bluuebunny/crossref_metadata_2025 huggingface dataset:
A laboratory perspective on Mycobacterium abscessus biofilm culture, characterization and drug activity testing
Authors: Meliefste Henriëtte Margarethe , Mudde Saskia Emily , Ammerman Nicole Christine , de Steenwinkel Jurriaan Evert M. , Bax Hannelore Iris
Published: April 2024

Mycobacterium abscessus is an emerging opportunistic pathogen causing severe pulmonary infections in patients with underlying lung disease and cystic fibrosis in particular. The rising prevalence of M. abscessus infections poses an alarming threat, as the success rates of available treatment options are limited. Central to this challenge is the absence of preclinical in vitro models that accurately mimic in vivo conditions and that can reliably predict treatment outcomes in patients. M. abscessus is notorious for its association with biofilm formation within the lung. Bacteria in biofilms are more recalcitrant to antibiotic treatment compared to planktonic bacteria, which likely contributes to the lack of correlation between preclinical drug activity testing (typically performed on planktonic bacteria) and treatment outcome. In recent years, there has been a growing interest in M. abscessus biofilm research. However, the absence of standardized methods for biofilm culture, biofilm characterization and drug activity testing has led to a wide spectrum of, sometimes inconsistent, findings across various studies. Factors such as strain selection, culture medium, and incubation time hugely impact biofilm development, phenotypical characteristics and antibiotic susceptibility. Additionally, a broad range of techniques are used to study M. abscessus biofilms, including quantification of colony-forming units, crystal violet staining and fluorescence microscopy. Yet, limitations of these techniques and the selected readouts for analysis affect study outcomes. Currently, research on the activity of conventional antibiotics, such as clarithromycin and amikacin, against M. abscessus biofilms yield ambiguous results, underscoring the substantial impact of experimental conditions on drug activity assessment. Beyond traditional drug activity testing, the exploration of novel anti-biofilm compounds and the improvement of in vitro biofilm models are ongoing. In this review, we outline the laboratory models, experimental variables and techniques that are used to study M. abscessus biofilms. We elaborate on the current insights of M. abscessus biofilm characteristics and describe the present understanding of the activity of traditional antibiotics, as well as potential novel compounds, against M. abscessus biofilms. Ultimately, this work contributes to the advancement of fundamental knowledge and practical applications of accurate preclinical M. abscessus models, thereby facilitating progress towards improved therapies for M. abscessus infections.
Current strategies for early epithelial ovarian cancer detection using miRNA as a potential tool
Authors: Bhadra Mridula , Sachan Manisha , Nara Seema
Published: April 2024

Ovarian cancer is one of the most aggressive and significant malignant tumor forms in the female reproductive system. It is the leading cause of death among gynecological cancers owing to its metastasis. Since its preliminary disease symptoms are lacking, it is imperative to develop early diagnostic biomarkers to aid in treatment optimization and personalization. In this vein, microRNAs, which are short sequence non-coding molecules, displayed great potential as highly specific and sensitive biomarker. miRNAs have been extensively advocated and proven to serve an instrumental part in the clinical management of cancer, especially ovarian cancer, by promoting the cancer cell progression, invasion, delayed apoptosis, epithelial-mesenchymal transition, metastasis of cancer cells, chemosensitivity and resistance and disease therapy. Here, we cover our present comprehension of the most up-to-date microRNA-based approaches to detect ovarian cancer, as well as current diagnostic and treatment strategies, the role of microRNAs as oncogenes or tumor suppressor genes, and their significance in ovarian cancer progression, prognosis, and therapy.
Mesenchymal stem cells in craniofacial reconstruction: a comprehensive review
Authors: Zheng Zizhuo , Liu Hanghang , Liu Shibo , Luo En , Liu Xian
Published: April 2024

Craniofacial reconstruction faces many challenges, including high complexity, strong specificity, severe injury, irregular and complex wounds, and high risk of bleeding. Traditionally, the “gold standard” for treating craniofacial bone defects has been tissue transplantation, which involves the transplantation of bone, cartilage, skin, and other tissues from other parts of the body. However, the shape of craniofacial bone and cartilage structures varies greatly and is distinctly different from ordinary long bones. Craniofacial bones originate from the neural crest, while long bones originate from the mesoderm. These factors contribute to the poor effectiveness of tissue transplantation in repairing craniofacial defects. Autologous mesenchymal stem cell transplantation exhibits excellent pluripotency, low immunogenicity, and minimally invasive properties, and is considered a potential alternative to tissue transplantation for treating craniofacial defects. Researchers have found that both craniofacial-specific mesenchymal stem cells and mesenchymal stem cells from other parts of the body have significant effects on the restoration and reconstruction of craniofacial bones, cartilage, wounds, and adipose tissue. In addition, the continuous development and application of tissue engineering technology provide new ideas for craniofacial repair. With the continuous exploration of mesenchymal stem cells by researchers and the continuous development of tissue engineering technology, the use of autologous mesenchymal stem cell transplantation for craniofacial reconstruction has gradually been accepted and promoted. This article will review the applications of various types of mesenchymal stem cells and related tissue engineering in craniofacial repair and reconstruction.
Case report: Transition from anti-CD20 therapy to inebilizumab for 14 cases of neuromyelitis optica spectrum disorder
Authors: Osborne Benjamin , Romanow Gabriela , Hemphill J. Michael , Zarif Myassar , DeAngelis Tracy , Kaplan Tyler , Oh Unsong , Pinkhasov Johnathan , Patterson Kristina , Levy Michael
Published: April 2024

Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disorder of the central nervous system characterized by recurrent, disabling attacks that affect the optic nerve, spinal cord, and brain/brainstem. While rituximab, targeting CD20-positive B-cells, is used as an off-label therapy for NMOSD, some patients continue to exhibit breakthrough attacks and/or adverse reactions. Inebilizumab, a humanized and glycoengineered monoclonal antibody targeting CD19-positive B-cells, has been FDA approved for the treatment of NMOSD in adult patients who are anti-aquaporin-4 (AQP4) antibody positive. Given the limited real-world data on the efficacy and safety of inebilizumab, especially in those transitioning from rituximab, a retrospective chart review was conducted on 14 NMOSD patients from seven centers. Of these, 71.4% (n = 10) experienced a combined 17 attacks during rituximab treatment, attributed to either breakthrough disease (n = 10) or treatment delay (n = 7). The mean duration of rituximab treatment was 38.4 months (3.2 years). Notably, no subsequent attacks were observed during inebilizumab treatment [mean duration of inebilizumab treatment was 19.3 months (1.6 years)], underscoring its potential as an effective treatment for NMOSD. Our data suggest that inebilizumab provides clinical benefit with effective disease control and a favorable safety profile for patients transitioning from rituximab.
Automatic segmentation of hemorrhagic transformation on follow-up non-contrast CT after acute ischemic stroke
Authors: Sun Jiacheng , Werdiger Freda , Blair Christopher , Chen Chushuang , Yang Qing , Bivard Andrew , Lin Longting , Parsons Mark
Published: April 2024

Background

Hemorrhagic transformation (HT) following reperfusion therapies is a serious complication for patients with acute ischemic stroke. Segmentation and quantification of hemorrhage provides critical insights into patients’ condition and aids in prognosis. This study aims to automatically segment hemorrhagic regions on follow-up non-contrast head CT (NCCT) for stroke patients treated with endovascular thrombectomy (EVT).

Methods

Patient data were collected from 10 stroke centers across two countries. We propose a semi-automated approach with adaptive thresholding methods, eliminating the need for extensive training data and reducing computational demands. We used Dice Similarity Coefficient (DSC) and Lin’s Concordance Correlation Coefficient (Lin’s CCC) to evaluate the performance of the algorithm.

Results

A total of 51 patients were included, with 28 Type 2 hemorrhagic infarction (HI2) cases and 23 parenchymal hematoma (PH) cases. The algorithm achieved a mean DSC of 0.66 ± 0.17. Notably, performance was superior for PH cases (mean DSC of 0.73 ± 0.14) compared to HI2 cases (mean DSC of 0.61 ± 0.18). Lin’s CCC was 0.88 (95% CI 0.79–0.93), indicating a strong agreement between the algorithm’s results and the ground truth. In addition, the algorithm demonstrated excellent processing time, with an average of 2.7 s for each patient case.

Conclusion

To our knowledge, this is the first study to perform automated segmentation of post-treatment hemorrhage for acute stroke patients and evaluate the performance based on the radiological severity of HT. This rapid and effective tool has the potential to assist with predicting prognosis in stroke patients with HT after EVT.
Case report: An ultrasound-based approach as an easy tool to evaluate hormone receptor-positive HER-2-negative breast cancer in advanced/metastatic settings: preliminary data of the Plus-ENDO study
Authors: Montella Liliana , Di Marino Luigi , Marino Maria Adele , Riccio Vittorio , Del Gaudio Nunzio , Altucci Lucia , Berretta Massimiliano , Facchini Gaetano
Published: April 2024

Background

Hormone receptor-positive tumors are unlikely to exhibit a complete pathological tumor response. The association of CDK 4/6 inhibitor plus hormone therapy has changed this perspective.

Case presentation

In this study, we retrospectively reviewed the charts of patients with a diagnosis of luminal A/B advanced/metastatic tumors treated with a CDK 4/6 inhibitor-based therapy. In this part of the study, we present clinical and ultrasound evaluation. Eight female patients were considered eligible for the study aims. Three complete and five partial responses were reported, including a clinical tumor response of 50% or more in five out of nine assessed lesions (55%). All patients showed a response on ultrasound. The mean lesion size measured by ultrasound was 27.1 ± 15.02 mm (range, 6–47 mm) at the baseline; 16.08 ± 14.6 mm (range, 0–40 mm) after 4 months (T1); and 11.7 ± 12.9 mm (range, 0–30 mm) at the 6 months follow-up (T2). Two patients underwent surgery. The radiological complete response found confirmation in a pathological complete response, while the partial response matched a moderate residual disease.

