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Cold temperature storage (lower than 10 °C) has been used as a management strategy to extend marketability and reduce potato storage losses. However, cold temperatures may result in dark-colored chips through a process known as cold-induced sweetening (CIS). ‘Dakota Crisp’ and ‘Dakota Diamond’ are two North Dakota State University potato breeding program cultivar releases selected for cold-chipping ability with high tuber yield potential. Two-year storage trials were conducted to examine sugar development and tuber processing quality of four cultivars grown at three nitrogen rates under irrigated and non-irrigated field conditions. The two-way interaction between storage period and storage temperature was significant for sucrose content, glucose content, visual chip color, and Agtron values, indicating a difference in sugar development for each storage temperature profile. Among the four cultivars evaluated under both irrigated and non-irrigated production conditions, ‘Dakota Pearl’ accumulated significantly less sucrose and glucose compared to other cultivars under the same storage conditions. ‘Dakota Crisp’ produced acceptable chip color from 8.9 °C after long term storage, while ‘Dakota Diamond’ produced acceptable chip color from 8.9 °C for up to 6 months of storage. These results emphasize the importance of developing cultivar-specific management profiles including storage and the informational need for producers and processors in determining the best practices for individual cultivars.

The present study aims to prepare and evaluate solid lipid nanoparticles (SLNs) loaded with irinotecan (IRN) drug and daidzein (DZN) isoflavonoid and surface coated with ligand materials such as hyaluronic acid (HA) and bovine serum albumin (BSA) with additional coating of chitosan for active targeting to receptors present on colon surface epithelium for oral targeted delivery. The optimized batch was evaluated for particle size, zeta potential exhibiting nanometric size with good entrapment efficiency. Nanoparticles were found to be spherical. FTIR and DSC revealed that all the excipients and formulation were compatabile to each other and showed better encapsulation exhibiting amorphous and crystallinity forms. In vitro drug release of SLNs confirmed that initially a burst release, followed by sustained release pattern was exhibited. Cell lines studied performed on HT-29 cells showed demonstrated that conjugated SLNs inhibited cytotoxicity at 75 μg/ml, indicating that cells were taken up through a receptor-mediated endocytosis process. Cell cycle analysis showed that cell arrest was done at 67.8 % (G0/G1 phase) and inhibited apoptosis by 56 %. Further during In vivo studies, RT-PCR study revealed downregulation of Carcinoembryonic antigen (CEA), a non-specific serum biomarker overexpressed in tumor cells and upregulation of pro-inflammatory cytokine TNF-α. Histopathological study revealed that conjugated (HA-BSA) coated with chitosan SLNs restored normal mucosa and colon architecture, depicting all mucosal layers. Hence, these conjugated SLNs may serve as a novel combination for the treatment of colon cancer., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: The present study aimed to objectively assess the charge integration efficiency (CIE) of the auditory nerve using electrically-evoked stapedial reflex threshold (eSRT) measurements in paediatric cochlear implant users., Design: The eSRT was estimated in two ways: by keeping pulse width constant while increasing pulse amplitude and vice versa. The electrical dynamic range (EDR) obtained for eSRT was measured with increasing pulse amplitude (EDR PA ) and pulse width (EDR PW ) by calculating the difference in charge units between eSRT and behavioural thresholds; further, CIE was estimated., Study Sample: Fifteen paediatric cochlear implant users., Results: EDR PW was 1.4 to 1.7 times larger than EDR PA . The EDR PW was significantly greater than the EDR PA . A significant correlation was observed between both EDR measures. However, the CIE measure did not significantly correlate with the behavioural threshold. Further, there was no significant effect of electrode location on the CIE., Conclusions: The CIE estimated with objective measures such as eSRT is comparable to those estimated using behavioural loudness judgments. eSRT can serve as a quick method to estimate the CIE, which can be easily implemented in the paediatric population. The CIE could be a valuable tool for differentiating electrodes with excellent and poor charge integration efficiency.

Cold temperature storage (lower than 10 °C) has been used as a management strategy to extend marketability and reduce potato storage losses. However, cold temperatures may result in dark-colored chips through a process known as cold-induced sweetening (CIS). 'Dakota Crisp' and 'Dakota Diamond' are two North Dakota State University potato breeding program cultivar releases selected for cold-chipping ability with high tuber yield potential. Two-year storage trials were conducted to examine sugar development and tuber processing quality of four cultivars grown at three nitrogen rates under irrigated and non-irrigated field conditions. The two-way interaction between storage period and storage temperature was significant for sucrose content, glucose content, visual chip color, and Agtron values, indicating a difference in sugar development for each storage temperature profile. Among the four cultivars evaluated under both irrigated and non-irrigated production conditions, 'Dakota Pearl' accumulated significantly less sucrose and glucose compared to other cultivars under the same storage conditions. 'Dakota Crisp' produced acceptable chip color from 8.9 °C after long term storage, while 'Dakota Diamond' produced acceptable chip color from 8.9 °C for up to 6 months of storage. These results emphasize the importance of developing cultivar-specific management profiles including storage and the informational need for producers and processors in determining the best practices for individual cultivars.

