English as a foreign language students' acceptance of Google Classroom in writing classes: A case study in Vietnam.

Google Classroom is a virtual education platform created by Google that allows both instructors and learners to actively participate in educational environments inside and outside of the classroom in an innovative way. This research aims to determine how university students perceived the adoption of Google Classroom in writing classes. This research was a convergent parallel mix-methods approach in which data were gathered through a 5-point Likert scale questionnaire and semi-structured interviews. The participants of this study included 130 university students in Vietnam. The results revealed that students expressed their approval of using Google Classroom in writing classes and that they had a positive view since it benefited them greatly in their learning writing process. This study suggests practical implications for language educators to use Google Classroom in writing classes.

Safety, immunogenicity and efficacy of the self-amplifying mRNA ARCT-154 COVID-19 vaccine: pooled phase 1, 2, 3a and 3b randomized, controlled trials.

Combination of waning immunity and lower effectiveness against new SARS-CoV-2 variants of approved COVID-19 vaccines necessitates new vaccines. We evaluated two doses, 28 days apart, of ARCT-154, a self-amplifying mRNA COVID-19 vaccine, compared with saline placebo in an integrated phase 1/2/3a/3b controlled, observer-blind trial in Vietnamese adults (ClinicalTrial.gov identifier: NCT05012943). Primary safety and reactogenicity outcomes were unsolicited adverse events (AE) 28 days after each dose, solicited local and systemic AE 7 days after each dose, and serious AEs throughout the study. Primary immunogenicity outcome was the immune response as neutralizing antibodies 28 days after the second dose. Efficacy against COVID-19 was assessed as primary and secondary outcomes in phase 3b. ARCT-154 was well tolerated with generally mild-moderate transient AEs. Four weeks after the second dose 94.1% (95% CI: 92.1-95.8) of vaccinees seroconverted for neutralizing antibodies, with a geometric mean-fold rise from baseline of 14.5 (95% CI: 13.6-15.5). Of 640 cases of confirmed COVID-19 eligible for efficacy analysis most were due to the Delta (B.1.617.2) variant. Efficacy of ARCT-154 was 56.6% (95% CI: 48.7- 63.3) against any COVID-19, and 95.3% (80.5-98.9) against severe COVID-19. ARCT-154 vaccination is well tolerated, immunogenic and efficacious, particularly against severe COVID-19 disease.

Lack of SPNS1 results in accumulation of lysolipids and lysosomal storage disease in mouse models.

Accumulation of sphingolipids, especially sphingosines, in the lysosomes is a key driver of several lysosomal storage diseases. The transport mechanism for sphingolipids from the lysosome remains unclear. Here, we identified SPNS1, which shares the highest homology to SPNS2, a sphingosine-1-phosphate (S1P) transporter, functions as a transporter for lysolipids from the lysosome. We generated Spns1-KO cells and mice and employed lipidomic and metabolomic approaches to reveal SPNS1 ligand identity. Global KO of Spns1 caused embryonic lethality between E12.5 and E13.5 and an accumulation of sphingosine, lysophosphatidylcholines (LPC), and lysophosphatidylethanolamines (LPE) in the fetal livers. Similarly, metabolomic analysis of livers from postnatal Spns1-KO mice presented an accumulation of sphingosines and lysoglycerophospholipids including LPC and LPE. Subsequently, biochemical assays showed that SPNS1 is required for LPC and sphingosine release from lysosomes. The accumulation of these lysolipids in the lysosomes of Spns1-KO mice affected liver functions and altered the PI3K/AKT signaling pathway. Furthermore, we identified 3 human siblings with a homozygous variant in the SPNS1 gene. These patients suffer from developmental delay, neurological impairment, intellectual disability, and cerebellar hypoplasia. These results reveal a critical role of SPNS1 as a promiscuous lysolipid transporter in the lysosomes and link its physiological functions with lysosomal storage diseases.

Comparative Antioxidant Potentials and Quantitative Phenolic Compounds Profiles among the Flowers and Leaves from Various Chrysanthemum morifolium Cultivars.

