Majorana-like Coulomb spectroscopy in the absence of zero-bias peaks.

Hybrid semiconductor-superconductor devices hold great promise for realizing topological quantum computing with Majorana zero modes1-5. However, multiple claims of Majorana detection, based on either tunnelling6-10 or Coulomb blockade (CB) spectroscopy11,12, remain disputed. Here we devise an experimental protocol that allows us to perform both types of measurement on the same hybrid island by adjusting its charging energy via tunable junctions to the normal leads. This method reduces ambiguities of Majorana detections by checking the consistency between CB spectroscopy and zero-bias peaks in non-blockaded transport. Specifically, we observe junction-dependent, even-odd modulated, single-electron CB peaks in InAs/Al hybrid nanowires without concomitant low-bias peaks in tunnelling spectroscopy. We provide a theoretical interpretation of the experimental observations in terms of low-energy, longitudinally confined island states rather than overlapping Majorana modes. Our results highlight the importance of combined measurements on the same device for the identification of topological Majorana zero modes.

Salvage endoscopic nasopharyngectomy for recurrent nasopharyngeal carcinoma in a non-endemic area.

PURPOSE: To analyze oncological outcomes of endoscopic surgical treatment of locally recurrent EBV-related undifferentiated non-keratinizing nasopharyngeal carcinoma (uNK-NPC) in a non-endemic area. METHODS: Retrospective review of patients affected by recurrent uNK-NPC treated with nasopharyngeal endoscopic resection (NER) in a tertiary-care referral center from 2003 to 2022, by evaluating survival rates, prognostic factors, and follow-up strategies. RESULTS: The oncological outcomes of 41 patients were analyzed, over a mean follow-up period of 57 months. The 5-year overall, disease-specific, and disease-free survival of the cohort were 60.7% ± 8.9%, 69% ± 9%, and 39.7% ± 9.2%, respectively. The local (rT) and regional (rN) extension of recurrent disease, stage of disease, and status of resection margins appeared to significantly influence survivals. After a mean follow-up period of 21 months, a further recurrence after NER was observed in 36.6% of cases. Skull base osteonecrosis induced by previous irradiation and post-surgical bone remodeling represent the major challenges for early detection of further local relapses during postoperative follow-up. CONCLUSION: NER appeared as a safe and effective treatment for recurrent uNK-NPC. The adequate selection of patients eligible for NER is essential, to maximize the chances to cure and minimize the risk of local complications.

Surgical Approaches for Possible Positions of an Olfactory Implant to Stimulate the Olfactory Bulb.

INTRODUCTION: Current scientific developments seem to allow for an "olfactory implant" in analogy to cochlear implants. However, the position and surgical approaches for electrical stimulation of the olfactory system are unclear. METHODS: In a human anatomic cadaver study, we investigated different endoscopic approaches to electrically stimulate the olfactory bulb (OB) based on the following considerations: (1) the stimulating electrode should be close to the OB. (2) The surgical procedure should be as non-invasive and safe as possible and (3) as easy as possible for an experienced ENT surgeon. RESULTS: In summary, the endoscopic intracranial positioning of the electrode via a widened ostium of the fila olfactoria or a frontal sinus surgery like a Draf IIb procedure is a good option in terms of patients' risk, degree of difficulty for ENT surgeons, and position to the OB. Endoscopic intranasal positioning appeared to be the best option in terms of patient risk and the degree of difficulty for ENT surgeons. Although a bigger approach to the OB using a drill and the combined intranasal endoscopic and external approach enabled a close placement of the electrode to the OB, they do not seem relevant in practice due to their higher invasiveness. CONCLUSION: The study suggested that an intranasal positioning of a stimulating electrode is possible, with placements beneath the cribriform plate, extra- or intracranially, applying elegant surgical techniques with low or medium risk to the patient and a close placement to OB.

Solitary fibrous tumor: A rare lesion with an unusual paravertebral presentation.

