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Cold desert soil microbiomes thrive despite severe moisture and nutrient limitations. In Eastern Antarctic soils, bacterial primary production is supported by trace gas oxidation and the light-independent RuBisCO form IE. This study aims to determine if atmospheric chemosynthesis is widespread within Antarctic, Arctic and Tibetan cold deserts, to identify the breadth of trace gas chemosynthetic taxa and to further characterize the genetic determinants of this process. H2 oxidation was ubiquitous, far exceeding rates reported to fulfill the maintenance needs of similarly structured edaphic microbiomes. Atmospheric chemosynthesis occurred globally, contributing significantly (p Chloroflexota, Firmicutes, Deinococcota and Verrucomicrobiota genomes. We identify a novel group of high-affinity [NiFe]-hydrogenases, group 1m, through phylogenetics, gene structure analysis and homology modeling, and reveal substantial genetic diversity within RuBisCO form IE (rbcL1E), and high-affinity 1h and 1l [NiFe]-hydrogenase groups. We conclude that atmospheric chemosynthesis is a globally-distributed phenomenon, extending throughout cold deserts, with significant implications for the global carbon cycle and bacterial survival within environmental reservoirs.

Aims The purpose was to compare the frequency of needs of patients with schizophrenia in forensic services across five European countries as assessed by both the patients and their care staff. Methods Patients with schizophrenia and a history of significant interpersonal violence were recruited from forensic psychiatric services in Austria, Germany, Italy, Poland and England. Participants’ needs were assessed using the Camberwell Assessment of Needs—Forensic Version (CANFOR). Multiple linear regression analyses were used to identify predictors of numbers of needs. Results In this sample, (n = 221) the most commonly reported need according to patients (71.0%) and staff (82.8%) was the management of psychotic symptoms. A need for information was mentioned by about 45% of staff and patients. Staff members reported a significantly higher number of total needs than patients (mean 6.9 vs. 6.2). In contrast, staff members reported a significantly lower number of unmet needs than patients (mean 2.0 vs. 2.5). Numbers of total needs and met needs differed between countries. Unmet needs as reported by patients showed positive associations with the absence of comorbid personality disorder, with higher positive symptom scores and lifetime suicide or self-harm history. Significant predictors of unmet needs according to staff were absence of comorbid personality disorder and higher positive as well as negative symptom scores according to PANSS. Conclusions Staff rated a significantly higher number of total needs than patients, while patients rated more unmet needs. This indicates that patients’ self-assessments of needs yield important information for providing sufficient help and support.

Mango peel, a by-product of the mango pulp industry, is rich in nutrients but with high moisture content. Drying is indicated to stabilize the residue and use of a drum-dryer is a little studied alternative. The present study evaluated the application of this technology for mango peels, investigating the influence of process conditions. The potential of mango peels from Palmer, Haden, Keitt, and Espada Vermelha varieties was also assessed using physicochemical analyses. The results showed differences between the varieties: Palmer exhibited the lowest moisture content (73.97 g per 100 g); Keitt the highest reducing sugar content (25.06 g per 100 g d.b.); Haden the highest soluble dietary fiber content (20.85 g per 100 g d.b.); and Espada Vermelha the highest phenolic compound content (5462 mg GAE per 100 g d.b.). Palmer mango peels were dried, varying temperature (130.6/146.4 ºC) and residence time (14/28 s). The independent variables influenced mass flow rate, moisture content, and color parameter a*. The antioxidant capacity, phenolic compounds and total carotenoid content, in addition to other color parameters, were not affected. The best process conditions were determined at 138.4-146.4 ºC and 14-21 s. The flakes exhibited phenolic compound contents of 3200 mg GAE per 100 g d.b., and antioxidant capacity of 360 μmol TE g-1 d.b. The product can be used as an ingredient in food formulations. Fundação de Amparo à Pesquisa do Estado de São Paulo - FAPESP