Chrysanthemum morifolium is a valuable plant that contains a wide range of phytochemical compounds and exhibits various biological activities. Ethanol extracts from both the leaves and flowers of 17 different cultivars of C. morifolium were tested for antioxidant activities using the 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) assays and were quantitatively analyzed for 12 phenolic compounds using high-performance liquid chromatography with diode-array detection. We found that the 'Ford' and 'Raina' cultivars demonstrated strong antioxidant abilities and high phenolic compound contents compared to other cultivars, while the flowers of 'Cielo' and the leaves of 'White Cap' exhibited low antioxidant capacity in both assays. The 'Cielo' cultivar also displayed the lowest compound contents. Additionally, in most samples, 3,5-dicaffeoylquinic acid and 4,5-dicaffeoylquinic acid stood out as high-content compounds in the extracts. This study provides foundational knowledge that can be used for selecting appropriate C. morifolium cultivars for further research. Moreover, the 'Ford' and 'Raina' cultivars, containing high amounts of bioactive compounds and showing superior antioxidant ability, could be applied to produce health-beneficial products.

MFSD7c functions as a transporter of choline at the blood-brain barrier.

Mutations in the orphan transporter MFSD7c (also known as Flvcr2), are linked to Fowler syndrome. Here, we used Mfsd7c knockout (Mfsd7c-/-) mice and cell-based assays to reveal that MFSD7c is a choline transporter at the blood-brain barrier (BBB). We performed comprehensive metabolomics analysis and detected differential changes of metabolites in the brains and livers of Mfsd7c-/-embryos. Particularly, we found that choline-related metabolites were altered in the brains but not in the livers of Mfsd7c-/- embryos. Thus, we hypothesized that MFSD7c regulates the level of choline in the brain. Indeed, expression of human MFSD7c in cells significantly increased choline uptake. Interestingly, we showed that choline uptake by MFSD7c is greatly increased by choline-metabolizing enzymes, leading us to demonstrate that MFSD7c is a facilitative transporter of choline. Furthermore, single-cell patch clamp analysis showed that the import of choline by MFSD7c is electrogenic. Choline transport function of MFSD7c was shown to be conserved in vertebrates, but not in yeasts. We demonstrated that human MFSD7c is a functional ortholog of HNM1, the yeast choline importer. We also showed that several missense mutations identified in patients exhibiting Fowler syndrome had abolished or reduced choline transport activity. Mice lacking Mfsd7c in endothelial cells of the central nervous system suppressed the import of exogenous choline from blood but unexpectedly had increased choline levels in the brain. Stable-isotope tracing study revealed that MFSD7c was required for exporting choline derived from lysophosphatidylcholine in the brain. Collectively, our work identifies MFSD7c as a choline exporter at the BBB and provides a foundation for future work to reveal the disease mechanisms of Fowler syndrome.

Deciphering the free energy landscapes of SARS-CoV-2 wild type and Omicron variant interacting with human ACE2.

The binding of the receptor binding domain (RBD) of the SARS-CoV-2 spike protein to the host cell receptor angiotensin-converting enzyme 2 (ACE2) is the first step in human viral infection. Therefore, understanding the mechanism of interaction between RBD and ACE2 at the molecular level is critical for the prevention of COVID-19, as more variants of concern, such as Omicron, appear. Recently, atomic force microscopy has been applied to characterize the free energy landscape of the RBD-ACE2 complex, including estimation of the distance between the transition state and the bound state, xu. Here, using a coarse-grained model and replica-exchange umbrella sampling, we studied the free energy landscape of both the wild type and Omicron subvariants BA.1 and XBB.1.5 interacting with ACE2. In agreement with experiment, we find that the wild type and Omicron subvariants have similar xu values, but Omicron binds ACE2 more strongly than the wild type, having a lower dissociation constant KD.

COVID-19 Vaccine Coverage and Factors Associated with Vaccine Hesitancy: A Cross-Sectional Survey in the City of Kinshasa, Democratic Republic of Congo.

