Anomalous Interlayer Exciton Diffusion in WS2/WSe2 Moiré Heterostructure.

Stacking van der Waals crystals allows for the on-demand creation of a periodic potential landscape to tailor the transport of quasiparticle excitations. We investigate the diffusion of photoexcited electron-hole pairs, or excitons, at the interface of WS2/WSe2 van der Waals heterostructure over a wide range of temperatures. We observe the appearance of distinct interlayer excitons for parallel and antiparallel stacking and track their diffusion through spatially and temporally resolved photoluminescence spectroscopy from 30 to 250 K. While the measured exciton diffusivity decreases with temperature, it surprisingly plateaus below 90 K. Our observations cannot be explained by classical models like hopping in the moiré potential. A combination of ab initio theory and molecular dynamics simulations suggests that low-energy phonons arising from the mismatched lattices of moiré heterostructures, also known as phasons, play a key role in describing and understanding this anomalous behavior of exciton diffusion. Our observations indicate that the moiré potential landscape is dynamic down to very low temperatures and that the phason modes can enable efficient transport of energy in the form of excitons.

Synthesis and Polymorph Manipulation of FeSe2 Monolayers.

Polymorph engineering involves the manipulation of material properties through controlled structural modification and is a candidate technique for creating unique two-dimensional transition metal dichalcogenide (TMDC) nanodevices. Despite its promise, polymorph engineering of magnetic TMDC monolayers has not yet been demonstrated. Here we grow FeSe2 monolayers via molecular beam epitaxy and find that they have great promise for magnetic polymorph engineering. Using scanning tunneling microscopy (STM) and spectroscopy (STS), we find that FeSe2 monolayers predominantly display a 1T' structural polymorph at 5 K. Application of voltage pulses from an STM tip causes a local, reversible transition from the 1T' phase to the 1T phase. Density functional theory calculations suggest that this single-layer structural phase transition is accompanied by a magnetic transition from an antiferromagnetic to a ferromagnetic configuration. These results open new possibilities for creating functional magnetic devices with TMDC monolayers via polymorph engineering.

Ultrasound features of cutaneous myiasis: a rare case in a child.

Cutaneous myiasis is an infestation of the skin with larvae of some dipteran species. Among humans, Dermatobia hominis is the most frequently encountered dipteran responsible for cutaneous myiasis. This insect is endemic to tropical and subtropical regions, consequently, individuals travelling from non-endemic areas are most susceptible to infection due to a lack of prior exposure. Three clinical variants of myiasis are distinguished: furuncular, migratory, and wound myiasis. Furuncular myiasis represents the most common form among travelers, yet it is a rare cause of pediatric skin manifestations in developed countries. Limited awareness of this condition in non-endemic regions contributes to diagnostic challenges. In this scenario, ultrasound is useful in the diagnostic workup, enabling the identification of the viable larva.

The prognostic role of albumin levels in lung cancer patients receiving third-line or advanced immunotherapy: a retrospective study.

Background: Immunotherapy functions by leveraging immunoregulation drugs to bolster the immune system's capacity to identify and eliminate cancerous cells. In contrast to radiotherapy and chemotherapy, immunotherapy exhibits diminished side effects, heightened efficacy, and prolonged survival rates. Nevertheless, meticulous exploration into the determinants governing the advantageous effects of immunotherapy among patients who have previously undergone multiple prior therapies has yet to be conducted. Albumin (ALB) as a nutritional indicator has not been thoroughly studied for its prognostic effect on efficacy or survival. This study aims to identify factors that influence treatment outcomes among patients undergoing third-line or later immunological therapies. Methods: A cohort of 250 lung cancer patients undergoing toripalimab or tislelizumab immunotherapy was the focal point of data collection. The determination of the median value facilitated the establishment of a cut-off point, enabling the categorization of continuous variables. After data collection, a series of statistical analyses of various clinical factors at baseline were performed, including nonparametric tests, logistic regression, and Cox proportional risk modeling. The last follow-up was in May 2022. The primary study endpoint was overall survival (OS). Results: A total of 250 patients were enrolled in the study, of which 129 patients received first- or second-line immunotherapy and 121 patients received third-line or subsequent immunotherapy. According to Cox multifactor regression analysis, in patients receiving either first- or second-line therapy, the ALB level exhibited negligible prognostic relevance (P>0.05). However, in patients subjected to immunotherapy beyond the second line, the ALB level manifested significant prognostic importance (P=0.039). Notably, patients demonstrating elevated ALB levels achieved a higher disease control rate (DCR) (70.0% vs. 52.5%, P=0.05) and displayed a tendency towards a heightened objective response rate (ORR) (20.0% vs. 16.4%, P=0.61) in comparison to those with lower ALB levels. Conclusions: Among patients undergoing immunotherapy in the third line or subsequent treatment phases, elevated ALB levels in baseline correlated with DCR and OS. Thus, the pre-immunotherapy ALB level emerges as an autonomous predictor of OS in patients subjected to third- or later line immunotherapy interventions.

