela Raquel , Mendoza Leonel
Published: January 2025

The identification of
Lagenidum
and
Paralagenidium
species is only possible using molecular methodologies, such as PCR and sequencing. Based on taxonomic and other morphological characteristics, these four anomalous species,
Lagenidium
,
Pythium
,
Rhinosporidium
, and the uncultivated fungus previously known as
Lacazia loboi
, were not well understood. Vilela recently reported that the uncultivated fungus developing skin granulomas in dolphin and humans, long believed to be
Lacazia loboi
, comprised two different
Paracoccidioides
species:
P. ceti
and
P. loboi
. Because few DNA sequences from dolphins with the disease were used in phylogenetic analysis, the separation of the dolphin DNA from the cultivated
Paracoccidioides
species remained a puzzle. Deep skin scrapings and tissue biopsies from human and dolphins suspected of skin disease due to uncultivated
Paracoccidioides
species should be submitted to the laboratory.
Mechanisms of Resistance to Antifungal Agents
Authors: Perlin David S.
Published: January 2025

This chapter focuses on the epidemiologic, biological, and molecular nature of antifungal drug resistance. Antifungal drug action and the host immune system often must work synergistically to control and clear an infection. “Microbiological resistance” refers to decreased susceptibility of a fungal strain to an antifungal agent, which is reflected in standardized antifungal in vitro susceptibility testing relative to susceptible standard reference strains, as defined by the Clinical Laboratory Standards Institute and the European Committee on Antimicrobial Susceptibility Testing. The azole antifungal agents are the most prominent example of drug selection for less susceptible species. The polyene drug amphotericin is fungicidal, and resistance rarely occurs. Fungi encode numerous putative drug efflux transporters that have the potential to influence susceptibility to azole antifungal agents by reducing the effective cellular concentration of drugs below their inhibitory threshold. Biofilms are among the most prevalent forms of microbial growth in nature.
Taxonomy and Classification of Human Eukaryotic Parasites
Authors: Adl Sina M. , Mathison Blaine A.
Published: January 2025

The eukaryotic parasites of medical importance are classically known as protozoan, arthropod, and helminthic parasites; the last includes nematodes, cestodes, trematodes, and acanthocephalans. The modern classification of biological species intends to reflect an evolutionary history of living organisms. Eukaryotes are divided into five monophyletic lineages called supergroups, of which four include human parasites: SAR, Excavata, Amoebozoa, and Opisthokonta. These supergroups replace the previous kingdoms that encompassed the eukaryotes. The chapter outlines basic characters of the parasitic protists by clade and the state of their classification at the level of family and genus. Species are identified by sequencing of the 18S small rRNA gene regions and phylogenetic analysis, and the species identification is verified against reference sequences. Modern specimen analysis is discovering new opportunistic pathogens related to known pathogenic groups, but others unrelated to known pathogenic genera will continue to be encountered.
Reagents, Stains, and Media: Parasitology
Authors: Potters Idzi , Linscott Andrea J.
Published: January 2025

The evaluation of clinical specimens for ova and parasites in the clinical laboratory can involve the use of direct macroscopic examination of the specimen and microscopic examination of fresh and fixed specimens, as well as culture for some parasitic organisms. Formalin has been used in parasitology as an all‐purpose fixative for concentration procedures. A solution of iodine can be used for preparing direct or concentrated wet mounts for parasitological examination. Iodine stains can be purchased commercially for use in routine parasitology. Examination of blood films for parasites includes the use of two common stains, the Giemsa stain and Wright's stain, both derivatives of the original Romanowsky stain. Cultures can be performed for only a few parasitic organisms, including
Acanthamoeba
species,
Naegleria fowleri
,
Plasmodium
species, intestinal amebae,
Trichomonas vaginalis
,
Leishmania
species, and
Trypanosoma
species. Culture media used for parasite recovery are sometimes referred to as being either defined or undefined.
Plasmodium
and
Babesia
Authors: Pritt Bobbi S.
Published: January 2025