Vaccination against COVID-19 has been the main strategy used by most countries to limit the spread of the virus. However, vaccine uptake has been low in Africa, leading to the implementation of several interventions in order to improve vaccine coverage. This study was conducted due to the lack of information about COVID-19 vaccine coverage and the factors associated with vaccine hesitancy. This cross-sectional study was carried out in Kinshasa city using multi-stage random sampling. A total of 2160 households were included in this study. The data were analyzed using Stata 17 software. The means and standard deviations were computed for continuous data that followed a normal distribution, whereas proportions together with their 95% confidence intervals (CIs) were computed for categorical variables. The connections between dependent variables and each independent variable were tested using either Pearson's chi-square test or Fisher's exact test. The logistic regression method was employed to determine the factors that are linked to hesitation in obtaining the COVID-19 immunization. The majority of respondents were aged between 25 and 34 and 35 and 49 (28.9%). During this study, 15% (95% CI [13.25-17.9]) of respondents had received at least one dose of the COVID-19 vaccine. The prevalence of vaccine hesitancy was 67% (CI95%:64.9-69.1). Among the reasons given for refusing to be vaccinated, most respondents cited concerns about the vaccine being unsafe or causing adverse reactions (45%). Among the reasons given for accepting the vaccine, 26% thought that the vaccine prevented superinfection. The factors associated with hesitancy toward the COVID-19 vaccine were female gender, an age of less than 35 years, and living in non-slum households. Despite the interventions implemented across the country, the reluctance to be vaccinated remains a problem; this could lead to poor health outcomes, especially among the elderly and those with pre-existing conditions. It is important to step up awareness-raising campaigns in the community in order to increase the uptake of vaccination.

Society of Surgical Oncology Breast Disease Site Working Group Statement on Contralateral Mastectomy: Indications, Outcomes, and Risks.

Rates of contralateral mastectomy (CM) among patients with unilateral breast cancer have been increasing in the United States. In this Society of Surgical Oncology position statement, we review the literature addressing the indications, risks, and benefits of CM since the society's 2017 statement. We held a virtual meeting to outline key topics and then conducted a literature search using PubMed to identify relevant articles. We reviewed the articles and made recommendations based on group consensus. Patients consider CM for many reasons, including concerns regarding the risk of contralateral breast cancer (CBC), desire for improved cosmesis and symmetry, and preferences to avoid ongoing screening, whereas surgeons primarily consider CBC risk when making a recommendation for CM. For patients with a high risk of CBC, CM reduces the risk of new breast cancer, however it is not known to convey an overall survival benefit. Studies evaluating patient satisfaction with CM and reconstruction have yielded mixed results. Imaging with mammography within 12 months before CM is recommended, but routine preoperative breast magnetic resonance imaging is not; there is also no evidence to support routine postmastectomy imaging surveillance. Because the likelihood of identifying an occult malignancy during CM is low, routine sentinel lymph node surgery is not recommended. Data on the rates of postoperative complications are conflicting, and such complications may not be directly related to CM. Adjuvant therapy delays due to complications have not been reported. Surgeons can reduce CM rates by encouraging shared decision making and informed discussions incorporating patient preferences.

Retinal Disease Diagnosis Using Deep Learning on Ultra-Wide-Field Fundus Images.

Ultra-wide-field fundus imaging (UFI) provides comprehensive visualization of crucial eye components, including the optic disk, fovea, and macula. This in-depth view facilitates doctors in accurately diagnosing diseases and recommending suitable treatments. This study investigated the application of various deep learning models for detecting eye diseases using UFI. We developed an automated system that processes and enhances a dataset of 4697 images. Our approach involves brightness and contrast enhancement, followed by applying feature extraction, data augmentation and image classification, integrated with convolutional neural networks. These networks utilize layer-wise feature extraction and transfer learning from pre-trained models to accurately represent and analyze medical images. Among the five evaluated models, including ResNet152, Vision Transformer, InceptionResNetV2, RegNet and ConVNext, ResNet152 is the most effective, achieving a testing area under the curve (AUC) score of 96.47% (with a 95% confidence interval (CI) of 0.931-0.974). Additionally, the paper presents visualizations of the model's predictions, including confidence scores and heatmaps that highlight the model's focal points-particularly where lesions due to damage are evident. By streamlining the diagnosis process and providing intricate prediction details without human intervention, our system serves as a pivotal tool for ophthalmologists. This research underscores the compatibility and potential of utilizing ultra-wide-field images in conjunction with deep learning.