Effects of KEAP1 Silencing on NRF2 and NOTCH Pathways in SCLC Cell Lines.

The KEAP1/NRF2 pathway is a master regulator of several redox-sensitive genes implicated in the resistance of tumor cells against therapeutic drugs. The dysfunction of the KEAP1/NRF2 system has been correlated with neoplastic patients' outcomes and responses to conventional therapies. In lung tumors, the growth and the progression of cancer cells may also involve the intersection between the molecular NRF2/KEAP1 axis and other pathways, including NOTCH, with implications for antioxidant protection, survival of cancer cells, and drug resistance to therapies. At present, the data concerning the mechanism of aberrant NRF2/NOTCH crosstalk as well as its genetic and epigenetic basis in SCLC are incomplete. To better clarify this point and elucidate the contribution of NRF2/NOTCH crosstalk deregulation in tumorigenesis of SCLC, we investigated genetic and epigenetic dysfunctions of the KEAP1 gene in a subset of SCLC cell lines. Moreover, we assessed its impact on SCLC cells' response to conventional chemotherapies (etoposide, cisplatin, and their combination) and NOTCH inhibitor treatments using DAPT, a γ-secretase inhibitor (GSI). We demonstrated that the KEAP1/NRF2 axis is epigenetically controlled in SCLC cell lines and that silencing of KEAP1 by siRNA induced the upregulation of NRF2 with a consequent increase in SCLC cells' chemoresistance under cisplatin and etoposide treatment. Moreover, KEAP1 modulation also interfered with NOTCH1, HES1, and DLL3 transcription. Our preliminary data provide new insights about the downstream effects of KEAP1 dysfunction on NRF2 and NOTCH deregulation in this type of tumor and corroborate the hypothesis of a cooperation of these two pathways in the tumorigenesis of SCLC.

The StuA Transcription Factor and Alternative Splicing Mechanisms Drive the Levels of MAPK Hog1 Transcripts in the Dermatophyte Trichophyton rubrum.

Trichophyton rubrum is a human fungal pathogen that causes dermatophytosis, an infection that affects keratinized tissues. Integrated molecular signals coordinate mechanisms that control pathogenicity. Transcriptional regulation is a core regulation of relevant fungal processes. Previous RNA sequencing data revealed that the absence of the transcription factor StuA resulted in the differential expression of the MAPK-related high glycerol osmolarity gene (hog1) in T. rubrum. Here we validated the role of StuA in regulating the transcript levels of hog1. We showed through RT-qPCR that transcriptional regulation controls hog1 levels in response to glucose, keratin, and co-culture with human keratinocytes. In addition, we also detected hog1 pre-mRNA transcripts that underwent alternative splicing, presenting intron retention in a StuA-dependent mechanism. Our findings suggest that StuA and alternative splicing simultaneously, but not dependently, coordinate hog1 transcript levels in T. rubrum. As a means of preventing and treating dermatophytosis, our results contribute to the search for new potential drug therapies based on the molecular aspects of signaling pathways in T. rubrum.

Congenital tibial pseudarthrosis: A challenge in pediatric radiology.