Photonic integrated circuits (PICs) for next-generation optical communication interconnects and all-optical signal processing require efficient (∼A/W) and fast (≥25 Gbs–1) light detection at low (–1) power consumption, in devices compatible with Si processing, so that the monolithic integration of electro-optical materials and electronics can be achieved consistently at the wafer scale. Graphene-based photodetectors can meet these criteria, thanks to their broadband absorption, ultra-high mobility, ultra-fast electron interactions, and strong photothermoelectric effect. High responsivities (∼ 1 A/W), however, have only been demonstrated in biased configurations, which introduce dark current, noise, and power consumption, while unbiased schemes, with low noise and zero consumption, have remained in the ∼ 0.1 A/W regime. Here, we consider the unbiased asymmetric configuration and show that optimized plasmonic enhanced devices can reach for both transverse-electric and transverse-magnetic modes (at λ = 1550 nm), ∼A/W responsivity, and ∼ 100 GHz operation speed at zero power consumption. We validate the model and material parameters by simulating experimental devices and derive analytical expressions for the responsivity. Our comprehensive modeling paves the way for efficient, fast, and versatile optical detection in PICs with zero power consumption.

Worldwide, the coronavirus 19 disease pandemic caused a worse chance of a timely diagnosis for cancer patients. We conducted a retrospective analysis of new diagnoses registered in the national pediatric oncology database, comparing the first lockdown period (March-May 2020) with the same period of 2015-2019. The total number of cases (0-19 years) dropped by 20.8% (from 441 between 2015 and 2019 to 349 in 2020). A major reduction was observed for adolescents (15-19 years) (-32.9%) and for adolescents with solid tumors (-56.4%, p = 0.03). Our data suggest that the enforced lockdown reduced the possibility for these already vulnerable patients to access the referral centers.

Robotic surgery is gaining more space in every country at every level. Wall surgery is one of the fields in which technology can help the surgeons and can give more opportunities to the patients. One of the biggest differences between laparoscopic surgery is that the use of the robot provides excellent 3D VISION of the abdomen and can ease the surgeon, during difficult and tricky situation mostly. One of this wall affection is diastasis recti. It affects about 1/3 of women after childbirth, yet it is still little talked about today. Often underestimated or confined to a cosmetic problem, most of the times abdominal diastasis is a functional problem primary and must be addressed in the correct way. In this video, we report a case of diastasis recti associated with a primary umbilical hernia in a multipara woman. She was 45 with a BMI of 26.4 kg/m2 and she came to our attention after a long period of discomfort and pain. She told us that her umbilical hernia was growing fast in the last months and that the condition of her abdomen was getting worse, with pain and digestive difficulties. At the physical examination we found an umbilical hernia of 3 cm of diameter and a diastasis recti of 6 cm of width. Due to the conditions of the patient, the young age and the will not to have children anymore, we decide to perform a robotic transabdominal retromuscular umbilical prosthetic (rTARUP) «bottom-up approach» (the patient never underwent abdominal surgery).

Supplementary Figure 2: T-cell immunological response to tetanus toxoid over time: Panel A: IFNγ ELISPOT data, similar to that as shown in Figure 3, were plotted over time, subtracting the pre-treatment value, to evaluate the magnitude and durability of immunity over time. Panel B: Immune response over time was plotted as "area under the curve," and evaluated with respect to treatment arm. Lines show median and interquartile range.

Supplementary methods and Figure S1

Purpose:Preclinical studies demonstrated that a DNA vaccine (pTVG-AR, MVI-118) encoding the androgen receptor ligand-binding domain (AR LBD) augmented antigen-specific CD8+ T cells, delayed prostate cancer progression and emergence of castration-resistant disease, and prolonged survival of tumor-bearing mice. This vaccine was evaluated in a multicenter phase I trial.Patients and Methods:Patients with metastatic castration-sensitive prostate cancer (mCSPC) who had recently begun androgen deprivation therapy were randomly assigned to receive pTVG-AR on one of two treatment schedules over one year, and with or without GM-CSF as a vaccine adjuvant. Patients were followed for 18 months. Primary objectives were safety and immune response. Secondary objectives included median time to PSA progression, and 18-month PSA-PFS (PPFS).Results:Forty patients were enrolled at three centers. Twenty-seven patients completed treatment and 18 months of follow-up. Eleven patients (28%) had a PSA progression event before the 18-month time point. No grade 3 or 4 adverse events were observed. Of 30 patients with samples available for immune analysis, 14 (47%) developed Th1-type immunity to the AR LBD, as determined by IFNγ and/or granzyme B ELISPOT. Persistent IFNγ immune responses were observed irrespective of GM-CSF adjuvant. Patients who developed T-cell immunity had a significantly prolonged PPFS compared with patients without immunity (HR = 0.01; 95% CI, 0.0–0.21; P = 0.003).Conclusions:pTVG-AR was safe and immunologically active in patients with mCSPC. Association between immunity and PPFS suggests that treatment may delay the time to castration resistance, consistent with preclinical findings, and will be prospectively evaluated in future trials.See related commentary by Shenderov and Antonarakis, p. 5056