Neonatal intensive care unit resuscitative care continually evolves and increasingly relies on data. Data driven precision resuscitation care can be enabled by leveraging informatics tools and artificial intelligence. Despite technological advancements, these data are often underutilized due to suboptimal data capture, aggregation, and low adoption of artificial intelligence and analytic tools. This review describes the fundamentals and explores the evidence behind informatics and artificial intelligence tools supporting neonatal intensive care unit resuscitative care, training and education. Key findings include the need for effective interface design for accurate data capture followed by storage and translation to wisdom using analytics and artificial intelligence tools. This review addresses the issues of data privacy, bias, liability and ethical frameworks when adopting these tools. While these emerging technologies hold great promise to improve resuscitation, further study of these applications in neonatal population and awareness of informatics and artificial intelligence principles among clinicians is imperative., (Copyright © 2024. Published by Elsevier Inc.)

Parkinson's disease (PD) is a progressive neurodegenerative disorder with limited symptomatic treatment options. Targeting phosphodiesterase 4 (PDE4) has shown a promising result in several preclinical studies. In our study, we aim to repurpose US FDA-approved PDE4 inhibitor for PD. Through in-silico study, we identified roflumilast (ROF) as the potential candidate targeting PDE4B2. In Drosophila PD expressing the A30P mutant α-synuclein model, ROF exhibited anti-PD effects as indicated by negative geotaxis and antioxidant activities. Given the low brain distribution of ROF (<50%) at clinical doses, incorporation into nanostructured lipid carriers (NLCs) was carried out to enhanced blood-brain barrier permeability. In vitro release studies indicated sustained ROF release from NLCs (≈75%) over 24 h. Single-dose oral toxicity studies reported no mortality or toxicity signs. ROF-loaded NLCs significantly alleviated behavioural deficits, increased antioxidant parameters ( p  < 0.05), and reduced TNF-α and IL-6 levels ( p  < 0.5) in the striatum compared to pure ROF. ROF-loaded NLCs demonstrated potential anti-PD effects with high efficacy than pure ROF. Our study suggests that nanostructured lipid carriers (NLCs) can be a promising drug delivery system to overcome limitations associated with poor brain bioavailability of lipophilic drugs like ROF for PD treatment. Further investigation related to brain occupancy and underlying mechanisms of our formulation is warranted to confirm and strengthen our current findings.

Background and Objectives: Constipation affects health-related quality of life and increases hospital visits. We conducted this prospective cohort study to assess laxative use, health outcomes of constipation in medically hospitalized patients, and related health outcomes. Materials and Methods: A prospective single-center study included all adult patients admitted under the General Internal Medicine Unit from 1 February 2022, to 31 August 2022. Constipation was defined using the Constipation Assessment Scale (CAS). Patients were assessed for 28 days during their hospital stay and up to 90 days post-discharge. Result: Among the included patients, 62.45% experienced constipation, which was associated with poor health outcomes including delirium ( p = 0.048), intensive care admission ( p < 0.01), cardiopulmonary arrest ( p < 0.01), inpatient mortality ( p < 0.01), longer hospital stay ( p < 0.01), 90-day mortality ( p < 0.01), and 90-day hospital readmission ( p < 0.01). Laxative treatment was administered to only 33.93% of patients with constipation and was more commonly used among older patients ( p < 0.01), those with high CAS scores ( p < 0.01), longer hospital stays ( p < 0.01), and critically ill patients (intensive care admission) ( p = 0.01), as well as those who had cardiopulmonary arrest ( p < 0.01) and high inpatient mortality ( p < 0.01). Conclusions: This study identified several associations between constipation and poor health outcomes and highlighted the underutilization of laxatives in treating constipation. It is vital to interpret our results with caution. Therefore, we believe that a randomized controlled trial will help enhance our understanding of the interaction between constipation, laxative use, and poor health outcomes.

Competing Interests: The author(s) declare no conflict of interest.