Congenital pseudarthrosis of the tibia (CPT) is a rare disorder affecting the skeletal system in pediatric population with an estimated incidence of 1:140,000 to 1:250,000 newborns. It is characterized by deformity of the tibia, including anterolateral bowing of the bone diaphysis and/or narrowing of the medullary canal, leading to instability or fracture. CPT can be either idiopathic or associated with underlying conditions such as type 1 neurofibromatosis (NF1), fibrous dysplasia, or Campanacci's osteofibrous dysplasia. Diagnosis is based on clinical and imaging findings, using conventional radiography and magnetic resonance imaging (MRI). The disorder is characterized by recurrent pathological fractures of the tibia or fibula during childhood, often beginning by the age of 2 years. Treatment options include surgical and nonsurgical management.

A substitutional quantum defect in WS2 discovered by high-throughput computational screening and fabricated by site-selective STM manipulation.

Point defects in two-dimensional materials are of key interest for quantum information science. However, the parameter space of possible defects is immense, making the identification of high-performance quantum defects very challenging. Here, we perform high-throughput (HT) first-principles computational screening to search for promising quantum defects within WS2, which present localized levels in the band gap that can lead to bright optical transitions in the visible or telecom regime. Our computed database spans more than 700 charged defects formed through substitution on the tungsten or sulfur site. We found that sulfur substitutions enable the most promising quantum defects. We computationally identify the neutral cobalt substitution to sulfur (Co S 0 ) and fabricate it with scanning tunneling microscopy (STM). The Co S 0 electronic structure measured by STM agrees with first principles and showcases an attractive quantum defect. Our work shows how HT computational screening and nanoscale synthesis routes can be combined to design promising quantum defects.

Single-port video-assisted thoracoscopic sleeve lobectomy after neoadjuvant immunochemotherapy: a case report.

Background: The morbidity and mortality of lung cancer have always ranked first among malignant tumors (MTs). Previous studies have shown that neoadjuvant chemotherapy can improve the 5-year survival rate of patients with non-small cell lung cancer (NSCLC), but the benefit is limited. Studies have proven that neoadjuvant immunotherapy combined with chemotherapy has unique advantages in prolonging patient survival, reducing distant recurrence, and inducing antitumor immunity. However, its impact remains to be more comprehensively investigated. Case Description: A 59-year-old male who was admitted to the hospital with a primary complaint of repeated cough and expectoration for 6 months. Preoperative assessment showed right upper lung squamous cell carcinoma with multiple hilar and mediastinal lymph node metastasis, and the clinical stage was cT2aN2M0 stage (IIIA). After three cycles of pembrolizumab + carboplatin + paclitaxel therapy were administered, the reexamination of the tumor was evaluated as partial response (PR), and a sleeve lobectomy of the right upper lung was performed under single-port thoracoscopic surgery. The operation proceeded smoothly without conversion to thoracotomy, and R0 resection was successfully achieved. Postoperative pathological stage was ypT1bN0M0 stage IA, and postoperative pathological remission was evaluated as major pathological response (MPR). After the operation, three cycles of immunotherapy combined with chemotherapy were completed, which was followed by maintenance therapy with pembrolizumab monotherapy for 1 year, and no signs of tumor recurrence and metastasis have been found in follow-up thus far. Conclusions: Through this case, we believe that for locally advanced NSCLC sleeve lobectomy after neoadjuvant therapy may be a safe and feasible treatment option, can avoid pneumonectomy, protect the lung function of patients, and still ensure the R0 resection rate. Moreover, it may does not significantly increase the difficulty of surgical operation or reduce safety. However, further research is needed to confirm our conclusion. And then, neoadjuvant therapy in the perioperative period may induce a series of side effects or adverse reactions, and thus greater attention should be paid to its timely management.

PD-1-induced encephalopathy: a report of 2 cases on neurological toxicities with immune checkpoint inhibitors.