Conclusion

The evaluation of breast cancer by ultrasound is basically informative of response and may be an easy and practical tool to monitor advanced tumors, especially in advanced/unfit patients who are reluctant to invasive exams.
Totally implantable venous ports in infants and children: a single-center retrospective study of indications and safety
Authors: Sosnowska-Sienkiewicz Patrycja , Moryciński Sebastian , Januszkiewicz-Lewandowska Danuta , Michalik Karolina , Madziar Klaudyna , Kukfisz Agata , Zielińska Daria , Mańkowski Przemysław
Published: April 2024

Introduction

Totally Implantable Venous Access Devices (TIVADs) contribute significantly to the treatment progress and comfort of patients requiring long-term therapy. However, the procedure for implanting TIVADs, as well as its very presence, may be associated with complications.

Aim

This study evaluates the indications, safety, and complication rates of venous port implantations in pediatric patients. It also explores factors influencing the occurrence of early and late complications post-implantation.

Materials and methods

The study included 383 pediatric patients treated at the Department of Pediatric Surgery, Traumatology, and Urology in Poznan between 2013 and 2020 who underwent 474 implantations of intravenous ports. Venous access was achieved using the Seldinger technique. Statistical analysis was performed using Statistica 13 with TIBCO and PQStat 1.8.2.156 with PQStat.

Results

Venous ports were used in 345 oncology patients requiring chemotherapy (90% of the total group) and in 38 children (10%) with non-oncology indications. There were 36 early complications (7.6%) and 18 late complications (3.8%), excluding infectious complications. The most common early, non-infectious complications included pneumothorax (15 patients; 3%) and port pocket hematoma (12 patients; 2.5%). The most common late, non-infectious complications observed were venous catheter obstruction (8 children; 1.7%) and port system leakage (5 children; 1%). Infectious complications occurred in 129 cases (27.2%). Children with a diagnosis of non-Hodgkin’s lymphoma, acute myeloid leukemia, and acute lymphoblastic leukemia had a significantly higher incidence of port infections. Venous ports equipped with a polyurethane catheter, compared to systems with a silicone catheter, functioned significantly shorter.

Conclusions

The Seldinger method of port implantation is quick, minimally invasive, and safe. The type of port, including the material of the port’s venous catheter, and the underlying disease have an impact on the durability of implantable intravenous systems. The experience of the surgeon is related to the frequency of complications associated with the procedure.
The clinical regimens and cell membrane camouflaged nanodrug delivery systems in hematologic malignancies treatment
Authors: Liu Yuanyuan , Yu Shanwu , Chen Yixiang , Hu Zhihong , Fan Lingling , Liang Gaofeng
Published: April 2024

Hematologic malignancies (HMs), also referred to as hematological or blood cancers, pose significant threats to patients as they impact the blood, bone marrow, and lymphatic system. Despite significant clinical strategies using chemotherapy, radiotherapy, stem cell transplantation, targeted molecular therapy, or immunotherapy, the five-year overall survival of patients with HMs is still low. Fortunately, recent studies demonstrate that the nanodrug delivery system holds the potential to address these challenges and foster effective anti-HMs with precise treatment. In particular, cell membrane camouflaged nanodrug offers enhanced drug targeting, reduced toxicity and side effects, and/or improved immune response to HMs. This review firstly introduces the merits and demerits of clinical strategies in HMs treatment, and then summarizes the types, advantages, and disadvantages of current nanocarriers helping drug delivery in HMs treatment. Furthermore, the types, functions, and mechanisms of cell membrane fragments that help nanodrugs specifically targeted to and accumulate in HM lesions are introduced in detail. Finally, suggestions are given about their clinical translation and future designs on the surface of nanodrugs with multiple functions to improve therapeutic efficiency for cancers.
Effects of different light intensity on leaf color changes in a Chinese cabbage yellow cotyledon mutant
Authors: Huo Jianyu , Zhang Ninan , Gong Ying , Bao Yongrong , Li Yinyin , Zhang Lugang , Nie Shanshan
Published: April 2024

Leaf color is one of the most important phenotypic features in horticultural crops and directly related to the contents of photosynthetic pigments. Most leaf color mutants are determined by the altered chlorophyll or carotenoid, which can be affected by light quality and intensity. Our previous study obtained a Chinese cabbage yellow cotyledon mutant that exhibited obvious yellow phenotypes in the cotyledons and the new leaves. However, the underlying mechanisms in the formation of yellow cotyledons and leaves remain unclear. In this study, the Chinese cabbage yellow cotyledon mutant 19YC-2 exhibited obvious difference in leaf color and abnormal chloroplast ultrastructure compared to the normal green cotyledon line 19GC-2. Remarkably, low-intensity light treatment caused turn-green leaves and a significant decrease in carotenoid content in 19YC-2. RNA-seq analysis revealed that the pathways of photosynthesis antenna proteins and carotenoid biosynthesis were significantly enriched during the process of leaf color changes, and many differentially expressed genes related to the two pathways were identified to respond to different light intensities. Remarkably, BrPDS and BrLCYE genes related to carotenoid biosynthesis showed significantly higher expression in 19YC-2 than that in 19GC-2, which was positively related to the higher carotenoid content in 19YC-2. In addition, several differentially expressed transcription factors were also identified and highly correlated to the changes in carotenoid content, suggesting that they may participate in the regulatory pathway of carotenoid biosynthesis. These findings provide insights into the molecular mechanisms of leaf color changes in yellow cotyledon mutant 19YC-2 of Chinese cabbage.
Reduction of flavonoid content in honeysuckle via Erysiphe lonicerae-mediated inhibition of three essential genes in flavonoid biosynthesis pathways
Authors: Zhang Mian , Zhang Jie , Xiao Qiaoqiao , Li Yulong , Jiang Shanshan
Published: April 2024