Predictors of mortality among inpatients in COVID-19 treatment centers in the city of Butembo, North Kivu, Democratic Republic of Congo.

Determining the risk factors for severe disease and death among hospitalized Covid-19 patients is critical to optimize health outcomes and health services efficiency, especially in resource-constrained and humanitarian settings. This study aimed to identify the predictors of mortality of Covid-19 patients in North Kivu province in the Democratic Republic of Congo.A retrospective cohort study was conducted in 6 Covid-19 treatment centers in the city of Butembo from 1 January to 31 December 2021. The time to event (death), the outcome variable, was visualized by Kaplan-Meier curves and the log-rank test was used to confirm differences in trends. Cox regression was used for all the predictors in the bivariate analysis and multivariate analysis was done using predictors found statistically significant in the bivariate analysis. The following variables were considered for inclusion to the Cox regression model: Age, Sex, Disease length, Treatment site, History of at least one co-morbidity, Body mass index, Stage according to SpO2 and the NEWS-modified score.Among the 303 participants (mean age of 53 years), the fatality rate was 33.8 deaths per 1000 patient-days. Four predictors were independently associated with inpatient death: age category (≥ 60 years) (adjusted HR: 9.90; 95% CI: 2.68-36.27), presence of at least one comorbidity (adjusted HR: 11.39; 95% CI: 3.19-40.71); duration of illness of > 5 days before hospitalization (adjusted HR:1.70, 95% CI: 1.04-2.79) and peripheral capillary oxygen saturation (SpO2) < 90% (adjusted HR = 14.02, 95% CI: 2.23-88.32). In addition to advanced age, comorbidity, and length of disease before hospitalization, ambient air SpO2 measured by healthcare providers using low-tech, affordable and relatively accessible pulse oximetry could inform the care pathways of Covid-19 inpatients in resource-challenged health systems in humanitarian settings.

Unexpected Single-Ligand Occupancy and Negative Cooperativity in the SARS-CoV-2 Main Protease.

Many homodimeric enzymes tune their functions by exploiting either negative or positive cooperativity between subunits. In the SARS-CoV-2 Main protease (Mpro) homodimer, the latter has been suggested by symmetry in most of the 500 reported protease/ligand complex structures solved by macromolecular crystallography (MX). Here we apply the latter to both covalent and noncovalent ligands in complex with Mpro. Strikingly, our experiments show that the occupation of both active sites of the dimer originates from an excess of ligands. Indeed, cocrystals obtained using a 1:1 ligand/protomer stoichiometry lead to single occupation only. The empty binding site exhibits a catalytically inactive geometry in solution, as suggested by molecular dynamics simulations. Thus, Mpro operates through negative cooperativity with the asymmetric activity of the catalytic sites. This allows it to function with a wide range of substrate concentrations, making it resistant to saturation and potentially difficult to shut down, all properties advantageous for the virus' adaptability and resistance.

Mfsd7b facilitates choline transport and missense mutations affect choline transport function.

MFSD7b belongs to the Major Facilitator Superfamily of transporters that transport small molecules. Two isoforms of MFSD7b have been identified and they are reported to be heme exporters that play a crucial role in maintaining the cytosolic and mitochondrial heme levels, respectively. Mutations of MFSD7b (also known as FLVCR1) have been linked to retinitis pigmentosa, posterior column ataxia, and hereditary sensory and autonomic neuropathy. Although MFSD7b functions have been linked to heme detoxification by exporting excess heme from erythroid cells, it is ubiquitously expressed with a high level in the kidney, gastrointestinal tract, lungs, liver, and brain. Here, we showed that MFSD7b functions as a facilitative choline transporter. Expression of MFSD7b slightly but significantly increased choline import, while its knockdown reduced choline influx in mammalian cells. The influx of choline transported by MFSD7b is dependent on the expression of choline metabolizing enzymes such as choline kinase (CHKA) and intracellular choline levels, but it is independent of gradient of cations. Additionally, we showed that choline transport function of Mfsd7b is conserved from fly to man. Employing our transport assays, we showed that missense mutations of MFSD7b caused reduced choline transport functions. Our results show that MFSD7b functions as a facilitative choline transporter in mammalian cells.

