Leucine and Isoleucine are two amino acids that differ only by the positioning of one methyl group. This small difference has however important consequences in α-helices, as the β-branching of Ile results in helix destabilization. We set out to investigate whether there are general trends for the occurrences of Leu and Ile residues in structures and sequences of class A GPCRs (G protein-coupled receptors). GPCRs are integral membrane proteins in which α-helices span the plasma membrane seven times and which play a crucial role in signal transmission into the cell. We found that Leu side chains are generally present in less densely packed regions and are more protein-surface exposed than Ile side chains. We explored whether this difference might be attributed to different functions of the two amino acids and tested if Leu adjusts the hydrophobicity of the transmembrane domain based on the Wimley-White whole-residue hydrophobicity scales. In class A GPCRs, Leu decreases the variation in hydropathy between receptors and Leu content correlates positively with hydropathy calculated without Leu. Both measures indicate that hydropathy is tuned by Leu. To test this idea further, we generated protein sequences with random amino acid compositions using a simple numerical model, in which hydropathy was tuned by adjusting the number of Leu residues. The model was able to replicate the observations made with class A GPCR sequences. We speculate that Leu tunes the hydropathy of the transmembrane domain of class A GPCRs to facilitate correct insertion into membranes and/or for stability within them.

This document focuses on ChatGPT, a natural language processing (NLP) model built by the transformer neural network. The document provides a comprehensive overview of the architecture, training, and fine-tuning of ChatGPT, as well as its applications in various fields, including customer service and support, healthcare, education, research, and development. The document analyzes the evaluation results of ChatGPT on different datasets, compares it with other NLP models, and proposes solutions to address security-related challenges. Finally, the document discusses the potential and challenges of ChatGPT in the future and its importance for humans and society, as well as the regulations and policies that need to be developed to ensure the proper and legal use of ChatGPT.

Natural fiber-reinforced composites are generally known as eco-friendly, long-lasting, and recyclable materials. Considering, this study characterizes cellulosic Helianthus tuberosus L. fiber for polymer-based green composites for the first time. It has been found that Helianthus tuberosus L. fiber has many advantages as a reinforcement material in polymer-based composites. For example, the high roughness provided by the fiber surface in cellular morphology increases the locking into the composite body. One of the most critical advantages is its high thermal stability temperature of 247.3 oC. Also, other advantages of the Helianthus tuberosus L. fiber can be listed as high cellulose content, high crystallinity, and high tensile strength. The hollow fiber structure can allow it to be used in materials used for insulation. Eventually, the high cellulose content of 62.65% supports its usage in various industries, including paper and paperboard manufacturing.

Ecosystems function in a series of feedback loops that can change or maintain vegetation structure. Vegetation structure influences the ecological niche space available for animals to partition, shaping many aspects of behavior and reproduction. In turn, animals perform ecological functions that shape vegetation structure. However, most studies concerning 3D vegetation structure consider only one of these relationships. Here, we review these separate lines of research and integrate them into a single concept that describes a feedback mechanism. We also show how remote sensing and animal tracking technologies are now available at the global scale to describe feedback loops and their consequences for ecosystem functioning. An improved understanding of how animals interact with vegetation structure in feedback loops is needed to conserve ecosystems that face major disruptions in response to climate and land use change.

In low- and middle-income countries, malignancies remain underreported due to lack of quality data. This study outlines the histopathological pattern of pediatric solid malignancies in children aged 0-15yrs at the largest referral hospital in Ethiopia. 432 solid malignancies were evaluated. The most common malignancies were Lymphoma (21.8%), Retinoblastoma (19.4%), and Wilms tumor (13.9%). Burkitt lymphoma accounted for 2.1%, despite being the most reported pediatric malignancy in sub-Saharan Africa in published literature. Definitive diagnosis could not be made in 7% of cases, related to the lack of confirmatory testing. The study highlights the need for improvements in diagnostic capabilities in LMIC.