BACKGROUND: Solitary fibrous tumor (SFT) is a rare spindle-cell neoplasm [1]. Although typically originating from pleura, head and neck presentation accounts for about 6-18 % and very few cases have been described in paravertebral and posterior neck spaces [2]. Both computed tomography (CT) scans and magnetic resonance imaging (MRI) help in differential diagnosis of such lesion [3]. However, only histological and immunohistochemical studies give a conclusive diagnosis: CD34, BCL-2, and in particular STAT6 stainings are strongly orientative [4]. Radical surgery with free margin excision is the first treatment option, rarely requiring adjuvant therapy [2]. Prognosis is typically good and strictly related to histological risk assessment [5]. Rare cases of local recurrence and distant metastasis have been described in literature [2]. OBJECTIVE: The purpose of this video is to describe the operative technique of a transcervical removal of a rare case of right paravertebral SFT. We present the diagnostic flowchart, management strategies, surgical technique and we provide anatomical dissection parallelism, which might be of interest to the readers. MATERIALS AND METHODS: A 59-years-old man with a one-year right cervical asymptomatic swelling was referred to our department. A contrasted MRI documented an expansive 6.5 cm capsulated lesion in the deep posterior neck spaces with diffuse contrast enhancement and inhomogeneous appearance. A core needle biopsy was performed, and the results from the initial immunohistochemical panel were not univocal showing positivity for cytokeratins AE1/AE3, PAX8, and no reactivity for CD34. A second immunohistochemical panel was then performed, displaying diffuse nuclear positivity for STAT6, which is a surrogate marker for the NAB2-STAT6 gene fusion, a specific driver mutation of SFT. Therefore, a radical excision was performed via transcervical approach (Video 1). No post-operative complications neither cranio-cervical neurological deficit occurred. RESULTS: In comparison to pre-operative histopathologic study, the definitive histological examination of the whole mass revealed a more classical morphology of SFT. It was classified as an intermediate risk SFT [5]. A complete free margin excision was confirmed. After a multidisciplinary discussion, no adjuvant therapies were suggested. A six- and twelve-months radiological follow-up with MRI showed no evidence of disease. CONCLUSION: SFT may represent a misdiagnosed entity in head and neck spaces and a correct diagnosis through immunohistochemistry is mandatory. Radical excision with free surgical margins should be pursued as adequate goal. Since SFTs show variable risk of metastatic disease, adjuvant radiotherapy should be contemplated in high-risk diseases and a clinico-radiological follow-up with MRI is required.

Forty-Eight-Month Monitoring of Disease Activity in Patients with Long-Standing Rheumatoid Arthritis Treated with TNF-α Inhibitors: Time for Clinical Outcome Prediction and Biosimilar vs Biologic Originator Performance.

BACKGROUND AND OBJECTIVES: Long-term treatment of patients with rheumatoid arthritis with tumor necrosis factor-α inhibitors leads to initial changes in disease activity that can predict a late treatment response. This observational and retrospective study aimed to determine when it is possible to foresee the response to therapy in the case of long-standing rheumatoid arthritis comparing also the efficacy of the original biologics with their biosimilars. METHODS: A total of 1598 patients were recruited and treated with the original biologics, adalimumab and etanercept, or with biosimilars. Patients were monitored over a period of 48 months and disease activity scores (28-Joint Disease Activity Score, Simplified Disease Activity Index, and Clinical Disease Activity Index) were measured every 6 months. RESULTS: No differences in disease activity levels were observed in etanercept versus biosimilars (GP2015/SB4) and adalimumab versus biosimilar (GP2017) patient groups. All scores significantly decreased in all treatments during the first 18 months of therapy, and after 24 months reached a minimum that lasted up to 48 months. CONCLUSIONS: We conclude that biosimilars of adalimumab and etanercept have equivalent effectiveness over a long period of time compared to their originator drugs, and also that the levels of disease activity after 6 months of tumor necrosis factor-α inhibitors (originator drugs and biosimilars) might predict the response to therapy at 4 years in patients with long-standing rheumatoid arthritis.

Parity-conserving Cooper-pair transport and ideal superconducting diode in planar germanium.

Superconductor/semiconductor hybrid devices have attracted increasing interest in the past years. Superconducting electronics aims to complement semiconductor technology, while hybrid architectures are at the forefront of new ideas such as topological superconductivity and protected qubits. In this work, we engineer the induced superconductivity in two-dimensional germanium hole gas by varying the distance between the quantum well and the aluminum. We demonstrate a hard superconducting gap and realize an electrically and flux tunable superconducting diode using a superconducting quantum interference device (SQUID). This allows to tune the current phase relation (CPR), to a regime where single Cooper pair tunneling is suppressed, creating a [Formula: see text] CPR. Shapiro experiments complement this interpretation and the microwave drive allows to create a diode with ≈ 100% efficiency. The reported results open up the path towards integration of spin qubit devices, microwave resonators and (protected) superconducting qubits on  the same silicon technology compatible platform.