Plasmodium
and
Babesia
are intraerythrocytic protozoan parasites that cause malaria and babesiosis, respectively. Both are transmitted through the bite of an infected arthropod and cause significant human morbidity and mortality worldwide. The
Plasmodium
parasite is transmitted primarily through the bite of an infected
Anopheles
mosquito, and competent mosquito vectors are found throughout the world. The antigens most commonly detected by the commercially available rapid diagnostic tests are pan‐ or species‐specific
Plasmodium
lactate dehydrogenase,
Plasmodium falciparum
histidine‐rich protein 2, and panspecific
Plasmodium
aldolase. Serologic testing plays only a small role in diagnosis of acute malaria, given that antibodies are frequently absent at the time of patient presentation. Members of the genus
Babesia
infect a wide range of wild and domestic animals worldwide using primarily ixodid tick vectors. Babesiosis due to
Babesia microti
and
Babesia duncani
/
B. duncani
‐like parasites can manifest as asymptomatic or mild infection to life‐threatening illness.
Toxoplasma
Authors: Robert‐Gangneux Florence
Published: January 2025

Toxoplasmosis is a worldwide zoonosis caused by infection with the parasite
Toxoplasma gondii
. It is one of the most common parasitic infections in humans and is most typically asymptomatic.
T. gondii
is a protozoan parasite classified in the Apicomplexa: Conoidasida: Coccidia: Eimeriorina, genus Toxoplasma. Serologic prevalence data indicate that toxoplasmosis is one of the most common infections of humans throughout the world. Serologic screening of organ donors and recipients allows the identification of patients at risk of donor‐derived primary infection. Toxoplasmosis can be categorized into four clinical groups: infection acquired in the immunocompetent patient; infection acquired or reactivated in the immunodeficient patient; congenital infection; and ocular infection. Diagnosis of toxoplasmosis is critical in four clinical settings: pregnant women with infection during gestation, newborns with suspected congenital toxoplasmosis, patients with retinochoroiditis, and immunocompromised patients.
Pathogenic and Opportunistic Free‐Living Amebae
Authors: Cope Jennifer R. , Ali Ibne Karim M. , Visvesvara Govinda S.
Published: January 2025

Free‐living amebae belonging to the genera
Naegleria
,
Acanthamoeba
, and
Balamuthia
can infect humans and other animals and cause potentially severe, life threatening disease. This chapter presents a list of clinical syndromes caused by free‐living amebae infections. Free‐living amebae can be cultivated in axenic conditions or in the presence of a mammalian cell culture for research purposes. The real‐time multiplex PCR assay is a fast, sensitive, and robust assay that detects all three pathogenic free‐living amebae,
Acanthamoeba
spp.,
B. mandrillaris
, and
N. fowleri
, simultaneously in a single specimen and has many advantages over conventional PCR. All clinical specimens should first be examined microscopically, and if amebae are visualized, then the clinician should be immediately notified.
Cryptosporidium
Authors: Xiao Lihua , Feng Yaoyu
Published: January 2025

Cryptosporidium
spp. are protozoan parasites that inhabit the brush borders of the gastrointestinal and respiratory epithelium of various vertebrates, causing enterocolitis, diarrhea, and cholangiopathy in humans.
Cryptosporidium
spp. are well‐recognized water and foodborne pathogens in industrialized nations, having caused many outbreaks of human illness.
Cryptosporidium
spp. are intracellular protozoan parasites that primarily infect epithelial cells of the intestine and biliary ducts, especially the ileum and colon. The distribution of
Cryptosporidium parvum
and
Cryptosporidium hominis
in humans is a reflection of the role of different transmission routes in cryptosporidiosis epidemiology. Cryptosporidiosis in immunocompromised persons, including patients with HIV, is frequently associated with chronic, life‐threatening diarrhea. In clinical laboratories,
Cryptosporidium
spp. in stool specimens are commonly detected by microscopic examinations of oocysts, immunologic detection of antigens, and nucleic acid amplification testing. Genotyping and subtyping have been used in characterizations of
Cryptosporidium
infections, especially in cryptosporidiosis surveillance and outbreak investigations.
Cestodes
Authors: Cabada Miguel M. , Jimenez Juan , Garcia Hector H.
Published: January 2025

Adult cestode tapeworms have a flattened body composed of the scolex, bearing the fixation organs such as suckers, hooks, and bothria; the neck, where the cellular reproduction occurs; and the strobila, formed by numerous segments called proglottids. The fish tapeworm,
Dibiothriocephalus latus
, is the largest intestinal parasite of humans.
Taenia saginata
, the beef tapeworm, is endemic to most of the world. Humans are the only definitive host for this tapeworm, and infection carries minimal health risks.
Taenia solium
, the pork tapeworm, has an extensive geographic distribution and a large impact on human health due to its association with seizure disorders.
T. solium
neurocysticercosis is the most common cause of acquired epilepsy in developing countries.
Hymenolepis nana
is the smallest of the intestinal tapeworms of humans and the most common tapeworm infection throughout the world. In its zoonotic cycle,
H. nana
is a parasite of mice, and beetles act as intermediate hosts.
Arthropods of Medical Importance
Authors: Mathison Blaine A.
Published: January 2025