Development of disposable, rapid and convenient biosensor with high sensitivity and reliability is the most desired method of viral disease prevention. To achieve this goal, in this work, a practical impedimetric biosensor has been implemented into a disposable electrode on a screen-printed carbon electrode (SPCE) for the detection of two mosquito-borne viruses. The biosensor fabrication has step-wisely carried out on the disposable electrode surface at room temperature: starting from conductive film formation, physical binding of the gold nanoparticles (AuNPs)-polyaniline (PAni) into the conductive film, and biofunctionalization. To get the maximum efficiency of the antibody, biotinylated antibody has been conjugated on the surface of AuNP-PAni /PAni-SPCE via the streptavidin-biotin conjugation method which is a critical factor for the high sensitivity. Using the antibody-antigen interaction, this disposable electrode has designed to detect mosquito-borne infectious viruses, Chikungunya virus (CHIKV) and Zika Virus (ZIKV) separately in a wide linear range of 100 fg/mL to 1 ng/mL with a low detection limit of 1.33 fg/mL and 12.31 fg/mL, respectively.

Background: Serotonin syndrome is a potentially life-threatening syndrome with manifestations spanning from mild adverse effects to life-threatening toxicity. The syndrome is caused by overstimulation of serotonin receptors by serotonergic drugs. Since the use of serotonergic drugs is increasing, primarily due to the widespread use of selective serotonin reuptake inhibitors, cases of serotonin syndrome have likely seen a parallel increase. The true incidence of serotonin syndrome remains unknown due to its diffuse clinical presentation. Objectives: This review aims to provide a clinically focused overview of serotonin syndrome, covering its pathophysiology, epidemiology, clinical manifestations, diagnostic criteria, differential diagnosis, and treatment as well as classifying serotonergic drugs and their mechanism of action. The pharmacological context is emphasized, as it is crucial for detection and management of serotonin syndrome. Methods: Focused review based on a literature search using the PubMed database. Findings and conclusion: Serotonin syndrome can occur through therapeutic use or overdose of a single serotonergic drug, or as a drug interaction between two or more serotonergic drugs. Central clinical features consist of neuromuscular excitation, autonomic dysfunction and altered mental status, occurring in a patient undergoing new or altered serotonergic therapy. Early clinically recognition and treatment are crucial to prevent significant morbidity.

Soil salinization is a serious problem leading to ecological degradation. Melia azedarach is highly salt-tolerant, and its application to saline-alkali land is a promising strategy for restoring degraded lands. In this study, we analyzed the soil properties and metabolome of M. azedarach roots grown in low- (< 3 g/kg; L), medium- (5~8 g/kg; M), and high- (> 10 g/kg; H) salinity soils to explore the amelioration effect and adaptation mechanism of M. azedarach to soils with differential salinity. Cultivation of M. azedarach was associated with a decrease in the concentration of Na + and increases in organic matter content and alkaline phosphatase and urease activities in the rhizosphere soil. The metabolome analysis revealed that a total of 382 (ESI+) and 277 (ESI-) differential metabolites (DEMs) were detected. The number of DEMs in roots rose with increased soil salinity, such as sugars and flavonoids in H vs. L, and amino acids in M vs. L. The most up-regulated DEMs were 13-S-hydroxyoctadecadienoic acid, 2’-Deoxyuridine and 20-hydroxyleukotriene B4. Combined analysis of soil properties and M. azedarach DEMs indicated that alkaline phosphatase activity was positively correlated with traumatic acid concentration. Taken together, these results indicate that M. azedarach has the potential to reduce soil salinity and enhance soil enzyme activity, and it can adapt to salt stress by regulating metabolites like sugars, amino acids, and flavonoids . This study provided a basis for understanding the mechanism underlying the adaptation of M. azedarach to saline-alkali soil and its amelioration.

Simultaneous utilization and remediation of soils contaminated with cadmium (Cd) is a propitious and economically beneficial task. Here, we undertook a pot experiment with biochar application at four rates (0, 5, 10, and 15%, denoted as BC0, BC5, BC10, and BC15, respectively) with the addition of 0.1% Cd, along with a control without Cd and biochar addition (CK). Erigeron breviscapus, a raw medicinal material used to extract scutellarin, was grown in all treatments to investigate a new method of utilizing and remediating heavily Cd-contaminated soil. The results showed that the high Cd-contaminated soil decreased the yield and scutellarin content of E. breviscapus by 33.6% and 70.8%, respectively. Compared to BC0, the yield and scutellarin content in BC15 increased by 24.7% and 312.0%, respectively. Biochar application (BC5, BC10, BC15) changed the soil Cd speciation and reduced the soil available Cd content by 17.4–121.8% and plant Cd content by 26.4–42.6% compared with BC0. However, chlorophyll content, catalase (CAT) activity, and acquisition of N, Fe 2+ and Cu 2+ of E. breviscapus increased in BC5, BC10, and BC15 compared to BC0. Additionally, the mitigation effect of Cd toxicity enhanced with increasing biochar application, and 15% biochar application resulted in the highest yield and scutellarin content of E. breviscapus. This study highlights the importance of biochar for improving the Cd adaptability of E. breviscapus and provides a reference for the simultaneous utilization and remediation of heavily Cd-contaminated soil.

