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Giao Huynh,1 Thien Thuan Tran,1 Thi Hoai Thuong Do,1 Thi Thuy Dung Truong,1 Phuc Thinh Ong,2 Thi Ngoc Han Nguyen,3 Le An Pham4 1Faculty of Public Health, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam; 2Center for Population Health Sciences, Hanoi University of Public Health, Hanoi, Vietnam; 3Infection Control Department, University Medical Center Ho Chi Minh City, Ho Chi Minh City, Vietnam; 4Family Medicine Training Center, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, VietnamCorrespondence: Le An Pham; Giao HuynhUniversity of Medicine and Pharmacy at Ho Chi Minh City, 217 Hong Bang Street, District 5, Ho Chi Minh City, VietnamTel +84908153743; +84908608338Email phamlean@uq.edu.au; hgiaoytcc@ump.edu.vnBackground: Diabetes-related distress (DRD) refers to the condition of negative emotion as a result of living with diabetes and the burden of self-care. This study aims to evaluate the prevalence and associated factors of DRD among people with type 2 diabetes.Methods: A cross-sectional study was carried out on people with Type 2 Diabetes at three hospitals in Ho Chi Minh City, between April and November 2020. The study used the Vietnamese version of the Diabetes Distress Scale (DDS) which includes 17 items. The mean total distress score was calculated on the average of the 17 items. A mean score of equal to 2.0 or higher was classified as moderate to severe distress. Descriptive statistics were performed by frequency and percentage, and the multivariate Logistic Regression Analysis was used to assess information where p-value < 0.05 was considered statistically significant.Results: A total of 517 participants, who were mainly over 60 years old (56.8%) with females being 65.0%, participated in the study. Results showed that 23.6% and 5.8% of them, respectively, were found as being moderately or highly distressed. Some factors that correlated with the total distress results included age, timescale of diabetes, and glycemic control level (HbA1c). The rate of total distress in those who were over 60 years old and had a HbA1c < 7 were less prevalent than those who were under 60, and had a HbA1c ≥ 7 (OR 0.5 95% CI 0.3– 0.7; OR 0.5 95% CI: 0.3– 0.9, respectively, all p< 0.05), whilst the timescale of diabetes between 5 and 10 years was significantly more prevalent than those who had a timescale less 5 years (OR 1.8 95% CI 1.1– 2.9, p< 0.05).Conclusion: A high rate of distress exists in people with diabetes. Therefore, combining the evaluation of distress as part of the regular diagnostic procedures of diabetes care, and recommending physicians apply a comprehensive approach to diabetes management, is necessary.Keywords: diabetes, diabetes distress scale, distress, Vietnam

Background: Headache disorders are among the leading causes of disability worldwide, especially in young adults. However, no data on the burden of these disorders in Vietnam have been published to date. This study is the first to assess the prevalence of headache disorders among Vietnamese medical students., Methods: This study was conducted in accordance with the recommended methodology of the Global Campaign. Data were collected through interviews using the HARDSHIP structured questionnaire, translated into Vietnamese, with diagnostic assessments based on ICHD-3 criteria. Participants were recruited from two medical universities in Vietnam. The 1-year prevalence rates of headache disorders of public health significance (migraine, tension-type headache [TTH], and probable medication-overuse headache [pMOH]) were estimated. Logistic regression analyses were performed to evaluate the associations between headache disorders and sociodemographic/anthropometric variables., Results: A total of 1,362 participants (42.7% males and 57.3% females) with a mean age of 21.1 ± 1.6 years were included. The overall 1-year prevalence of any headache was 82.6% [95% CI: 80.5-84.6], with a prevalence of 74.7% [71.0-78.2] among males and 88.5% [86.0-90.6] among females. The 1-year prevalences for specific headache types were as follows: migraine 21.8% [19.6-24.1], TTH 54.0% [51.3-56.7], pMOH 0.4% [0.2-1.0], and other headaches on ≥ 15 days/month 3.7% [2.7-4.8]. The one-day prevalence of any headache was 12.1%. Female gender (adjusted OR = 1.77 [1.32-2.36]; p < 0.001) was independently associated with a higher prevalence of migraine, while older age (aOR = 0.84 [0.77-0.91] per year increase) was associated with a lower prevalence. In contrast, TTH was more common among older participants (aOR = 1.07 [1.005-1.15] per year increase)., Conclusions: This study highlights the high prevalence of headache disorders, particularly migraine and TTH, among medical students in Vietnam. These findings underscore the critical need for public health initiatives to improve early diagnosis and effective management of headache disorders within this population., Competing Interests: Declarations Ethics and approvals The study was conducted in accordance with the Declaration of Helsinki, and informed consent was obtained from all subjects and their legal guardian(s). The protocol and questionnaire were reviewed and approved by the Institutional Review Board at the University of Medicine and Pharmacy, Vietnam National University, Hanoi, Vietnam. To protect privacy, any personal information that could be used to identify a specific individual has been removed. Data were collected anonymously and managed in compliance with data protection legislation. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Cancer remains a formidable global health challenge, demanding the exploration of innovative treatment modalities with minimized side effects. One promising avenue involves the synergistic integration of targeted photothermal/photodynamic therapy (PTT/PDT), utilizing specially designed functional nanomaterials for precise cancer diagnosis and treatment. This study introduces a composite biomaterial, anti-epidermal growth factor receptor-conjugated manganese core phthalocyanine bismuth (anti-EGFR-MPB), synthesized for precise cancer imaging and treatment. The biomaterial, synthesized via a solvothermal process, effectively treats and images breast cancer in mouse models. Its biomimetic design targets cancer cells precisely, with dual imaging for real-time monitoring. The biomimetic design of the composite enables precise targeting of cancer cells, whereas the dual imaging allows for real-time visualization and monitoring of the treatment. In vivo examinations confirm substantial damage to tumor tissues with no recurrence following 808-nm laser irradiation. The composite shows strong fluorescence/photoacoustic imaging (PAI) contrast, aiding malignancy detection. Biological assays and histological analyses confirmed the efficacy of the nanocomposite in inducing apoptosis in cancer cells. The integrated targeted dual image-guided phototherapy offered by this composite substantially enhances the precision and efficacy of cancer therapy, achieving an impressive photothermal efficiency of ~33.8%. Our findings demonstrate the utility of the anti-EGFR-MPB nanocomposite for both in vitro and in vivo photoacoustic image-guided PTT and PDT. The optimal treatment strategy for triple-negative breast cancer is found to be the use of 250 μg/ml of nanocomposite irradiated with 1.0 W/cm 2 808-nm laser for 7 min., Competing Interests: Competing interests: The authors declare that they have no competing interests., (Copyright © 2024 Sudip Mondal et al.)