Background: Immune-related adverse effects (irAEs) often occur during immune checkpoint inhibitor (ICI) therapy. In the nervous system, the incidence of irAEs ranges from 0.1-12%, with 80% occurring within the first 4 months of ICI application. For complications of the nervous system, adequate diagnosis is made by signs, symptoms, imaging and cerebrospinal fluid. If severe irAEs occur, ICIs should be discontinued and patients should be treated with high-dose glucocorticoids, immunoglobulins, or immunosorbent therapy with systemic support. Patients who develop severe neurologic irAEs have a poorer prognosis. Case Description: In this article, we report 2 cases of encephalopathy induced by anti-programmed cell death protein 1 (PD-1) monoclonal antibodies at the initial diagnoses. Our findings may help clinicians to differentiate between encephalopathy caused by immunotherapy and other neurological disorders. Case 1 was a 24-year-old male patient who had undergone PD-1 immunotherapy to treat olfactory neuroblastoma. After the 6th course of therapy, he began to develop persistent epilepsy, which decreased significantly after high doses of glucocorticoid and immunosorbent therapy were administered. Based on his medical history and laboratory examination results, PD-1-induced encephalopathy was the most likely diagnosis. Case 2 was a 67-year-old female patient who had been treated with PD-1/programmed death ligand-1 therapy for lung adenocarcinoma. She began to have headaches after 1 cycle of treatment, and her cognitive function gradually decreased with the continuation of immunotherapy. Conclusions: These case reports show the difficulty in distinguishing PD-1-induced encephalopathy from other neurological disorders, especially paraneoplastic neurological syndromes. If not treated properly, patients' lives may be endangered. Thus, early identification and early treatment are very important.

An evaluation of root resorption associated with the use of photobiomodulation during orthodontic treatment with clear aligners: a retrospective cohort pilot study.

OBJECTIVES: To evaluate the change in tooth root volume using cone-beam computed tomography (CBCT) in a group of patients treated concurrently with clear aligners and an adjunctive photobiomodulation (PBM) device. MATERIALS AND METHODS: This retrospective cohort pilot study included the records of 32 consecutively treated clear aligner patients (23 female, 9 male) from the private practice of one orthodontist. The PBM group (n = 16) used the device once per day for 5 minutes per arch and was compared with a matched control group (n = 16). A semiautomated segmentation technique was used to obtain tooth volume of anterior teeth from CBCT imaging prior to (T0) and during or immediately following (T1) orthodontic treatment with clear aligners. The change in root volume between time points was assessed. RESULTS: There was no statistically significant difference between the pre- and posttreatment root volumes of maxillary and mandibular anterior teeth, regardless of which intervention group the patient belonged to (P > .05). There was also no difference in the mean percentage change in root volume between clear aligner patients in this study who were treated with the PBM device compared with a matched control group (P > .05). CONCLUSIONS: Clear aligner patients in this study who changed their aligners every 3 to 5 days and used adjunctive photobiomodulation therapy did not experience clinically relevant orthodontically induced external root resorption. Due to the small sample size and measurement error in the root segmentation process, the results should be interpreted with caution.

Molecular Signaling and Metabolic Responses during the Interaction between Human Keratinocytes (HaCaT) and the Dermatophyte Trichophyton rubrum.

Trichophyton rubrum is the leading causative agent of dermatophytosis worldwide. Keratinocytes are the first line of defense that drives an immune response against fungal invasion. Host-specific pattern recognition receptors (PRRs) recognize pathogen-associated molecular patterns (PAMPs) to trigger immunological pathways. Fungal cell wall components are the primary sources of fungal PAMPs, and some pathogens increase cell wall rearrangement to evade the immune system. Glycolysis and enhanced lactate levels are critical for improving host immune responses to fungal infections. Using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), we evaluated the transcriptional responses of human genes involved in fungal recognition and glycolytic metabolism and fungal cell-wall-related genes in a co-culture model of human keratinocytes with T. rubrum. We observed the upregulation of several Toll-like receptors (TLRs), NOD-like receptors (NLRs), and glycolytic genes. Complementarily, we measured intra- and extracellular glucose levels and the increase in lactate production in the co-culture supernatant. We noted a distinct transcriptional regulation pattern of fungal cell-wall-related genes from fungal growth on keratin as the primary carbon source compared to co-culture with human keratinocytes. Our results showed new insights into the transcriptional adaptation of keratinocytes, particularly in regulating genes involved in sensing and metabolic processes, during the interaction with T. rubrum.

Clinical impact of mixed pulmonary carcinoma and carcinoid: the driver from their mono-clonal origin.