Honeysuckle, valued for its wide-ranging uses in medicine, cuisine, and aesthetics, faces a significant challenge in cultivation due to powdery mildew, primarily caused by the Erysiphe lonicerae pathogen. The interaction between honeysuckle and E. lonicerae, especially concerning disease progression, remains insufficiently understood. Our study, conducted in three different locations, found that honeysuckle naturally infected with E. lonicerae showed notable decreases in total flavonoid content, with reductions of 34.7%, 53.5%, and 53.8% observed in each respective site. Controlled experiments supported these findings, indicating that artificial inoculation with E. lonicerae led to a 20.9% reduction in flavonoid levels over 21 days, worsening to a 54.8% decrease by day 42. Additionally, there was a significant drop in the plant’s total antioxidant capacity, reaching an 81.7% reduction 56 days after inoculation. Metabolomic analysis also revealed substantial reductions in essential medicinal components such as chlorogenic acid, luteolin, quercetin, isoquercetin, and rutin. Investigating gene expression revealed a marked decrease in the relative expression of the LjPAL1 gene, starting as early as day 7 post-inoculation and falling to a minimal level (fold change = 0.29) by day 35. This trend was mirrored by a consistent reduction in phenylalanine ammonia-lyase activity in honeysuckle through the entire process, which decreased by 72.3% by day 56. Further analysis showed significant and sustained repression of downstream genes LjFNHO1 and LjFNGT1, closely linked to LjPAL1. We identified the mechanism by which E. lonicerae inhibits this pathway and suggest that E. lonicerae may strategically weaken the honeysuckle’s disease resistance by targeting key biosynthetic pathways, thereby facilitating further pathogen invasion. Based on our findings, we recommend two primary strategies: first, monitoring medicinal constituent levels in honeysuckle from E. lonicerae-affected areas to ensure its therapeutic effectiveness; and second, emphasizing early prevention and control measures against honeysuckle powdery mildew due to the persistent decline in crucial active compounds.
Role of social support in the relationship between resilience and sleep quality among cancer patients
Authors: Cui ChunYing , Wang Lie
Published: April 2024

Introduction

The present study aimed to investigate the effect of resilience on sleep quality and explore the role of social support between resilience and sleep quality in cancer patients.

Methods

A multicenter and cross-sectional study was conducted in China from May to November 2021. A total of 202 cancer patients were recruited to complete the questionnaires composed of demographic information, Pittsburg Sleep Quality Index (PSQI), Resilience Scale-14 (RS-14), and Multidimensions Scale of Perceived Social Support (MSPSS). The associations between resilience, social support, and sleep quality were explored through hierarchical regression analysis.

Results

The prevalence of poor sleep quality was 50% among cancer patients. Resilience, social support, and the interaction between resilience and social support were all found to be significantly associated with sleep quality. Results of simple slope analysis indicated that the association between resilience and sleep quality were gradually decreased with the increasing social support levels (1 SD below the mean, B=-0.225, β=-0.551, P<0.001), mean social support (B=-0.147, β=-0.353, P<0.001) and high social support (1 SD above the mean, B=-0.065, β=-0.156, P<0.001). Additionally, social support mediated the effect of resilience on sleep quality among cancer patients.

Discussion

Poor sleep quality has been common in cancer patients. Social support could mediate and alleviate the relationship between resilience and sleep quality among cancer patients. Besides providing sufficient social support, interventions based on resilience should be applied to address sleep problems in cancer patients.
A systematic review of economic evaluations of pharmacological treatments for active tuberculosis
Authors: Nagar Sarosh , Nicholls David , Dawoud Dalia
Published: April 2024

Objectives

The continuing spread of tuberculosis (TB) worldwide, especially drug-resistant TB, poses a major challenge to healthcare systems globally. Addressing this requires appraising the cost effectiveness of existing pharmacological interventions against TB to identify key drivers of cost effectiveness and value and guide pharmaceutical innovation and novel drug regimen development.

Methods

Studies were identified from a search of six database: MEDLINE MEDLINE-In Process, MEDLINE Epub Ahead of Print, EMBASE, Cochrane Database of Systematic Reviews, and Econlit in July 2022. Two reviewers independently assessed all identified studies and reports using pre-defined inclusion/exclusion criteria. Study methodological quality was assessed, data were extracted in standard tables, and results were narratively synthesized.