Purpose:This study assesses the action of panobinostat, a histone deacetylase inhibitor (HDACI), in restoring sensitivity to bicalutamide in a castration-resistant prostate cancer (CRPC) model and the efficacy and safety of the panobinostat/bicalutamide combination in CRPC patients resistant to second-line antiandrogen therapy (2ndLAARx).Patients and Methods:The CWR22PC xenograft and isogenic cell line were tested for drug interactions on tumor cell growth and on the androgen receptor (AR), AR-splice variant7, and AR targets. A phase I trial had a 3 × 3 panobinostat dose-escalation design. The phase II study randomized 55 patients to panobinostat 40 mg (A arm) or 20 mg (B arm) triweekly ×2 weeks with bicalutamide 50 mg/day in 3-week cycles. The primary endpoint was to determine the percentage of radiographic progression-free (rPF) patients at 36 weeks versus historic high-dose bicalutamide.Results:In the model, panobinostat/bicalutamide demonstrated synergistic antitumor effect while reducing AR activity. The dose-limiting toxicity was not reached. The probabilities of remaining rPF were 47.5% in the A arm and 38.5% in the B arm, exceeding the protocol-specified threshold of 35%. The A arm but not the B arm exceeded expectations for times (medians) to rP (33.9 and 10 weeks), and from PSA progression to rP (24 and 5.9 weeks). A arm/B arm events included: adverse events (AE), 62%/19%; treatment stopped for AEs, 27.5%/11.5%; dose reduction required, 41%/4%. The principal A-arm grade ≥ 3 AEs were thrombocytopenia (31%) and fatigue (14%).Conclusions:The 40 mg panobinostat/bicalutamide regimen increased rPF survival in CRPC patients resistant to 2ndLAARx. Panobinostat toxicity was tolerable with dose reductions. Epigenetic HDACI therapy reduces AR-mediated resistance to bicalutamide in CRPC models with clinical benefit in patients. The combination merits validation using a second-generation antiandrogen.

Supplemental Figure 1: T-cell immunological response to PSA over time: Panel A: IFNγ ELISPOT data, similar to that as shown in Figure 3, were plotted over time, subtracting the pre-treatment value, to evaluate the magnitude and durability of immunity over time. Panel B: Immune response over time was plotted as "area under the curve," and evaluated with respect to treatment arm. Lines show median and interquartile range.

Supplementary figure legends

Funder: European Commission, Funder: Digital, Industry and Space, Funder: European Research Council, Graphene is an ideal platform to study the coherence of quantum interference pathways by tuning doping or laser excitation energy. The latter produces a Raman excitation profile that provides direct insight into the lifetimes of intermediate electronic excitations and, therefore, on quantum interference, which has so far remained elusive. Here, we control the Raman scattering pathways by tuning the laser excitation energy in graphene doped up to 1.05 eV. The Raman excitation profile of the G mode indicates its position and full width at half-maximum are linearly dependent on doping. Doping-enhanced electron-electron interactions dominate the lifetimes of Raman scattering pathways and reduce Raman interference. This will provide guidance for engineering quantum pathways for doped graphene, nanotubes, and topological insulators.

A co-sputtering process for pre-lithiation of vanadium oxide was successfully developed. The performance is comparable to an electrochemical lithiation of vanadium oxide, which enables its use as a cathode layer in thin-film solid-state batteries.