Sinonasal Malignancies Involving the Frontal Sinus: A Mono-Institutional Experience of 84 Cases and Systematic Literature Review.

Frontal sinus involvement by malignant tumors is a rare finding. Therefore, a systematic literature review along with a personal case series may contribute to defining more accurately the epidemiology, treatment options, and outcomes of these neoplasms. This is a retrospective review of patients affected by frontal sinus malignancies surgically treated in a tertiary-care referral center over a period of 20 years. Moreover, a systematic literature review of studies describing frontal sinus cancers from 2000 to date was performed according to PRISMA guidelines in order to analyze current evidence about the treatment and outcomes of such a rare disease. Our retrospective review was basedon 84 cases, treated with an exclusive endoscopic approach in 43 cases (51.2%), endoscopic approach with frontal osteoplastic flap in 6 cases (7.1%), and transfacial or transcranial approaches in 35 cases (41.7%). The five-year overall, disease-specific, disease-free, and recurrence-free survivals were 54.6%, 62.6%, 33.1%, and 59.1%, respectively. Age, dural involvement, type of surgical resection, and surgical margin status were significantly associated with the survival endpoints. In conclusion, the involvement of the frontal sinus is associated with a poor prognosis. Multidisciplinary management, including specific histology-driven treatments, represents the gold standard for improving outcomes and minimizing morbidity.

Aerosolization risk during endoscopic transnasal surgery: a prospective qualitative and quantitative microscopic analysis of particles spreading in the operating room.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic represents the greatest public health emergency of this century. The primary mode of viral transmission is droplet transmission through direct contact with large droplets generated during breathing, talking, coughing, and sneezing. However, the virus can also demonstrate airborne transmission through smaller droplets (< 5 µm in diameter) generated during various medical procedures, collectively termed aerosol-generating procedures. The aim of this study was to analyze droplet contamination of healthcare workers and splatter patterns in the operating theater that resulted from endoscopic transnasal procedures in noninfected patients. METHODS: A prospective nonrandomized microscopic evaluation of contaminants generated during 10 endoscopic transnasal procedures performed from May 14 to June 11, 2020, in the same operating theater was carried out. A dilution of monosodium fluorescein, repeatedly instilled through nasal irrigation, was used as a marker of contaminants generated during surgical procedures. Contaminants were collected on detectors worn by healthcare workers and placed in standard points in the operating theater. Analysis of number, dimensions, and characteristics of contaminants was carried out with fluorescence microscopy. RESULTS: A total of 70 samples collected from 10 surgical procedures were analyzed. Liquid droplets and solid-tissue fragments were identified as contaminants on all detectors analyzed. All healthcare workers appeared to have been exposed to a significant number of contaminants. A significant degree of contamination was observed in every site of the operating room. The mean (range) diameter of liquid droplets was 4.1 (1.0-26.6) µm and that of solid fragments was 23.6 (3.5-263.3) µm. CONCLUSIONS: Endoscopic endonasal surgery is associated with the generation of large amounts of contaminants, some of which measure less than 5 µm. All healthcare workers in the surgical room are exposed to a significant and similar risk of contamination; therefore, adequate personal protective equipment should be employed when performing endoscopic endonasal surgical procedures.

Endoscopic Endonasal Removal of Orbital Schwannoma: Focus on Surgical Technique.

Orbital schwannomas are a rare disease, representing about 1% of orbital tumors, potentially involving any subsite within the orbit. They usually present with painless, nonpulsatile proptosis, while diplopia and vision impairment due to extrinsic ocular muscles or optic nerve involvement are rarely observed.1 A wait-and-see policy is advocated in case of small asymptomatic lesions. However, if progressive dimensional increase or symptoms are observed, surgical resection represents the treatment of choice.2 Different surgical approaches have been proposed, mainly depending on tumor dimension and location inside the orbit, as well as surgical expertise. With advances in technology,3 knowledge,4 and surgical techniques,5 transnasal endoscopic approaches have emerged as a valid option in the management of lesions located medially to the optic nerve, with the advantage of improved visualization and overall decreased morbidity as compared with external approaches.6 We present the case of a 19-year-old woman, affected by an intraextraconal orbital schwannoma located in the left orbit's inferomedial aspect, with a 1-year history of left proptosis associated with retrobulbar pain exacerbated by the upward gaze. The lesion was completely removed with an endoscopic transnasal approach (Video 1), without evidence of postoperative sequelae or visual impairment. Magnetic resonance imaging performed 3 months after surgery showed good surgical results without evidence of persistence of disease. A multidisciplinary approach, involving different specialists familiar with orbital anatomy and physiology, is required for a proper management of patients affected by orbital pathologies.