Results

Overall, 991 studies and 53 HTA reports were identified with 20 studies and 3 HTA reports meeting the inclusion criteria. Quality assessment of the 20 studies identified 4 with minor limitations, while the remainder were assessed as having potentially or very serious limitations. Sixteen studies conducted cost-utility analyses, 6 conducted cost-effectiveness analyses, and 2 conducted cost-comparison analyses with some studies performing multiple analyses. The majority (n = 16) were model-based. Eleven studies analyzed the cost-effectiveness of bedaquiline, 6 compared shorter to longer/standard duration regimens, 2 assessed ethambutol, and 1 assessed delamanid. Key drivers of cost effectiveness were drug costs, the number of TB cases, the portion of cases with sputum culture conversion, treatment delivery costs, and treatment efficacy. Common value elements considered included adverse events, drug resistance, and improving treatment adherence.

Conclusion

Our results suggest that out of the pharmacological treatments assessed, bedaquiline is likely a cost-effective addition to existing treatment regimens/background treatment regimens, while ethambutol is not likely to be. Newer shorter regimens, even if more costly, seem to be more cost-effective compared to longer regimens. These results illustrate the limited number of novel cost-effective pharmacological interventions and highlight a need to develop new drugs/regimens against TB to overcome resistance, taking into account the key drivers of cost effectiveness and other value attributes identified from this review.
Relationship between perceived physical literacy and obesity-related outcomes in adolescents: the EHDLA study
Authors: Domínguez-Martín Gabriel , Tárraga-López Pedro J. , López-Gil José Francisco
Published: April 2024

Purpose

The aim of the present study was to examine the relationship between perceived physical literacy and obesity-related outcomes among adolescents from Spain.

Methods

This is a secondary cross-sectional analysis including a total sample of 845 Spanish adolescents (55.3% girls) aged 12–17 years from the Valle de Ricote (Region of Murcia) from the Eating Healthy and Daily Life Activities (EHDLA) project. Physical literacy was evaluated using the Spanish Perceived Physical Literacy Instrument for adolescents (S-PPLI). Body mass index was computed by taking the participants’ body weight in kilograms and dividing it by the square of their height in meters, and body mass index (z score) and overweight/obesity and obesity were computed by the World Health Organization age- and sex-specific thresholds. Waist circumference was measured using a constant tension tape. Moreover, the waist-to-height ratio was calculated, and therefore, abdominal obesity was determined. Skinfold measurements were taken at the triceps and medial calf using calibrated steel calipers.

Results

In general, the overall trend was downward (i.e., the higher the PPLI score the lower the obesity-related indicators), with the approximate significance of smooth terms being statistically significant for all models examined (p < 0.001). Adolescents with lower perceived physical literacy (PPL) showed the highest estimated marginal means of body mass index, body mass index z score, waist circumference, waist-to-height ratio, and skinfold (triceps and calf) and predictive probabilities of having excess weight, obesity, and abdominal obesity, while their counterparts with high PPL had the lowest. In addition, significant differences were observed for all the obesity-related indications between adolescents with low PPL and those with medium PPL (p-adjusted < 0.05 for all indicators), as well as with those with high PPL (p-adjusted < 0.05 for all indicators). Moreover, these significant differences were also shown for most indicators between adolescents with medium PPL and those with high PPL (except for obesity).

Conclusion

Physical literacy could play a crucial role in maintaining more desirable obesity-related outcomes in adolescents. Adolescents with high perceived physical literacy showed lower obesity-related indicators (i.e., body mass index, body mass index z score, waist circumference, waist-to-height ratio, skinfolds), as well as a lower probability of having excess weight, obesity, and abdominal obesity.
Epidemiology of antibiotic consumption and resistance in Mauritius
Authors: Veerapa-Mangroo Lovena Preeyadarshini , Rasamoelina-Andriamanivo Harena , Issack Mohammad Iqbal , Cardinale Eric
Published: April 2024

Introduction

This study aims at determining the pattern of antibiotic consumption and resistance in Mauritius, a tropical island in the Indian Ocean.

Methodology

Antibiotic consumption was measured in kilograms of purchased antibiotics and also in defined daily dose (DDD) in different health institutions from 2015 to 2017. Data on antibiotic resistance was collected at the Central Health Laboratory (CHL) at Victoria Hospital and at Jeetoo Hospital Laboratory, where antibiotic sensitivity testing is done for all public health institutions. For this study, Escherichia coli, Klebsiella species, Acinetobacter species, and Pseudomonas aeruginosa isolates from blood samples of patients from 2015 to 2023 were included. The resistance rate and prevalence of multi-drug-resistant (MDR) organisms were calculated.

Results

The amount of antibiotics (in kilograms) distributed to the human sector was between 11,000 to 13,000 kg, compared to only 700 to 1,500 kg in the animal sector. The DDD per 1,000 inhabitants per day was 20.9, 22.1, and 21.7 in 2015, 2016, and 2017, respectively, with a greater consumption of WATCH and RESERVE group antibiotics in the private sector. In public health institutions, health centers in the northern region had the highest DDD per 1,000 outpatients per day for beta-lactams penicillins and quinolones. Concerning antibiotic resistance, the proportion of MDR Acinetobacter baumannii and Pseudomonas aeruginosa has increased from 58% to 74% and from 33% to 45%, respectively, from 2015 to 2023. During the same period, the proportion of E. coli and K. pneumoniae isolates sensitive to ceftriaxone decreased from 55% to 39% and from 37% to 22%, respectively, while the proportion of E. coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa isolates sensitive to meropenem decreased from 98% to 94%, 83% to 53%, 45% to 28%, and 63% to 47%, respectively.