Arthropods comprise a diverse group of invertebrate animals, united by a common body plan of a jointed, chitinous exoskeleton. Four major extant groups of arthropods have members of medical importance: hexapods (insects), arachnids, crustaceans, and myriapods (e.g., millipedes and centipedes). Arthropods are thought of by many in clinical settings with respect to their role as vectors, transmitters of infectious agents, including viruses, bacteria, protozoans, helminths, and, in the case of
Dermatobia hominis
(the “human” botfly), other arthropods. There are five major groups of vectors: the Diptera (flies and mosquitoes), Hemiptera (kissing bugs), Siphonaptera (fleas), Psocodea (lice), and the order Acarina (ticks and mites). Arthropods that invade a host's body and cause disease include mites (scabies), fleas (tungiasis), fly larvae (myiasis), and pentastomes. Delusion of parasitosis can be a serious illness which can be treated by experienced mental health professionals.
Anisotropic Shape‐Memory Cryogel with Oriented Macroporous Channel for Hemorrhage Control and Tissue Generation
Authors: Pan Zheng , He Gang , Xian Yiwen , Huang Qiqi , Li Shuqi , Li Huangting , Zhang Chong , Wu Decheng
Published: January 2025

Injectable shape‐memory materials represent a promising solution for managing severe bleeding from deep, inaccessible wounds. However, many existing expandable hemostats consist of randomly porous networks and often exhibit inadequate liquid absorption, non‐degradability, and potential cytotoxicity, which limits their effectiveness in hemostasis and wound repair. To overcome these challenges, this study introduces an anisotropic hemostatic cryogel, SALC, featuring oriented macroporous channels made from biocompatible polymers (poly(ethylene glycol), gelatin, and lignin) through a simple one‐step cryo‐structuration process. This structural alignment provides the cryogel with low water flow resistance, efficient fluid transport, and rapid shape recovery. SALC demonstrates superior liquid adsorption and retention, in vitro tamponade sealing, and pro‐coagulant properties compared to commercial gelatin sponges and XSTAT, along with favorable biocompatibility and biodegradability. The hemostatic efficacy of SALC surpasses clinically used counterparts in rat models of liver perforation and femoral artery transection. Remarkably, SALC achieves effective hemostasis in porcine models of severe hepatic, femoral artery, and cardiac injuries. Additionally, this anisotropic cryogel supports liver tissue regeneration by promoting cell migration and angiogenesis while mitigating inflammatory responses. The cryogel is also lightweight and easy to carry and implement. Overall, SALC shows promising clinical applications for treating severe hemorrhages and improving wound healing.
Multiplexed Bio‐detection on an Interferometric Optical Waveguide Assembly
Authors: Bratash Oleksii , Courson Rémi , Malaquin Laurent , Leichle Thierry , Buhot Arnaud , Leroy Loïc , Engel Elodie
Published: January 2025

Multiplexed remote bio‐detection is demonstrated through an optical waveguide assembly coated with interferometric layers. Image conduits (IC)s, composed of 3012 individual cores, are coated with interferometric layers of tantalum pentoxide (Ta2O5) and silica (SiO2) to transform each core into a sensitive sensor. The spectral response of the IC as a function of refractive index (RI) changes is obtained and compared with the simulated one. The experimental sensitivities and resolutions of individual cores of the waveguide are assessed in remote detection mode by imaging through the optical assembly. For 75% of the cores, a sensitivity better than 510%. RIU−1 (RI Unit) is obtained, corresponding to a resolution better than 7 × 10−4 RIU. Furthermore, the coated face of IC is functionalized with two localized arrays of hundred‐micrometer droplets containing two different oligonucleotide (ODN) probes using a polymeric 3D‐printed microcantilever. Hybridization of complementary ODN strands is detected for one of the probes, the second being a negative control. Interaction kinetics are monitored in functionalized areas by grouping several cores or on individual cores. Thus, multiplexed bio‐detection on the surface of an interferometric waveguide is demonstrated for the first time paving the way for applications in multiplex in situ biosensing, and, ultimately, in vivo endoscopic diagnosis.
High‐Performance Droplet‐Based Triboelectric Nanogenerators: A Comparison of Device Configuration and Operating Parameters
Authors: Chaithaweep Kanokwan , Pharino Utchawadee , Pongampai Satana , Hajra Sugato , Kim Hoe Joon , Charoonsuk Thitirat , Maluangnont Tosapol , Sriphan Saichon , Vittayakorn Naratip
Published: January 2025