Nanotechnology is a rapidly developing discipline that has the potential to transform the way we approach problems in a variety of fields, including agriculture. The use of nanotechnology in sustainable agriculture has gained popularity in recent years. It has various applications in agriculture, such as the development of nanoscale materials and devices to boost agricultural productivity, enhance food quality and safety, improve the efficiency of water and nutrient usage, and reduce environmental pollution. Nanotechnology has proven to be very beneficial in this field, particularly in the development of nanoscale delivery systems for agrochemicals such as pesticides, fertilizers, and growth regulators. These nanoscale delivery technologies offer various benefits over conventional delivery systems, including better penetration and distribution, enhanced efficacy, and lower environmental impact. Encapsulating agrochemicals in nanoscale particles enables direct delivery to the targeted site in the plant, thereby reducing waste and minimizing off-target effects. Plants are fundamental building blocks of all ecosystems and evaluating the interaction between nanoparticles (NPs) and plants is a crucial aspect of risk assessment. This critical review therefore aims to provide an overview of the latest advances regarding the positive and negative effects of nanotechnology in agriculture. It also explores potential future research directions focused on ensuring the safe utilization of NPs in this field, which could lead to sustainable development. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Background: Cancer immunotherapy approaches that elicit immune cell responses, including T and NK cells, have revolutionized the field of oncology. However, immunosuppressive mechanisms restrain immune cell activation within solid tumors so additional strategies to augment activity are required., Methods: We identified the co-stimulatory receptor NKG2D as a target based on its expression on a large proportion of CD8+ tumor infiltrating lymphocytes (TILs) from breast cancer patient samples. Human and murine surrogate NKG2D co-stimulatory receptor-bispecifics (CRB) that bind NKG2D on NK and CD8+ T cells as well as HER2 on breast cancer cells (HER2-CRB) were developed as a proof of concept for targeting this signaling axis in vitro and in vivo., Results: HER2-CRB enhanced NK cell activation and cytokine production when co-cultured with HER2 expressing breast cancer cell lines. HER2-CRB when combined with a T cell-dependent-bispecific (TDB) antibody that synthetically activates T cells by crosslinking CD3 to HER2 (HER2-TDB), enhanced T cell cytotoxicity, cytokine production and in vivo antitumor activity. A mouse surrogate HER2-CRB (mHER2-CRB) improved in vivo efficacy of HER2-TDB and augmented NK as well as T cell activation, cytokine production and effector CD8+ T cell differentiation., Conclusion: We demonstrate that targeting NKG2D with bispecific antibodies (BsAbs) is an effective approach to augment NK and CD8+ T cell antitumor immune responses. Given the large number of ongoing clinical trials leveraging NK and T cells for cancer immunotherapy, NKG2D-bispecifics have broad combinatorial potential., (© 2024. The Author(s).)

Competing Interests: The author(s) declare no conflict of interest.

Gout is a common form of inflammatory arthritis characterized by the deposition of MSU in the joints and surrounding tissues, which results in inflammation and recurrent painful attacks. Currently, xanthine oxidase inhibitors, i.e., Allopurinol and Febuxostat, are used in the therapy. Recently, nanoparticles (NPs) containing metal oxides and non-metal oxides have also been developed to better manage gout. This comprehensive review summarizes the pathophysiology of gout, currently used drugs in the treatment, followed by emerging therapies for gout., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Tuberculosis and Mental Illness (TB-MI) often co-occur with a varying range of interactions of both. The rising incidence of both in Low- and Middle-income countries (LMICs) is an emergent public health problem with accompanying higher morbidity and complications in management. The objective of this review is to gather insights into how healthcare providers can enhance their support for patients with TB-MI, to improve treatment adherence and overall health outcomes. Addressing the complexities of TB-MI treatment requires a multi-component approach that includes psychological interventions, monitoring the course of mental health comorbidities, patient education, looking into barriers to adherence, and involving healthcare providers. These coupled with increased patient awareness, integrated care model, patient education and empowerment, simplified treatment approaches, social support programs, and sensitizing healthcare providers can decrease the burden on the healthcare system while improving patient outcomes., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Soumya Swaroop Sahoo reports was provided by All India Institute of Medical Sciences, Bathinda. Soumya Swaroop Sahoo reports a relationship with All India Institute of Medical Sciences, Bathinda that includes: employment., (Copyright © 2023 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.)

Mental illness is a hidden epidemic in modern science that has gradually spread worldwide. According to estimates from the World Health Organization (WHO), approximately 10% of the world's population suffers from various mental diseases each year. Worldwide, financial and health burdens on society are increasing annually. Therefore, understanding the different factors that can influence mental illness is required to formulate novel and effective treatments and interventions to combat mental illness. Gut microbiota, consisting of diverse microbial communities residing in the gastrointestinal tract, exert profound effects on the central nervous system through the gut-brain axis. The gut-brain axis serves as a conduit for bidirectional communication between the two systems, enabling the gut microbiota to affect emotional and cognitive functions. Dysbiosis, or an imbalance in the gut microbiota, is associated with an increased susceptibility to mental health disorders and psychiatric illnesses. Gut microbiota is one of the most diverse and abundant groups of microbes that have been found to interact with the central nervous system and play important physiological functions in the human gut, thus greatly affecting the development of mental illnesses. The interaction between gut microbiota and mental health-related illnesses is a multifaceted and promising field of study. This review explores the mechanisms by which gut microbiota influences mental health, encompassing the modulation of neurotransmitter production, neuroinflammation, and integrity of the gut barrier. In addition, it emphasizes a thorough understanding of how the gut microbiome affects various psychiatric conditions., Competing Interests: Declaration of Competing Interest None to declare, (Copyright © 2024 Elsevier B.V. All rights reserved.)