The combination of neuroendocrine/non neuroendocrine lung tumors (CNNELT) mentioned in the last edition of the World Health Organization (WHO) of Thoracic Tumors refers to small cell carcinoma (SCLC) or large cell neuroendocrine carcinoma (LCNEC) mixed with any other non-small cell lung carcinoma (NSCLC). Typical Carcinoid (TC)/Atypical Carcinoid (AC) combined with NSCLC is not included among this category. However, case reports of TC/AC combined with NSCLC have been described. We previously reported 2 cases of lung adenocarcinoma (LUA) mixed with carcinoid sharing mutations in both components supporting the hypothesis of a clonal origin. We extended our analysis to other four cases of mixed NSCLC-carcinoid by performing targeted-DNA and RNA-based NGS analysis in both primary and their paired lymph nodes metastasis. In all cases, LUA and AC components shared at least 1 common mutation (KRAS driver mutation p.Gly12Val in cases 1 and 3, AKAP13-RET fusion in case 2, and missense KRAS driver mutation p.Gly12Ala in case 4, reinforcing the hypothesis of a clonal origin. Moreover, the same mutation was detected in the metastasis constituted only by AC (cases 2 and 4). Although it is a rare malignancy in the lung, mixed LUA and TC/AC could be included among the histotypes for which a deep molecular characterization of both components is needed to identify the presence of potential druggable genetic alterations.

Type 2 diabetes mellitus pharmacological remission with dapagliflozin plus oral semaglutide.

Dapagliflozin, a sodium-glucose co-transporter-2 inhibitor and semaglutide, a glucagon-like peptide 1 receptor agonist, have both demonstrated efficacy in glycemic control, reducing blood pressure, body weight, risk of renal and heart failure in type 2 diabetes mellitus. In this observational, real-world, study we aimed to investigate the efficacy of the combination therapy with those two agents over glycemic control. We thus obtained the data of 1335 patients with type 2 diabetes followed by 11 Diabetes centers in Lombardia, Italy. A group of 443 patients was treated with dapagliflozin alone, the other group of 892 patients was treated with the combination therapy of dapagliflozin plus oral semaglutide. We analyzed changes in glycated hemoglobin from baseline to 6 months of follow-up, as well as changes in fasting glycemia, body weight, body mass index, systolic and diastolic pressure, heart rate, creatinine, estimated glomerular filtration rate and albuminuria. Both groups of patients showed an improvement of glycometabolic control after 6 months of treatment; indeed, the treatment with dapagliflozin plus oral semaglutide showed a reduction of glycated hemoglobin of 1.2% as compared to the 0.5% reduction observed in the dapagliflozin alone group. Significant changes were observed in body mass index, fasting plasmatic glucose, blood pressure, total cholesterol, LDL and albumin to creatinine ratio, with a high rate (55%) of near-normalization of glycated hemoglobin. Our real world data confirmed the potential of the oral combination therapy dapagliflozin with semaglutide in inducing pharmacological remission of type 2 diabetes mellitus.

B7-H3/CD276 and small-cell lung cancer: What's new?

Immunotherapy revolutionized the treatment landscape of several cancers, including small-cell lung cancer (SCLC), with a huge number of practice-changing trials, and becoming a new frontier for their management. The addition of an anti-PD-L1, atezolizumab or durvalumab, to platinum/etoposide regimen became the standard of care for first-line therapy of extensive-stage (ES)-SCLC with the 12 months median survival exceeded for the first time. Nevertheless, most patients show primary or acquired resistance to anti-PD-L1 therefore new promising therapeutic immune-targets are under clinical investigation in several solid tumors. Among these, B7-H3, also known as CD276, is a member of the B7 family overexpressed in tumor tissues, including SCLC, while showing limited expression in normal tissues becoming an attractive and promising target for cancer immunotherapy. B7-H3 plays a dual role in the immune system during the T-cell activation, acting as a T-cell costimulatory/coinhibitory immunoregulatory protein, and promoting pro-tumorigenic functions such as tumor migration, invasion, metastases, resistance, and metabolism. Immunohistochemistry, flow cytometry, and immunofluorescence were the most used methods to assess B7-H3 expression levels and validate a possible relationship between B7-H3 staining patterns and clinicopathological features in lung cancer patients. To date, there are no clinically available therapeutics/drugs targeting B7-H3 in any solid tumors. The most promising preliminary clinical results have been reported by DS7300a and HS-20093, both are antibody-drug conjugates, that are under investigation in ongoing trials for the treatment of pretreated SCLC. This review will provide an overview of B7-H3 and corresponding inhibitors and the clinical development in the management of SCLC.