We created a 2-week, dual-module summer course introducing high school students to environmental toxicology by teaching them quantitative polymerase chain reaction (qPCR) as a way to quantify gene expression of chemical defense proteins in response to exposure to environmental pollutants. During the course, students are guided through the various stages of a successful qPCR experiment: in silico primer design and quality control, total RNA extraction and isolation, cDNA conversion, primer test PCR, and evaluation of results via agarose gel electrophoresis or UV/Vis spectra. The course combines lectures, discussions, and demonstrations with dry and wet laboratory sections to give students a thorough understanding of the scope, utility, and chemical principles of qPCR. At the end of the course, the students are taught how to analyze qPCR data and are encouraged to discuss their findings with other classmates to evaluate their hypotheses and assess possible sources of error. This course was designed to be easily adaptable to multiple test species, chemical exposures, and genes of interest. To explore both terrestrial and aquatic toxicology, the students use honey bees (Apis mellifera) and mosquitofish (Gambusia affinis) as test organisms, as well as ABC-type efflux transporters, antioxidant enzymes, and cytochrome P450 enzymes as endpoints for assessing gene expression. We share this course setup and applied protocols to encourage others to design and offer similar courses that give high school students a hands-on introduction to a broad swath of environmental toxicology research and an opportunity to develop scientific skills necessary for university-level research., (© 2024 The Author(s). Biochemistry and Molecular Biology Education published by Wiley Periodicals LLC on behalf of International Union of Biochemistry and Molecular Biology.)

Leishmaniasis is a rare disease in the United States, with an estimated annual incidence of dozens of cases occurring primarily in travelers, migrants, and military personnel. True disease incidence is unknown, since leishmaniasis is not a nationally notifiable condition. Here, we describe the results of molecular leishmaniasis over a 1-year interval (September 2021 to August 2022) when our laboratory served as the primary national reference laboratory for molecular diagnosis of civilian leishmaniasis. We tested 218 specimens submitted from 36 states yielding 94 of the 186 (50.5%) positive cases with species or species complex-level identification and 18 novel mini-exon alleles. Most species belonged to subgenus Viannia (75.6%) and associated with cutaneous or mucocutaneous disease. Cases were associated with recent travel (18.1%), travel timing unspecified (7.4%), migration (7.4%), remote travel (2.1%), military (1.1%), or unknown history (63.8%). These data illustrate the clinical utility of molecular testing for leishmaniasis and provide unique insight into disease epidemiology., Importance: Leishmaniasis is a disfiguring, neglected parasitic infection endemic to the Southern United States and the Americas. Despite significant populations at risk-travelers, military and foreign service members, and migrating persons-the epidemiology of the disease in the United States is poorly understood. Moreover, few clinical laboratories in the United States can test for the disease. Here, we present results from 1 year of testing for this disease at a major reference laboratory. These findings are particularly relevant because they coincide with a temporary "pause" on all clinical testing at the CDC. Our findings suggest at least several hundred cases occur each year in the United States. In particular, mucosal leishmaniasis may be more common than previously reported. We also highlight greater genetic diversity in Leishmania species endemic to the Americas than has been previously sampled, with implications for diagnostic specificity., Competing Interests: The authors declare no conflict of interest.

The growing field of nanotechnology has witnessed numerous advancements over the past few years, particularly in the development of engineered nanoparticles. Compared with bulk materials, metal nanoparticles possess more favorable properties, such as increased chemical activity and toxicity, owing to their smaller size and larger surface area. Metal nanoparticles exhibit exceptional stability, specificity, sensitivity, and effectiveness, making them highly useful in the biomedical field. Metal nanoparticles are in high demand in biomedical nanotechnology, including Au, Ag, Pt, Cu, Zn, Co, Gd, Eu, and Er. These particles exhibit excellent physicochemical properties, including amenable functionalization, non-corrosiveness, and varying optical and electronic properties based on their size and shape. Metal nanoparticles can be modified with different targeting agents such as antibodies, liposomes, transferrin, folic acid, and carbohydrates. Thus, metal nanoparticles hold great promise for various biomedical applications such as photoacoustic imaging, magnetic resonance imaging, computed tomography (CT), photothermal, and photodynamic therapy (PDT). Despite their potential, safety considerations, and regulatory hurdles must be addressed for safe clinical applications. This review highlights advancements in metal nanoparticle surface engineering and explores their integration with emerging technologies such as bioimaging, cancer therapeutics and nanomedicine. By offering valuable insights, this comprehensive review offers a deep understanding of the potential of metal nanoparticles in biomedical research., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The Hydrocephalus Clinical Research Network-quality group (HCRNq) historically defined all abdominal pseudocysts associated with a ventriculoperitoneal shunt as a surgical site infection regardless of culture result., Methods: We retrospectively reviewed broad-range polymerase chain reaction (BRPCR) results sent between January 2017 and July 2023 from abdominal pseudocyst fluid sent from hospitals around the country to a reference laboratory to help further characterize these collections., Results: A total of 19 samples were tested via BRPCR between 1/2017 and 7/2023. Two (10.5 %) had organisms identified; one with Staphylococcus epidermidis and one with Candida parapsilosis. No fastidious organisms that would be expected to not grow with typical culture techniques were identified., Conclusions: Few abdominal pseudocysts had organisms identified by BRPCR, suggesting that not all pseudocysts are due to infectious causes. Consideration should be given to alternate causes of pseudocyst development when cultures are negative., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The linear undecapeptide BP52 was previously reported to have antibacterial activity against phytopathogenic bacteria species. Due to the structural similarities to naturally occurring cationic helical antimicrobial peptides, it was speculated that this peptide could potentially target microbial pathogens and cancer cells found in mammals. Consequently, this study aims to further investigate the structural and biological properties of this peptide. Our findings indicate that BP52 exhibits strong antimicrobial and anticancer activity while displaying relatively low levels of hemolytic activity. Hence, this study suggests that BP52 could be a potential lead compound for drug discovery against infectious diseases and cancer. Besides, new insights into the relationships between the structure and the multifunctional properties of antimicrobial peptides were also explored., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Competing Interests: J.D.B. is a consultant for BioFire Diagnostics and has received research funding for other studies not related to this work. All other authors have no conflicts of interest to report.