Personalized cancer therapeutics bring directed treatment options to patients based on their tumor's genetic signature. Unfortunately, tumor genomes are remarkably adaptable, and acquired resistance through gene mutation frequently occurs. Identifying mutations that promote resistance within drug-treated patient populations can be cost, resource, and time intensive. Accordingly, base editing, enabled by Cas9-deaminase domain fusions, has emerged as a promising approach for rapid, large-scale gene variant screening in situ. Here, we adapt and optimize a conditional activation-induced cytidine deaminase (AID)-dead Cas9 (dCas9) system, which demonstrates greater heterogeneity of edits with an expanded footprint compared to the most commonly utilized cytosine base editor, BE4. In combination with a custom single guide RNA (sgRNA) library, we identify individual and compound variants in epidermal growth factor receptor (EGFR) and v-raf murine sarcoma viral oncogene homolog B1 (BRAF) that confer resistance to established EGFR inhibitors. This system and analytical pipeline provide a simple, highly scalable platform for cis or trans drug-modifying variant discovery and for uncovering valuable insights into protein structure-function relationships., Competing Interests: Declaration of interests All authors are or were previously full-time employees of Genentech and are shareholders of Roche., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Bromocriptine (BCR) presents poor bioavailability when administered orally because of its low solubility and prolonged first-pass metabolism. This poses a significant challenge in its utilization as an effective treatment for managing Parkinson's disease (PD). The utilization of lipid nanoparticles can be a promising approach to overcome the limitations of BCR bioavailability. The aim of the research work was to develop and evaluate bromocriptine-loaded solid lipid nanoparticles (BCR-SLN) and bromocriptine-loaded nanostructured lipid carriers (BCR-NLC) employing the Box-Behnken design (BBD). BCR-SLNs and BCR-NLCs were developed using the high-pressure homogenization method. The prepared nanoparticles were characterized for particle size (PS), polydispersity index (PDI), and entrapment efficiency (EE). In vitro drug release, cytotoxicity studies, in vivo plasma pharmacokinetic, and brain distribution studies evaluated the optimized lipid nanoparticles. The optimized BCR-SLN had a PS of 219.21 ± 1.3 nm, PDI of 0.22 ± 0.02, and EE of 72.2 ± 0.5. The PS, PDI, and EE of optimized BCR-NLC formulation were found to be 182.87 ± 2.2, 0.16 ± 0.004, and 83.57 ± 1.8, respectively. The in vitro release profile of BCR-SLN and BCR-NLC showed a biphasic pattern, immediate release, and then trailed due to the sustained release. Furthermore, a pharmacokinetic study indicated that both the optimized BCR-SLN and BCR-NLC formulations improve the plasma and brain bioavailability of the drug compared to the BCR solution. Based on the research findings, it can be concluded that the BCR-loaded lipid nanoparticles could be a promising carrier by enhancing the BBB penetration of the drug and helping in the improvement of the bioavailability and therapeutic efficacy of BCR in the management of PD.

