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Millet products have garnered global recognition for their exceptional nutritional profile, appealing to various age demographics, and, therefore, fortifying such products with minerals can ensure nutritional security. This research explores the feasibility of utilizing millet as a substitute for refined wheat flour in biscuit production. Three distinct millet varieties were investigated: finger, pearl, and buckwheat. Employing response surface methodology (RSM), the optimal ratio of these flours was determined, resulting in a blend of 1.5:1:1, respectively. The optimized multi-millet biscuits were further enhanced with calcium fortification and subjected to comprehensive physico-chemical analysis. Proximate composition analysis revealed favorable levels of protein (5.472 ± 0.31%), ash (2.80 ± 0.57 g/100 g), and energy density (5.8015 ± 0.004 kcal/g), indicating a significantly higher protein content, enriched mineral profile, and high energy density as compared to refined wheat flour products. Sensory evaluation encompassing attributes such as color and texture and organoleptic assessment using a nine-point hedonic scale demonstrated favorable acceptance. Additionally, the overall acceptability of the biscuits remained consistently high throughout storage, ranging from 8.263 ± 0.65 (day 0) to 8.053 ± 0.85 (day 14). This study underscores the potential of multi-millet biscuits as a nutritious and palatable alternative to traditional wheat-based snacks, offering an avenue for diversifying dietary options and promoting healthier food choices.

Purpose: The overall aim of the study is to analyze and provide a comprehensive understanding of the demographics, educational backgrounds, and scholarly activities of musculoskeletal imaging fellowship program directors across the United States., Methods: A list of all members of the Society of Skeletal Radiology was obtained and musculoskeletal imaging fellowship program directors across the US were included. Publicly available online sources were used to gather demographic and educational information about each musculoskeletal imaging fellowship program director, which included the online curriculum vitae from the program websites, Health Grades, Doximity, and Elsevier's Scopus database. Demographic and educational data including age, gender, educational background (medical school, residency, fellowship), additional degrees, academic rank, prior leadership positions, and metrics of scholarly activity were recorded. Fellowships in diagnostic musculoskeletal radiology along with additional degrees were recorded. A two-tailed unpaired t-test was used to calculate the difference between means of scholarly activity between male and female PDs., Results: In this study encompassing 92 programs across the United States, the majority (88) were dedicated to pure Musculoskeletal (MSK) Imaging Fellowship, while one each offered combined training in MSK and Body Imaging, MSK, and Emergency Imaging, MSK Sports, and Interventional Spine, and Pediatric MSK Imaging. Program directors were identified for 90 out of 92 programs, revealing a regional distribution of 29 in the South (31.5 %), 24 in the North East (26.1 %), 20 in the Midwest (21.74 %) and 19 in the West (20.65 %). Gender analysis unveiled a predominantly male representation, with 71 male directors compared to 17 female directors, while age ranged from 30 to 70 years, with a mean age of 47.17 ± 7.4 years. Medical school backgrounds predominantly featured MD degrees (80), followed by IMG (7) and DO (4) degrees, with the most common IMG source being India. Faculty positions were mainly distributed among Assistant Professors (35), Associate Professors (32), and Professors (11). Research output metrics showcased a mean of 41.943 publications and an h-index of 10.625. Extra degrees were obtained by 31 directors, with common additions being other fellowships, MBAs, MS degrees, and PhDs. Notably, some directors held previous or current leadership positions, while a few had completed residencies outside of Radiology or pursued fellowships beyond MSK Imaging., Conclusion: Musculoskeletal imaging fellowship program directors across the United States are predominantly male, with approximately 8 % having graduated from international medical schools. The most common training pathway for these directors is completing a diagnostic radiology residency followed by a musculoskeletal radiology fellowship. This study highlighted the gender disparity within this leadership group and emphasized the diverse educational backgrounds that contribute to the field of musculoskeletal imaging., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: Error related to incorrect use of rating scales is problematic in the assessment and treatment of dysarthria. The main purpose of this project was to determine scale fit for cardinal speech features of hypokinetic dysarthria. A secondary aim was to determine rater reliability for the two different scales explored., Method: Forty-three speakers with Parkinson's disease (PD) and 25 neurologically healthy control talkers were recorded reading sentences from the Speech Intelligibility Test. Twenty-two healthy female listeners used both an equal appearing interval (EAI) scale and a direct magnitude estimation (DME) scale to rate five perceptual speech features (i.e., overall speech severity, articulatory imprecision, reduced loudness, short rushes of speech, and monotony) from these recordings. Regression analyses were used to determine the linearity of the relationship between the means of the EAI and DME ratings. Inter- and intrarater reliability was calculated using intraclass correlation coefficients and Spearman's correlation coefficients, respectively, for both EAI and DME ratings., Results: There was a linear relationship between EAI and DME means for monotony, indicating it is a metathetic dimension. Curvilinear relationships were observed between the EAI and DME means for the other four features, indicating prothetic dimensions. Intra- and interrater reliability values were similar for EAI and DME ratings., Discussion: Overall, results of this work suggest that DME is the best fit for scaling several hypokinetic dysarthria features, and not the conventionally used EAI scale. Prothetic dimensions best scaled by DME include overall speech severity, articulatory imprecision, reduced loudness, and short rushes of speech. Monotony was the only feature found to be a metathetic dimension and would be best scaled using EAI or DME. Findings call for rethinking the widespread use of EAI scales for rating perceptual features as part of the assessment and treatment of motor speech disorders.