Nontopological zero-bias peaks in full-shell nanowires induced by flux-tunable Andreev states.

A semiconducting nanowire fully wrapped by a superconducting shell has been proposed as a platform for obtaining Majorana modes at small magnetic fields. In this study, we demonstrate that the appearance of subgap states in such structures is actually governed by the junction region in tunneling spectroscopy measurements and not the full-shell nanowire itself. Short tunneling regions never show subgap states, whereas longer junctions always do. This can be understood in terms of quantum dots forming in the junction and hosting Andreev levels in the Yu-Shiba-Rusinov regime. The intricate magnetic field dependence of the Andreev levels, through both the Zeeman and Little-Parks effects, may result in robust zero-bias peaks-features that could be easily misinterpreted as originating from Majorana zero modes but are unrelated to topological superconductivity.

Combined Endonasal-Transorbital Approach to Manage the Far Lateral Frontal Sinus: Surgical Technique.

In recent decades, the ever-expanding use of endoscopes and development of dedicated instrumentation have reshaped the panorama of surgical approaches to the frontal sinus.1 Nonetheless, the far lateral portion of the sinus might still represent a concern, especially in cases with unfavorable or distorted anatomy.2,3 We report the case of a 52-year-old man, referred to our department for recurrent episodes of left orbital swelling and supraorbital headache, 3 months after Draf III frontal sinusotomy for marsupialization of multiple frontal mucoceles. Computed tomography and magnetic resonance imaging scans were consistent with persistent inflammatory tissue in the far lateral left frontal sinus. Revision surgery was performed, adopting a combined endonasal orbital transposition3 and superior eyelid transorbital approach.4,5 The postoperative course was uneventful, and the microbiologic and histologic examinations demonstrated noninvasive Aspergillus fumigatus infection. The radiologic control showed patency of the frontal recess and complete clearance of the sinus. The patient is asymptomatic after 16 months (Video 1). The transorbital approach is effective in managing orbital and frontal sinus diseases,6 and the combination with the endonasal route grants complete access to the frontal sinus, even in cases of high pneumatization and lateral extension.4,7 Multiportal transorbital approaches represent additional techniques in the rhinologist's surgical armamentarium, which can overcome the limits of a single port approach.8,9 Reports on their use providing technical hints and critical considerations are to be encouraged to ease and stimulate the surgical training in this field.

Endoscopic Endonasal Prelacrimal Approach: Radiological Considerations, Morbidity, and Outcomes.

OBJECTIVE/HYPOTHESIS: This study describes a multicentric experience with the use of prelacrimal approach (PLA), focusing on preoperative radiological parameters potentially associated with surgical outcomes and postoperative morbidity. STUDY DESIGN: Retrospective case-series. METHODS: A retrospective review of patients undergoing PLA in three European referral centers was performed. The post-operative morbidity was analyzed in relation to two radiological parameters: width of prelacrimal recess (WPR) and internal angle of pyriform notch (APN). RESULTS: The study included 28 patients affected by Schneiderian papilloma (20 cases), inflammatory disease (6 cases), schwannoma (1 case), and osteoma (1 case). The most reported sequela was paresthesia of ipsilateral anterior superior alveolar process (25% of the cases). An association between post-operative morbidity and APN was observed (P = .047). CONCLUSIONS: Preoperative radiological evaluation of WPR is crucial in understanding the feasibility of the approach, while APN measurement may predict postoperative morbidity, which is paramount in the patients' counseling. LEVEL OF EVIDENCE: 4 case-series Laryngoscope, 131:1715-1721, 2021.

GMP-based CD133(+) cells isolation maintains progenitor angiogenic properties and enhances standardization in cardiovascular cell therapy.