Conclusion

This study provides valuable insights on antibiotic consumption and resistance in the country and emphasizes the significance of adopting a One Health approach to combat antimicrobial resistance (AMR) effectively. These findings will aid policymakers in formulating targeted strategies to address the challenge of AMR and should be integrated into the National Action Plan on AMR in Mauritius.
PED: a novel predictor-encoder-decoder model for Alzheimer drug molecular generation
Authors: Liu Dayan , Song Tao , Na Kang , Wang Shudong
Published: April 2024

Alzheimer's disease (AD) is a gradually advancing neurodegenerative disorder characterized by a concealed onset. Acetylcholinesterase (AChE) is an efficient hydrolase that catalyzes the hydrolysis of acetylcholine (ACh), which regulates the concentration of ACh at synapses and then terminates ACh-mediated neurotransmission. There are inhibitors to inhibit the activity of AChE currently, but its side effects are inevitable. In various application fields where Al have gained prominence, neural network-based models for molecular design have recently emerged and demonstrate encouraging outcomes. However, in the conditional molecular generation task, most of the current generation models need additional optimization algorithms to generate molecules with intended properties which make molecular generation inefficient. Consequently, we introduce a cognitive-conditional molecular design model, termed PED, which leverages the variational auto-encoder. Its primary function is to adeptly produce a molecular library tailored for specific properties. From this library, we can then identify molecules that inhibit AChE activity without adverse effects. These molecules serve as lead compounds, hastening AD treatment and concurrently enhancing the AI's cognitive abilities. In this study, we aim to fine-tune a VAE model pre-trained on the ZINC database using active compounds of AChE collected from Binding DB. Different from other molecular generation models, the PED can simultaneously perform both property prediction and molecule generation, consequently, it can generate molecules with intended properties without additional optimization process. Experiments of evaluation show that proposed model performs better than other methods benchmarked on the same data sets. The results indicated that the model learns a good representation of potential chemical space, it can well generate molecules with intended properties. Extensive experiments on benchmark datasets confirmed PED's efficiency and efficacy. Furthermore, we also verified the binding ability of molecules to AChE through molecular docking. The results showed that our molecular generation system for AD shows excellent cognitive capacities, the molecules within the molecular library could bind well to AChE and inhibit its activity, thus preventing the hydrolysis of ACh.
Prevalence of co-occurring conditions among youths receiving treatment with primary anxiety, ADHD, or depressive disorder diagnoses
Authors: Ware Orrin D. , Zerden Lisa D. , Duron Jacquelynn F. , Xu Yanfeng , McCarthy Lauren P. , Verbiest Sarah , Afkinich Jenny , Brown Qiana , Williams Denise Yookong , Goings Trenette
Published: April 2024

Introduction

Anxiety disorders, depressive disorders, and attention-deficit/hyperactivity disorder (ADHD) are some of the most common conditions that youths (<18 years old) receive mental health treatment for. These conditions are associated with high-risk substance use or substance use disorders (SUDs). This study sought to identify the proportion of youths (<18 years old) with anxiety disorders, depressive disorders, or ADHD as a primary diagnosis in community mental health centers (CMHCs) having co-occurring high-risk substance use or a SUD.

Methods

Analysis included binary logistic regression models using the Mental Health Client-Level Data 2017–2019 datasets which contains annual cross-sectional administrative data from mental health treatment facilities. The final sample included n = 458,888 youths with an anxiety disorder as a primary diagnosis, n = 570,388 youths with a depressive disorder as a primary diagnosis, and n = 945,277 youths with ADHD as a primary diagnosis.

Results

In the subsample with anxiety as a primary diagnosis, approximately 5% of youth had high-risk substance use or a SUD. Approximately 10% of youth with depression as a primary diagnosis had high-risk substance use or a SUD. Among youth with ADHD as a primary diagnosis, 5% had high-risk substance use or a SUD. Odds of having a co-occurring high-risk substance use or SUD differed based on the youth’s age, race and ethnicity, gender, and other mental health diagnoses.

Conclusions

Effective care for this high-need youth population at CMHCs will require mental health clinicians to possess knowledge and skills related to substance use treatment.
Validity and reliability of the 2-min step test in individuals with stroke and lower-limb musculoskeletal disorders
Authors: Ishigaki Tomoya , Kubo Hiroki , Yoshida Keishi , Shimizu Natsuki , Ogawa Tatsuya
Published: April 2024

Introduction

We investigated the reliability and validity of the 2-min step test (2MST) for assessing the exercise endurance of individuals with stroke and lower-limb musculoskeletal disorders.

Participants and methods

The participants were 39 individuals with stroke and 42 with lower-limb musculoskeletal disorders (mainly hip fractures) from the convalescent rehabilitation wards of four hospitals. The concurrent validity and congruence between the 2MST and the 6-min walk test (6MWT) and construct validity by hypotheses testing, including mobility and lower limb muscle strength, were also confirmed. A subset of participants (stroke-group, n = 15; musculoskeletal-group, n = 19) underwent a retest 2MST for our evaluation of relative and absolute reliability using the intraclass correlation coefficient (ICC1,1) and Bland–Altman plot.