Goals: To determine long-term efficacy and safety of tCS for treatment of EoE., Background: Maintenance therapy with topical corticosteroids (tCS) is recommended for eosinophilic esophagitis (EoE), but data for long-term use are still needed., Study: This retrospective cohort study assessed newly diagnosed patients with EoE who were treated with a tCS and had a follow-up endoscopy with biopsy after at least 5 years. Histologic symptomatic and endoscopic responses were extracted from medical records. Patients who did and did not have long-term tCS treatment were compared at baseline, and outcomes for patients were assessed at their last endoscopy while on tCS., Results: Of 431 patients with EoE treated with tCS, 104 met inclusion criteria for long-term use. For patients with long-term tCS use, the median time (IQR) on tCS was 6.5 years (5.4 to 8.8 y). At the last endoscopy, 54% had histologic response (<15 eos/hpf), but those with excellent adherence had a histologic response of 64%. Endoscopic severity also decreased with improved adherence which was strongly associated with EREFS (1.7 vs. 2.8 vs. 4.0 for excellent, good, and poor adherence; P<0.001). Symptomatic response was 68% overall, but only 40% in those with poor adherence (P=0.07). Complications of taking tCS were uncommon (adrenal insufficiency: 1%; osteopenia: 1%; and esophageal candidiasis: 4% at final endoscopy)., Conclusions: Long-term tCS (median 6.5 y) were generally effective, especially with better adherence, and also safe, with only rare serious complications. These data can be used to help patients make clinical decisions about chronic tCS use in EoE., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: There is limited caregiver-reported evidence determining health care transition (HCT) outcomes for their adolescents/young adults with special health care needs (AYA-SHCN). A subcommittee of the International and Interdisciplinary Healthcare Transition Research Consortium aimed to identify multidimensional outcomes of a successful HCT among AYA-SHCN based on parents/caregivers' perspectives., Methods: After literature review and expert interviews, a three-stage Delphi process identified HCT outcomes based on parents/caregivers' perspectives. Participants were parents/caregivers of patients attending the Victory Junction Therapeutic Camp and a nationally representative sample from Cint Healthcare Digital Solutions Platform. The cumulative 272 responses collected on a Health Insurance Portability and Accountability Act-compliant web-based engine (Qualtrics) rated potential HCT outcomes by level of importance on a Likert scale from 1 (not important) to 9 (very important) and narrowed in subsequent iterations., Results: The Delphi process included 127 (Stage 1), 82 (Stage 2), and 63 (Stage 3) parents/caregivers. The initial 25 HCT outcomes were narrowed to 13, across four major domains: coping/satisfaction, behavioral, structural, and HCT/healthcare-focused outcomes. The top outcome was "My child takes their medications as prescribed." Several traditionally considered important outcomes for HCT were eliminated., Discussion: Thirteen HCT outcomes for AYA-SHCN were identified in four major domains: coping/satisfaction, behavioral, structural, and HCT/healthcare focused. Future research in larger samples would allow stratification to represent diverse patients and caregiver populations. Identifying international consensus-derived outcomes among parents/caregivers is imperative for the evaluation of HCT preparation strategies that ensure appropriate support for diverse AYA-SHCN and their families during this process and enable implementation of the most effective interventions., (Copyright © 2024 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Among the goals of patient-centric care are the advancement of effective personalized treatment, while minimizing toxicity. The phase 2 I-SPY2.2 trial uses a neoadjuvant sequential therapy approach in breast cancer to further these goals, testing promising new agents while optimizing individual outcomes. Here we tested datopotamab-deruxtecan (Dato-DXd) in the I-SPY2.2 trial for patients with high-risk stage 2/3 breast cancer. I-SPY2.2 uses a sequential multiple assignment randomization trial design that includes three sequential blocks of biologically targeted neoadjuvant treatment: the experimental agent(s) (block A), a taxane-based regimen tailored to the tumor subtype (block B) and doxorubicin-cyclophosphamide (block C). Patients are randomized into arms consisting of different investigational block A treatments. Algorithms based on magnetic resonance imaging and core biopsy guide treatment redirection after each block, including the option of early surgical resection in patients predicted to have a high likelihood of pathological complete response, the primary endpoint. There are two primary efficacy analyses: after block A and across all blocks for the six prespecified breast cancer subtypes (defined by clinical hormone receptor/human epidermal growth factor receptor 2 (HER2) status and/or the response-predictive subtypes). We report results of 103 patients treated with Dato-DXd. While Dato-DXd did not meet the prespecified threshold for success (graduation) after block A in any subtype, the treatment strategy across all blocks graduated in the hormone receptor-negative HER2 - Immune - DNA repair deficiency - subtype with an estimated pathological complete response rate of 41%. No new toxicities were observed, with stomatitis and ocular events occurring at low grades. Dato-DXd was particularly active in the hormone receptor-negative/HER2 - Immune - DNA repair deficiency - signature, warranting further investigation, and was safe in other subtypes in patients who followed the treatment strategy. ClinicalTrials.gov registration: NCT01042379 ., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Sequential adaptive trial designs can help accomplish the goals of personalized medicine, optimizing outcomes and avoiding unnecessary toxicity. Here we describe the results of incorporating a promising antibody-drug conjugate, datopotamab-deruxtecan (Dato-DXd) in combination with programmed cell death-ligand 1 inhibitor, durvalumab, as the first sequence of therapy in the I-SPY2.2 phase 2 neoadjuvant sequential multiple assignment randomization trial for high-risk stage 2/3 breast cancer. The trial includes three blocks of treatment, with initial randomization to different experimental agent(s) (block A), followed by a taxane-based regimen tailored to tumor subtype (block B), followed by doxorubicin-cyclophosphamide (block C). Subtype-specific algorithms based on magnetic resonance imaging volume change and core biopsy guide treatment redirection after each block, including the option of early surgical resection in patients predicted to have a high likelihood of pathologic complete response, which is the primary endpoint assessed when resection occurs. There are two primary efficacy analyses: after block A and across all blocks for six prespecified HER2-negative subtypes (defined by hormone receptor status and/or response-predictive subtypes). In total, 106 patients were treated with Dato-DXd/durvalumab in block A. In the immune-positive subtype, Dato-DXd/durvalumab exceeded the prespecified threshold for success (graduated) after block A; and across all blocks, pathologic complete response rates were equivalent to the rate expected for the standard of care (79%), but 54% achieved that result after Dato-DXd/durvalumab alone (block A) and 92% without doxorubicin-cyclophosphamide (after blocks A + B). The treatment strategy across all blocks graduated in the hormone-negative/immune-negative subtype. No new toxicities were observed. Stomatitis was the most common side effect in block A. No patients receiving block A treatment alone had adrenal insufficiency. Dato-DXd/durvalumab is a promising therapy combination that can eliminate standard chemotherapy in many patients, particularly the immune-positive subtype.ClinicalTrials.gov registration: NCT01042379 ., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: The Centers for Disease Control and Prevention's Active Bacterial Core surveillance (ABCs) identified increased serotype 4 invasive pneumococcal disease (IPD), particularly among adults experiencing homelessness (AEH)., Methods: We quantified IPD cases during 2016-2022. Employing genomic-based characterization of IPD isolates, we identified serotype-switch variants. Recombinational analyses were used to identify the genetic donor and recipient strains that generated a serotype 4 progeny strain. We performed phylogenetic analyses of the serotype 4 progeny and serotype 12F genetic recipient to determine genetic distances., Results: We identified 30 inter-related (0-21 nucleotide differences) IPD isolates recovered during 2022-2023, corresponding to a serotype 4 capsular-switch variant. This strain arose through a multi-fragment recombination event between serotype 4/ST10172 and serotype 12F/ST220 parental strains. Twenty-five of the 30 cases occurred within Oregon. Of 29 cases with known residence status, 16 occurred in AEH. Variant emergence coincided with a 2.6-fold increase (57 to 148) of cases caused by the serotype 4/ST10172 donor lineage in 2022 compared to 2019 and its first appearance in Oregon. Most serotypes showed sequential increases of AEH IPD/all IPD ratios during 2016-2022 (for all serotypes combined, 247/2198, 11.2% during 2022 compared to 405/5317, 7.6% for 2018-2019, p<0.001). Serotypes 4 and 12F each caused more IPD than any other serotypes in AEH during 2020-2022 (207 combined reported cases primarily in 4 western states accounting for 38% of IPD in AEH)., Conclusion: Expansion and increased transmission of serotypes 4 and 12F among adults potentially led to recent genesis of an impactful hybrid "serotype-switch" variant., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)

Background: Atopic dermatitis (AD) is the most common inflammatory skin condition which affects all ages. New therapies, including the monoclonal antibody therapy dupilumab, offer excellent efficacy. However, in clinical trials, and emphasised in real-world observations, the unexpected increased frequency of ocular adverse effects became apparent. The effectiveness of dupilumab and the unpredictability of ocular adverse effects mean that clinicians need guidance on counselling patients prior to treatment and on managing them if they arise., Objectives: The British Association of Dermatologists (BAD) and Royal College of Ophthalmologists collaborated on this consensus guidance on managing dupilumab-related ocular surface disorders (DROSD)., Methods: A multidisciplinary group was formed of adult and paediatric dermatologists and ophthalmologists with DROSD expertise, patient representation, and BAD Clinical Standards Unit. A literature search was conducted, and the results reviewed. All recommendations were reviewed, discussed and voted on., Results: The recommendations pertain to dermatology and ophthalmology management, and apply to all ages, unless otherwise stated. Importantly, initiation of dupilumab for AD should not be delayed for most eye disorders except acute new problems, e.g. infections, or potentially severe conditions, e.g. a history of corneal transplant (ophthalmology advice should be sought first). There is insufficient evidence to recommend lubricant drops prophylactically. Dermatologists should assess eye complaints to diagnose DROSD; a severity grading system is provided. DROSD management differs slightly in those aged <7 years as ocular complications may affect neuro-ocular development; therefore, irrespective of DROSD severity, this population should be referred for ophthalmology advice. In those aged ≥7 years, dermatologists should feel confident to trial treatment and reserve ophthalmology advice for severe or non-responding cases. Discussion about dupilumab withdrawal should be prompted by a significant impact on quality of life, threat to sight, or other complications., Conclusions: Although dupilumab is a highly effective agent for treating AD, the risk of ocular adverse effects should not inhibit clinicians or patients from using it, but clinicians should be aware of them. If a patient develops DROSD, there are clear pathways to assess severity and offer initial management; where ineffective, dermatologists should assess the urgency and seek advice from or initiate referral to ophthalmology. While the evidence reviewed for these guidelines reflects the extensive literature on dupilumab, we believe our advice has relevance for ocular surface disorders in atopic dermatitis (AD) patients treated with tralokinumab and lebrikizumab., (© British Association of Dermatologists 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Backgrounds: Research shows that medical students' knowledge and skills concerning the assessment of cognition in various neuropsychiatric conditions (e.g., Alzheimer's disease and schizophrenia) are unsatisfactory. This research aims to conduct a training needs analysis (TNA) for medical students to identify and refer patients with neuropsychiatric conditions., Methods: The study comprised two phases. First, developing a TNA toolkit to assess training needs in clinical tasks related to cognitive function assessment (by adopting the Hennessy-Hicks TNA toolkit); and second, through a self-reported survey, their training needs in cognitive function assessment were assessed. Data analysis involved calculating training gaps, importance scores, performance scores, training scores, and organization scores for various clinical tasks-stratified participants' study year; for training needs and trends, factor analysis and post-hoc analyses were conducted., Results: A total of 153 medical students from a tertiary care center participated in the survey. The participants rated their performance lower than the perceived importance of tasks, indicating a need for improvement in all competencies ( P < .01). Pre-final-year students had the highest training needs, particularly in accessing literature, planning, and organizing care for patients with cognitive impairment, performing mental status examination, screening patients for cognitive deficits, and counseling them/caregivers about interventions ( P < .01). Factor analysis identified a single dominant factor, suggesting a correlation among these skills., Conclusion: Pre-final-year students require targeted training, whereas students beyond this stage can benefit from special training modules and awareness of available resources for cognitive assessment. The findings also suggest the importance of a hybrid approach involving training and organizational modifications., Competing Interests: The author declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article., (© 2024 The Author(s).)