Recent advancements in computing have led to the development of artificial intelligence (AI) enabled healthcare technologies. AI-assisted clinical decision support (CDS) integrated into electronic health records (EHR) was demonstrated to have a significant potential to improve clinical care. With the rapid proliferation of AI-assisted CDS, came the realization that a lack of careful consideration of socio-technical issues surrounding the implementation and maintenance of these tools can result in unanticipated consequences, missed opportunities, and suboptimal uptake of these potentially useful technologies. The 48-h Discharge Prediction Tool (48DPT) is a new AI-assisted EHR CDS to facilitate discharge planning. This study aimed to methodologically assess the implementation of 48DPT and identify the barriers and facilitators of adoption and maintenance using the validated implementation science frameworks. The major dimensions of RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) and the constructs of the Consolidated Framework for Implementation Research (CFIR) frameworks have been used to analyze interviews of 24 key stakeholders using 48DPT. The systematic assessment of the 48DPT implementation allowed us to describe facilitators and barriers to implementation such as lack of awareness, lack of accuracy and trust, limited accessibility, and transparency. Based on our evaluation, the factors that are crucial for the successful implementation of AI-assisted EHR CDS were identified. Future implementation efforts of AI-assisted EHR CDS should engage the key clinical stakeholders in the AI tool development from the very inception of the project, support transparency and explainability of the AI models, provide ongoing education and onboarding of the clinical users, and obtain continuous input from clinical staff on the CDS performance., (© 2024. The Author(s).)

Esophageal epidermoid metaplasia (EEM) is a rare condition that has not been described in Stevens-Johnson syndrome (SJS) and has only been described once in pediatrics. Neither the relationship, treatment, nor surveillance between SJS, esophageal strictures, and EEM has been established. We report the first case of EEM in an 8-year-old girl with esophageal stricture after SJS. Pediatric patients presenting with dysphagia after SJS should be evaluated for esophageal stricture and subsequent EEM development. Owing to EEM's, association with esophageal squamous cell cancer, close follow-up, biopsy surveillance for dysplasia, endoscopic treatment, and TP53 genetic sequencing should be considered., (© 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

SARS-CoV-2 infection of immunocompromised individuals often leads to prolonged detection of viral RNA and infectious virus in nasal specimens, presumably due to the lack of induction of an appropriate adaptive immune response. Mutations identified in virus sequences obtained from persistently infected patients bear signatures of immune evasion and have some overlap with sequences present in variants of concern. We characterized virus isolates obtained greater than 100 days after the initial COVID-19 diagnosis from two COVID-19 patients undergoing immunosuppressive cancer therapy, wand compared them to an isolate from the start of the infection. Isolates from an individual who never mounted an antibody response specific to SARS-CoV-2 despite the administration of convalescent plasma showed slight reductions in plaque size and some showed temperature-dependent replication attenuation on human nasal epithelial cell culture compared to the virus that initiated infection. An isolate from another patient-who did mount a SARS-CoV-2 IgM response-showed temperature-dependent changes in plaque size as well as increased syncytia formation and escape from serum-neutralizing antibodies. Our results indicate that not all virus isolates from immunocompromised COVID-19 patients display clear signs of phenotypic change, but increased attention should be paid to monitoring virus evolution in this patient population.

Research Question: What is the diagnostic accuracy of hysterosalpingo-foam sonography (HyFoSy), using two-dimensional ultrasound in tubal patency assessment in infertile women compared with laparoscopy with dye chromotubation?, Design: This prospective study was conducted at My Duc Hospital, Vietnam. Infertile women aged 18 years or older, who were scheduled for laparoscopy, were included. Visual Analogue Scale (VAS) score for perception of pain during HyFoSy was used. Laparoscopy was carried out on the same day. Clinicians undertaking laparoscopy were blinded to HyFoSy results. Sensitivity, specificity, negative and positive predictive value, and 95% confidence intervals were calculated. A sample size of 455 women (n = 910 fallopian tubes) was needed to demonstrate a fluctuation hypothesis, not exceeding 6%, for sensitivity and specificity (power 0.80, two-sided alpha 5%, loss to follow-up 5%)., Results: Between 2019 and 2022, 455 participants were recruited. Hysterosalpingo-foam sonography was unsuccessfully carried out in six participants. Two withdrew their consent. Data analysis was conducted on the remaining 447 participants (n = 868 fallopian tubes). The sensitivity and specificity of hysterosalpingo-foam sonography compared with laparoscopy were 0.75 (95% CI 0.71 to 0.79) and 0.70 (95% CI 0.65 to 0.74), respectively. Hysterosalpingo-foam sonography gave a positive predictive value of 0.76 (95% CI 0.73 to 0.80) and negative predictive value of 0.68 (95% CI 0.64 to 0.73). A total of 42.8% of women reported a VAS score of no pain. No adverse event was reported., Conclusion: Compared with laparoscopy with dye chromotubation, two-dimensional HyFoSy is a well-tolerated, reliable technique for assessing tubal patency., (Copyright © 2024 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Digital PCR (dPCR) is a powerful method for highly sensitive and precise quantification of nucleic acids. However, designing and optimizing new multiplex dPCR assays using target sequence specific probes remains cumbersome, since fluorescent signals must be optimized for every new target panel. As a solution, we established a generic fluorogenic 6-plex reporter set, based on mediator probe technology, that decouples target detection from signal generation. This generic reporter set is compatible with different target panels and thus provides already optimized fluorescence signals from the start of new assay development. Generic reporters showed high population separability in a colorimetric 6-plex mediator probe dPCR, due to their tailored fluorophore and quencher selection. These reporters were further tested using different KRAS , NRAS and BRAF single-nucleotide polymorphisms (SNP), which are frequent point mutation targets in liquid biopsy. We specifically quantified SNP targets in our multiplex approach down to 0.4 copies per microliter (cp/µL) reaction mix, equaling 10 copies per reaction, on a wild-type background of 400 cp/µL for each, equaling 0.1% variant allele frequencies. We also demonstrated the design of an alternative generic reporter set from scratch in order to give detailed step-by-step guidance on how to systematically establish and optimize novel generic reporter sets. Those generic reporter sets can be customized for various digital PCR platforms or target panels with different degrees of multiplexing.