Droplet‐based electricity generators (DEGs) harness liquid‐solid electrification to convert water droplets impacts into electrical energy. This study systematically examines how droplet height, droplet volume, flow rate, and substrate tilt angle influence DEG performance using polytetrafluoroethylene (PTFE) as a triboelectric layer and deionized water. Three electrode designs (double, top, bottom) are evaluated, revealing that the double‐electrode configuration delivers the highest output. This enhanced performance arises from synergistic droplet motion, electrical double‐layer formation, and charge discharge, as validated by an equivalent circuit model. By varying droplet heights from 1–20 cm, volumes of 7.7–50 µL, flow rates of 50–300 drops/min, and tilt angles of 0–90°, an optimized setup yields −70 V and 22 mA, translating to a power density of 0.28 µW cm−2. High‐speed imaging correlates these outputs with droplet impact dynamics and the resulting charge transfer. Additionally, the optimized DEG can power small electronic devices, charge capacitors, and monitor artificial acid rain in real‐time, displaying distinct electrical signals compared to typical rainwater. These findings underscore the potential of DEGs as renewable energy harvesters and smart environmental sensors, paving the way for advanced on‐demand power generation in diverse settings.
Mannose Promotes β‐Amyloid Pathology by Regulating BACE1 Glycosylation in Alzheimer's Disease
Authors: Liang Chensi , Yuan Ziqi , Yang Shangchen , Zhu Yufei , Chen Zhenlei , Can Dan , Lei Aiyu , Li Huifang , Leng Lige , Zhang Jie
Published: January 2025

Hyperglycemia accelerates Alzheimer's disease (AD) progression, yet the role of monosaccharides remains unclear. Here, it is demonstrated that mannose, a hexose, closely correlates with the pathological characteristics of AD, as confirmed by measuring mannose levels in the brains and serum of AD mice, as well as in the serum of AD patients. AD mice are given mannose by intra‐cerebroventricular injection (ICV) or in drinking water to investigate the effects of mannose on cognition and AD pathological progression. Chronic mannose overload increases β‐amyloid (Aβ) burdens and exacerbates cognitive impairments, which are reversed by a mannose‐free diet or mannose transporter antagonists. Mechanistically, single‐cell RNA sequencing and metabolomics suggested that mannose‐mediated N‐glycosylation of BACE1 and Nicastrin enhances their protein stability, promoting Aβ production. Additionally, reduced mannose intake decreased BACE1 and Nicastrin stability, ultimately lowering Aβ production and mitigating AD pathology. this results highlight that high‐dose mannose consumption may exacerbate AD pathogenesis. Restricting dietary mannose may have therapeutic benefits.
Organelle‐Targeting Nanoparticles
Authors: Soukar John , Peppas Nicholas A. , Gaharwar Akhilesh K.
Published: January 2025

Organelles are specialized subunits within cells which carry out vital functions crucial to cellular survival and form a tightly regulated network. Dysfunctions in any of these organelles are linked to numerous diseases impacting virtually every organ system in the human body. Targeted delivery of therapeutics to specific organelles within the cell holds great promise for overcoming challenging diseases and improving treatment outcomes through the minimization of therapeutic dosage and off‐target effects. Nanoparticles are versatile and effective tools for therapeutic delivery to specific organelles. Nanoparticles offer several advantageous characteristics, including a high surface area‐to‐volume ratio for efficient therapeutic loading and the ability to attach targeting moieties (tethers) that enhance delivery. The choice of nanoparticle shape, size, composition, surface properties, and targeting ligands depends on the desired target organelle and therapeutic effect. Various nanoparticle platforms have been explored for organelle targeting, such as liposomes, polymeric nanoparticles, dendrimers, and inorganic nanoparticles. In this review, current and emerging approaches to nanoparticle design are examined in the context of various diseases linked to organelle dysfunction. Specifically, advances in nanoparticle therapies targeting organelles such as the nucleus, mitochondria, lysosomes/endosomes, Golgi apparatus, and endoplasmic reticulum are comprehensively and critically discussed.
Organic Photo‐Responsive Piezoelectric Materials Based on Pyrene Molecules for Flexible Sensors
Authors: Song Xinyi , Wang Xiaohui , Liu Wei , Chen Xiaoxue , Li Shaoling , Islam Md Shariful , Li Ling , Zhao Xiaobo , Redshaw Carl , Zhao Yu , Cao Changyong (Chase) , Feng Xing
Published: January 2025