Objective: The aim of this study was to assess the feasibility of digitally scanning dentures and 3D printing replica dentures for care home residents. The study also investigated whether the process and replacement denture was acceptable to the resident., Background: Denture loss is a significant issue for people living in care homes and impacts on nutrition, quality of life and dignity. Denture loss is underreported, and care home residents have barriers to accessing dental care. The conventional process for remaking a denture can often take approximately 2 months with multiple clinical stages, often not feasible in adults with frailty and cognitive impairment. Scanning and 3D (3 dimensional) printing are increasingly used in dentistry, this rapidly evolving technology may provide an innovative solution to denture loss., Materials and Methods: A digital workflow was established using a handheld scanner and 3D printing technology. Care home residents wearing functional acrylic dentures were recruited. Dentures were scanned within the care home, and the scan was sent to a dental laboratory for 3D printing. The dentures were fitted at a subsequent visit, and semi-structured interviews were undertaken with the resident. Using thematic analysis, the feasibility of this pathway was assessed, and the use of digital scanning technology was explored., Results: Eight residents successfully had dentures scanned and replicated to a satisfactory standard. It took, on average, 10 minutes to scan a denture and 20 minutes to print the denture. All replica dentures were satisfactory to the resident. Qualitative data from semi-structured interviews showed that study participants were satisfied with denture replacements and the process. The 3 main themes that emerged were: the significance of dentures to the individual, satisfaction with the scanning process and general low self-esteem and fatigue., Conclusions: This study has established a workflow for digitally storing dentures and replicating them satisfactorily. In the context of a care home setting, a scan of a denture can be used to provide a replacement denture if lost or broken. A large-scale study could follow now that the feasibility of this pathway has been demonstrated., (© 2023 Gerodontology Association and John Wiley & Sons Ltd.)

Meiosis is required for the formation of gametes in all sexually reproducing species and the process is well conserved across the tree of life. However, meiosis is sensitive to a variety of external factors, which can impact chromosome pairing, recombination, and fertility. For example, the optimal temperature for successful meiosis varies between species of plants and animals. This suggests that meiosis is temperature sensitive, and that natural selection may act on variation in meiotic success as organisms adapt to different environmental conditions. To understand how temperature alters the successful completion of meiosis, we utilized two species of the budding yeast Saccharomyces with different temperature preferences: thermotolerant Saccharomyces cerevisiae and cold tolerant Saccharomyces uvarum . We surveyed three metrics of meiosis: sporulation efficiency, spore viability, and recombination rate in multiple strains of each species. As per our predictions, the proportion of cells that complete meiosis and form spores is temperature sensitive, with thermotolerant S. cerevisiae having a higher temperature threshold for successful meiosis than cold tolerant S. uvarum . We confirmed previous observations that S. cerevisiae recombination rate varies between strains and across genomic regions, and add new results that S. uvarum has higher recombination rates than S. cerevisiae . We find that temperature significantly influences recombination rate plasticity in S. cerevisiae and S. uvarum , in agreement with studies in animals and plants. Overall, these results suggest that meiotic thermal sensitivity is associated with organismal thermal tolerance, and may even result in temporal reproductive isolation as populations diverge in thermal profiles.

Introduction: Invasive fungal infections are a primary cause of morbidity and mortality in patients with haematological malignancies., Case Presentation: We describe an unusual clinical and radiological presentation of invasive mucormycosis (IM) in a 69-year-old patient with relapsed acute myeloid leukaemia. The patient was diagnosed with disseminated IM with involvement of the central nervous system in an atypical location, lung, spleen, muscle, bone, and heart, after having completed induction and bridging chemotherapy to allogeneic haematopoietic stem cell transplant (HSCT). Her clinical presentation was atypical with mild neurological symptoms slowly progressing over 2 months and without appropriate signs of systemic inflammation. Mucorales was eventually confirmed from bronchoalveolar lavage and subdural collection., Conclusion: This report highlights the difficult challenges of managing disseminated IM in an immunocompromised patient, where close multidisciplinary specialist care enabled successful treatment, followed by T-cell-depleted allogeneic HSCT for a high-risk haematological malignancy., (© 2024 S. Karger AG, Basel.)

Cytotoxic T lymphocytes (CTLs) mediate host defense against viral and intracellular bacterial infections and tumors. However, the magnitude of CTL response and their function needed to confer heterosubtypic immunity against influenza virus infection are unknown. We addressed the role of CD8 + T cells in the absence of any cross-reactive antibody responses to influenza viral proteins using an adenoviral vector expressing a 9mer amino acid sequence recognized by CD8 + T cells. Our results indicate that both CD8 + T cell frequency and function are crucial for heterosubtypic immunity. Low morbidity, lower viral lung titers, low to minimal lung pathology, and better survival upon heterosubtypic virus challenge correlated with the increased frequency of NP-specific CTLs. NP-CD8 + T cells induced by differential infection doses displayed distinct RNA transcriptome profiles and functional properties. CD8 + T cells induced by a high dose of influenza virus secreted significantly higher levels of IFN-γ and exhibited higher levels of cytotoxic function. The mice that received NP-CD8 + T cells from the high-dose virus recipients through adoptive transfer had lower viral titers following viral challenge than those induced by the low dose of virus, suggesting differential cellular programming by antigen dose. Enhanced NP-CD8 + T-cell functions induced by a higher dose of influenza virus strongly correlated with the increased expression of cellular and metabolic genes, indicating a shift to a more glycolytic metabolic phenotype. These findings have implications for developing effective T cell vaccines against infectious diseases and cancer., Importance: Cytotoxic T lymphocytes (CTLs) are an important component of the adaptive immune system that clears virus-infected cells or tumor cells. Hence, developing next-generation vaccines that induce or recall CTL responses against cancer and infectious diseases is crucial. However, it is not clear if the frequency, function, or both are essential in conferring protection, as in the case of influenza. In this study, we demonstrate that both CTL frequency and function are crucial for providing heterosubtypic immunity to influenza by utilizing an Ad-viral vector expressing a CD8 epitope only to rule out the role of antibodies, single-cell RNA-seq analysis, as well as adoptive transfer experiments. Our findings have implications for developing T cell vaccines against infectious diseases and cancer., Competing Interests: The authors declare no conflict of interest.

Hypertriglyceridemia is characterized by elevated triglyceride levels in the blood, which increases the risk of cardiovascular disease and pancreatitis. This condition stems from multiple factors including lifestyle choices, genetics, and conditions such as diabetes and metabolic syndrome. Apolipoprotein C-III (APOC3), a protein for lipid metabolism, hinders enzymes necessary for breaking down triglycerides and thus plays a key role in hypertriglyceridemia. Variations in the APOC3 gene are associated with varying triglyceride levels among individuals. Recent genetic studies and clinical trials have shed light on the potential of targeting APOC3 as a potentially promising therapeutic modality of hypertriglyceridemia. Antisense oligonucleotides like volanesorsen have displayed effectiveness in lowering triglyceride levels in individuals with severe hypertriglyceridemia. This review article delves into how APOC3 influences triglyceride control and its potential use in targeting APOC3 to manage severe hypertriglyceridemia., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Shah et al.)