The scalable synthesis and transfer of large-area graphene underpins the development of nanoscale photonic devices ideal for new applications in a variety of fields, ranging from biotechnology, to wearable sensors for healthcare and motion detection, to quantum transport, communications, and metrology. We report room-temperature zero-bias thermoelectric photodetectors, based on single- and polycrystal graphene grown by chemical vapor deposition (CVD), tunable over the whole terahertz range (0.1-10 THz) by selecting the resonance of an on-chip patterned nanoantenna. Efficient light detection with noise equivalent powers

We present a micrometer-scale, on-chip integrated, plasmonic enhanced graphene photodetector (GPD) for telecom wavelengths operating at zero dark current. The GPD is designed to directly generate a photovoltage by the photothermoelectric effect. It is made of chemical vapor deposited single layer graphene, and has an external responsivity ∼12.2 V/W with a 3 dB bandwidth ∼42 GHz. We utilize Au split-gates to electrostatically create a p-n-junction and simultaneously guide a surface plasmon polariton gap-mode. This increases the light-graphene interaction and optical absorption and results in an increased electronic temperature and steeper temperature gradient across the GPD channel. This paves the way to compact, on-chip integrated, power-efficient graphene based photodetectors for receivers in tele- and datacom modules.

Resistive-switching memories are alternative to Si-based ones, which face scaling and high power consumption issues. Tetrahedral amorphous carbon (ta-C) shows reversible, non-volatile resistive switching. Here we report polarity independent ta-C resistive memory devices with graphene-based electrodes. Our devices show ON/OFF resistance ratios$\sim$4x$10^5$, ten times higher than with metal electrodes, with no increase in switching power, and low power density$\sim$14$\mu$W/$\mu$m$^2$. We attribute this to a suppressed tunneling current due to the low density of states of graphene near the Dirac point, consistent with the current-voltage characteristics derived from a quantum point contact model. Our devices also have multiple resistive states. This allows storing more than one bit per cell. This can be exploited in a range of signal processing/computing-type operations, such as implementing logic, providing synaptic and neuron-like mimics, and performing analogue signal processing in non-von-Neumann architectures

Introduction Two recent prospective trials have been published, reporting opposite results on the efficacy and utility of the MitraClip (MC) procedure in patients with secondary mitral regurgitation (SMR). A ratio between the effective regurgitant orifice area (EROA) and left ventricular end-diastolic volume (LVEDV) ≥0.150 by two-dimensional (2D) transthoracic echocardiography (TTE) has been proposed to identify patients with disproportionate SMR, who would benefit from MC. Purpose To assess the prognostic role of clinical and echocardiographic parameters in a real-world population of SMR patients undergoing the MC procedure at our Institute. Methods Ninety-two patients underwent MC implantation. We retrospectively reviewed their clinical, and laboratory data, as well as 2D and three-dimensional (3D) TTE, and intraoperative transoesophageal echocardiography (Figure 1). The primary endpoint was a composite of cardiovascular death and/or hospitalisation for heart failure within 12-months follow-up. Results Thirty-one patients reached the endpoint (EP+), 61 did not (EP−). Demographics and anti-remodelling drugs were similar in EP+ and EP. Among comorbidities and laboratory data, EP+ significantly differed from EP− in smoking history, and extracardiac artery disease prevalence (65% vs. 39%, and 39% vs. 16%, respectively); EuroScoreII (12.2% vs. 5.2%); NYHA class ≥3 (94% vs. 69%); haemoglobin (12±2 vs. 13±2 g/dL), and brain natriuretic peptide levels (855 [426–1500] vs. 357 [170–902] pg/mL). At 2D TTE no significant difference emerged, including the SMR grade, except for the tricuspid annular plane systolic excursion (Figure 2). Biventricular 3D ejection fraction was significantly lower in EP+ vs. EP− (Figure 2). Residual intraoperative SMR grade after MC deployment was 1.9±0.6 in EP+ vs. 1.3±0.5 in EP− (p Conclusion The proposed cut-off for EROA/LVEDV ratio may be suboptimal for predicting the MC utility in real-world populations. Rather, prognosis may be more influenced by the patient's pre-operative clinical status, right ventricular systolic function, 3D left ventricular ejection fraction, and by the success of the procedure. Funding Acknowledgement Type of funding sources: None.