The aim of the present study was to develop and validate a good manufacturing practice (GMP) compliant procedure for the preparation of bone marrow (BM) derived CD133(+) cells for cardiovascular repair. Starting from available laboratory protocols to purify CD133(+) cells from human cord blood, we implemented these procedures in a GMP facility and applied quality control conditions defining purity, microbiological safety and vitality of CD133(+) cells. Validation of CD133(+) cells isolation and release process were performed according to a two-step experimental program comprising release quality checking (step 1) as well as 'proofs of principle' of their phenotypic integrity and biological function (step 2). This testing program was accomplished using in vitro culture assays and in vivo testing in an immunosuppressed mouse model of hindlimb ischemia. These criteria and procedures were successfully applied to GMP production of CD133(+) cells from the BM for an ongoing clinical trial of autologous stem cells administration into patients with ischemic cardiomyopathy. Our results show that GMP implementation of currently available protocols for CD133(+) cells selection is feasible and reproducible, and enables the production of cells having a full biological potential according to the most recent quality requirements by European Regulatory Agencies.

Antirheumatic drugs for COVID-19 treatment based on the phases of the disease: Current concept.

COVID-19 disease is the most recent pandemic, since it has affected more than four and a half million people and caused more than 300,000 deaths. It is a very complex systemic disease in terms of pathogenesis, treatment, and prognosis. Pharmacological treatment may include antiviral and antimalarial drugs, antibiotics, monoclonal antibodies, corticosteroids as well as low-molecular-weight heparins to prevent the evolution of the disease from reaching the severe inflammatory phase that can lead to respiratory complications, multiple organ failure, disseminated intravascular coagulation (DIC), and finally death. Therefore, pending the development of the much sought-after vaccine, there needs to be a multidisciplinary approach to tackling this disease, and it is essential to use different medical treatments at the correct pathogenic moment. The aim of this article is to evaluate the rationale and reason behind the use of antirheumatic drugs, by expert point of view, in the various phases of the disease. Another important aspect in the management of the disease is to identify patients at high risk, both to change their lifestyle and to correct the state of their health through non-pharmacological measures for improving their immuno-balance. Our literature review reveals the important role and the therapeutic potential of antirheumatic agents in preventing the progression of the disease and aiding recovery from the disease. However, there is a lack of clinical evidence to support the use of these agents, indicating that further randomized controlled studies are required.

MicroRNA expression profiles of human iPSCs differentiation into insulin-producing cells.

AIMS: MicroRNAs are a class of small noncoding RNAs, which control gene expression by inhibition of mRNA translation. MicroRNAs are involved in the control of biological processes including cell differentiation. Here, we aim at characterizing microRNA expression profiles during differentiation of human induced pluripotent stem cells (hiPSCs) into insulin-producing cells. METHODS: We differentiated hiPSCs toward endocrine pancreatic lineage following a 18-day protocol. We analyzed genes and microRNA expression levels using RT real-time PCR and TaqMan microRNA arrays followed by bioinformatic functional analysis. RESULTS: MicroRNA expression profiles analysis of undifferentiated hiPSCs during pancreatic differentiation revealed that 347/768 microRNAs were expressed at least in one time point of all samples. We observed 18 microRNAs differentially expressed: 11 were upregulated (miR-9-5p, miR-9-3p, miR-10a, miR-99a-3p, miR-124a, miR-135a, miR-138, miR-149, miR-211, miR-342-3p and miR-375) and 7 downregulated (miR-31, miR-127, miR-143, miR-302c-3p, miR-373, miR-518b and miR-520c-3p) during differentiation into insulin-producing cells. Selected microRNAs were further evaluated during differentiation of Sendai-virus-reprogrammed hiPSCs using an improved endocrine pancreatic beta cell derivation protocol and, moreover, in differentiated NKX6.1+ sorted cells. Following Targetscan7.0 analysis of target genes of differentially expressed microRNAs and gene ontology classification, we found that such target genes belong to categories of major significance in pancreas organogenesis and development or exocytosis. CONCLUSIONS: We detected a specific hiPSCs microRNAs signature during differentiation into insulin-producing cells and demonstrated that differentially expressed microRNAs target several genes involved in pancreas organogenesis.

Photodetectors based on carbon nanotubes deposited by using a spray technique on semi-insulating gallium arsenide.

In this paper, a spray technique is used to perform low temperature deposition of multi-wall carbon nanotubes on semi-insulating gallium arsenide in order to obtain photodectors. A dispersion of nanotube powder in non-polar 1,2-dichloroethane is used as starting material. The morphological properties of the deposited films has been analysed by means of electron microscopy, in scanning and transmission mode. Detectors with different layouts have been prepared and current-voltage characteristics have been recorded in the dark and under irradiation with light in the range from ultraviolet to near infrared. The device spectral efficiency obtained from the electrical characterization is finally reported and an improvement of the photodetector behavior due to the nanotubes is presented and discussed.