Background: Rare disorders comprise of ~ 7500 different conditions affecting multiple systems. Diagnosis of rare diseases is complex due to dearth of specialized medical professionals, testing labs and limited therapeutic options. There is scarcity of data on the prevalence of rare diseases in different populations. India being home to a large population comprising of 4600 population groups, of which several thousand are endogamous, is likely to have a high burden of rare diseases. The present study provides a retrospective overview of a cohort of patients with rare genetic diseases identified at a tertiary genetic test centre in India., Results: Overall, 3294 patients with 305 rare diseases were identified in the present study cohort. These were categorized into 14 disease groups based on the major organ/ organ system affected. Highest number of rare diseases (D = 149/305, 48.9%) were identified in the neuromuscular and neurodevelopmental (NMND) group followed by inborn errors of metabolism (IEM) (D = 47/305; 15.4%). Majority patients in the present cohort (N = 1992, 61%) were diagnosed under IEM group, of which Gaucher disease constituted maximum cases (N = 224, 11.2%). Under the NMND group, Duchenne muscular dystrophy (N = 291/885, 32.9%), trinucleotide repeat expansion disorders (N = 242/885; 27.3%) and spinal muscular atrophy (N = 141/885, 15.9%) were the most common. Majority cases of β-thalassemia (N = 120/149, 80.5%) and cystic fibrosis (N = 74/75, 98.7%) under the haematological and pulmonary groups were observed, respectively. Founder variants were identified for Tay-Sachs disease and mucopolysaccharidosis IVA diseases. Recurrent variants for Gaucher disease (GBA:c.1448T > C), β-thalassemia (HBB:c.92.+5G > C), non-syndromic hearing loss (GJB2:c.71G > A), albinism (TYR:c.832 C > T), congenital adrenal hyperplasia (CYP21A2:c.29-13 C > G) and progressive pseudo rheumatoid dysplasia (CCN6:c.298T > A) were observed in the present study., Conclusion: The present retrospective study of rare disease patients diagnosed at a tertiary genetic test centre provides first insight into the distribution of rare genetic diseases across the country. This information will likely aid in drafting future health policies, including newborn screening programs, development of target specific panel for affordable diagnosis of rare diseases and eventually build a platform for devising novel treatment strategies for rare diseases., (© 2024. The Author(s).)

Background: The value of histologic assessment after ileal pouch-anal anastomosis (IPAA) has not been definitively determined. We evaluated the correlation between histology and endoscopic findings, as well as the proportion of patients with inflammation in areas beyond the pouch body on their initial pouchoscopy after IPAA., Methods: In a retrospective cohort study, we evaluated patients who underwent IPAA for UC between 2012 and 2020 and subsequently underwent a pouchoscopy with routine biopsies of the pouch body, pre-pouch ileum, and rectal cuff. We compared endoscopic and histologic assessments in each location using χ2 testing and Spearman correlation, as well as the development of pouchitis and Crohn's-like disease of the pouch (CLDP) in longitudinal follow-up., Results: Among 126 patients, the median time to pouchoscopy after IPAA was 384 days, with 82 patients (65%) having inflammation of the pouch body. Significantly more patients with pouch body inflammation had histologic inflammation compared with patients without pouch body inflammation (96% vs 22%, P < .001, r = 0.769). Additionally, 16 patients (13%) were found to have endoscopic inflammation of the pre-pouch ileum with corresponding histologic inflammation in 88%; of these, 31% later developed CLDP. In contrast, 13% of patients with no endoscopic inflammation displayed histologic inflammation, with none later developing CLDP. Forty-six percent of patients had rectal cuff inflammation (correlation with histologic inflammation r = 0.580)., Conclusions: In our evaluation, the added benefit of histology in the presence of visible endoscopic inflammation for disease activity assessment scores is unclear. The prognostic value of histologic inflammation without endoscopic inflammation warrants a longitudinal study., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Carbapenem-resistant Enterobacter cloacae complex (CRECC) constitutes a global public health threat challenging clinical treatment and infection control, especially in low- and middle-income countries such as India. We analyzed the antimicrobial susceptibility, major β-lactamase genes, plasmid profiles, and genetic relatedness to understand the molecular epidemiology of CRECC clinical isolates (n = 44) in West Bengal, India, during 2021-2022. The majority (> 55%) of the isolates were resistant to fluoroquinolones, aminoglycosides, and co-trimoxazole, even > 20% for tigecycline and > 35% were extensively drug-resistant. Co-β-lactamase production was categorized into twenty-seven types, importantly NDM (84%), OXA-48 (40%), TEM (61%), CTX-M (46%), OXA-1 (55%), and MIR (27%). The NDM-1 and OXA-181 were major variants with the first observations of NDM-24 and -29 variants in India. Wide-range of plasmids (2 to > 212 kb) were harbored by the β-lactamase-producing isolates: small (91%), medium (27%), large (9%), and mega (71%). IncX3, ColE1, and HI2 were noted in about 30% of isolates, while IncF and R were carried by < 20% of isolates. The clonally diverse CRECC isolates were noted to cause cross-infections, especially at superficial site, bloodstream, and urinary-tract. This is the first molecular surveillance on CRECC in India. The study isolates serve as the dockyard of NDM, TEM, and CTX-M harboring a wide range of plasmids. The outcomes of the study may strengthen local and national policies for infection prevention and control practices, clarifying the genetic diversity among CRECC. Extensive genomic study may further intersect the relationships between these different plasmids, especially with their sizes, types, and antibiotic resistance markers., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Patients who have sustained a profound brain injury often bite their lips and tongue, damaging their oral tissues. Lip and tongue biting usually occurs in patients with atypical oral reflexes and can lead to severe trauma to soft tissues, resulting in pain, lacerations, swelling, bleeding, ulceration and difficulties providing oral care. Due to the prevalence of lip and tongue biting, healthcare professionals involved in their care must be aware of the presentation, prevention and management, and when and how to refer to dental services., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Extremely preterm infants (EPIs) are at high-risk of white matter injury (WMI), leading to long-term neurodevelopmental impairments. We aimed to develop nomograms for WMI., Methods: The study included patients from 31 provinces, spanning ten years. 6074 patients before 2018 were randomly divided into a training and internal validation group (7:3). The external validation group comprised 1492 patients from 2019. Predictors were identified using the least absolute shrinkage and selection operator (LASSO) and multivariable logistic regression and nomograms were constructed. Models' performance was evaluated using receiver operating characteristic (ROC), decision curve analysis (DCA) and calibration curves., Results: The prenatal nomogram included multiple gestation, premature rupture of membranes (PROM), chorioamnionitis, prenatal glucocorticoids, hypertensive disorder complicating pregnancy (HDCP) and Apgar 1 min, with area under the curve (AUC) of 0.805, 0.816 and 0.799 in the training, internal validation and external validation group, respectively. Days of mechanical ventilation (MV), shock, patent ductus arteriosus (PDA) ligation, intraventricular hemorrhage (IVH) grade III-IV, septicemia, hypothermia and necrotizing enterocolitis (NEC) stage II-III were identified as postpartum predictors. The AUCs were 0.791, 0.813 and 0.823 in the three groups, respectively. DCA and calibration curves showed good clinical utility and consistency., Conclusion: The two nomograms provide clinicians with precise and efficient tools for prediction of WMI., Impact: This study is a large-sample multicenter study, spanning 10 years. The two nomograms are convenient for identifying high-risk infants early, allowing for reducing poor prognosis., (© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Land-use change is the main driver of carbon storage change in terrestrial ecosystems. Currently, domestic and international studies mainly focus on the impact of carbon storage changes on climate, while studies on the impact of land-use changes on carbon storage in complex terrestrial ecosystems are few. The Jialing River Basin (JRB), with a total area of ~ 160,000 km 2 , diverse topography, and elevation differences exceeding 5 km, is an ideal case for understanding the complex interactions between land-use change and carbon storage dynamics. Taking the JRB as our study area, we analyzed land-use changes from 2000 to 2020. Subsequently, we simulated land-use patterns for business-as-usual (BAU), cropland protection (CP), and ecological priority (EP) scenarios in 2035 using the PLUS model. Additionally, we assessed carbon storage using the InVEST model. This approach helps us to accurately understand the carbon change processes in regional complex terrestrial ecosystems and to formulate scientifically informed land-use policies. The results revealed the following: (1) Cropland was the most dominant land-use type (LUT) in the region, and it was the only LUT experiencing net reduction, with 92.22% of newly designated construction land originating from cropland. (2) In the JRB, total carbon storage steadily decreased after 2005, with significant spatial heterogeneity. This pattern was marked by higher carbon storage levels in the north and lower levels in the south, with a distinct demarcation line. The conversion of cropland to construction land is the main factor driving the reduction in carbon storage. (3) Compared with the BAU and EP scenarios, the CP scenario demonstrated a smaller reduction in cropland area, a smaller addition to construction land area, and a lower depletion in the JRB total carbon storage from 2020 to 2035. This study demonstrates the effectiveness of the PLUS and InVEST models in analyzing complex ecosystems and offers data support for quantitatively assessing regional ecosystem services. Strict adherence to the cropland replenishment task mandated by the Chinese government is crucial to increase cropland areas in the JRB and consequently enhance the carbon sequestration capacity of its ecosystem. Such efforts are vital for ensuring the food and ecological security of the JRB, particularly in the pursuit of the "dual-carbon" objective., (© 2024. The Author(s).)