Osimertinib versus comparator first-generation epidermal growth factor receptor tyrosine kinase inhibitors as first-line treatment in patients with advanced EGFR-mutated non-small cell lung cancer: a Chinese, multicenter, real-world cohort study.

Background: In the phase 3 FLAURA trial, osimertinib was compared with first-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) as a first-line treatment for EGFR-mutant non-small cell lung cancer (NSCLC). Osimertinib showed longer progression-free survival (PFS), overall survival (OS), and a similar safety profile. However, more studies demonstrating the effectiveness and safety of osimertinib as a first-line strategy are needed in real-world populations. Methods: We enrolled 1,556 patients with EGFR-mutated stage IIIc-IV NSCLC from the CAPTRA-Lung database. All patients received either osimertinib (n=202) or a first-generation EGFR-TKI (n=1,354) as their initial treatment. To adjust for differences in baseline characteristics between two groups, 1:2 propensity score matching (PSM) was performed. Propensity scores included gender, age, Eastern Cooperative Oncology Group performance status score, smoking history, family history of tumor, pathology, EGFR mutations, and central nervous system (CNS) metastases. The standardized mean differences (SMD) before and after PSM were calculated to examine the balance of covariate distributions between two groups. Results: After PSM, 202 patients receiving osimertinib and 404 patients receiving first-generation EGFR-TKIs were finally identified. SMD of each matched variable is less than 0.10. The median PFS was 19.4 months [95% confidence interval (CI): 14.3-24.4] in the osimertinib arm and 10.9 months (95% CI: 9.3-12.5) in the comparator arm [hazard ratio (HR) for progression, 0.47; 95% CI: 0.38-0.59; P<0.001). The median OS was 40.5 months (95% CI: 27.1-54.0) vs. 34.3 months (95% CI: 30.6-38.0) in two groups, respectively (HR for death, 0.76; 95% CI: 0.58-1.00; P=0.045). The incidence of grade 3 adverse events (AEs) between the two groups was 1% and 4.2%, respectively. No grade 4 AEs and treatment-related deaths were reported in both groups. Conclusions: In real-world settings, osimertinib demonstrates longer PFS and OS, with a similar safety profile to that of comparator EGFR-TKIs when used as a first-line strategy in NSCLC patients.

Unlocking New Horizons in Small-Cell Lung Cancer Treatment: The Onset of Antibody-Drug Conjugates.

Small-cell lung cancer (SCLC) is a highly aggressive disease, accounting for about 15% of all lung cancer cases. Despite initial responses to chemoimmunotherapy, SCLC recurs and becomes resistant to treatment. Recently, antibody-drug conjugates (ADCs) have emerged as a promising therapeutic option for SCLC. ADCs consist of an antibody that specifically targets a tumor antigen linked to a cytotoxic drug. The antibody delivers the drug directly to the cancer cells, minimizing off-target toxicity and improving the therapeutic index. Several ADCs targeting different tumor antigens are currently being evaluated in clinical trials for SCLC. Despite the negative results of rovalpituzumab tesirine (Rova-T), other ADCs targeting different antigens, such as B7-H3, seizure-related homolog 6 (SEZ6), and CEACAM5, have also been investigated in clinical trials, including for SCLC, and their results suggest preliminary activity, either alone or in combination with other therapies. More recently, sacituzumab govitecan, an anti-TROP2 ADC, demonstrated promising activity in lung cancer, including SCLC. Furthermore, an anti-B7-H3 (CD276), ifinatamab deruxtecan (DS7300A), showed a high response rate and durable responses in heavily pretreated SCLC. Overall, ADCs represent an intriguing approach to treating SCLC, particularly in the relapsed or refractory setting. Further studies are needed to determine their efficacy and safety and the best location in the treatment algorithm for SCLC. In this review, we aim to collect and describe the results regarding the past, the present, and the future of ADCs in SCLC.

Daytime hypoglycemic episodes during the use of an advanced hybrid closed loop system.