Depression is a complex psychiatric disorder influenced by various genetic and environmental factors. Strong evidence has established the contribution of genetic factors in depression through twin studies and the heritability rate for depression has been reported to be 37%. Genetic studies have identified genetic variations associated with an increased risk of developing depression. Imaging genetics is an integrated approach where imaging measures are combined with genetic information to explore how specific genetic variants contribute to brain abnormalities. Neuroimaging studies allow us to examine both structural and functional abnormalities in individuals with depression. This review has been designed to study the correlation of the significant genetic variants with different regions of neural activity, connectivity, and structural alteration in the brain as detected by imaging techniques to understand the scope of biomarkers in depression. This might help in developing novel therapeutic interventions targeting specific genetic pathways or brain circuits and the underlying pathophysiology of depression based on this integrated approach can be established at length., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In the intricate landscape of cellular function, proper protein folding is pivotal for cellular processes, particularly within the endoplasmic reticulum (ER). In a recent study, Ko et al. reveal a signaling role for inositol-requiring enzyme 1 (IRE1) in ER stress and identify PHOSPHATASE TYPE 2CA (PP2CA)-INTERACTING RING FINGER PROTEIN 1 (PIR1) as a crucial plant-specific regulator, balancing the unfolded protein response (UPR) and ubiquitin-proteasome system (UPS) by modulating ABI5 stability, unveiling intricate stress response connections., Competing Interests: Declaration of interests None declared., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Managing critically ill neonates has unique challenges, and the transport team plays an important role in stabilizing and facilitating the transfer of these neonates from lower-level nurseries to tertiary centers, and the use of telemedicine in transport (tele-transport) can potentially benefit patient care. We conducted a multicenter study to assess the readiness for utilizing telemedicine as an adjunct to guide the care of critically ill neonates among physicians and transport team members (TTMs). This is the first multicenter study that explored physicians' and TTMs' perceptions of telemedicine usage and its value in neonatal transport., Methods: A confidential, voluntary survey on pre-implementation attitudes toward telemedicine usage during neonatal transport was conducted as part of a quality improvement initiative. This survey involved physicians and TTMs from four academic institutions whose responses were entered into an online survey using REDCap®. The survey inquired about satisfaction with the current practice of phone consultation and the perception of using telemedicine to optimize the management of neonates during transport., Results: The overall response rate for the survey was 60.1%; 82 of 127 (64.6%) physicians and 64 of 116 (55.2%) TTMs responded to the surveys. Half of the physicians and less than one-fourth of the TTMs had prior experience with telemedicine other than that used on neonatal transport. TTMs expressed greater concern about the inconvenience of video (55% vs. physicians 35% agree or strongly agree ) and its time consumption (84% vs. physicians 50%). More than 70% of physicians and less than half of TTMs endorsed the potential for added value and quality improvement with video capability. Almost half of TTMs reported concern about video calls reducing their autonomy in patient care. Physicians expressed confidence in management decisions they would make after video calls (72% confident or very confident ) and less confidence (49%) about both the phone assessment by TTMs and their decisions based on phone assessment. In contrast, TTMs were confident or very confident (94%) in both sharing their assessment over the phone and executing patient management after a phone call, compared with 70% for decisions made after video calls., Conclusions: Physicians and TTMs had distinct opinions on the use of telemedicine during neonatal transport. Physicians were more likely than TTMs to agree with statements about the potential for improving quality of care, while TTMs were more likely than physicians to say video calls would be time-consuming and inconvenient. We speculate some differences may stem from the TTMs' concern about losing their autonomy. Therefore, during implementation, it is critical for physicians and TTMs to agree on a shared mental model of indications for telemedicine during transport and its value to the patient care., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Outpatient clinical notes are a rich source of information regarding drug safety. However, data in these notes are currently underutilized for pharmacovigilance due to methodological limitations in text mining. Large language models (LLMs) like Bidirectional Encoder Representations from Transformers (BERT) have shown progress in a range of natural language processing tasks but have not yet been evaluated on adverse event (AE) detection. We adapted a new clinical LLM, University of California - San Francisco (UCSF)-BERT, to identify serious AEs (SAEs) occurring after treatment with a non-steroid immunosuppressant for inflammatory bowel disease (IBD). We compared this model to other language models that have previously been applied to AE detection. We annotated 928 outpatient IBD notes corresponding to 928 individual patients with IBD for all SAE-associated hospitalizations occurring after treatment with a non-steroid immunosuppressant. These notes contained 703 SAEs in total, the most common of which was failure of intended efficacy. Out of eight candidate models, UCSF-BERT achieved the highest numerical performance on identifying drug-SAE pairs from this corpus (accuracy 88-92%, macro F1 61-68%), with 5-10% greater accuracy than previously published models. UCSF-BERT was significantly superior at identifying hospitalization events emergent to medication use (P < 0.01). LLMs like UCSF-BERT achieve numerically superior accuracy on the challenging task of SAE detection from clinical notes compared with prior methods. Future work is needed to adapt this methodology to improve model performance and evaluation using multicenter data and newer architectures like Generative pre-trained transformer (GPT). Our findings support the potential value of using large language models to enhance pharmacovigilance., (© 2024 The Authors. Clinical Pharmacology & Therapeutics © 2024 American Society for Clinical Pharmacology and Therapeutics.)

We were attracted to the therapeutic potential of inhibiting Casitas B-lineage lymphoma proto-oncogene-b (Cbl-b), a RING E3 ligase that plays a critical role in regulating the activation of T cells. However, given that only protein-protein interactions were involved, it was unclear whether inhibition by a small molecule would be a viable approach. After screening an ∼6 billion member DNA-encoded library (DEL) using activated Cbl-b, we identified compound 1 as a hit for which the cis -isomer ( 2 ) was confirmed by biochemical and surface plasmon resonance (SPR) assays. Our hit optimization effort was greatly accelerated when we obtained a cocrystal structure of 2 with Cbl-b, which demonstrated induced binding at the substrate binding site, namely, the Src homology-2 (SH2) domain. This was quite noteworthy given that there are few reports of small molecule inhibitors that bind to SH2 domains and block protein-protein interactions. Structure- and property-guided optimization led to compound 27 , which demonstrated measurable cell activity, albeit only at high concentrations., Competing Interests: The authors declare no competing financial interest., (© 2024 American Chemical Society.)