Nucleic acid aptamers have captivated the attention of analytical and medicinal scientists globally due to their several advantages as recognition molecules over conventional antibodies because of their small size, simple and inexpensive synthesis, broad target range, and high stability in varied environmental conditions. These recognition molecules can be chemically modified to make them resistant to nuclease action in blood serum, reduce rapid renel clearance, improve the target affinity and selectivity, and make them amenable to chemically conjugate with a support system that facilitates their selective applications. This review focuses on the development of efficient aptamer candidates and their application in clinical diagnosis and therapeutic applications. Significant advances have been made in aptamer-based diagnosis of infectious and non-infectious diseases. Collaterally, the progress made in therapeutic applications of aptamers is encouraging, as evident from their use in diagnosing cancer, neurodegenerative diseases, microbial infection, and in imaging. This review also updates the progress on clinical trials of many aptamer-based products of commercial interests. The key development and critical issues on the subject have been summarized in the concluding remarks., Competing Interests: Declaration of competing interest Authors have no conflict of interest to declare., (Copyright © 2023. Published by Elsevier B.V.)

Millet products have garnered global recognition for their exceptional nutritional profile, appealing to various age demographics, and, therefore, fortifying such products with minerals can ensure nutritional security. This research explores the feasibility of utilizing millet as a substitute for refined wheat flour in biscuit production. Three distinct millet varieties were investigated: finger, pearl, and buckwheat. Employing response surface methodology (RSM), the optimal ratio of these flours was determined, resulting in a blend of 1.5:1:1, respectively. The optimized multi-millet biscuits were further enhanced with calcium fortification and subjected to comprehensive physico-chemical analysis. Proximate composition analysis revealed favorable levels of protein (5.472 ± 0.31%), ash (2.80 ± 0.57 g/100 g), and energy density (5.8015 ± 0.004 kcal/g), indicating a significantly higher protein content, enriched mineral profile, and high energy density as compared to refined wheat flour products. Sensory evaluation encompassing attributes such as color and texture and organoleptic assessment using a nine-point hedonic scale demonstrated favorable acceptance. Additionally, the overall acceptability of the biscuits remained consistently high throughout storage, ranging from 8.263 ± 0.65 (day 0) to 8.053 ± 0.85 (day 14). This study underscores the potential of multi-millet biscuits as a nutritious and palatable alternative to traditional wheat-based snacks, offering an avenue for diversifying dietary options and promoting healthier food choices.

Objective: To present the comprehensive methodology for generating personalized three-dimensional (3D) printed uterine models from 3D ultrasound (US) volumes in individuals diagnosed with Müllerian anomalies and discuss potential applications in the field of reproductive endocrinology and infertility., Design: Pilot study., Setting: Single large university-affiliated teaching hospital., Patients: Patients with the presence of a Müllerian anomaly between the ages of 18 and 45 years attending the maternal-fetal medicine as well as reproductive endocrinology and infertility outpatient offices from 2018 to 2023 were included in the study., Interventions: Subjects underwent 3D US transvaginal scanning for the collection of data. The 3D US volumes were acquired, edited, and exported from a US cart Voluson E10 system (GE Healthcare, Chicago, IL). High-definition virtual models were created and modified, making them suitable for printing using Materialise 3-Matic Medical (Materialise NV, Leuven, Belgium). The models were printed on a J5 MediJet 3D printer (Stratasys, Rehovot, Israel). Colors were set to mimic a realistic appearance, and shore values were set before printing., Main Outcome Measures: Successful creation and utilization of personalized 3D-printed uterine models for individuals with Müllerian anomalies., Resultss: Three-dimensional models were created for a uterus without anomalies, 2 variations of a partial septum, a unicornuate, and a didelphys uterus. Models were used as a tactile and customized tool for patient education, counseling, and medical student and resident teaching. This technique illustrates that the creation of personalized 3D-printed uterine models for utilization in the fields of reproductive endocrinology and infertility is feasible., Conclusions: We propose a novel use of individualized 3D-printed uterine models in the evaluation of individuals with Müllerian anomalies. These models may play a complementary role to standard imaging options in the assessment of these anomalies, with a special potential for application in highly complex or yet-to-be-determined types of anomalies., Competing Interests: J.G.d.P. has nothing to disclose. J.G. has nothing to disclose. M.T. has nothing to disclose. M.C. has nothing to disclose., (© 2024 The Authors.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into numerous lineages with unique spike mutations and caused multiple epidemics domestically and globally. Although COVID-19 vaccines are available, new variants with the capacity for immune evasion continue to emerge. To understand and characterize the evolution of circulating SARS-CoV-2 variants in the U.S., the Centers for Disease Control and Prevention (CDC) initiated the National SARS-CoV-2 Strain Surveillance (NS3) program and has received thousands of SARS-CoV-2 clinical specimens from across the nation as part of a genotype to phenotype characterization process. Focus reduction neutralization with various antisera was used to antigenically characterize 143 SARS-CoV-2 Delta, Mu and Omicron subvariants from selected clinical specimens received between May 2021 and February 2023, representing a total of 59 unique spike protein sequences. BA.4/5 subvariants BU.1, BQ.1.1, CR.1.1, CQ.2 and BA.4/5 + D420N + K444T; BA.2.75 subvariants BM.4.1.1, BA.2.75.2, CV.1; and recombinant Omicron variants XBF, XBB.1, XBB.1.5 showed the greatest escape from neutralizing antibodies when analyzed against post third-dose original monovalent vaccinee sera. Post fourth-dose bivalent vaccinee sera provided better protection against those subvariants, but substantial reductions in neutralization titers were still observed, especially among BA.4/5 subvariants with both an N-terminal domain (NTD) deletion and receptor binding domain (RBD) substitutions K444M + N460K and recombinant Omicron variants. This analysis demonstrated a framework for long-term systematic genotype to antigenic characterization of circulating and emerging SARS-CoV-2 variants in the U.S., which is critical to assessing their potential impact on the effectiveness of current vaccines and antigen recommendations for future updates.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy characterized by an immunosuppressive tumor microenvironment enriched with cancer-associated fibroblasts (CAF). This study used a convergence approach to identify tumor cell and CAF interactions through the integration of single-cell data from human tumors with human organoid coculture experiments. Analysis of a comprehensive atlas of PDAC single-cell RNA sequencing data indicated that CAF density is associated with increased inflammation and epithelial-mesenchymal transition (EMT) in epithelial cells. Transfer learning using transcriptional data from patient-derived organoid and CAF cocultures provided in silico validation of CAF induction of inflammatory and EMT epithelial cell states. Further experimental validation in cocultures demonstrated integrin beta 1 (ITGB1) and vascular endothelial factor A (VEGFA) interactions with neuropilin-1 mediating CAF-epithelial cell cross-talk. Together, this study introduces transfer learning from human single-cell data to organoid coculture analyses for experimental validation of discoveries of cell-cell cross-talk and identifies fibroblast-mediated regulation of EMT and inflammation., Significance: Adaptation of transfer learning to relate human single-cell RNA sequencing data to organoid-CAF cocultures facilitates discovery of human pancreatic cancer intercellular interactions and uncovers cross-talk between CAFs and tumor cells through VEGFA and ITGB1., (©2024 American Association for Cancer Research.)