Competing Interests: The authors declare no conflict of interest.

Human p97 ATPase is crucial in various cellular processes, making it a target for inhibitors to treat cancers, neurological, and infectious diseases. Triazole allosteric p97 inhibitors have been demonstrated to match the efficacy of CB-5083, an ATP-competitive inhibitor, in cellular models. However, the mechanism is not well understood. This study systematically investigates the structures of new triazole inhibitors bound to  both wild-type and disease mutant forms of p97 and measures their effects on function. These inhibitors bind at the interface of the D1 and D2 domains of each p97 subunit, shifting surrounding helices and altering the loop structures near the C-terminal α2 G helix to modulate domain-domain communications. A key structural moiety of the inhibitor affects the rotameric conformations of interacting side chains, indirectly modulating the N-terminal domain conformation in p97 R155H mutant. The differential effects of inhibitor binding to wild-type and mutant p97 provide insights into drug design with enhanced specificity, particularly for oncology applications., (© 2024. The Author(s).)

Three-dimensional cell spheroids show promise for the reconstruction of native tissues. Herein, we report a sophisticated, uniform, and highly reproducible spheroid culture system for tissue reconstruction. A mesh-integrated culture system was designed to precisely control the uniformity and reproducibility of spheroid formation. Furthermore, we synthesized hexanoyl glycol chitosan, a material with ultralow cell adhesion properties, to further improve spheroid formation efficiency and biological function. Our results demonstrate improved biological function in various types of cells and ability to generate spheroids with complex structures composed of multiple cell types. In conclusion, our spheroid culture system offers a highly effective and widely applicable approach to generating customized spheroids with desired structural and biological features for a variety of biomedical applications., (Creative Commons Attribution license.)

Deep learning (DL) is becoming more popular as a useful tool in various scientific domains, especially in chemistry applications. In the infrared spectroscopy field, where identifying functional groups in unknown compounds poses a significant challenge, there is a growing need for innovative approaches to streamline and enhance analysis processes. This study introduces a transformative approach leveraging a DL methodology based on transformer attention models. With a data set containing approximately 8677 spectra, our model utilizes self-attention mechanisms to capture complex spectral features and precisely predict 17 functional groups, outperforming conventional architectures in both functional group prediction accuracy and compound-level precision. The success of our approach underscores the potential of transformer-based methodologies in enhancing spectral analysis techniques.

Hydrophobic drugs, while designed to interact with specific receptors or enzymes located in lipid-rich cell membranes, often face challenges of limited bioavailability and insufficient circulation time due to their insolubility in aqueous environments. One plausible pathway to increase their blood circulation time is to load these drugs into biocompatible and hydrophilic carriers to enhance their uptake. In this study, mesoporous silica (mSiO 2 ) nanocarriers of various morphologies (including cubes, capsules, and spheres) were synthesized. These nanocarriers were then surface-functionalized with alkyl chain hydrocarbons, specifically octadecyl-trimethoxysilane, (OCH 3 ) 3 Si(CH 2 ) 17 CH 3 , to render them hydrophobic. The resulting nanocarriers (((OCH 3 ) 3 Si(CH 2 ) 17 CH 3 )@mSiO 2 ) showed up to 80% uptake for hydrophobic drugs. However, a significant drawback was observed as most of the drugs were prone to uncontrollable release within 6 h. This challenge of premature drug release was successfully mitigated by effectively sealing the drug-loaded nanocarriers with a pH-sensitive lipid overlayer. The lipid-coated nanocarriers prolonged drug containment and sustained release up to 72 h, compared to 6 h for uncoated nanocarriers, thereby facilitating longer blood circulation times. Moreover, the shape and size of nanocarriers were found to influence both drug entrapment capacity and release behavior with cubic forms exhibiting superior loading capacity due to higher surface area and porosity. Additionally, it was observed that the molecular weight and chemical structure of the drug molecules played a crucial role in determining their uptake and release profiles. Furthermore, the influence of different morphologies of nanocarriers on cell uptake and cytotoxicity in immune cells was elucidated. These findings underscore the importance of nanocarrier morphology and drug properties to enhance loading capacities and controlled release profiles, for designing drug delivery systems tailored for hydrophobic drugs.

This study represents an innovative approach to construct multi-functional nanoplatforms for cancer diagnosis and therapy by combining hyaluronic acid (HA) with iron-platinum nanoparticles (FePt NPs). These HA-coated FePt NPs, referred to as FePt@HA NPs, demonstrated remarkable biocompatibility, high absorption, and excellent light-to-heat conversion properties in the near-infrared (NIR) region, making them ideal candidates for photothermal therapy (PTT). In vitro studies revealed their effective cancer cell eradication under NIR laser irradiation, while in vivo experiments on mice showcased their superior heating capabilities. Moreover, FePt@HA NPs exhibited a distinct and strong photoacoustic (PA) signal, facilitating enhanced and precise intra-tumoral PA imaging. Our results highlight the potential of FePt@HA NPs as promising photothermal agents for future PTT applications. They offer high selectivity, precision, and minimal side effects in cancer treatment, along with their valuable PA imaging application for tumor localization and characterization., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Germline epigenetic programming, including genomic imprinting, substantially influences offspring development. Polycomb Repressive Complex 2 (PRC2) plays an important role in Histone 3 Lysine 27 trimethylation (H3K27me3)-dependent imprinting, loss of which leads to growth and developmental changes in mouse offspring. In this study, we show that offspring from mouse oocytes lacking the PRC2 protein Embryonic Ectoderm Development (EED) were initially developmentally delayed, characterised by low blastocyst cell counts and substantial growth delay in mid-gestation embryos. This initial developmental delay was resolved as offspring underwent accelerated fetal development and growth in late gestation resulting in offspring that were similar stage and weight to controls at birth. The accelerated development and growth in offspring from Eed -null oocytes was associated with remodelling of the placenta, which involved an increase in fetal and maternal tissue size, conspicuous expansion of the glycogen-enriched cell population, and delayed parturition. Despite placental remodelling and accelerated offspring fetal growth and development, placental efficiency, and fetal blood glucose levels were low, and the fetal blood metabolome was unchanged. Moreover, while expression of the H3K27me3-imprinted gene and amino acid transporter Slc38a4 was increased, fetal blood levels of individual amino acids were similar to controls, indicating that placental amino acid transport was not enhanced. Genome-wide analyses identified extensive transcriptional dysregulation and DNA methylation changes in affected placentas, including a range of imprinted and non-imprinted genes. Together, while deletion of Eed in growing oocytes resulted in fetal growth and developmental delay and placental hyperplasia, our data indicate a remarkable capacity for offspring fetal growth to be normalised despite inefficient placental function and the loss of H3K27me3-dependent genomic imprinting., Competing Interests: RO, SP, EJ, ZQ, TT, NY, GP, TT, DF, HB, RB, Mv, DG, NS, DA, PW No competing interests declared, (© 2024, Oberin, Petautschnig et al.)