Due to the advantages of multiplicity, functionality, and flexibility of organic building blocks, organic piezoelectric materials are regarded as next‐generation materials for potential applications in flexible sensors and energy harvesting devices. Here, a new pure organic pyrene‐based molecule, PyPT is presented, which crystallizes in a non‐centrosymmetric structure. PyPT is synthesized and demonstrated to be suitable for developing flexible sensors due to its remarkable piezoelectric properties. The pyrene‐based piezoelectric molecule exhibits excitation wavelength‐dependent emission behavior and aggregation‐caused quenching properties and demonstrated a piezoelectric coefficient (d33) of 8.02 ± 0.26 pm V−1. The output electronic signal of a PyPT‐based flexible sensor shows a significant increase from 30 to 721 pA as the strain increases from 0.12% to 0.59% with a low Young's modulus of 1.63 Gpa. This high‐performance piezoelectric sensor can serve as a sensitive sound sensor for sound detection and recognition based on the basic characteristics of sound, such as amplitude, frequencies, and timbres. This research offers new insights into advancing pure organic luminescent materials with piezoelectric properties, paving the way for applications in flexible electronics for wearables, human–machine interfaces, and the Internet of Things.
Cost‐effectiveness analysis of postoperative surveillance for stage IV colorectal cancer in Japan: An economic modeling study
Authors: Tsukamoto Fumio , Tsukamoto Shunsuke , Kato Takeharu , Nagata Hiroshi , Takamizawa Yasuyuki , Moritani Konosuke , Kinugasa Yusuke , Esaki Minoru , Kanemitsu Yukihide , Igarashi Ataru
Published: January 2025

Background

The optimal postoperative surveillance strategy after curative resection in patients with stage IV colorectal cancer remains unclear. The present study aimed to assess the cost‐effectiveness of postoperative surveillance strategies recommended by the various academic societies for stage IV colorectal cancer after curative resection.

Methods

This economic evaluation used a Markov state‐transition model to compare the cost‐effectiveness of postoperative surveillance programs proposed in guidelines published by the American Society of Clinical Oncology, American Society of Colon and Rectal Surgeons, European Society for Medical Oncology, National Comprehensive Cancer Network, and Japanese Society for Cancer of the Colon and Rectum. Model parameters were extracted from our retrospective data for patients with colorectal cancer who had synchronous liver and/or lung metastases and underwent curative resection. Cost‐effectiveness was assessed using an incremental cost‐effectiveness ratio for quality‐adjusted life years, with a maximum acceptable value of 5 000 000–6 000 000 JPY/33333–40 000 USD. Uncertainty in the model was assessed by probabilistic sensitivity analyses.

Results

For patients with stage IV colorectal cancer after curative resection, the JSCCR‐strategy was the most cost‐effective, with an incremental cost‐effectiveness ratio of 2 888 628 JPY/19256 USD compared with the next most cost‐effective program. Probabilistic sensitivity analysis showed that the JSCCR‐strategy was most likely to be selected as the most cost‐effective (76.1%–77.9%).

Conclusions

This modeling analysis found that the JSCCR‐strategy was the most cost‐effective strategy for stage IV colorectal cancer. Our findings suggest that intensive postoperative surveillance is acceptable for stage IV colorectal cancer.
Clinical utility of plasma p‐tau217 in identifying abnormal brain amyloid burden in an Asian cohort with high prevalence of concomitant cerebrovascular disease
Authors: Chong Joyce R. , Hilal Saima , Tan Boon Yeow , Venketasubramanian Narayanaswamy , Schöll Michael , Zetterberg Henrik , Blennow Kaj , Ashton Nicholas J. , Chen Christopher P. , Lai Mitchell K. P.
Published: January 2025

INTRODUCTION

Using an Asian cohort with high prevalence of concomitant cerebrovascular disease (CeVD), we evaluated the performance of a plasma immunoassay for tau phosphorylated at threonine 217 (p‐tau217) in detecting amyloid beta positivity (Aβ+) on positron emission tomography and cognitive decline, based on a three‐range reference, which stratified patients into low‐, intermediate‐, and high‐risk groups for Aβ+.