Terrestrial planets and their moons have impact craters, contributing significantly to the complex geomorphology of planetary bodies in our Solar System. Traditional crater identification methods struggle with accuracy because of the diverse forms, locations, and sizes of the craters. Our main aim is to locate lunar craters using images from Terrain Mapping Camera-2 (TMC-2) onboard the Chandrayaan-II satellite. The crater-based U-Net model, a convolutional neural network frequently used in image segmentation tasks, is a deep learning method presented in this study. The task of crater detection was accomplished with the proposed model in two steps: initially, it was trained using Resnet18 as the backbone and U-Net based on Image Net as weights. Secondly, TMC-2 images from Chandrayaan-2 were used to detect craters based on the trained model. The model proposed in this study comprises a neural network, feature extractor, and optimization technique for lunar crater detection. The model achieves 80.95% accuracy using unannotated data and precision and recall are much better with annotated data with an accuracy of 86.91% in object detection with TMC-2 ortho images. 2000 images have been considered for the present work as manual annotation is a time-consuming process and the inclusion of more images can enhance the performance score of the model proposed., (© 2024. The Author(s).)

Background: Students from Bangladesh pursuing STEM education often encounter obstacles when tackling diverse mathematical problems within various educational settings. Frequently, they find themselves lacking the essential prerequisite knowledge and strong foundational skills necessary to engage with the teaching and learning resources utilized at the undergraduate level, resulting in a significant number of students needing to seek readmission annually., Objective: The objective of this study is to explore the determinants of academic achievement among university undergraduates majoring in mathematics in Bangladesh. Employing a mixed-method research approach, the study combines quantitative and qualitative data analysis to examine the viewpoints of both students and educators concerning these factors. The authors primarily emphasize classifying the factors that impact the efficacy of mathematics pedagogical methods., Methodology: The study is structured into three phases: i. An initial exploratory qualitative survey. ii. A quantitative triangulation survey. iii. Followed by explanatory semi-structured interviews., Findings: To begin, the initial qualitative survey identified significant factors that contribute to students' achievements and setbacks in mathematics. Subsequently, the quantitative analysis verified both similarities and distinctions in the perspectives of students and educators. Furthermore, the correlation coefficient analysis revealed that male students frequently exhibit inconsistency and a lack of enthusiasm for studying, resulting in subpar performance. Conversely, female students frequently cited challenges like the difficulty of connecting mathematical theories to real-world applications, heavy course loads, and limited resources as reasons for their academic difficulties. Lastly, insights from interviews with students highlighted their acknowledgment of inadequate study practices, excessive reliance on memorization, suboptimal teaching methods, low motivation, and external distractions as key factors leading to their struggles. They also recognized the importance of consistent practice, a solid comprehension of concepts, regular study routines, and effective learning strategies for successful mathematics education. In contrast, educators emphasized the significance of students having clear concepts, natural aptitude, motivation, and a sense of curiosity as pivotal elements for successful learning in mathematics., Conclusion: This conclusion suggests a new beginning in the realm of local mathematics pedagogy, achieved by scrutinizing teacher-student feedback about the factors influencing success and failure, considering the diverse individual and contextual variables at play. To foster mutual trust and understanding between students and teachers, it may be beneficial to engage in open discussions and interactions., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:The corresponding author, Goutam Saha, is an advisory board member of the journal Heliyon and declares no conflicts of interest. Other authors also declare no conflicts of interest. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: The Heartmate 3 (HM3) risk score (HM3RS) was derived and validated internally from within the Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy with HeartMate 3 (MOMENTUM 3) trial population and provides 1- and 2-year mortality risk prediction for patients in those before HM3 left ventricular assist device (LVAD) implantation. We aimed to evaluate the HM3RS in nontrial unselected patients, including those not meeting inclusion criteria for MOMENTUM 3 trial enrollment., Methods: Patients who underwent HM3 LVAD implant at 1 of 7 US centers between 2017 and 2021, with at least 1-year follow-up, were included in this analysis. Patients were retrospectively assessed for their eligibility for the MOMENTUM 3 trial based on study inclusion and exclusion criteria. HM3RS risk discrimination was evaluated using time-dependent receiver operating characteristic curve analysis for 1-year mortality for all patients and further stratified by MOMENTUM 3 trial eligibility. Kaplan-Meier curves were constructed using the HM3RS-based risk categories., Results: Of 521 patients included in the analysis, 266 (51.1%) would have met enrollment criteria for MOMENTUM 3. The 1- and 2-year survival for the total cohort was 85% and 81%, respectively. There was no statistically significant difference in survival between those who met and did not meet enrollment criteria at 1 (87% vs 83%; p = 0.21) and 2 years postimplant (80% vs 78%; p = 0.39). For the total cohort, HM3RS predicted 1-year survival with an area under the curve (AUC) of 0.63 (95% confidence interval [CI]: 0.57-0.69, p < 0.001). HM3RS performed better in the subset of patients meeting enrollment criteria: AUC 0.69 (95% CI:0.61-0.77, p < 0.001) compared to the subset that did not: AUC 0.58 (95% CI: 0.49-0.66, p = 0.078)., Conclusions: In this real-world evidence, multicenter cohort, 1- and 2-year survival after commercial HM3 LVAD implant was excellent, regardless of trial eligibility. The HM3RS provided adequate risk discrimination in "trial-like" patients, but predictive value was reduced in patients who did not meet trial criteria., (Copyright © 2023 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Consumer behavior research and neurology are combined in the emerging discipline of neuromarketing. Neuromarketing is considered to be one of emerging field to study how consumer's brain reacts to advertisement and other brand's message by observing brainwave, eye, and skin response. The current study examined the emerging field of constructs of neuromarketing like social, attention, technology, and emotions to examine Indian consumer's buying behavior., Purpose: To study the validity and reliability of constructs of neuromarketing that examines consumer's buying behavior among Indian consumers., Methods: A sample of 191 people of different age groups was considered in the study. A random sampling technique was used for data collection. The self-designed questionnaire used for the measurement of neuromarketing constructs and consumers' buying behavior. The current study applied SPSS and AMOS software to validate the measurement model of neuromarketing., Results: The Kaiser-Meyer-Olkin (KMO) and Bartlett's Test's value is 0.784 and this value confirmed that the sample is adequate for factor analysis. Apart from that, the five constructs of neuromarketing - Attention (A), Social (SC), Technological (T), Emotion (E), and Consumer Buying Behavior (BB) had shown the value of Cronbach's alpha to be more than 0.7. Confirmatory Factor Analysis (CFA) had shown value of average variance explained of each constructs 0.5 and composite reliability more than 0.7 which indicates excellent construct validity of constructs for model formation of neuromarketing. The study also validates measurement research model of neuromarketing on the basis of model fit index (chi-square/df = 3.397, RMSEA = 0.10, GFI = 0.92, and CFI = 0.87)., Conclusion: The present study had shown good validity and reliability of constructs of neuromarketing and also proved that marketers can apply these constructs to examine behavior pattern of consumers., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article, (© The Author(s) 2023.)