Ferritin is a multivalent, self-assembling protein scaffold found in most human cell types, in addition to being present in invertebrates, higher plants, fungi, and bacteria, that offers an attractive alternative to polymer-based drug delivery systems (DDS). In this study, the utility of the ferritin cage as a DDS was demonstrated within the context of T cell agonism for tumor killing. Members of the tumor necrosis factor receptor superfamily (TNFRSF) are attractive targets for the development of anticancer therapeutics. These receptors are endogenously activated by trimeric ligands that occur in transmembrane or soluble forms, and oligomerization and cell-surface anchoring have been shown to be essential aspects of the targeted agonism of this receptor class. Here, we demonstrated that the ferritin cage could be easily tailored for multivalent display of anti-OX40 antibody fragments on its surface and determined that these arrays are capable of pathway activation through cell-surface clustering. Together, these results confirm the utility, versatility, and developability of ferritin as a DDS.

Objectives: This study aimed to report the demographic features, clinical presentation, pathological types and long-term outcomes of patients diagnosed with endometrial cancer (EC) in Oman. EC is the sixth most common cancer in women worldwide and the fifth most common cancer in women in Oman. Survival outcomes of EC have not been reported previously from Oman., Methods: This retrospective study was carried out on consecutive patients treated at the Sultan Qaboos University Hospital, Muscat, Oman, between 2008 and 2020. Survival was estimated using the Kaplan and Meier method., Results: A total of 50 patients with EC were included. The median age was 61 years (range: 31-86 years), and 72% of the patients had type I histology. Most patients were diagnosed with stage IA and IB EC (49% and 20%, respectively), and the majority had grade 1 or 2 tumours (40% and 34%, respectively). Overall, the 5-year survival and 10-year survival rates were estimated to be 70% and 56%, respectively. Weight (>75 kg) and body mass index (>30 kg/m 2 ) were significantly associated with better survival. Tumour histology (type I versus type II or carcinosarcoma), grade (1 versus 2 versus 3) and stage (IA or IB versus II-IV) were associated with better overall survival ( P = 0.007, P <0.0001 and P <0.0003, respectively). Patients diagnosed with EC with co-morbidities, other than obesity, had inferior survival compared to those without co-morbidities., Conclusion: Median age at presentation, histological sub-type, clinical stage and outcomes are comparable to the published literature. Almost two-thirds of the patients were obese. These data could be used as a benchmark for outcomes of EC in the region., Competing Interests: CONFLICTS OF INTEREST: The authors declare no conflict of interest., (© Copyright 2024, Sultan Qaboos University Medical Journal, All Rights Reserved.)

Strigolactones (SLs) are fundamental to the ability of plants to cope with phosphate deficiency. A recent study by Yuan et al. indicates that the genetic module PHR2/NSP1/NSP2 is crucial in activating SL biosynthesis and signaling under inorganic phosphate (Pi) deficiency. Furthermore, this genetic module is essential for improving Pi and nitrogen homeostasis in rice., Competing Interests: Declaration of interests The authors declare that this manuscript was written without any commercial or financial relationship that could be constructed as a potential conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: More than half of mesothelioma tumours show alterations in the tumour suppressor gene BAP1. BAP1-deficient mesothelioma is shown to be sensitive to EZH2 inhibition in preclinical settings but only showed modest efficacy in clinical trial. Adding a second inhibitor could potentially elevate EZH2i treatment efficacy while preventing acquired resistance at the same time., Methods: A focused drug synergy screen consisting of 20 drugs was performed by combining EZH2 inhibition with a panel of anti-cancer compounds in mesothelioma cell lines. The compounds used are under preclinical investigation or already used in the clinic. The synergistic potential of the combinations was assessed by using the Bliss model. To validate our findings, in vivo xenograft experiments were performed., Results: Combining EZH2i with ATMi was found to have synergistic potential against BAP1-deficient mesothelioma in our drug screen, which was validated in clonogenicity assays. Tumour growth inhibition potential was significantly increased in BAP1-deficient xenografts. In addition, we observe lower ATM levels upon depletion of BAP1 and hypothesise that this might be mediated by E2F1., Conclusions: We demonstrated the efficacy of the combination of ATM and EZH2 inhibition against BAP1-deficient mesothelioma in preclinical models, indicating the potential of this combination as a novel treatment modality using BAP1 as a biomarker., (© 2024. The Author(s).)

Competing Interests: There are no conflicts of interest.