Results

Both groups showed a moderate correlation between the 2MST and 6MWT (ρ = 0.55–0.60), but the congruence was not sufficient. The 6MWT was correlated with mobility in both groups and with muscle strength in the stroke group, whereas the 2MST did not show a significant correlation with mobility. The relative reliability was excellent in both groups (ICC1,1 > 0.9). In terms of absolute reliability, the width of the limit of agreement was 18.8% for the stroke group and 15.4% for the musculoskeletal group, relative to their respective sample means of 2MST. A fixed bias was identified in the stroke group, in which step counts increased by 6.5 steps upon retesting.

Discussion

Our analyses revealed that the 2MST is a valid and reliable tool for assessing the exercise endurance of individuals with stroke or lower-limb musculoskeletal disorders. However, it is necessary to validate the absolute reliability observed herein by using a larger sample size. In addition, when assessing the exercise endurance of individuals with stroke, it may be necessary to consider the potential bias of an increased step count during retesting.
Decentralized multi-agent reinforcement learning based on best-response policies
Authors: Gabler Volker , Wollherr Dirk
Published: April 2024

Introduction: Multi-agent systems are an interdisciplinary research field that describes the concept of multiple decisive individuals interacting with a usually partially observable environment. Given the recent advances in single-agent reinforcement learning, multi-agent reinforcement learning (RL) has gained tremendous interest in recent years. Most research studies apply a fully centralized learning scheme to ease the transfer from the single-agent domain to multi-agent systems.

Methods: In contrast, we claim that a decentralized learning scheme is preferable for applications in real-world scenarios as this allows deploying a learning algorithm on an individual robot rather than deploying the algorithm to a complete fleet of robots. Therefore, this article outlines a novel actor–critic (AC) approach tailored to cooperative MARL problems in sparsely rewarded domains. Our approach decouples the MARL problem into a set of distributed agents that model the other agents as responsive entities. In particular, we propose using two separate critics per agent to distinguish between the joint task reward and agent-based costs as commonly applied within multi-robot planning. On one hand, the agent-based critic intends to decrease agent-specific costs. On the other hand, each agent intends to optimize the joint team reward based on the joint task critic. As this critic still depends on the joint action of all agents, we outline two suitable behavior models based on Stackelberg games: a game against nature and a dyadic game against each agent. Following these behavior models, our algorithm allows fully decentralized execution and training.

Results and Discussion: We evaluate our presented method using the proposed behavior models within a sparsely rewarded simulated multi-agent environment. Although our approach already outperforms the state-of-the-art learners, we conclude this article by outlining possible extensions of our algorithm that future research may build upon.
Model-based trajectory tracking of a compliant continuum robot
Authors: Pekris Solomon , Williams Robert D. , Atkins Thibaud , Georgilas Ioannis , Bailey Nicola
Published: April 2024

Introduction: Compliant mechanisms, especially continuum robots, are becoming integral to advancements in minimally invasive surgery due to their ability to autonomously navigate natural pathways, significantly reducing collision severity. A major challenge lies in developing an effective control strategy to accurately reflect their behavior for enhanced operational precision.

Methods: This study examines the trajectory tracking capabilities of a tendon-driven continuum robot at its tip. We introduce a novel feedforward control methodology that leverages a mathematical model based on Cosserat rod theory. To mitigate the computational challenges inherent in such models, we implement an implicit time discretization strategy. This approach simplifies the governing equations into space-domain ordinary differential equations, facilitating real-time computational efficiency. The control strategy is devised to enable the robot tip to follow a dynamically prescribed trajectory in two dimensions.

Results: The efficacy of the proposed control method was validated through experimental tests on six different demand trajectories, with a motion capture system employed to assess positional accuracy. The findings indicate that the robot can track trajectories with an accuracy within 9.5%, showcasing consistent repeatability across different runs.

Discussion: The results from this study mark a significant step towards establishing an efficient and precise control methodology for compliant continuum robots. The demonstrated accuracy and repeatability of the control approach significantly enhance the potential of these robots in minimally invasive surgical applications, paving the way for further research and development in this field.
Fundamental physics studies in time domain and multi-messenger astronomy
Authors: Fryer Chris
Published: April 2024

The era of ime domain and multi-messenger astronomy is not only leading to the development of a much broader set of detectors and instruments for astrophysical observations, but is also providing the means for astronomy to tie directly to cutting-edge studies in physics. In this manner, fundamental physics (theory and experiment) coupled with a strong theoretical understanding of astrophysical phenomena (guided by high-performance computing simulations) can tie directly to the amazing new observations in astronomy. This paper discusses how physics, astrophysical models, and observations can not only help astronomy probe fundamental physics but guide the needs for next-generation astrophysical missions.
Case Report: The molecular fingerprint and the clinical implication of an exceptional response to neoadjuvant therapy in a metastatic cardia adenocarcinoma
Authors: Lorenzon Laura , Campisi Andrea , Di Paolo Alessandra , Giuliante Felice , Buttitta Fiamma , D’Ugo Domenico
Published: April 2024