Co-circulation and genetic characteristics of porcine circoviruses in postweaning multisystemic wasting syndrome cases in commercial swine farms.

This study aimed to investigate the co-infection and genetic characteristics of Porcine circoviruses in PMWS-affected pigs in five commercial farrow-to-finish swine farms in Vietnam. By the end of 2022, the percentage of PMWS-affected pigs in these farms has increased significantly compared to previous years. The lymph node samples from ten PMWS typical cases were randomly collected to test for the presence of PRRSV, PCV2, PCV3 and PCV4. While PRRSV and PCV4 were not found in these cases, 10 and 3 out of 10 samples were positive for PCV2 and PCV3, respectively. Three farms in the study showed the co-infection of PCV2 and PCV3 in affected pigs. Besides, all PCV-positive samples were sequenced to evaluate genetic characterization of PCVs in PMWS-affected cases. Phylogenetic analysis showed that all PCV3 strains in the study were clustered into PCV3b genotype. 8 out of 10 PCV2 strains belonged to PCV2d genotype while the remaining two strains belonged to PCV2b genotypes. Two farms had co-circulation of PCV2b and PCV2d genotypes in two different age groups of pigs, which is reported for the first time in Vietnam. Several amino acid substitutions were identified in important antigenic regions in the capsid protein of the PCV2 field strains compared to vaccine strains. Taken together, the results showed the high co-prevalence of PCV3 and PCV2, and the wide genetic diversity of PCV2 field and vaccine strains may be the cause of the increased PMWS situation in these pig farms. Supplementary Information: The online version contains supplementary material available at 10.1007/s13337-023-00849-4.

Using AI to Improve Radiologist Performance in Detection of Abnormalities on Chest Radiographs.

Background Chest radiography remains the most common radiologic examination, and interpretation of its results can be difficult. Purpose To explore the potential benefit of artificial intelligence (AI) assistance in the detection of thoracic abnormalities on chest radiographs by evaluating the performance of radiologists with different levels of expertise, with and without AI assistance. Materials and Methods Patients who underwent both chest radiography and thoracic CT within 72 hours between January 2010 and December 2020 in a French public hospital were screened retrospectively. Radiographs were randomly included until reaching 500 radiographs, with about 50% of radiographs having abnormal findings. A senior thoracic radiologist annotated the radiographs for five abnormalities (pneumothorax, pleural effusion, consolidation, mediastinal and hilar mass, lung nodule) based on the corresponding CT results (ground truth). A total of 12 readers (four thoracic radiologists, four general radiologists, four radiology residents) read half the radiographs without AI and half the radiographs with AI (ChestView; Gleamer). Changes in sensitivity and specificity were measured using paired t tests. Results The study included 500 patients (mean age, 54 years ± 19 [SD]; 261 female, 239 male), with 522 abnormalities visible on 241 radiographs. On average, for all readers, AI use resulted in an absolute increase in sensitivity of 26% (95% CI: 20, 32), 14% (95% CI: 11, 17), 12% (95% CI: 10, 14), 8.5% (95% CI: 6, 11), and 5.9% (95% CI: 4, 8) for pneumothorax, consolidation, nodule, pleural effusion, and mediastinal and hilar mass, respectively (P < .001). Specificity increased with AI assistance (3.9% [95% CI: 3.2, 4.6], 3.7% [95% CI: 3, 4.4], 2.9% [95% CI: 2.3, 3.5], and 2.1% [95% CI: 1.6, 2.6] for pleural effusion, mediastinal and hilar mass, consolidation, and nodule, respectively), except in the diagnosis of pneumothorax (-0.2%; 95% CI: -0.36, -0.04; P = .01). The mean reading time was 81 seconds without AI versus 56 seconds with AI (31% decrease, P < .001). Conclusion AI-assisted chest radiography interpretation resulted in absolute increases in sensitivity for all radiologists of various levels of expertise and reduced the reading times; specificity increased with AI, except in the diagnosis of pneumothorax. © RSNA, 2023 Supplemental material is available for this article.