This concise review navigates the intricate realm of Interleukin-6 (IL-6), an important member of the cytokine family. Beginning with an introduction to cytokines, this narrative review unfolds with the historical journey of IL-6, illuminating its evolving significance. A crucial section unravels the three distinct signaling modes employed by IL-6, providing a foundational understanding of its versatile interactions within cellular landscapes. Moving deeper, the review meticulously dissects IL-6's signaling mechanisms, unraveling the complexities of its pleiotropic effects in both physiological responses and pathological conditions. A significant focus is dedicated to the essential role IL-6 plays in inflammatory diseases, offering insights into its associations and implications for various health conditions. The review also takes a therapeutic turn by exploring the emergence of anti-IL-6 monoclonal inhibitors, marking a profound stride in treatment modalities. Diving into the molecular realm, the review explores small molecules as agents for IL-6 inhibition, providing a nuanced perspective on diverse intervention strategies. As the review embarks on the final chapters, it contemplates future aspects, offering glimpses into potential research trajectories and the evolving landscape of IL-6-related studies., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Human papillomavirus (HPV) is associated with cervical cancer and cervical dysplasia worldwide. Data on HPV prevalence in a region is important because it serves as a predictor of the likelihood of the population in that particular region acquiring cervical cancer. Moreover, with the availability of effective vaccines, the public health system must be aware of the preponderance of HPV to implement the vaccine. The present study was designed to understand the prevalence of HPV and associated factors among the women of South Andaman Island., Methods: A cross-sectional study was conducted among married women of reproductive age (18-59 years) from South Andaman District from 2018 to 2022. Cervical scrapes were collected from participants after obtaining informed written consent for HPV molecular testing (HPV DNA) such as PCR assay. Demographic data was collected using a standard questionnaire and statistical analyses were performed to determine the associated factors., Results: The study showed prevalence of HPV as 5.9%(95% CI: 3.9-7.9) and prevalence of HR-HPV16 was 4.1% (95% CI 2.6 - 5.5) and HR-HPV18 prevalence was 1.8(95% CI: 0.6-3). The independent factors associated the HPV positivity were age above 55 years, menopause, post-menopausal bleeding, blood-stained vaginal discharge and loss of weight. Age was associated with all HPV infections among the South Andaman women., Conclusions: HPV 16 was reported as the predominant high risk HPV type circulating among women of South Andaman. Cervical cancer and precancerous lesions were significantly associated with HPV positivity and High risk HPV 16. Based on the knowledge of the risk factors associated with HPV, implementation of stronger public health awareness and prophylactic HPV vaccination is crucial among the women of this remote island., (© 2024. The Author(s).)

Craniomaxillofacial trauma is primarily diagnosed and managed by oral and maxillofacial surgeons. Among the cases encountered, midface fractures involving orbital walls are highly prevalent. In these fractures, involvement of the orbital walls, particularly floor of the orbit, can lead to considerable aesthetic and functional limitations. From a maxillofacial perspective, indications for surgical repair of orbital floor encompass marked decrease in ocular motility, fracture affecting more than 50% of surface area, an increase in orbital volume exceeding 18% and enophthalmos greater than 2 mm. In the absence of these discernible signs, surgical intervention is not generally indicated. However, in this case, an early adolescent with a history of midface trauma and minimal orbital floor fracture 8 months earlier presented with progressively delayed onset enophthalmos and hypoglobus closely resembling features of silent sinus syndrome. The enophthalmos and hypoglobus were corrected by placing custom-made non-resorbable high-density polyethylene implant in the orbital floor. Postoperative follow-up demonstrated aesthetically and functionally satisfactory outcomes., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To determine the correlation of lymphocyte subsets and soluble serum inflammatory biomarkers with disease severity in coronavirus disease-2019 infection., Methods: The retrospective study was conducted at the Department of Immunology, Sindh Institute of Urology and Transplantation (SIUI), Karachi, Pakistan from September 1 to November 30, 2021, and comprised data of patients admitted from June to July 2021 who tested positive for coronavirus disease-2019 on the basis of reverse transcription-polymerase chain reaction of nasopharyngeal swab specimens. The patients were categorised into severe group A and non-severe group B. Initial investigations included complete blood count, neutrophil-to-lymphocytes ratio, C-reactive protein, D-Dimers and serum ferritin levels. Lymphocyte subsets included cluster of differentiation-3+, cluster of differentiation-4+/ cluster of differentiation-3+, cluster of differentiation-8+ T lymphocytes, cluster of differentiation-19+B lymphocytes, cluster of differentiation-16+ cluster of differentiation-56+ Natural Killer cells and serum cytokine levels of interleukin-2, interleukin- 4, interleukin-6, interleukin-10, tumour necrosis factor-alpha and interferon gamma. They were correlated with disease severity. Data was analysed using SPSS 20., Results: Of the 54 patients, 33(61.1%) were males and 21(38.9%) were females. There were 29(53.70%) patients in group A with median age 52 years (interquartile range: 43.5-65 years), and 25(46.29%) in group B with median age 50 years (interquartile range: 36.5-59 years) (p=0.241). Disease was significantly more severe in male patients compared to female (p=0.002). In group A, cluster of differentiation-3+ T cells were reduced in 21(72.4%) patients, cluster of differentiation-8+ T cells in 16(55.2%), cluster of differentiation-4+ T cells in 23(79.3%) and cluster of differentiation-19+ B cells in 8(27.6%). In group B, cluster of differentiation-3+ T cells were reduced in 10(40%) subjects, cluster of differentiation-8+ T cells in 7(28%), cluster of differentiation-4+ T cells in 12(48%) and cluster of differentiation-19+ B cells in 4(16%) patients. Serum cytokine levels were not significantly different between the groups (p>0.05). In group A, 7(24.13%) patients died, and in such cases, the neutrophil-to-lymphocytes ratio was significantly higher (p=0.037)., Conclusion: Pro-inflammatory markers and cytokine levels increased, while lymphocyte subsets decreased with increasing severity of the disease.