In the hybrid Positron Emission Tomography/Computed Tomography (PET/CT) method, the functional evaluation is integrated with the morphological information provided by co-registered CT, still performed for attenuation correction and lesion localization. However, co-registered CT images could provide additional diagnostic information that PET alone could underestimate. To optimize the diagnostic potential of this hybrid examination, we evaluated the prevalence and the clinical significance of incidental findings detected on co-registered CT images in a cohort of multiple myeloma (MM) patients.We evaluated 112 MM patients (mean age 65.8 y), who underwent [18F]FDG-PET/CT during their regular workup. All co-registered CT images were retrospectively reviewed by two expert radiologists and each non-myelomatous incidental finding (nM-IF) was collected and clinically graded according to a nM-IF Reporting and Data System (nM-RADS). In addition, nM-IFs were classified according to anatomic localization (skull, lung, mediastinum, abdomen, breast, gastrointestinal, genitourinary and cardiovascular system and muscle/soft tissue).163 nM-IFs were detected in 94/112 patients (83.9%) (mean value: 1.5 IFs per patient). The most interested anatomic districts were the lung (n=33; 20.2%), genitourinary (n=33; 20.2%) and gastrointestinal (n=30; 18.4%) systems. Focusing on the clinically significant findings (nM3+nM4), 92/163 (56.4%) IFs could have been required further investigations, of which 38/163 (23.3%) were potentially important and detected in 33/112 (29.5%) patients.The high percentage of potentially clinically significant IFs detected in MM patients emphasizes that co-registered CT images hold precious information often missed. Giving more relevance to co-registered CT with tailored acquisition and reconstruction protocols and dedicated reporting could optimize the potentiality of this multimodality imaging method with impact on clinical management.

Rhabdomyosarcoma (RMS), an aggressive soft tissue sarcoma of the skeletal muscle generally affecting children and adolescents, shows extensive heterogeneity in histology, site and age of onset, clinical course, and prognosis. Tumorigenesis of RMS is multifactorial and genetic predisposition together with the family history of cancer may provide critical information to enhance the current knowledge and foster genetic counseling and testing. In our study, we evaluated the possible correlation of oncological family history with clinical outcomes in a cohort of RMS 512 patients and treated at the Pediatric Oncology Unit of our Institute. Family history was retrospectively collected from the specific ad hoc form available in medical records and filled in through an interview with the patients’ parents at the time of RMS diagnosis. While our series did not show a specific association between oncological family history and clinical variables, we observed an association with survival probabilities: among patients with a history of cancer-affected first-degree relatives at the time of the diagnosis, all children with alveolar RMS (ARMS) died of disease. Our study not only reports an interesting and not previously described association between a poor clinical outcome and ARMS in patients with young cancer-affected relatives, but also stimulates the discussion on oncological family history in RMS, to improve the clinical management of these young patients and their families.

Antimicrobial resistance is an escalating health crisis requiring urgent action. Most antimicrobials are natural products (NPs) sourced from Actinomycetota, particularly the Streptomyces. Underexplored and extreme environments are predicted to harbour novel microorganisms with the capacity to synthesise unique metabolites. Herring Island is a barren and rocky cold desert in East Antarctica, remote from anthropogenic impact. We aimed to recover rare and cold-adapted NP-producing bacteria, by employing two culturing methods which mimic the natural environment: direct soil culturing and the soil substrate membrane system. First, we analysed 16S rRNA gene amplicon sequencing data from 18 Herring Island soils and selected the soil sample with the highest Actinomycetota relative abundance (78%) for culturing experiments. We isolated 166 strains across three phyla, including novel and rare strains, with 94% of strains belonging to the Actinomycetota. These strains encompassed thirty-five ‘species’ groups, 18 of which were composed of Streptomyces strains. We screened representative strains for genes which encode polyketide synthases and non-ribosomal peptide synthetases, indicating that 69% have the capacity to synthesise polyketide and non-ribosomal peptide NPs. Fourteen Streptomyces strains displayed antimicrobial activity against selected bacterial and yeast pathogens using an in situ assay. Our results confirm that the cold-adapted bacteria of the harsh East Antarctic deserts are worthy targets in the search for bioactive compounds.