A new method utilizing fluorescent ratiometry is proposed for detecting putrescine and spermidine. The method involves the use of a fluorescent probe comprising a 2D halide perovskite synthesized from octadecylamine-iodine and PbI 2 via a grinding-sonicating technique, along with a Eu 3+ -complex. Upon excitation at 290 nm, the probe fluoresces at two distinguishable wavelengths. The addition of putrescine and spermidine significantly decreases the emission of the 2D halide perovskite at 496 nm, while the emission of the Eu 3+ -complex at 618 nm remains stable. The color changes of the probe depend on the concentration of putrescine and spermidine, and the assay offers linearity over a wide concentration range (30-4000 ng mL -1 ), a low detection limit (4 ng mL -1 for putrescine, and 7 ng mL -1 for spermidine), and a quick response time. Furthermore, a portable device based on a smartphone can be used to record the color change of the paper test strip using the prepared fluorescent materials. The fluorescence quenching mechanism of the probe is explained as dynamic quenching.

Objective: The study aimed to quantify milk production and urinary nitrogen (UN) excretion of dairy cows grazing pastures containing varying contents of plantain (Plantago lanceolata) in different seasons, under a typical farm practice., Methods: Four pasture treatments: perennial ryegrass (Lolium perenne) - white clover (Trifolium repens) (RGWC), RGWC + low plantain rate, RGWC + medium plantain rate, and RGWC + high plantain rate, were established in four adaptation areas (1 ha each) and 20 experimental plots (800 m2 each), and rotationally grazed by dairy cows over 14 grazing events during two lactation years. In each grazing (8-9 days), 60 or 80 Jersey-Friesian lactation cows were assigned to their pasture treatments, adapted to their pastures over the first six days, then each group of 15 or 20 cows were randomly allocated for grazing in five treatment plots over a two or three-day measurement period. Milk, urine, and faecal samples were collected from individual cows during the measurement period., Results: The pasture treatments did not affect milk production, the yield and composition of milk solids, protein, fat, and lactose. However, cows grazing pastures containing between 17-28% dietary plantain reduced UN concentration by 15-27%, decreased UN excretion by 4-9%, and increased urine volume by 22-40%, compared to grazing the RGWC pasture. The change in UN concentration, and urine volume were associated with plantain proportion in the diet and were greater during late summer and autumn than during early summer., Conclusion: Incorporating 17%-28% dietary plantain with RGWC pastures can reduce the risk of nitrogen losses from pastoral systems, while maintaining the milk production of dairy cows.

Previous studies on the intricate interactions between plants and microorganisms have revealed that fungal volatile compounds (VCs) can affect plant growth and development. However, the precise mechanisms underlying these actions remain to be delineated. In this study, we discovered that VCs from the soilborne fungus Tolypocladium inflatum GT22 enhance the growth of Arabidopsis. Remarkably, priming Arabidopsis with GT22 VCs caused the plant to display an enhanced immune response and mitigated the detrimental effects of both pathogenic infections and copper stress. Transcriptomic analyses of Arabidopsis seedlings treated with GT22 VCs for 3, 24 and 48 h revealed that 90, 83 and 137 genes were differentially expressed, respectively. The responsive genes are known to be involved in growth, hormone regulation, defense mechanisms and signaling pathways. Furthermore, we observed the induction of genes related to innate immunity, hypoxia, salicylic acid biosynthesis and camalexin biosynthesis by GT22 VCs. Among the VCs emitted by GT22, exposure of Arabidopsis seedlings to limonene promoted plant growth and attenuated copper stress. Thus, limonene appears to be a key mediator of the interaction between GT22 and plants. Overall, our findings provide evidence that fungal VCs can promote plant growth and enhance both biotic and abiotic tolerance. As such, our study suggests that exposure of seedlings to T. inflatum GT22 VCs may be a means of improving crop productivity. This study describes a beneficial interaction between T. inflatun GT22 and Arabidopsis. Our investigation of microorganism function in terms of VC activities allowed us to overcome the limitations of traditional microbial application methods. The importance of this study lies in the discovery of T. inflatun GT22 as a beneficial microorganism. This soilborne fungus emits VCs with plant growth-promoting effects and the ability to alleviate both copper and pathogenic stress. Furthermore, our study offers a valuable approach to tracking the activities of fungal VC components via transcriptomic analysis and sheds light on the mechanisms through which VCs promote plant growth and induce resistance. This research significantly advances our knowledge of VC applications and provides an example for further investigations within this field., (© The Author(s) 2023. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The hypothalamic paraventricular nucleus (PVN) is strongly inhibited by γ-aminobutyric acid (GABA) from the surrounding peri-nuclear zone (PNZ). Because glutamate mediates fast excitatory transmission and is substrate for GABA synthesis, we tested its capacity to dynamically strengthen GABA inhibition. In PVN slices from male mice, bath glutamate applied during ionotropic glutamate receptor blockade increased PNZ-evoked inhibitory postsynaptic currents (eIPSCs) without affecting GABA-A receptor agonist currents or single-channel conductance, implicating a presynaptic mechanism(s). Consistent with this interpretation, bath glutamate failed to strengthen IPSCs during pharmacological saturation of GABA-A receptors. Presynaptic analyses revealed that glutamate did not affect paired-pulse ratio, peak eIPSC variability, GABA vesicle recycling speed, or readily releasable pool (RRP) size. Notably, glutamate-GABA strengthening (GGS) was unaffected by metabotropic glutamate receptor blockade and graded external Ca 2+ when normalized to baseline amplitude. GGS was prevented by pan- but not glial-specific inhibition of glutamate uptake and by inhibition of glutamic acid decarboxylase (GAD), indicating reliance on glutamate uptake by neuronal excitatory amino acid transporter 3 (EAAT3) and enzymatic conversion of glutamate to GABA. EAAT3 immunoreactivity was strongly localized to presumptive PVN GABA terminals. High bath K + also induced GGS, which was prevented by glutamate vesicle depletion, indicating that synaptic glutamate release strengthens PVN GABA inhibition. GGS suppressed PVN cell firing, indicating its functional significance. In sum, PVN GGS buffers neuronal excitation by apparent "over-filling" of vesicles with GABA synthesized from synaptically released glutamate. We posit that GGS protects against sustained PVN excitation and excitotoxicity while potentially aiding stress adaptation and habituation., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 the authors.)