Studying the interactions between humans, landscapes and biodiversity is necessary for the sustainable management of socio-ecosystems and requires long-term reconstructions of past landscapes, improving the integration of slow ecological processes. The main source of information on past vegetation is fossil pollen, but pollen data are biased by inter-taxonomic differential production and dispersal. The Landscape Reconstruction Algorithm (LRA) approach is today the most widely used to correct pollen data for these biases and also allows to identify the spatial extent of the local vegetation reconstruction zone via the Relevant Source Area of Pollen (RSAP). While LRA estimates have already been integrated into certain past land-cover mapping approaches, none have been designed to allow the diachronic reconstruction of the land-cover mosaic of a landscape over the long term combining the following points: the direct integration of LRA estimates as a source of variability in the composition and distribution of pollen taxa, without resorting to multiple scenarios, and the integration of spatiotemporal autocorrelation in the taxa distribution between two periods. In this study, we propose an innovative approach for Backward Landscape reconstruction (BACKLAND), combining these previous points and estimating past landscapes within a set of RSAPs. Based on three stages using parsimonious assumptions and easy-to-implement probabilistic and statistical tools, the implementation of this approach requires LRA estimates of sites with overlapping RSAPs, botanical data, a Digital Elevation Model and two recent land-cover maps. Developed and tested on a small study area within the mountain landscape of the Bassiès valley (French Pyrenees), BACKLAND achieved the reconstruction of a past land-cover map representing eight land-cover types at a spatial resolution of 20m with a good level of accuracy. We showed in this study the originality of this approach and discussed its potential for palaeoenvironmental studies, historical ecology and the management of socio- ecosystems.