Resumen La deformacion de los dedos laterales del pie es un impedimento para el ajuste del pie al calzado y para la marcha, con independencia de su etiologia. El desequilibrio muscular crea la deformacion. Un mejor conocimiento de la anatomia permite una optima comprension de su genesis y facilita el tratamiento podologico y quirurgico. La anamnesis es fundamental. Los cuidados de pedicura son paliativos, pero a corto plazo; la educacion terapeutica del paciente y los consejos sobre el calzado completan el tratamiento preventivo. La ortoplastia de correccion trata la deformacion flexible, combinada con kinesiterapia y autorrehabilitacion; la ortesis plantar estabiliza el pie desde el punto de vista dinamico y corrige los trastornos estaticos asociados. La cirugia da buenos resultados en la deformacion, tanto si es flexible como si es fija; las tecnicas a cielo abierto compiten cada vez mas con las tecnicas minimamente invasivas o percutaneas, que son intervenciones tendinosas y oseas progresivas menos agresivas cuando el cirujano las domina bien. Una consulta en binomio (cirujano y podologo) es interesante en el tratamiento de la deformacion de los dedos del pie.

The rate of cesarean section (CS) delivery has steadily increased over the past decades despite epidemiological studies reporting higher risks of neonatal morbidity and neurodevelopmental disorders. Yet, little is known about the immediate impact of CS birth on the brain, hence the need of experimental studies to evaluate brain parameters following this mode of delivery. Using the solvent clearing method iDISCO and 3D imaging technique, we report that on the day of birth, whole-brain, hippocampus, and striatum volumes are reduced in CS-delivered as compared to vaginally-born mice, with a stronger effect observed in preterm CS pups. These results stress the impact of CS delivery, at term or preterm, during parturition and at birth. In contrast, cellular activity and apoptosis are reduced in mice born by CS preterm but not term, suggesting that these early-life processes are only impacted by the combination of preterm birth and CS delivery.

Candidatus phylum Eremiobacterota (formerly WPS-2) is an as-yet-uncultured bacterial clade that takes its name from Ca. Eremiobacter, an Antarctic soil aerobe proposed to be capable of a novel form of chemolithoautotrophy termed atmospheric chemosynthesis, that uses the energy derived from atmospheric H(2)-oxidation to fix CO(2) through the Calvin-Benson-Bassham (CBB) cycle via type 1E RuBisCO. To elucidate the phylogenetic affiliation and metabolic capacities of Ca. Eremiobacterota, we analysed 63 public metagenome-assembled genomes (MAGs) and nine new MAGs generated from Antarctic soil metagenomes. These MAGs represent both recognized classes within Ca. Eremiobacterota, namely Ca. Eremiobacteria and UBP9. Ca. Eremiobacteria are inferred to be facultatively acidophilic with a preference for peptides and amino acids as nutrient sources. Epifluorescence microscopy revealed Ca. Eremiobacteria cells from Antarctica desert soil to be coccoid in shape. Two orders are recognized within class Ca. Eremiobacteria: Ca. Eremiobacterales and Ca. Baltobacterales. The latter are metabolically versatile, with individual members having genes required for trace gas driven autotrophy, anoxygenic photosynthesis, CO oxidation, and anaerobic respiration. UBP9, here renamed Ca. Xenobia class. nov., are inferred to be obligate heterotrophs with acidophilic adaptations, but individual members having highly divergent metabolic capacities compared to Ca. Eremiobacteria, especially with regard to respiration and central carbon metabolism. We conclude Ca. Eremiobacterota to be an ecologically versatile phylum with the potential to thrive under an array of “extreme” environmental conditions.