METHODS

Brain amyloid status (Aβ– [n = 142] vs Aβ+ [n = 73]) on amyloid PET scans was assessed along with the plasma ALZpath p‐tau217 assay to derive three‐range reference points for PET Aβ+ based on 90% sensitivity (lower threshold) and 90% specificity (upper threshold).

RESULTS

Plasma p‐tau217 (area under the curve [AUC] = 0.923) outperformed routine clinical assessments (AUC = 0.760–0.819; p ≤ 0.003) and other plasma biomarkers (AUC = 0.817–0.834; p < 0.001). The high‐risk group showed significantly higher rates of cognitive decline than the low‐risk group.

DISCUSSION

Risk stratification for PET Aβ+ based on a plasma p‐tau217 assay demonstrated potential diagnostic and prognostic utility in an Asian cohort with concomitant CeVD.

Highlights

The utility of plasma p‐tau217 to detect brain amyloid beta pathology (Aβ+) was studied in an Asian cohort with concomitant cerebrovascular disease

Plasma tau phosphorylated at threonine 217 (p‐tau217) showed superior utility in detecting Aβ+ compared to neuroimaging measures, clinical workup, or other blood biomarkers including p‐tau181, glial fibrillary protein (GFAP), and Aβ

Higher plasma p‐tau217 correlated with faster cognitive decline

Plasma p‐tau217 shows promise as an Alzheimer's disease (AD) diagnostic and prognostic biomarker in diverse populations
Inhibition of IFITM3 in cerebrovascular endothelium alleviates Alzheimer's‐related phenotypes
Authors: Feng Yijia , Wang Shengya , Yang Danlu , Zheng Wu , Xia Huwei , Zhu Qinxin , Wang Zhipeng , Hu Bolang , Jiang Xinyi , Qin Xuemei , Ni Chenkang , Pan Wenhao , Zhao Yifan , Pan Sipei , Zhang Yun , Song Weihong
Published: January 2025

INTRODUCTION

Interferon‐induced transmembrane protein 3 (IFITM3) modulates γ‐secretase in Alzheimer's Disease (AD). Although IFITM3 knockout reduces amyloid β protein (Aβ) production, its cell‐specific effect on AD remains unclear.

METHODS

Single nucleus RNA sequencing (snRNA‐seq) was used to assess IFITM3 expression. Adeno‐associated virus‐BI30 (AAV‐BI30) was injected to reduce IFITM3 expression in the cerebrovascular endothelial cells (CVECs). The effects on AD phenotypes in cells and AD mice were examined through behavioral tests, two‐photon imaging, flow cytometry, Western blot, immunohistochemistry, and quantitative polymerase chain reaction assay (qPCR).

RESULTS

IFITM3 expression was increased in the CVECs of patients with AD. Overexpression of IFITM3 in primary endothelial cells enhanced Aβ generation through regulating beta‐site APP cleaving enzyme 1 (BACE1) and γ‐secretase. Aβ further increased IFITM3 expression, creating a vicious cycle. Knockdown of IFITM3 in CVECs decreased Aβ accumulation within cerebrovascular walls, reduced Alzheimer's‐related pathology, and improved cognitive performance in AD transgenic mice.

DISCUSSION

Knockdown of IFITM3 in CVECs alleviates AD pathology and cognitive impairment. Targeting cerebrovascular endothelial IFITM3 holds promise for AD treatment.

Highlights

Interferon‐induced transmembrane protein 3 (IFITM3) expression was increased in the cerebrovascular endothelial cells (CVECs) of patients with Alzheimer's Disease (AD).

Cerebrovascular endothelial IFITM3 regulates amyloid β protein (Aβ) generation through regulating beta‐site APP cleaving enzyme 1 (BACE1) and γ‐secretase.

Knockdown of IFITM3 in CVECs reduces Aβ deposits and improves cognitive impairments in AD transgenic mice.