Abstract- Lipoma is most common mesenchymal benign tumor in the body. Lipoma at retropharyngeal location is rare and clinical presentation in a pediatric age group is even rarer. We are presenting a case of huge retropharyngeal lipoma with mediastinal extension in an 11 year old boy who presented with progressive dysphagia and dyspnea. Diagnosis of lipoma was made on computed tomography, and it was surgically managed with complete resolution of symptoms on post operative follow up.Key words- Retropharyngeal lipoma, computed tomography, dysphagia, dyspnea, case report.Introduction- Lipoma is the most common mesenchymal benign tumor in the body and only 15% of them are located in head and neck region(1). Head and neck lipomas are usually located in posterior triangle region and incidence in retropharyngeal region is rare(2). Other masses in this region, especially in paediatric age group are mostly infectious in nature- pyogenic or tuberculous(3). Retropharyngeal lipomas are slow growing benign tumour, which becomes symptomatic after achieving a large size(4). Clinical presentation is usually abnormal sensation in the throat, noisy breathing, hoarseness, dyspnea, dysphagia, obstructive sleep apnoea, excessive day time sleepiness (5). In this report we present a rare case of huge retropharyngeal lipoma with mediastinal extension in an 11 year old boy who presented with progressive dysphagia and dyspnea for last 5 years. Diagnosis was made on computed tomography and disease was managed with complete surgical excision.Case Presentation- An 11 year old boy with history of progressive dysphagia and dyspnea for 5 years with significant weight loss. Dysphagia was more for solids. Patient used to push the food bolus in mouth with his fingers to ease the deglutition. On general examination, patient was cachexic. Respiratory rate was increased with nasal flaring and retraction of chest wall muscles with breathing. On inspection a bulge was noted in posterior pharyngeal wall with normal overlying mucosa which was seen in approximation with uvula. On chest x ray AP view a homogenous right upper mediastinal radiopacity was present with well defined lateral margin. Both lung fields were unremarkable. On lateral view of chest X ray a cervical soft tissue density with well-defined anterior border was noted anterior to vertebrae(Figure 1). Cross sectional imaging was performed for characterization of cervicothoracic mass. Contrast enhanced CT cervical and thoracic region showed a homogenous fat attenuating retropharyngeal mass measuring 15 x 5 x 3 cm with mediastinal extension with caudo- cranial extent from C1 to D5 vertebral level(Figure 2A). The mass was seen effacing oro-hypopharynx, compressing inlet of larynx and trachea. On axial section of neck, mass was extending to lateral aspect of pharynx and larynx on both sides and displacing bilateral carotid vessels laterally (Figure 2B). The mass was displacing trachea and oesophagus anteriorly and upper mediastinal vessels laterally (Figure 2C). Diagnosis of lipoma was made. There was no evidence of enhancing soft tissue component within mass or invasion of adjacent organs, suggestive of its benign nature.Under general anaesthesia complete surgical excision of mass was done through lateral cervical approach. A vertical incision done on left side of neck, skin was retracted and lipoma was exposed. The mass was separated from surrounding tissue like carotid vessels, internal jugular veins, thyroid, trachea and oesophagus. Mass was resected intact and wound was closed with sutures. Macroscopically it was yellowish with shiny surface and encapsulated appearance (Figure 3). Microscopically tumour composed of mature adipocytes, typical of lipoma with no evidence of malignant changes. Patient’s dyspnea was alleviated on same day. Post operative course was unremarkable and patient was discharged on fourth post operative day. On 2 months follow up, patients’ symptoms were completely alleviated. CT scan was performed to confirm complete removal of mass, which revealed no residual lesion at follow up scan. On 6 months follow up, patient had no complain of dysphagia/dyspnea to suggest recurrence and patient started to regain weight.Discussion- The retropharyngeal space is an anatomical region that spans from the base of the skull to the mediastinum. Its location is anterior to the prevertebral muscles and posterior to the pharynx and oesophagus. It is bounded anteriorly by the buccopharyngeal fascia, laterally by the carotid sheath, and posteriorly by the prevertebral fascia(6). Cerebral palsy, acquired/traumatic brain injury, neuromuscular disorders, craniofacial malformations and airway malformations are various causes of dysphagia in paediatric age group(7). Retropharyngeal tumours are rare cause of dysphagia. Common causes of retropharyngeal mass in paediatric group are infective (abscess, oedema, lymphadenopathy). Other causes are lymphoma and to a lesser extent hematoma(3).Haddad et al reported a case of retropharyngeal lipoma in 2005 and they collected total 52 cases of retropharyngeal lipoma after review of worldwide literature till date(3). After an extensive search of worldwide literature, we could find additional 26 case reports including our case. Total 78 cases of retropharyngeal lipoma are reported till date including our case and out of these only 9 cases were reported previously in paediatric age group. Our case is likely to be 10th case report of retropharyngeal lipoma in paediatric age group. A huge retropharyngeal lipoma in paediatric age group was previously reported in a single case report by Kurilin, with tumour size 14 cm(8). Our case is second case report of huge retropharyngeal lipoma in paediatric age group with tumour size 15 cm. This benign tumour at retropharyngeal location can be potentially life threatening due to severe compression on aerodigestive tract(3). Diagnosis is usually made on imaging, either computed tomography or magnetic resonance imaging. Role of imaging is also in evaluation of extent of tumour and in differentiation from liposarcoma.Transoral approach is preferred surgical approach for retropharyngeal lipoma due to its less post operative morbidity and lack of scar(1), however lateral cervical approach should be considered in large tumours extending in mediastinum.Conclusion - Lipoma at retropharyngeal location is rare, and It should be suspected if clinical presentation is slowly progressive dysphagia and dyspnea with a bulge in posterior pharyngeal wall on oral examination. Diagnosis is based on imaging and complete surgical excision is treatment of choice.

Successful use of anti-PD-1 antibody to treat multiple metastatic carcinomas in a patient with xeroderma pigmentosum: case report and literature reviewMai Itoyama1, Akihiro Ohara1, Kazuki Yokoyama1, Shun Yamamoto1, Ken Kato1, Taisuke Mori2, Hiroshi Igaki3, Eiji Nakano4,5, Naoya Yamazaki4, Kuniko Sunami6, Chikako Nishigori5,7, Yoshitaka Honma11. Department of Head and Neck, Esophageal Medical Oncology, National Cancer Center Hospital2. Department of Diagnostic Pathology, National Cancer Center Hospital3. Department of Radiation Oncology, National Cancer Center Hospital4. Department of Dermatologic Oncology, National Cancer Center Hospital5. Department of Dermatology, Kobe University Graduate School of Medicine6. Department of Laboratory Medicine, National Cancer Center Hospital7. Hyogo Blood Center, Japanese Red CrossContact (Mai Itoyama):Adress: 5-1-1 Tsukiji, Chuo-ku, Tokyo, JapanEmail: mitoyama@ncc.go.jp