AIMS: The use of advanced hybrid closed loop systems is spreading due to the beneficial effects on glycometabolic control obtained in patients with type 1 diabetes. However, hypoglycemic episodes can be sometimes a matter of concern. We aim to compare the hypoglycemic risk of an advanced hybrid closed loop system and a predictive low glucose suspend sensor augmented pump. METHODS: In this retrospective three months observational study, we included 30 patients using Medtronic Minimed™ 780G advanced hybrid closed loop system and 30 patients using a Medtronic Minimed™ predictive low glucose suspend sensor augmented pump. RESULTS: The advanced hybrid closed loop system reduced the time spent above 180 mg/dL threshold and increased the time in range as compared to the predictive low glucose suspend. No severe hypoglycemia occurred in both groups and no differences were observed in the percentage of time spent below 70 mg/dl and 54 mg/dl glucose threshold. Nevertheless, more hypoglycemic episodes were recorded during daytime, but not in nighttime, with the use of the advanced hybrid closed loop system. CONCLUSIONS: Our results confirmed the general improvement of glycemic outcomes obtained with the advanced hybrid closed loop system; however more hypoglycemic episodes during daytime were evident.

The FDA-approved drug nitazoxanide is a potent inhibitor of human seasonal coronaviruses acting at postentry level: effect on the viral spike glycoprotein.

Coronaviridae is recognized as one of the most rapidly evolving virus family as a consequence of the high genomic nucleotide substitution rates and recombination. The family comprises a large number of enveloped, positive-sense single-stranded RNA viruses, causing an array of diseases of varying severity in animals and humans. To date, seven human coronaviruses (HCoV) have been identified, namely HCoV-229E, HCoV-NL63, HCoV-OC43 and HCoV-HKU1, which are globally circulating in the human population (seasonal HCoV, sHCoV), and the highly pathogenic SARS-CoV, MERS-CoV and SARS-CoV-2. Seasonal HCoV are estimated to contribute to 15-30% of common cold cases in humans; although diseases are generally self-limiting, sHCoV can sometimes cause severe lower respiratory infections and life-threatening diseases in a subset of patients. No specific treatment is presently available for sHCoV infections. Herein we show that the anti-infective drug nitazoxanide has a potent antiviral activity against three human endemic coronaviruses, the Alpha-coronaviruses HCoV-229E and HCoV-NL63, and the Beta-coronavirus HCoV-OC43 in cell culture with IC50 ranging between 0.05 and 0.15 µg/mL and high selectivity indexes. We found that nitazoxanide does not affect HCoV adsorption, entry or uncoating, but acts at postentry level and interferes with the spike glycoprotein maturation, hampering its terminal glycosylation at an endoglycosidase H-sensitive stage. Altogether the results indicate that nitazoxanide, due to its broad-spectrum anti-coronavirus activity, may represent a readily available useful tool in the treatment of seasonal coronavirus infections.

Liposarcoma of the spermatic cord: The state of art and our experience.

Liposarcoma of the spermatic cord is a malignant neoformation so rare that less than 200 cases are reported in the world. It is a tumor that originates from adipose tissue and when it is found in the spermatic cord it can deceptively simulate an inguinal hernia and not be easily identified. The present work describes the case of a 37-year-old man with liposarcoma of the spermatic cord who arrives at our institution with painless swelling of the left testicle. Physical examination revealed a painless swelling in the scrotal sac. The scrotal ultrasound examination revealed a mass, measuring 8 cm (cranio-caudal) × 5.4 cm (latero-lateral) × 8 cm (antero-posterior) and characterized later with a basal CT examination of the abdomen. The patient was subsequently surgically treated with excision of the tumor, plus hernial plastic with plug and mesh. Histological examination revealed a mature adipocyte neoplasm whose morphological and molecular characteristics (amplification of the MDM2 gene) are consistent with the diagnosis of dediferrentiated liposarcoma variety CO-MINGLED, G2 (sec. FNCLCC). The patient is currently under cancer surveillance with no signs of loco-regional recurrence. Spermatic cord liposarcoma is an extremely rare malignancy. It's not easy to identify as it can simulate an inguinal hernia, hydrocele, lipoma, funicular cyst, or testicular tumor. Diagnosis is usually established postsurgery, however, relapses are common and the role of chemo-radiotherapy remains to be defined.