Evaluating the effects of China's carbon emission trading scheme (ETS) is crucial for the coordinated development of Chinese cities. Therefore, based on the panel data of 242 cities in China from 2008 to 2019, this paper uses the multi-period difference-in-difference (DID) model to comprehensively evaluate the impact of carbon market on the coordinated development of cities from the perspectives of carbon market policy and carbon market efficiency, and then analyzes the mechanism and heterogeneity of the effect of carbon market efficiency. The results show that both carbon market policy and carbon market efficiency can promote the coordinated development of cities. Science and education expenditure plays a significant intermediary role in the impact of carbon market efficiency on the coordinated development of cities. The heterogeneity test finds that the stricter the performance penalty system, the higher the level of urban coordinated development, and the stronger the effect of carbon market efficiency. The findings of this paper provide policy recommendations for further improving the construction of China's pilot and national ETS and enhancing the coordinated development of Chinese cities., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Recycling spent Li-ion batteries (LIBs) is paramount to pursuing resource efficiency and environmental sustainability. This study introduces a synergistic approach for selectively leaching and separating strategic metals from waste LIBs, representing a more efficient alternative to traditional single-acid-based leaching methods. The research also thoroughly analyzes diverse extraction parameters, aiming to achieve clean metal separation through synergistic concepts rather than single-phase extraction. The outcome of this study is developing a comprehensive downstream process, advancing the cause of sustainable waste management in the LIB industry. Under specific conditions with 0.6 mol/L total acid content (0.5 mol/L tartaric acid + 0.1 mol/L ascorbic acid), 99.9% cobalt and 100% lithium were effectively leached. The subsequent extraction process achieved a clean separation, with 48.3% of cobalt extracted using a mixture of 0.1 mol/L Alamine-336-Cyanex-272 (A-336-Cy-272) from the leach liquor with no coextraction of lithium, and this efficiency was improved to 67.3% by adjusting the pH from 2.44 to 7.5. However, it is worth noting that increasing the extractant concentration led to an antagonistic effect. To further enhance cobalt enrichment in the organic phase, the McCabe-Thiele plot method was recommended, employing saponified Cy-272. Moreover, the regeneration of saponified Cy-272 was investigated, and the stripped solution was processed with NaOH to form Co(OH) 2 , subsequently converting it into cobalt oxide (Co 3 O 4 ) through calcination., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Cardiovascular diseases exert a significant burden on the healthcare system worldwide. This narrative literature review discusses the role of artificial intelligence (AI) in the field of cardiology. AI has the potential to assist healthcare professionals in several ways, such as diagnosing pathologies, guiding treatments, and monitoring patients, which can lead to improved patient outcomes and a more efficient healthcare system. Moreover, clinical decision support systems in cardiology have improved significantly over the past decade. The addition of AI to these clinical decision support systems can improve patient outcomes by processing large amounts of data, identifying subtle associations, and providing a timely, evidence-based recommendation to healthcare professionals. Lastly, the application of AI allows for personalized care by utilizing predictive models and generating patient-specific treatment plans. However, there are several challenges associated with the use of AI in healthcare. The application of AI in healthcare comes with significant cost and ethical considerations. Despite these challenges, AI will be an integral part of healthcare delivery in the near future, leading to personalized patient care, improved physician efficiency, and anticipated better outcomes.

Background: Homemakers are the backbones of families, but in rural India, females suffer from many musculoskeletal problems due to excessive workload in their houses. The objective of the present study is to compare body composition parameters as predictors of low back pain (LBP) in nonworking rural homemakers of North India., Materials and Methods: The study was conducted among 296 homemakers from rural areas of Lucknow district in Uttar Pradesh. Details of LBP and body composition parameters (body mass index, body fat, visceral fat) were taken., Results: The prevalence of LBP among homemakers was found to be 15.54%. BMI was found to be a better predictor of LBP than body fat and visceral fat. The risk of LBP is 7.24 times higher in BMI ≥23 than in women with BMI <23. The risk of LBP is 3.67 times more in visceral fat % ≥10% than in women with visceral fat % <10%., Conclusion: Age, type of family, socioeconomic status income was identified as risk factors in this population. Maintaining an adequate BMI is essential for the prevention of LBP., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Family Medicine and Primary Care.)

Background: DNA sequencing could become an alternative to in vitro antibiotic susceptibility testing (AST) methods for determining antibiotic resistance by detecting genetic determinants associated with decreased antibiotic susceptibility. Here, we aimed to assess and improve the accuracy of antibiotic resistance determination from Enterococcus faecium genomes for diagnosis and surveillance purposes., Methods: In this retrospective diagnostic accuracy study, we first conducted a literature search in PubMed on Jan 14, 2021, to compile a catalogue of genes and mutations predictive of antibiotic resistance in E faecium. We then evaluated the diagnostic accuracy of this database to determine susceptibility to 12 different, clinically relevant antibiotics using a diverse population of 4382 E faecium isolates with available whole-genome sequences and in vitro culture-based AST phenotypes. Isolates were obtained from various sources in 11 countries worldwide between 2000 and 2018. We included isolates tested with broth microdilution, Vitek 2, and disc diffusion, and antibiotics with at least 50 susceptible and 50 resistant isolates. Phenotypic resistance was derived from raw minimum inhibitory concentrations and measured inhibition diameters, and harmonised primarily using the breakpoints set by the European Committee on Antimicrobial Susceptibility Testing. A bioinformatics pipeline was developed to process raw sequencing reads, identify antibiotic resistance genetic determinants, and report genotypic resistance. We used our curated database, as well as ResFinder, AMRFinderPlus, and LRE-Finder, to assess the accuracy of genotypic predictions against phenotypic resistance., Findings: We curated a catalogue of 228 genetic markers involved in resistance to 12 antibiotics in E faecium. Very accurate genotypic predictions were obtained for ampicillin (sensitivity 99·7% [95% CI 99·5-99·9] and specificity 97·9% [95·8-99·0]), ciprofloxacin (98·0% [96·4-98·9] and 98·8% [95·9-99·7]), vancomycin (98·8% [98·3-99·2] and 98·8% [98·0-99·3]), and linezolid resistance (after re-testing false negatives: 100·0% [90·8-100·0] and 98·3% [97·8-98·7]). High sensitivity was obtained for tetracycline (99·5% [99·1-99·7]), teicoplanin (98·9% [98·4-99·3]), and high-level resistance to aminoglycosides (97·7% [96·6-98·4] for streptomycin and 96·8% [95·8-97·5] for gentamicin), although at lower specificity (60-90%). Sensitivity was expectedly low for daptomycin (73·6% [65·1-80·6]) and tigecycline (38·3% [27·1-51·0]), for which the genetic basis of resistance is not fully characterised. Compared with other antibiotic resistance databases and bioinformatic tools, our curated database was similarly accurate at detecting resistance to ciprofloxacin and linezolid and high-level resistance to streptomycin and gentamicin, but had better sensitivity for detecting resistance to ampicillin, tigecycline, daptomycin, and quinupristin-dalfopristin, and better specificity for ampicillin, vancomycin, teicoplanin, and tetracycline resistance. In a validation dataset of 382 isolates, similar or improved diagnostic accuracies were also achieved., Interpretation: To our knowledge, this work represents the largest published evaluation to date of the accuracy of antibiotic susceptibility predictions from E faecium genomes. The results and resources will facilitate the adoption of whole-genome sequencing as a tool for the diagnosis and surveillance of antimicrobial resistance in E faecium. A complete characterisation of the genetic basis of resistance to last-line antibiotics, and the mechanisms mediating antibiotic resistance silencing, are needed to close the remaining sensitivity and specificity gaps in genotypic predictions., Funding: Wellcome Trust, UK Department of Health, British Society for Antimicrobial Chemotherapy, Academy of Medical Sciences and the Health Foundation, Medical Research Council Newton Fund, Vietnamese Ministry of Science and Technology, and European Society of Clinical Microbiology and Infectious Disease., Competing Interests: Declaration of interests SJP and JP are consultants to Next Gen Diagnostics. SJP is also a consultant for Specific Technologies. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Cell and gene therapy is a fast-growing field for cancer therapeutics requiring reliable instrumentation and technologies. Key parameters essential for satisfying Chemistry Manufacturing and Controls criteria standards are routinely performed using flow cytometry. Recently, image cytometry was developed for cell characterization and cell-based assays but had not yet demonstrated sufficient sensitivity for surface marker detection. We developed the Cellaca® PLX image cytometry system and the respective methodologies required for immunophenotyping, GFP and RFP transfection/transduction efficiencies, and cell health analyses for routine cell characterization. All samples tested were compared directly to results from the CytoFLEX flow cytometer. PBMCs were stained with T-cell surface markers for immunophenotyping, and results show highly comparable CD3, CD4, and CD8 populations (within 5 %). GFP- or RFP-expressing cell lines were analyzed for transfection/transduction efficiencies, and the percentage positive cells and respective viabilities were equivalent on both systems. Staurosporine-treated Jurkat cells were stained for apoptotic markers, where annexin V and caspase-3 positive cells were within 5 % comparing both instruments. The proposed system may provide a complementary tool for performing routine cell-based experiments with improved efficiency and sensitivity compared to prior image cytometers, which may be significantly valuable to the cell and gene therapy field., Competing Interests: Declaration of competing interest All authors in this work declare competing financial interests. The novel image cytometry system and methods demonstrated in this manuscript were developed using the high-throughput image cytometer and fluorescent staining kits from Revvity Health Sciences, Inc., an indirect parent company of Nexcelom Biosciences, LLC., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The construction of versatile functional hydrogel interfaces holds promising prospects in biosensing and bioengineering. Herein, we introduced a light-induced protein conjugation strategy for on-demand surface modification of hydrogel interface based on the photoclick cyclization between primary amine and o-nitrobenzyl alcohol. We achieved the on-demand protein conjugation by grafting the molecular plugin, 4-(hydroxymethyl)-3-nitrobenzoic acid (HNBA), onto the hydrogel surface, followed by the mask-aided photoclick reaction with the protein of interest. This method enables the creation of protein patterns on hydrogel interface with a lower limit of pattern width at ∼70 μm. With this method, we demonstrated the surface engineering of epidermal growth factor (EGF) on hydrogel interface for selective capture of EGF receptor-positive cancer cells with an efficiency over 80%. Moreover, we applied the mask-aided photoclick conjugation method for antigen capture and developed a photoclickable hydrogel interface-based dot blotting assay. Due to the high-efficient antigen capture of photoclick conjugation, the photoclickable hydrogel interface-based dot blotting assay shows improved sensitivity for antigen detection with a limit of detection as 0.065 ng. We believed that this light-induced protein conjugation method holds the potential as a robust strategy for the construction of bioactive hydrogel interfaces for various bio-related applications., 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 © 2023 Elsevier B.V. All rights reserved.)