Pemphigus Vulgaris Presenting with Epigastric PainAuthors: Marawan Elmassry MD1, Jerapas Thongpiya MD1, Pitchaporn Yingchoncharoen MD1, Jali Garza MS1, Matthew Soape MD2, Kanak Das MD11Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA2Department of Gastroenterology, Covenant Medical Center, Lubbock, TX, USA

Clostridium sordellii: A cause of toxic shock syndrome after a breach in the GI tractSydney Pence,1 Rajshri Joshi,2Kasturi Shrestha31. Ohio University Heritage College of Osteopathic Medicine, 4180 Warrensville Center Rd, Warrensville Heights, OH 44122. Email: sp883713@ohio.edu2. Internal Medicine, Cleveland Clinic Akron General, 1 Akron General Ave, Akron, OH 44307. Email: JOSHIR4@ccf.org3. Infectious Disease, Cleveland Clinic Akron General, 1 Akron General Ave, Akron, OH 44307. Email: SHRESTK2@ccf.org

Rhinoscleroma is a granulomatous infectious disease that typically affects the nasopharynx and upper respiratory tract. Non-endemic (e.g., North American) and laryngeal cases are rare. This case highlights the importance of pathognomonic Mikulicz cells for diagnosis.

Background: Neonatal foals are born essentially agammaglobulinemic and therefore must ingest colostrum or receive immunoglobulins to maintain health. Failure of passive transfer treatment involves administration of equine colostrum, plasma or commercial powdered colostrum (CPC). Anecdotal reports suggest a risk of anaphylaxis associated with plasma transfusion in neonates that received CPC prior to gut closure. Bovine serum albumin (BSA) in CPC may serve as a target for BSA-specific immunoglobulin E (IgE) in donor equine plasma. Objectives: To determine presence of BSA-specific IgE in samples collected post-routine vaccination in healthy horses, horses experiencing adverse vaccine reactions and commercial equine plasma. Study Design: Prospective Observational Methods: Serum was collected from 65 healthy horses at day 0, 14, 28, 90, 180, 270 and 365 post-vaccination, 26 horses after vaccine reaction at day 1, 180 or 270 post-vaccination, 4 horses not vaccinated and 10 horses from a commercial plasma donor herd. BSA-specific IgE was determined using enzyme-linked immunosorbent assay (ELISA). Results: BSA-specific IgE was not detected in non-vaccinated horses and was identified in all vaccinated horses. Younger horses demonstrated higher fold changes in post-vaccination BSA-specific IgE expression compared to older horses. No significant difference in BSA-specific IgE levels between commercial plasma donors and healthy horses was identified. No significant difference in post-vaccination anti-BSA IgE levels between reactor and healthy horses at day 180 and 270 post-vaccination were identified. Main Limitations: Small number of reactor horses at day 180 and 270 post-vaccination with most samples being collected 24 hours. There were no healthy horse samples for 24 hours post-vaccination; therefore, it was not possible to compare the two groups at this timepoint. Conclusions: Horses may express BSA specific IgE following vaccination. There may be risk of hypersensitivity type reaction when veterinarians administer commercial plasma to neonatal foals that have consumed CPC prior to gut closure.

Aim of the study: Given the known synergistic relationship between magnetic field (MF) and cholinergic receptor activation in the cholinergic system, the present study aims to investigate whether the combined use of a static MF and an agonist for nicotinic acetylcholine receptors (nAChR) can preserve motor behavior in ischemic gerbils. Materials & methods: We randomly allocated 72 Mongolian gerbils into nine groups (n=8), distributed according to surgical procedure and treatment. The animals were trained and evaluated on the Rotarod (RR) to assess motor performance. Results: Our main finding was the preservation of motor behavior in the Sham Ischemia + Nicotine + Sham Magnetic Stimulation (Sh+N+SMS) and Ischemia + Nicotine + South Pole (I+N+SP) groups, as evidenced by the results of the RR test. Conclusions: Our findings are consistent with previous literature and provide insight into the mechanism of potentiation, as results showed that adding a nAChR agonist to the MF preserved motor performance in the RR test of ischemic animals.