Cerebrovascular endothelial IFITM3 could be a potential target for the treatment of AD.
Building Three‐Dimensional Complexity by Intramolecular 2‐Aminoallyl Cation−Diene (4+3) Cycloaddition
Authors: Shen Lulu , Qin Tianzhu , Jiao Chongling , Zi Weiwei
Published: January 2025

Reliable methods for rapidly constructing C(sp3)‐rich three‐dimensional polycycles are in high demand for organic synthesis and medicinal chemistry. Although there are various mature systems for synthesizing five‐ or six‐membered polycycles, a catalytic platform for accessing diverse cycloheptanoid‐containing polycyclic scaffolds is lacking. Herein, we describe a method for copper‐catalyzed intramolecular 2‐aminoallyl cation−diene (4+3) cycloaddition reactions. By using 1,3‐diene‐tethered ethynyl methylene cyclic carbamates as substrates, we were able to construct various cycloheptanoid‐containing polycyclic scaffolds, which are present in many bioactive molecules. The cycloaddition products were rich in functionality that could undergo various chemical transformations. The synthetic utility of the method was illustrated by total synthesis of the natural products (±)‐mint ketone and (±)‐aphanamol I. Mechanistic studies indicated that the cycloadditions proceed by a concerted [4π+2π] mechanism and that an endo‐selective pathway is favored.
A Metastable State Facilitates Low Temperature CO Oxidation over Pt Nanoparticles
Authors: Le Samantha L. , O'Connor Christopher R. , Kim Taek‐Seung , Reece Christian
Published: January 2025

The dynamic response of heterogeneous catalytic materials to their environment opens a wide variety of possible surface states which may have increased catalytic activity. In this work, we find that it is possible to generate a surface state with increased catalytic activity over metallic 2 nm Pt nanoparticles by performing a thermal treatment of the CO*‐covered Pt catalyst. This state is characterised by its ability to oxidise CO to CO2 at room temperature. By combining pressure pulse experiments with in situ spectroscopy we correlate the formation of this high‐activity state with the desorption of weakly bound CO* molecules from well‐coordinated Pt sites. This high‐activity state is metastable, degrading after elevated thermal treatments or upon readsorption of CO at room temperature. We conclude that this metastable state is highly localised to the surface of the nanoparticle, however its exact atomic structure remains open to speculation.
Fluorescent Artificial Receptor for Dopamine based on Molecular Recognition‐driven Dynamic Covalent Chemistry in a Lipid Nanoreactor
Authors: Kozibroda Bohdan , Lehn Jean‐Marie , Klymchenko Andrey S.
Published: January 2025

Molecular recognition and detection of small bioactive molecules, like neurotransmitters, remain a challenge for chemists, whereas nature found an elegant solution in the form of protein receptors. Here, we introduce a concept of a dynamic artificial receptor that synergically combines molecular recognition with dynamic imine bond formation inside a lipid nanoreactor, inducing a fluorescence response. The designed supramolecular system combines a lipophilic recognition ligand derived from a boronic acid, a fluorescent aldehyde based on push‐pull styryl pyridine and a phenol‐based catalyst. The recognition ligand specifically captures dopamine inside lipid nanodroplets and thus triggers imine bond formation with the aldehyde, producing the emission color change. The rational design of the fluorescent aldehyde, the catalyst, and the recognition ligand allows dramatic acceleration of the imine bond formation required for rapid sensing of dopamine. The nanoprobe enables dopamine detection with micromolar sensitivity and singe‐nanoprobe imaging of dopamine gradients through its robust two‐color ratiometric response. It displays remarkable selectivity without the interference of competing biogenic primary amines and biological media: blood serum, plasma, urine and cell lysate. The proposed concept of a dynamic artificial receptor offers a solution to the long‐standing problem of molecular recognition and sensing of small molecules in complex biological media.
Mn‐Doped Ni(OH)2 Nanosheets as High‐Performance Electrocatalyst for 5‐Hydroxymethylfurfural Electrooxidation
Authors: Xu Hui , Wang Wenke , Sang Ting , Hao Jingcheng , Zhang Xiaoyu , Li Zhonghao
Published: January 2025