Introduction Denture loss prevalence in community settings is unknown and results in deteriorating residents' systemic and psychosocial wellbeing.Materials and methods An electronic survey was distributed nationally through professional networks to community residential settings.Results Of the 156 responses from community residential settings, 69% of settings experienced at least one denture lost in the last two years. Sixty percent of responders reported no dentures were labelled, only 64% had received training about how to care for dentures and 86% felt they would benefit from further training on mouth care. In addition, 68% of staff found arranging dental care for their residents challenging.Discussion Extrapolated data suggest that at least 10,205 dentures are lost annually in community residential settings and are never found, costing the NHS Business Service Authority more than £3 million. A high prevalence of denture loss in community residential settings is likely due to residents with multiple comorbidities and frailty. Remaking dentures poses financial, logistical, and patient challenges, which may result in patients being unable to wear a remade denture.Conclusion The prevalence of denture loss within community residential settings needs to be understood to encourage targeted interventions, inform stakeholders, and encourage workflows that will improve service delivery and patients' oral health-related quality of life., (© 2024. The Author(s), under exclusive licence to the British Dental Association.)

Importance: The COVID-19 pandemic was accompanied by an unprecedented surveillance effort. The resulting data were and will continue to be critical for surveillance and control of SARS-CoV-2. However, some genomic surveillance methods experienced challenges as the virus evolved, resulting in incomplete and poor quality data. Complete and quality coverage, especially of the S-gene, is important for supporting the selection of vaccine candidates. As such, we developed a robust method to target the S-gene for amplification and sequencing. By focusing on the S-gene and imposing strict coverage and quality metrics, we hope to increase the quality of surveillance data for this continually evolving gene. Our technique is currently being deployed globally to partner laboratories, and public health representatives from 79 countries have received hands-on training and support. Expanding access to quality surveillance methods will undoubtedly lead to earlier detection of novel variants and better inform vaccine strain selection., Competing Interests: The authors declare no conflict of interest.

Introduction: Metastatic cancer presents a treatment challenge to clinicians, particularly for patients with bone marrow infiltration. For tumor staging, therapy selection, and prognosis risk stratification, the status of the bone marrow should be known for the presence or absence of metastasis. The study aimed to evaluate the hematological findings and comprehensive analysis of bone marrow in cases of nonhematological malignancies with bone marrow metastasis., Materials and Methods: This retrospective study comprised a record retrieval of the departmental archives for the past 6 years. A total of 331 patients with nonhematological malignancies were found, of whom 31.42% (104/331) showed bone marrow metastasis. An integrated clinical approach with bone marrow examination findings and immunohistochemistry whenever necessary was used to achieve a definitive diagnosis of bone marrow metastasis., Results: Among the study population, 31.42% (104/331) of patients had nonhematological malignancies that metastasized to the bone marrow. Most of the patients with bone marrow metastasis had anemia, which was found in 77.88% (81/104) of the cases. Leukoerythroblastic reaction was noted in 31.73% (33/104) of the cases, and thrombocytopenia was found in 25% (26/104) of the cases. The most common malignancy with bone marrow metastasis in adults was prostatic adenocarcinoma (28.1%) (9/32) and in pediatric cases, neuroblastoma (53.9%) (52/98)., Conclusions: It is essential to diagnose nonhematological malignancies that have metastasized to the bone marrow since this necessitates tumor staging, therapy selection, and prognosis risk stratification. To conclude, not a single hematological parameter is predictive of bone marrow metastasis; however, unexplained anemia, a leukoerythroblastic blood picture, and thrombocytopenia in peripheral blood should raise suspicion for bone marrow metastasis in cases of nonhematological malignancies., Competing Interests: None

Older adults often experience poorer levels of oral health than younger adults, especially if they have become dependent on a third party to support their daily oral care routine. However, the deterioration of oral health does not need to be a part of the ageing process. Most oral diseases are largely preventable with the daily removal of dental plaque that forms on teeth and dentures, using a fluoride toothpaste, eating a healthy diet and reducing any tobacco consumption. The dental team have a duty of care to ensure that older people receive evidence-based oral health preventative advice tailored to the individual, taking into account individual risk factors that can increase with age. This can include the clinical application of topical fluoride and minimally invasive dentistry. Older people at an increased risk of poor oral health include those with cognitive conditions, physical impairments and certain medical conditions. Care home residents face particular barriers to attaining a satisfactory standard of oral care which are discussed herein. Good oral health preventative routines must be established early after the diagnosis of progressive chronic conditions and will help to prevent the need for dental intervention later in life when treatment can be more difficult to tolerate. Inclusion of oral health prevention within health policy and legislation is necessary to improve the oral health for older people living in all health and care settings., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG 2022. Republished.)

Older adults often experience poorer levels of oral health than younger adults, especially if they have become dependent on a third party to support their daily oral care routine. However, the deterioration of oral health does not need to be a part of the ageing process. Most oral diseases are largely preventable with the daily removal of dental plaque that forms on teeth and dentures, using a fluoride toothpaste, eating a healthy diet and reducing any tobacco consumption. The dental team have a duty of care to ensure that older people receive evidence-based oral health preventative advice tailored to the individual, taking into account individual risk factors that can increase with age. This can include the clinical application of topical fluoride and minimally invasive dentistry. Older people at an increased risk of poor oral health include those with cognitive conditions, physical impairments and certain medical conditions. Care home residents face particular barriers to attaining a satisfactory standard of oral care which are discussed herein. Good oral health preventative routines must be established early after the diagnosis of progressive chronic conditions and will help to prevent the need for dental intervention later in life when treatment can be more difficult to tolerate. Inclusion of oral health prevention within health policy and legislation is necessary to improve the oral health for older people living in all health and care settings., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG 2022. Republished.)