Abstract Background This study aimed to establish a method to determine tigecycline (TGC) in cerebrospinal fluid (CSF) and serum of 12 patients with Multidrug-resistant acinetobacter baumannii (MDRAB) central nervous system infection (CNSI) and evaluate the correlation of TGC in CSF and serum samples. Methods TGC in CSF and serum was extracted by acetonitrile and detected by HPLC-MS/MS. The separation was performed on the Waters XBridge® BEH Shield RP18 column. This method could achieve the quantification accurately in a very short time. Results For these 12 patients, the trough concentration ranges of TGC in CSF and serum at steady-state were 16.35-53.56 ng/mL and 67.76-211.9 ng/mL. The CSF-to-serum ratio of TGC at steady-state trough concentration was ranged from 21.46% to 44.46%, and the mean value was 31.61 ± 8.13%. The correlation of TGC in CSF and serum was 0.5065. CNSI might have no potential to increase the penetration ability of TGC to CSF. Conclusion The method was validated to be accurate and effective. The correlation between the concentrations of TGC in CSF and serum at steady-state was demonstrated to be positive based on quantification of TGC in bio-samples from 12 MDRAB patients.

Objectives: To evaluate cellular immune responses induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines immunization in population based on HLA-E-restricted CD8 + T cell epitopes identification. Methods: HLA-E-restricted SARS-CoV-2 CD8 + T cell nonamer peptides were predicted with software. HLA-E-transfected K562 cells binding assay was used to screen for high-affinity peptides. IFN-γ enzyme-linked immunospot assay were used to identify HLA-E-restricted epitopes. HLA-E/epitope tetramer was employed to detect the frequencies of epitope-specific CD8 + T cells. Results: Four CD8 + T cell epitopes on spike protein of SARS-CoV-2 restricted by both HLA-E*0101 and E*0103 were identified. HLA-E-restricted epitope specific IFN-γ-secreting CD8 + T cell responses could be detected in individuals vaccinated with SARS-CoV-2 vaccines. Importantly, the frequencies of epitope-specific CD8 + T cell in Ad5-nCoV vaccinated individual were higher than that in individuals vaccinated with recombinant protein or inactivated vaccines. Moreover, frequencies of epitope-specific CD8 + T cells could maintain for at least 120 days after only one dose Ad5-nCoV vaccination. While frequencies of epitope-specific CD8 + T cells decreased in individuals after two doses of Ad5-nCoV vaccination. Conclusions: These findings may contribute to more comprehensive evaluating protective effects of vaccines for SARS-CoV-2, meanwhile may provide information to characterize HLA-E-restricted CD8 + T cell immunity against SARS-CoV-2 infection.

Chronic hepatitis B virus (HBV) infection causes hepatitis, liver cirrhosis and hepatocellular carcinoma. Covalently closed circular DNA (cccDNA) is the transcription template for HBV RNAs and not affected by current treatment options. Effective therapeutics with ability to remove cccDNA need to be developed. Previously, we established an HBV persistence mouse model via hydrodynamic injection of a clinical isolate (BPS) and identified IL-21 as a potent inducer of viral clearance. Here, we aimed to explore the anti-HBV effects of IL-21 messenger RNA (mRNA) delivered by lipid nanoparticle (LNP-IL-21) system. First, LNP-IL-21 was prepared and analyzed for its safety, expression, biodistribution and stability in vitro and in vivo. Next, LNP-IL-21 was injected into two HBV persistence mouse models based on BPS and recombinant cccDNA (rcccDNA) respectively. LNP-IL-21 administration successfully cleared HBV serum markers, and more importantly, BPS replicons and rcccDNA in livers, which was associated with activation of viral specific immune responses. Notably, transfer of peripheral blood mononuclear cells from BPS persistence mice stimulated ex vivo with LNP-IL-21 and viral antigen could induce HBV clearance in recipient mice. These findings suggested that both LNP-IL-21-based gene and cellular therapies provided novel therapeutic strategies against chronic HBV infection.