Strongyloides stercoralis Infection in Humans: A Narrative Review of the Most Neglected Parasitic Disease.

Strongyloidiasis is a helminth infection affecting 613.9 million people annually, mainly in the tropics and subtropics. The reported seroprevalence in the United States is 4% with most of the cases reported in immigrants. Human T-lympho-tropic virus 1 (HTLV-1) infections, hypogammaglobulinemia, immunosuppressant use - particularly steroid use, alcoholism, and malnutrition have been associated with an increased risk of strongyloidiasis. Recently, cases of strongyloidiasis hyperinfection syndrome have been described in coronavirus disease 2019 (COVID-19) patients treated with steroids as well. This brief review discusses the epidemiology, clinical features, management, and prevention of strongyloidiasis including some facts about the infection in pregnancy, transplant recipients, and COVID-19 patients. We conducted an online search using the PubMed, Scopus, and Google Scholar databases. Strongyloidiasis can be asymptomatic or present with mild symptoms. Strongyloides stercoralis is known to cause autoinfection. In immunocompromised individuals, it can present with severe symptoms, hyperinfection, or disseminated disease. Reported mortality in cases of disseminated Strongyloidiasis is 87.1%. Serology and detection of larvae in stool by direct microscopy are the most commonly used methods to diagnose strongyloidiasis. The drug of choice for the treatment is ivermectin. However, the use of ivermectin in human pregnancy is not well studied, and its teratogenic risks are unknown. Proactive screening of strongyloidiasis is necessary in immunocompromised individuals to prevent severe disease.

Influence of cuff stiffness on hemodynamics and perceived cuff pressure in the upper extremities in males and females: implications for practical blood flow restriction training.

BACKGROUND: Practical blood flow restriction (pBFR) during exercise is a cost-saving alternative to traditional blood flow restriction using pneumatic cuffs, particularly when exercising in a group setting. Depending on the pBFR technique, several factors (e.g., cuff width, limb circumference) have already been shown to be of importance when applying the pBFR pressure. Given that elastic cuffs are often used for pBFR, the cuff stiffness might be an additional influencing factor. Therefore, the present study compared the acute effects of three elastic cuffs with identical width but different stiffness (high stiffness (HS), medium stiffness (MS), and low stiffness (LS)) on hemodynamic measures and perceived cuff pressure at rest. METHODS: In a randomized, counter-balanced cross-over study, 36 young and normotensive participants completed three experimental trials. After a 10-min rest period in supine position, the cuff was loosely and proximally applied to the right upper arm. Following baseline data recording, the cuff was successively tightened in 10%-increments with respect to the limb circumference (%overlap) until arterial blood flow was occluded. At baseline and during each %overlap, systolic peak blood flow velocity of the brachial artery, rating of perceived cuff pressure, as well as muscle oxygen saturation and total hemoglobin concentration of the biceps brachii muscle were recorded. RESULTS: The %overlap required to occlude arterial blood flow was different between the three cuffs (HS: 30.9 ± 3.8%, MS: 43.9 ± 6.1%, LS: 54.5 ± 8.3%). Furthermore, at 30% overlap, systolic peak blood flow velocity was lower when applying the HS (9.0 ± 10.9 cm∙s- 1) compared to MS (48.9 ± 21.9 cm∙s- 1) and LS cuff (62.9 ± 19.1 cm∙s- 1). Rating of perceived cuff pressure at 30% overlap was higher when using the HS (6.5 ± 1.5 arbitrary unit (a.u.)) compared to MS (5.1 ± 1.4 a.u.) and LS cuff (4.9 ± 1.5 a.u.) with no difference between the MS and LS cuff. However, muscle oxygen saturation and total hemoglobin concentration were not different between the three cuffs. CONCLUSIONS: The present study revealed that the cuff stiffness influenced blood flow velocity and arterial occlusion pressure. Therefore, cuff stiffness seems an important factor for the application of pBFR.

Self-FI: Self-Supervised Learning for Disease Diagnosis in Fundus Images.