Hospital at Home (HaH) provides hospital-level services in the home to eligible patients who would otherwise require facility-based hospitalization. In the last two decades, studies have shown that HaH can improve patient outcomes and satisfaction and reduce hospital readmissions. Improved technology and greater experience with the model have led to expansion in the scope of patients served and services provided by the model, but dissemination in the United States has been hampered by lack of insurance coverage until recently. HaH is likely at the tipping point for wide adoption in the United States. To realize its full benefits, HaH will need to continue volume expansion to achieve culture change in clinical practice as facilitated by increased insurance coverage, technological advancements, and improved workforce expertise. It is also essential that HaH programs maintain high-quality acute hospital care, ensure that their benefits can be accessed by hard-to-reach rural populations, and continue to advance health equity.

Indoor air pollution is a global problem and one of the main stress factors that has negative effects on plant and human health. 3-methyl-1-butanol (3MB), an indoor air pollutant, is a microbial volatile organic compound (mVOC) commonly found in damp indoor dwellings. In this study, we reported that 1 mg/L of 3MB can elicit a significant reduction in the stomatal aperture ratio in Arabidopsis and tobacco. Our results also showed that 3MB enhances the reactive oxygen species (ROS) production in guard cells of wild-type Arabidopsis after 24 h exposure. Further investigation of 24 h 3MB fumigation of rbohD, the1-1, mkk1, mkk3, and nced3 mutants revealed that ROS production, cell wall integrity, MAPK kinases cascade, and phytohormone abscisic acid are all involved in the process of 3MB-induced stomatal. Our findings proposed a mechanism by which 3MB regulates stomatal closure in Arabidopsis. Understanding the mechanisms by which microbial indoor air pollutant induces stomatal closure is critical for modulating the intake of harmful gases from indoor environments into leaves. Investigations into how stomata respond to the indoor mVOC 3MB will shed light on the plant's "self-defense" system responding to indoor air pollution., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The study of small RNAs is a field that is expanding quickly. Other functional short RNA molecules other than microRNAs, and gene expression regulators, have been found in animals and plants. MicroRNAs play a significant role in host-microbe interactions, and parasite microRNAs may affect the host's innate immunity. Furthermore, short RNAs are intriguing non-invasive biomarker possibilities because they can be found in physiological fluids. These trends suggest that for many researchers, quick and simple techniques for expression profiling and subsequent downstream analysis of miRNA-seq data are crucial. We selected sRNAtoolbox to make integrated sRNA research easier. Each tool can be used separately or to explore and analyze sRNAbench results in further depth. A special focus was placed on the tools' usability. We review available miRNA research tools to have an overview of the evaluation of the tools. Mainly we evaluate the tool sRNAtoolbox., (Copyright © 2024. Published by Elsevier Inc.)

What Is Known on the Subject: Research has shown effectiveness of nonpharmacological interventions in improving or maintaining cognition, mood, functioning, self-efficacy and quality of life for persons with mild-to-moderate dementia (PWDs). These interventions are critical during the earlier stages of dementia. However, Canadian and international literature report underutilization of and difficulty accessing the interventions., What This Paper Adds to Existing Knowledge: To our knowledge, this is the first review that explored factors influencing seniors' utilization of nonpharmacological interventions in the earlier stages of dementia. This review contributed to the discovery of unique factors such as PWDs' beliefs, fears, perceptions, and acceptability of nonpharmacological interventions and environmental influences on intervention provision. PWDs' intervention uptake may appear as a matter of personal choices related to individuals' knowledge, beliefs and perceptions. However, the analysis of the research evidence suggests that PWDs' choices are shaped by environmental factors such as formal and informal caregiver support, acceptability and accessibility of nonpharmacological interventions, dementia care workforce, community's attitudes towards dementia and funding. The complex interplay among factors highlights the importance of targeting health promotion strategies at both individuals and their environments., What Are the Implications for Practice: The review findings feature opportunities for healthcare practitioners, including mental health nurses, in advocating for PWDs' evidence-informed decision-making and access to desired nonpharmacological treatments. Involvement of patients and families in care-planning through ongoing assessment of health and learning needs, as well as enablers and barriers to using interventions, continuing information provision, and personalized referrals to appropriate services can promote PWDs' rights to healthcare., Abstract: INTRODUCTION: Despite the significance of nonpharmacological interventions in optimal management of mild-to-moderate dementia, it remains unclear in the literature how persons with mild-to-moderate dementia (PWDs) view, understand and access nonpharmacological interventions., Aim: The purpose of this review was to explore the extent and nature of evidence concerning factors that influence the use of nonpharmacological interventions for community-dwelling seniors with mild-to-moderate dementia., Method: An integrative review was undertaken following Toronto and Remington (A step-by-step guide to conducting an integrative review, 2020)'s instruction which expanded Torraco (Human Resource Development Review, 2016, 15, 404)'s and Whittemore and Knafl (Journal of Advanced Nursing, 2005, 52, 546)'s guidance., Results: The review of 16 studies suggests that PWDs' use of nonpharmacological interventions is shaped by a complex interplay of various personal, interpersonal, organizational, community and political influences., Discussion: The findings highlight the complex, interrelated relationships among multiple factors and subsequent limitations of behaviour-oriented health promotion strategies. To assist PWDs in making healthier choices, health promotion strategies need to direct attention to both individuals' behaviours and environmental conditions impacting the behaviours., Implications for Practice: The findings of this review can inform multidisciplinary health practitioners' (including mental health nurses) practice with seniors living with mild-to-moderate dementia. We recommend actionable ways in which they can empower patients and their families in dementia management., (© 2023 The Authors. Journal of Psychiatric and Mental Health Nursing published by John Wiley & Sons Ltd.)