Background: No study has directly compared the efficacy of nirmatrelvir-ritonavir and azvudine for treatment. The efficacy of these two drugs at high altitudes was compared. Materials and Methods: This was a retrospective cohort research on hospitalized patients with COVID-19 who were treated with nirmatrelvir-ritonavir or azvudine in Tibet between August 1 and September 30, 2022. Results: The electronic health data of 731 patients were retrospectively reviewed. Nirmatrelvir-ritonavir and azvudine groups enrolled 338 and 147 patients, respectively. Among patients with mild, common, and severe (including critical) COVID-19, there was no difference in the median duration of hospitalization between treatment with nirmatrelvir-ritonavir and that with azvudine: 8 (5–10.25) vs. 9 (5–13) (P=0.096); 8 (5–11) vs. 8 (5–13) (P=0.227); and 13 (7–17.75) vs. 10 (7.5–17.5) (P=0.994) days, respectively. Moreover, patients in the nirmatrelvir-ritonavir group had a shorter median time for nuclear acid negative conversions (NANC) than those in azvudine group: 6 (4–9) vs. 10 (6.25–13.75) (P=0.000), 8 (5–12) vs. 10.5 (7–14) (P=0.013), and 7 (5.25–12.75) vs. 15 (7.5–23.5) (p=0.023) days, respectively. Conclusion: Azvudine yielded a longer time for NANC and an equivalent duration of hospitalization and may have comparable efficacy with nirmatrelvir-ritonavir, making it a viable treatment option for COVID-19.

Two cases of Monkeypox virus infection without detectable cutaneous/mucosal lesionsGiulia Ciccarese1, Giorgia Brucci2,3, Antonio Di Biagio2,3, Francesco Drago4,Bruno Caccianotti5, Sergio Lo Caputo5, Gaetano Serviddio6, Teresa Santantonio51Unit of Dermatology, Department of Medical and Surgical Sciences, University of Foggia, Viale Pinto 1, 71122, Foggia, Italy;2Infectious Diseases Unit, San Martino Policlinico Hospital, IRCCS for Oncology and Neurosciences, Largo R. Benzi, 10, 16132 Genoa, Italy;3Department of Health Sciences (DiSSal), University of Genova, Via Pastore, 1, 16132 Genova, Italy;4Unit of Dermatology, San Martino Policlinico Hospital, IRCCS for Oncology and Neurosciences, Largo R. Benzi, 10, 16132 Genoa, Italy;5Clinic of Infectious Diseases, Department of Clinical and Surgical Sciences, University of Foggia, Viale Pinto, 1, 71122 Foggia, Italy;6C.U.R.E. (University Centre for Liver Disease Research and Treatment), Liver Unit, Department of Medical and Surgical Sciences, University of Foggia, Viale Pinto 1, 71122, Foggia, Italy.Email addresses of the co-authors:giorgia.brucci@libero.it; antonio.dibiagio@hsanmartino.it; francescodrago007@gmail.com; bcaccianotti@ospedaliriunitifoggia.it; sergio.locaputo@unifg.it; gaetano.serviddio@unifg.it; teresa.santantonio@unifg.itCorresponding author : Giulia Ciccarese, MD, PhD, Unit of Dermatology, Department of Medical and Surgical Sciences, University of Foggia, Viale Pinto 1, 71122, Foggia, Italy. Telephone: +390881736093. Email address: giulia.ciccarese@unifg.itKeywords: Monkeypox virus infection, anal pain, risky behaviors, sexually transmitted infections.Data availability statement: data available on reasonable request.Funding statement: this research did not receive founds.Conflict of interest: nonePatient consent statement: obtained.Dear Editor,in our case series of 16 human Monkeypox virus (MPX) infected patients diagnosed from 1th July until 31thAugust 2022 in the Dermatology Unit and in the Infectious Disease Unit of the San Martino Hospital, Genoa, Italy1, two patients had no detectable cutaneous/mucosal manifestations at the time of MPX diagnosis.The first patient was a 37-year-old Italian homosexual man presenting to the Infectious Disease Unit for the pre-exposure prophylaxis (PrEP) against HIV follow-up appointment. He had been complaining of anal pain without anal bleeding or secretions for 5 days and admitted risky sexual behaviors (unprotected sex with casual partners) in the previous two weeks, when he had travelled to Indonesia and France. His stable partner, a 24-year-old Italian homosexual man, complained of sore throat and reported the same risky behaviors. He had not travelled abroad in the last month.At physical examination, the patients had not visible cutaneous/mucosal lesions. They performed a complete sexually transmitted infections (STIs) screening including serology for T.pallidum infection, human immunodeficiency virus (HIV), hepatitis B and C viruses, anal, urethral and oropharyngeal swabs for the search of DNA ofChlamydia Trachomatis , Neisseria gonorrhoeae, Mycoplasma hominis, Mycoplasma genitalium, Ureaplasma urealyticum, Ureaplasma parvum, Trichomonas vaginalis by polymerase chain reaction (PCR) and, lastly, anal and oropharyngeal swabs for the search of MPX DNA by PCR, as previously described2,3. The laboratory investigations resulted all negative, except for the detection of MPX DNA at the oropharyngeal and anal swabs, that resulted positive in both sites and in both patients. The clinical presentation of these patients could be misdiagnosed with other STIs, especially with non-gonococcal proctitis and pharyngitis. Indeed, we suggest considering MPX infection in all at-risk patients presenting with traditional or atypical STIs signs/symptoms to avoid incorrect diagnosis.Unlike the patient with MPX virus infection manifesting as single cutaneous lesion that we recently described4, these two patients had not detectable cutaneous/mucosal lesions but only signs/symptoms of systemic involvement. Indeed, MPX virus traditionally causes a systemic infection: once acquired through close contact with skin/mucosal lesions, large respiratory droplets or fomites, the virus replicates at the inoculation site, then it spreads to the local lymph nodes and subsequently to the bloadstrem (initial viremia), causing the viral spread to other organs. These infection phases represent the viral incubation period, lasting 7-14 days. Signs/symptom onset correlates with a secondary MPX viremia corresponding to 1-2 days of prodromal signs/symptoms (mainly fever and lymphadenopathy) before appearance of skin/mucosal lesions5. Noteworthy, the MPX systemic spread during the acute infection represents a potential threat to the safety of blood transfusion and organ transplantation6.According to one of the largest case series describing MPX related signs and symptoms, presentation of MPX infection without skin/mucosal lesions accounts for about 5% of all cases7. We can speculate that in such cases, as in our patients and in those described by Quattri et al.8, the cutaneous/mucosal MPX viral load was so low to cause only localized, single or even undetectable lesions. Unfortunately, we were not able to quantitatively assess the MPX viral load in the swabs that resulted positive nor in the patient’s blood samples to confirm this hypothesis.In conclusion, MPX infection can represent a diagnostic challenge, especially when it occurs as a single cutaneous lesion of the genito-anal site4,8 or with acute anal or oropharyngeal pain in absence of associated cutaneous/mucosal lesions. Physicians should be aware of the possible atypical and scant manifestations of the disease and, in case of high clinical suspicion, should not exclude MPX infection even if cutaneous/mucosal lesions are undetectable.Authors’ contributions : Giulia Ciccarese, Giorgia Brucci: conceptualization, methodology, writing-original draft; Francesco Drago, Antonio Di Biagio: investigation, resources; Bruno Caccianotti, Sergio Lo Caputo, Teresa Santantonio, Gaetano Serviddio: writing review and editing, supervision.