Self-supervised learning has been successful in computer vision, and its application to medical imaging has shown great promise. This study proposes a novel self-supervised learning method for medical image classification, specifically targeting ultra-wide-field fundus images (UFI). The proposed method utilizes contrastive learning to pre-train a deep learning model and then fine-tune it with a small set of labeled images. This approach reduces the reliance on labeled data, which is often limited and costly to obtain, and has the potential to improve disease detection in UFI. This method employs two contrastive learning techniques, namely bi-lateral contrastive learning and multi-modality pre-training, to form positive pairs using the data correlation. Bi-lateral learning fuses multiple views of the same patient's images, and multi-modality pre-training leverages the complementary information between UFI and conventional fundus images (CFI) to form positive pairs. The results show that the proposed contrastive learning method achieves state-of-the-art performance with an area under the receiver operating characteristic curve (AUC) score of 86.96, outperforming other approaches. The findings suggest that self-supervised learning is a promising direction for medical image analysis, with potential applications in various clinical settings.

Do Personal Nurse-Initiated Medication Boxes Work in Prison? A Cross-Sectional Study Involving Incarcerated Persons and Prison Officers in a Swiss Prison.

INTRODUCTION: Daily in-hand medication dispensing in prisons and jails is resource intensive, disempowering, and nonconfidential. This research aimed to assess a nurse-initiated, low-frequency medication dispensing system using personal lockable boxes. METHODS: A cross-sectional study was carried out in a Swiss prison involving 47 box users and 19 custodial officers. FINDINGS: Box users agreed or strongly agreed about the perceived advantages of the box system, including user-friendliness, lower theft risk, and increased dignity, confidentiality, compliance, and autonomy to self-manage medication. Officers, who must accompany nurses during dispensing rounds, concurred that medication boxes were more time-efficient and improved role differentiation between custodial and clinical staff. Patients and officers were overall satisfied with the system and would recommend scaling it up in other facilities. DISCUSSION: This study suggests that medication boxes are feasible, acceptable, easy to use, and secure. Boxes could promote patients' autonomy, protect confidentiality, and allow nurses to dedicate more time to individual visits and health promotion and prevention activities.

Use of Payload Binding Selectivity Enhancers to Improve Therapeutic Index of Maytansinoid-Antibody-Drug Conjugates.

Systemic exposure to released cytotoxic payload contributes to the dose-limiting off-target toxicities of anticancer antibody-drug conjugates (ADC). In this work, we present an "inverse targeting" strategy to optimize the therapeutic selectivity of maytansinoid-conjugated ADCs. Several anti-maytansinoid sdAbs were generated via phage-display technology with binding IC50 values between 10 and 60 nmol/L. Co-incubation of DM4 with the anti-maytansinoid sdAbs shifted the IC50 value of DM4 up to 250-fold. Tolerability and efficacy of 7E7-DM4 ADC, an anti-CD123 DM4-conjugated ADC, were assessed in healthy and in tumor-bearing mice, with and without co-administration of an anti-DM4 sdAb. Co-administration with anti-DM4 sdAb reduced 7E7-DM4-induced weight loss, where the mean values of percentage weight loss at nadir for mice receiving ADC+saline and ADC+sdAb were 7.9% ± 3% and 3.8% ± 1.3% (P < 0.05). In tumor-bearing mice, co-administration of the anti-maytansinoid sdAb did not negatively affect the efficacy of 7E7-DM4 on tumor growth or survival following dosing of the ADC at 1 mg/kg (P = 0.49) or at 10 mg/kg (P = 0.9). Administration of 7E7-DM4 at 100 mg/kg led to dramatic weight loss, with 80% of treated mice succumbing to toxicity before the appearance of mortality relating to tumor growth in control mice. However, all mice receiving co-dosing of 100 mg/kg 7E7-DM4 with anti-DM4 sdAb were able to tolerate the treatment, which enabled reduction in tumor volume to undetectable levels and to dramatic improvements in survival. In summary, we have demonstrated the utility and feasibility of the application of anti-payload antibody fragments for inverse targeting to improve the selectivity and efficacy of anticancer ADC therapy.