Converting 5‐hydroxymethylfurfural (HMF) to 2,5‐furandicarboxylic acid (FDCA) via electrooxidation is a sustainable approach for generating high‐value chemicals from biomass. This study presents Mn‐doped Ni(OH)2 nanosheets as an effective electrocatalyst for HMF electrooxidation. The Mn‐doped Ni(OH)2 nanosheets were synthesized through a microwave‐assisted deep eutectic solvent (DES) strategy, followed by an alkaline reflux process. The as synthesized Mn‐doped Ni(OH)2 nanosheets demonstrated remarkable catalytic performance, achieving 100 % HMF conversion, 99.0 % FDCA yield, and 98.8 % Faraday efficiency. Analysis using X‐ray photoelectron spectroscopy (XPS), open circuit potential (OCP), and density functional theory (DFT) revealed that Mn doping induced surface charge redistribution and electron hole formation, enhancing HMF adsorption and facilitating its oxidation. This study not only elucidates the role of Mn doping in Ni(OH)2 catalyst for HMF electrooxidation but also introduces an efficient electrocatalyst for biomass conversion.
Zum abschnittsweisen Rückbau von Betonbrücken mit spannungsrisskorrosionsempfindlichem Spannstahl
Authors: Wetzel Timm , Albrecht Felix
Published: January 2025

Die rechnerische Nachweisführung der Rückbauzustände von Großbrücken, die mit Spannstahl errichtet wurden, der gegenüber Spannungsrisskorrosion empfindlich ist, stellt eine besondere Herausforderung dar. Insbesondere die Beantwortung der Frage nach den noch ansetzbaren Restspannstahlflächen sowie ein darauf abgestimmtes Rückbaukonzept sind entscheidend für einen störungsfreien Bauablauf. In der vorliegenden Arbeit wird ein wahrscheinlichkeitstheoretischer Ansatz vorgestellt, mit dessen Hilfe die mit ausreichender Sicherheit ansetzbaren Restspannstahlflächen bestimmt werden können. Einhergehend mit den weiterhin unterbreiteten Vorschlägen soll hiermit ein Beitrag zu einer rechtssicheren Planung und letztlich zur Ausschreibung von Brückenrückbauten geleistet werden.
Crystal structure and photoluminescence properties of CuBrxI1−x(melamine) (0 ≤ x ≤ 1) complexes
Authors: Kim Juhyun , Kim Donghyeon , Khefif Fouzia , Yoon Woojin , Yun Hoseop , Yoo Chung‐Yul , Kim Seung‐Joo
Published: January 2025

Organic–inorganic copper(I) halide complexes have attracted attention due to their optoelectronic properties and non‐toxic nature. In this study, we systematically synthesized copper(I) halide melamine complexes as single crystals, (CuBr(melamine) and CuI(melamine)) and polycrystalline powders, CuBrxI1‐x(melamine) (0 ≤ x ≤ 1). The crystal structures of CuBr(melamine) and CuI(melamine) are isotypic with a triclinic space group P , where copper(I) is connected with three adjacent halides along the a‐axis and a single melamine ligand along the c‐axis, forming an infinite stair‐chain structure. The photoluminescence emission peaks of CuBrxI1‐x(melamine) (0 ≤ x ≤ 1) show a red shift from 455 nm to 520 nm with the substitution of Br for I. This finding explains the structure–property relationship of organic–inorganic copper(I) halide complexes and provides guidelines for developing new organic–inorganic optoelectronic materials.
Further Disadvantages of Socioeconomic Status: The Role of Subjective Social Status in University Students' Sense of Belonging
Authors: Fernandez Daniela , Wong Chuk Yan , Bedford Summer , Oliveria‐Silva Ligia , Begeny Christopher , Ryan Michelle
Published: January 2025

Attention has been given to increasing the sense of belonging of students from disadvantaged socioeconomic groups in higher education (HE). Research in belonging has focused on objective indicators of socioeconomic status (SES; i.e., educational status, household income), yet focus on subjective socioeconomic status (SSS) is more limited. We address this gap in two studies, including a cross‐sectional survey (N = 503) and semi‐structured interviews (N = 16), to address two questions: (a) to what extent SSS and a sense of belonging are associated; and (b) what are the social identity processes that might help to explain the relationship between SSS and belonging. As expected, SSS was positively associated with a sense of belonging, such that higher SSS was associated with higher levels of a sense of belonging. Together, these studies illustrate that SSS (a) is yet another way that SES operates to benefit some and disadvantage others; (b) provides an opportunity to analyse the role of intergroup relations in individuals' experiences and (c) is interlocked with intersectional identities, such as ethnicity and race.