Context: Computational materials science (CMS) focuses on in silico experiments to compute the properties of known and novel materials, where many software packages are used in the community. The NOMAD Laboratory1 offers to store the input and output files in its FAIR data repository. Since the file formats of these software packages are non-standardized, parsers are used to provide the results in a normalized format. Objective: The main goal of this article is to report experience and findings of using grammar-based fuzzing on these parsers. Method: We have constructed an input grammar for four common software packages in the CMS domain and performed an experimental evaluation on the capabilities of grammar-based fuzzing to detect failures in the NOMAD parsers. Results: With our approach, we were able to identify three unique critical bugs concerning the service availability, as well as several additional syntactic, semantic, logical, and downstream bugs in the investigated NOMAD parsers. We reported all issues to the developer team prior to publication. Conclusion: Based on the experience gained, we can recommend grammar-based fuzzing also for other research software packages to improve the trust level in the correctness of the produced results.

“Management fashion” is a term used to describe the study of how certain management concepts became popular and adopted by organizations. The research aims to evaluate why JCI accreditation is seen as a fashion in the health sector in Turkey and to understand how it is adopted by organizations in response to institutional pressures. The research combines in-depth interviews, content analysis and analysis of certification indicators. The findings of the research show that JCI has become a management fashion in Turkey, and this is the first study to address the issue of JCI as a management fashion from the perspective of institutional theory and is one of the first studies to show that managerial fashion can be studied through certifications.