Background: Restless legs syndrome (RLS) is a neuro-sensorimotor disorder which is scarcely researched and is commonly missed in routine psychiatry practice., Aim: To evaluate the prevalence of RLS and its correlates in patients with anxiety, depression, and somatoform disorders., Methods: A cross-sectional single-center study was undertaken in patients aged 18-65 years suffering from ICD-10 (International Statistical Classification of Diseases-10 th edition) diagnosis of anxiety, depressive, and somatoform disorders. RLS was evaluated by using diagnostic criteria of International Restless Legs Syndrome Study Group (IRLSSG) and severity measured on IRLSSG scale. Depression and anxiety were rated on Hamilton Depression and Anxiety Rating Scales respectively, insomnia severity measured by Insomnia Severity Index (ISI), and quality of life measured by WHO Quality of Life-Brief version (WHO-QOL BREF) scale. Serum ferritin levels were measured for evaluating iron deficiency., Results: The rate of RLS was 66.7%, 50%, and 48% in patients with depressive, anxiety, and somatoform disorders, respectively, with no significant inter-group difference. Nearly one-third of patients suffered from severe to very severe symptoms of RLS, and quality of life was poorest in those with depressive disorders. RLS was significantly higher in females ( P = 0.019), who were married ( P = 0.040), diagnosed with severe depression ( P = 0.029), and abused benzodiazepines ( P = 0.045). On binary logistic regression, female gender and presence of clinical insomnia predicted occurrence of RLS., Conclusion: The prevalence of RLS is very high in patients with common psychiatric disorders which is often missed. Clinical enquiry and examination for reversible causes such as iron deficiency may assist in its diagnosis and improve clinical outcome., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Indian Journal of Psychiatry.)

Objective: To investigate the impact of testosterone replacement therapy (TRT) on cardiovascular outcomes in hypogonadal men., Methods: A meta-analysis of 26 randomized controlled trials involving 10 941 participants was conducted. Various clinical outcomes, including all-cause mortality, cardiovascular-related mortality, myocardial infarction, stroke, congestive heart failure, atrial fibrillation, pulmonary embolism, and venous thrombosis, were assessed., Results: No statistically significant differences were observed between the TRT group and the control group in terms of these clinical outcomes. Sensitivity analysis and publication bias assessment supported the robustness of the findings. Meta-regression analysis found no significant associations between clinical outcomes and potential covariates, including age, diabetes, hypertension, dyslipidemia, and smoking., Discussion: Previous research on TRT and cardiovascular events, with comparisons to studies like the Testosterone Trials and the studies conducted by Vigen et al, Finkle et al, Layton et al, and Wallis et al, is provided. The significance of the systematic review and meta-analysis approach is emphasized, particularly its exclusive focus on hypogonadal patients., Conclusion: This study offers reassurance that TRT does not increase mortality risk or worsen cardiovascular outcomes in hypogonadal men. However, further research, especially long-term studies involving diverse populations, is essential to strengthen the evidence base and broaden the applicability of these findings., Competing Interests: Disclosure The authors have no multiplicity of interest to disclose., (Copyright © 2023 AACE. Published by Elsevier Inc. All rights reserved.)

Background: The use of telemedicine to provide care for critically ill newborn infants has significantly evolved over the last two decades. Children's Health System of Texas and University of Texas Southwestern Medical Center established TeleNICU, the first teleneonatology program in Texas., Objective: To evaluate the effectiveness of Tele Neonatal Intensive Care Unit (TeleNICU) in extending quaternary neonatal care to more rural areas of Texas., Materials and Methods: We conducted a retrospective review of TeleNICU consultations from September 2013 to October 2018. Charts were reviewed for demographic data, reasons for consultation, and consultation outcomes. Diagnoses were classified as medical, surgical, or combined. Consultation outcomes were categorized into transferred or retained. Transport cost savings were estimated based on the distance from the hub site and the costs for ground transportation., Results: TeleNICU had one hub (Level IV) and nine spokes (Levels I-III) during the study period. A total of 132 direct consultations were completed during the study period. Most consultations were conducted with Level III units (81%) followed by level I (13%) and level II (6%) units. Some common diagnoses included prematurity (57%), respiratory distress (36%), congenital anomalies (25%), and neonatal surgical emergencies (13%). For all encounters, 54% of the patients were retained at the spoke sites, resulting in an estimated cost savings of USD0.9 million in transport costs alone. The likelihood of retention at spoke sites was significantly higher for medical diagnoses compared to surgical diagnoses (89% vs. 11%)., Conclusion: Telemedicine effectively expands access to quaternary neonatal care for more rural communities, helps in the triage of neonatal transfers, promotes family centered care, and significantly reduces health care costs., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.