A new approach that combines analytical two-parameter kinematic theory (2PKT) with machine learning (ML) models for estimating the shear capacity of embedded through-section (ETS)-strengthened reinforced concrete (RC) beams is proposed. The 2PKT was first developed to validate its representativeness and confidence against the available experimental data of ETS-retrofitted RC beams. Given the deficiency of the test data, the developed 2PKT was utilized to generate a large data pool with 2643 samples. The aim was to optimize the ML algorithms, namely, the random forest, extreme gradient boosting (XGBoost), light gradient boosting machine, and artificial neural network (ANN) algorithm. The optimized ANN model exhibited the highest accuracy in predicting the total shear strength of ETS-strengthened beams and ETS shear contribution. In terms of predicting the total shear strength of ETS-strengthened beams, the ANN model achieved R 2 values of 0.99, 0.98, and 0.96 for the training, validation, and testing data, respectively. By contrast, the ANN model could predict ETS shear contribution with high accuracy, with R 2 values of 0.99, 0.99, and 0.97 for the training, validation, and testing data, respectively. Then, the effects of all design variables on the shear capacity of the ETS-strengthened beams were investigated using the hybrid 2PKT-ML. The obtained trends could well appraise the reasonability of the proposed approach., (© 2023. The Author(s).)

Microbial volatile compounds (mVCs) may cause stomatal closure to limit pathogen invasion as part of plant innate immune response. However, the mechanisms of mVC-induced stomatal closure remain unclear. In this study, we co-cultured Enterobacter aerogenes with Arabidopsis (Arabidopsis thaliana) seedlings without direct contact to initiate stomatal closure. Experiments using the reactive oxygen species (ROS)-sensitive fluorescent dye, H 2 DCF-DA, showed that mVCs from E. aerogenes enhanced ROS production in guard cells of wild-type plants. The involvement of ROS in stomatal closure was then demonstrated in an ROS production mutant (rbohD). In addition, we identified two stages of signal transduction during E. aerogenes VC-induced stomatal closure by comparing the response of wild-type Arabidopsis with a panel of mutants. In the early stage (3 h exposure), E. aerogenes VCs induced stomatal closure in wild-type and receptor-like kinase THESEUS1 mutant (the1-1) but not in rbohD, plant hormone-related mutants (nced3, erf4, jar1-1), or MAPK kinase mutants (mkk1 and mkk3). However, in the late stage (24 h exposure), E. aerogenes VCs induced stomatal closure in wild-type and rbohD but not in nced3, erf4, jar1-1, the1-1, mkk1 or mkk3. Taken together, our results suggest that E. aerogenes mVC-induced plant immune responses modulate stomatal closure in Arabidopsis by a multi-phase mechanism., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Research Question: Does in vitro exposure of preimplantation mouse embryos to the ketone bodies β-hydroxybutyrate (βOHB) and acetoacetate (AcAc) impact post-transfer fetal and placental gene expression?, Design: Blastocysts cultured in vitro with or without 2 mmol/l βOHB alone ('βOHB') or combined with 0.8 mmol/l AcAc ('Keto') underwent embryo transfer. Transcriptional profiles of sexed placenta, liver and brain at gestational day 14.5 were examined via RNA sequencing and DAVID functional analysis., Results: A sexually dimorphic response to in vitro ketone exposure was observed. Both βOHB and Keto exposure down-regulated genes related to oxidative phosphorylation specifically in female liver. βOHB down-regulated female placental steroid biosynthetic processes, while Keto treatment up-regulated genes relevant to blood vessel formation and cell migration in male placenta. Brain transcriptomes were minimally affected. X-linked genes and chromatin modifiers were identified as differentially expressed in both liver and placenta, alluding to a sex-specific regulatory mechanism., Conclusions: Transient preimplantation ketone exposure perturbs sex-specific fetal liver and placental gene expression, demonstrating a developmental programming effect that warrants future investigation of the postnatal metabolic health of male and female offspring., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Hemophilia A (HEMA) is an X-linked bleeding disorder caused by reduced/absent coagulation factor VIII expression, as a result of pathogenic variants in the F8 gene. Preimplantation prevention of HEMA should ideally include direct pathogenic F8 variant detection, complemented by linkage analysis of flanking markers to identify the high-risk F8 allele. Linkage analysis is particularly indispensable when the pathogenic variant cannot be detected directly or identified. This study evaluated the suitability of a panel of F8 intragenic and extragenic short tandem repeat markers for standalone linkage-based preimplantation genetic testing for monogenic disorder (PGT-M) of the Inv22 pathogenic variant, an almost 600 kb paracentric inversion responsible for almost half of all severe HEMA globally, for which direct detection is challenging., Methods: Thirteen markers spanning 1 Mb and encompassing both F8 and the Inv22 inversion interval were genotyped in 153 unrelated females of Viet Kinh ethnicity., Results: All individuals were heterozygous for ≥ 1 marker, ~ 90% were heterozygous for ≥ 1 of the five F8 intragenic markers, and almost 98% were heterozygous for ≥ 1 upstream (telomeric) and ≥ 1 downstream (centromeric) markers. A prospective PGT-M couple at risk of transmitting F8 Inv22 were fully informative at four marker loci (2 intra-inversion, 1 centromeric, 1 telomeric) and partially informative at another five (2 intra-inversion, 3 centromeric), allowing robust phasing of low- and high-risk haplotypes. In vitro fertilization produced three embryos, all of which clearly inherited the low-risk maternal allele, enabling reliable unaffected diagnoses. A single embryo transfer produced a clinical pregnancy, which was confirmed as unaffected by amniocentesis and long-range PCR, and a healthy baby girl was delivered at term., Conclusion: Robust and reliable PGT-M of HEMA, including the common F8 Inv22 pathogenic variant, can be achieved with sufficient informative intragenic and flanking markers., (© 2023. BioMed Central Ltd., part of Springer Nature.)