Background

Globally, gastric cancer holds the fifth position in terms of prevalence among malignant tumors and is the fourth leading cause of cancer-related mortality. Particular attention should be paid to cardia adenocarcinoma (CA) due to its increasing incidence and poor prognosis. Diagnosis of CA frequently occurs in advanced stages because of its late symptoms. In such cases, neoadjuvant chemotherapy is the primary treatment option. The response to chemotherapy depends on multiple variables including the tumor's molecular profile, the patient's performance status, and the feasibility of using targeted therapy. Patients exhibiting an exceptional response, defined as a complete response to medical therapy lasting more than 1 year, or a partial response or stable disease lasting more than 2 years, are rarely described. This case report presents one of the longest-lasting exceptional responses to chemotherapy in metastatic cardia adenocarcinoma and discusses its clinical implications.

Case presentation

A 49-year-old male patient presented with cardia adenocarcinoma (human epidermal growth factor receptor 2 negative, mismatch repair proficient) and liver metastases. Molecular profiling identified a pathogenic mutation in the TP53 gene (R123W; Arg123Trp) as the sole alteration found. Five months after initiating the neoadjuvant chemotherapy with fluorouracil–leucovorin–oxaliplatin–docetaxel, the patient achieved a complete clinical response. The molecular profile was compared with others previously documented in an international data portal, revealing a similar pattern. At 4 years and 3 months from diagnosis, the exceptional response was still confirmed. The patient underwent a cumulative number of 33 cycles of chemotherapy, leading to chemotherapy-induced liver damage.

Conclusions

Exceptional responses to neoadjuvant chemotherapy in cardia adenocarcinomas are rarely reported. The documentation of exceptional responses to cancer therapies should be included in large data repositories to explore the molecular fingerprint of these tumors. In such cases, the clinical implications of long-term chemotherapy should always be taken into account.
Assessing the Contribution of Smallholder Irrigation to Household Food Security in Zimbabwe
Authors: Mupaso Norman , Makombe Godswill , Mugandani Raymond , Mafongoya Paramu L.
Published: April 2024

Sustainable Development Goal (SDG) 2 seeks to end hunger and guarantee food and nutrition security worldwide by 2030. Smallholder irrigation development remains a key strategy to achieve SDG 2. This study assesses how smallholder irrigation contributes to household food security in Mberengwa district, Zimbabwe. Primary data were gathered from a randomly chosen sample of 444 farmers (344 irrigators and 100 non-irrigators) using a structured questionnaire. Microsoft Excel and Statistical Package for Social Sciences version 27 software packages were used to analyse the data. Descriptive statistics, chi-square test, t-test, and binary logistic regression were performed. The t-test results show significant differences in mean between irrigators and non-irrigators for household size, the dependency ratio, farming experience, farm income, food expenditure share, and livestock owned (p < 0.05). Irrigators had significantly higher area planted, yield, and quantity sold for maize during the summer than non-irrigators (p < 0.05). Food Consumption Score results show that 97% of irrigators and 45% of non-irrigators were food secure. Binary logistic regression results reveal a significant association between food security and household size, irrigation access, and farm income (p < 0.05). In conclusion, access to smallholder irrigation increases household food security. The government and its development partners should prioritise investments in smallholder irrigation development, expansion, and rehabilitation.
Maize Kernel Quality Detection Based on Improved Lightweight YOLOv7
Authors: Yang Lili , Liu Chengman , Wang Changlong , Wang Dongwei
Published: April 2024

As an important cereal crop, maize is a versatile and multi-purpose crop, primarily used as a feed globally, but also is important as a food crop, and has other uses such as oil and industrial raw materials. Quality detection is an indispensable part of functional and usage classification, avoiding significant waste as well as increasing the added value of the product. The research on algorithms for real-time, accurate, and non-destructive identification and localization of corn kernels based on quality classification and equipped with non-destructive algorithms suitable for embedding in intelligent agricultural machinery systems is a key step in improving the effective utilization rate of maize kernels. The difference in maize kernel quality leads to significant differences in price and economic benefits. This algorithm reduced unnecessary waste caused by the low efficiency and accuracy of manual and mechanical detection. Image datasets of four kinds of maize kernel quality were established and each image contains a total of about 20 kernels of different quality randomly distributed. Based on the self-built dataset, the YOLOv7-tiny, as the backbone network, was used to design a maize kernel detection and recognition model named “YOLOv7-MEF”. Firstly, the backbone feature layer of the algorithm was replaced by MobileNetV3 as the feature extraction backbone network. Secondly, ESE-Net was used to enhance feature extraction and obtain better generalization performance. Finally, the loss function was optimized and replaced with the Focal-EOIU loss function. The experiment showed that the improved algorithm achieved an accuracy of 98.94%, a recall of 96.42%, and a Frame Per Second (FPS) of 76.92 with a model size of 9.1 M. This algorithm greatly reduced the size of the model while ensuring high detection accuracy and has good real-time performance. It was suitable for deploying embedded track detection systems in agricultural machinery equipment, providing a powerful theoretical research method for efficient detection of corn kernel quality.