The fifth generation achieved tremendous success, which brings high hopes for the next generation, as evidenced by the sixth generation (6G) key performance indicators, which include ultra-reliable low latency communication (URLLC), extremely high data rate, high energy and spectral efficiency, ultra-dense connectivity, integrated sensing and communication, and secure communication. Emerging technologies such as intelligent reflecting surface (IRS), unmanned aerial vehicles (UAVs), non-orthogonal multiple access (NOMA), and others have the ability to provide communications for massive users, high overhead, and computational complexity. This will address concerns over the outrageous 6G requirements. However, optimizing system functionality with these new technologies was found to be hard for conventional mathematical solutions. Therefore, using the ML algorithm and its derivatives could be the right solution. The present study aims to offer a thorough and organized overview of the various machine learning (ML), deep learning (DL), and reinforcement learning (RL) algorithms concerning the emerging 6G technologies. This study is motivated by the fact that there is a lack of research on the significance of these algorithms in this specific context. This study examines the potential of ML algorithms and their derivatives in optimizing emerging technologies to align with the visions and requirements of the 6G network. It is crucial in ushering in a new era of communication marked by substantial advancements and requires grand improvement. This study highlights potential challenges for wireless communications in 6G networks and suggests insights into possible ML algorithms and their derivatives as possible solutions. Finally, the survey concludes that integrating Ml algorithms and emerging technologies will play a vital role in developing 6G networks.

Highly positively charged poly(vinyl benzyl trimethylammonium chloride) (PVBMA) was successfully synthesized with approximately 82% of yield. The PVBMA was characterized by the molecular weight (M w ) of 343.45 g mol -1 and the molecular weight distribution, (Đ) of 2.4 by 1 H NMR and SEC measurements. The PVBMA was applied as an effective agent for α-Al 2 O 3 surface modification in the adsorptive removal of the azo dye acid orange G (AOG). The AOG removal performance was significantly enhanced at all pH compared to without surface modification. The experimental parameters were optimal at pH 8, free ionic strength, 15 min of adsorption time, and 5 mg mL -1 α-Al 2 O 3 adsorbents. The AOG adsorption which was mainly controlled by the PVBMA-AOG electrostatic attractions was better applicable to the Langmuir isotherm and the pseudo-second kinetic model. The PVBMA-modified α-Al 2 O 3 demonstrates a high-performance and highly reusable adsorbent with great AOG performances of approximately 90.1% after 6 reused cycles., (© 2023 Wiley-VCH GmbH.)

Green synthesis and nanomaterials have been the current trends in biomedical materials. In this study, Piper chaudocanum L. leaf extract-doped ZnO nanoparticles (PLE-doped ZnO NPs), a novel nanomaterial, were studied including the synthesis process, and the biomedical activity was evaluated. PLE-doped ZnO NPs were synthesized by the co-precipitation method, with differences in the synthesis procedures and dosages of the extract. The X-ray diffraction, Fourier transform infrared, scanning electron microscopy, energy dispersive X-ray spectroscopy, Brunauer-Emmett-Teller, ultraviolet-visible diffuse reflectance spectroscopy, and photoluminescence spectrum analysis results showed that the biosynthesized PLE-doped ZnO NPs were pure and in a hexagonal wurtzite phase. The PLE-doped NPs were synthesized by adding the extract to the zinc acetate solution before adjusting the pH and exhibited the smallest size (ZPS50 was 22 nm), the richest in the surface organic functional groups and the best optical activity. The highest antibacterial activity against P. aeruginosa and S. aureus was observed at 100 µg/mL of ZPS50 NPs, and the inhibition zone reached 42 and 39 nm, respectively. Moreover, ZPS50 NPs showed a moderate effectiveness against KB cancer cells with an IC 50 value of 43.53 ± 2.98 µg/mL. This present study's results suggested that ZPS50 NPs could be a promising nanomaterial in developing drugs for treating human epithelial carcinoma cells and infectious illnesses.

Background: Using History and Physical Examination (H&P) notes, we investigated potential racial differences in documented chief complaints and problems among sepsis patients admitted to the intensive care unit., Methods: Patient records from Medical Information Mart for Intensive Care (MIMIC-III) dataset indicating a diagnosis of sepsis were included. First recorded clinical notes for each hospital admission were assessed; free text information was specifically extracted on (1) chief complaints, and (2) problems recorded in the Assessment & Plan (A&P) section. The top 10 for each were compared between Black and White patients., Results: In initial H&P notes of 17 434 sepsis patients (n = 1229 Black and n = 9806 White), the top 10 most common chief complaints were somewhat similar between Black and White patients. However, relative differences existed in terms of ranking, specifically for altered mental status which was more commonly reported in Black versus White patients (11.7% vs 7.8% P  < .001). Among text in the A&P, sepsis was documented significantly less frequently among Black versus White patients: 11.8% versus 14.3%, P  = .001. Racial differences were not detected in vital signs and laboratory values., Conclusions: This analysis supports the hypothesis that there may be racial differences in early sepsis presentation and possible provider interpretation of these complaints.

We estimate the impact of temperature extremes on mortality in Vietnam, using daily data on temperatures and monthly data on mortality during the 2000-2018 period. We find that both cold and heat waves cause higher mortality, particularly among older people and those living in the hot regions in Southern Vietnam. This effect on mortality tends to be smaller in provinces with higher rates of air-conditioning and emigration, and provinces with higher public spending on health. Finally, we estimate economic cost of cold and heat waves using a framework of willingness to pay to avoid deaths, then project the cost to the year 2100 under different Representative Concentration Pathway scenarios., (© 2023 The Authors. Health Economics published by John Wiley & Sons Ltd.)

The implementation process in the routine clinical care of a new predictive tool based on machine learning algorithms has been investigated using the RE-AIM framework. Semi-structured qualitative interviews have been conducted with a broad range of clinicians to elucidate potential barriers and facilitators of the implementation process across five major domains: Reach, Efficacy, Adoption, Implementation, and Maintenance. The analysis of 23 clinician interviews demonstrated a limited reach and adoption of the new tool and identified areas for improvement in implementation and maintenance. Future implementation efforts of machine learning tools should support the proactive engagement of a wide range of clinical users since the very initiation of the predictive analytics project, provide higher transparency of the underlying algorithms, employ broader onboarding of all potential users on a periodic basis, and collect feedback from clinicians on an ongoing basis.