Background Percutaneous core needle biopsy (PCNB) has become an accepted method to collect tumour tissue samples given its safety, minimal invasiveness, high accuracy and cost-effectiveness. Procedure It is a single centre, retrospective evaluation of 213 ultrasound (US) or computed tomography (CT) guided PCNBs of paediatric solid tumours performed from 2005 to 2017. Safety, diagnostic yield, accuracy, and efficacy assessments of the PCNB procedure were performed. Univariate logistic models were applied to assess the relation of the diagnostic yield with patient, procedure and lesion features. Results The image-guide was US in 91.08% of biopsies; the needle gauge was ≥16 G in 69.01% of the biopsies. The anatomical site of lesion was deep in 113 biopsies (53.05%). The nature of the lesion was the only factor associated with diagnostic yield (OR: 4.04; 95% CI 1.23–13.28; p: 0.022), with benign lesion as an unfavourable factor. Complication incidence was 1.41%. Overall, the diagnostic yield of PCNB was 93.90% (95% CI: 89.79-96.71%), the diagnostic accuracy was 96.86% (95% CI: 93.29–98.84%) and the diagnostic efficacy was 93.33% (95% CI: 86.75–97.28%). Sensitivity was 97.94% (95% CI: 92.75–99.75%) and specificity 100% (95% CI: 66.37–100%). Conclusion PCNB can be recommended as the first-choice method for solid tumours diagnosis in paediatric, adolescent and young adult patients because of its high diagnostic success, safety and accessibility.

Layered materials (LMs) produced by liquid phase exfoliation (LPE) can be used as building blocks for optoelectronic applications. However, when compared with mechanically exfoliated flakes, or films prepared by chemical vapor deposition (CVD), LPE-based printed optoelectronic devices are limited by mobility, defects and trap states. Here, we present a scalable fabrication technique combining CVD with LPE LMs to overcome such limitations. We use black phosphorus inks, inkjet-printed on graphene on Si/SiO2, patterned by inkjet printing based lithography, and source and drain electrodes printed with an Ag ink, to prepare photodetectors (PDs). These have an external responsivity (R ext)∼337 A W−1 at 488 nm, and operate from visible (∼488 nm) to short-wave infrared (∼2.7 µm, R ext ∼ 48 mA W−1). We also use this approach to fabricate flexible PDs on polyester fabric, one of the most common used in textiles, achieving R ext ∼ 6 mA W−1 at 488 nm for an operating voltage of 1 V. Thus, our combination of scalable CVD and LPE techniques via inkjet printing is promising for wearable and flexible applications.

Background Heart failure (HF) therapy has been disrupted by the introduction of 2 new prognostic–relevant drugs: Sacubitril/Valsartan and SGLT2i. However, the amount of evidence for guideline–directed HF therapies in the context of chronic kidney disease (CKD) is relatively modest, especially in advanced stages (e.g., on haemodialysis). Aim of this report is to describe the feasibility and the efficacy of HF medical therapy in a patient with naive HFrEF and CKD on haemodialysis. Case report: A woman in her 40’s, with no cardiovascular history, affected by polycystic kidney disease end end–stage CKD placed on hemodialysis for the previous 9 months, underwent a echocardiography (TTE) in 09/2021, as part of investigations for kidney transplantation. The TTE showed a picture consistent with dilated cardiomyopathy with reduced EF, severe left atrium (LA) dilation and moderate–to–severe mitral regurgitation (MR). Thus, the patient was temporarily suspended from the transplant list. She was on chronic diuretic therapy with high dose of furosemide (250mg b.i.d.), with a residual diuresis of 400–500 mL per day. An elective coronary angiography showed normal coronary arteries. A Cardiac Magnetic Resonance (CMR) confirmed the diagnosis of DCM with severe dilation of the left ventricle (LV), reduced EF and severe MR. A cardiopulmonary exercise test (CPET) showed mild functional limitation with no pulmonary vascular limitation. After a multidisciplinary evaluation involving HF specialists and nephrologists, the recommended quadruple HF therapy was started and gradually up–titrated during the following 10 months. Neither the hemodialysis protocol nor the diuretic therapy was changed throughout this period. No adverse events were observed (e.g., increased sessions or dialysis schedule, hyperkalemia, hypotension). During this timeframe, the patients was asymptomatic and a progressive and sustained decrease in N–terminal pro B–type natriuretic peptide (NT–proBNP) from 26356 to 1556 ng/ml was observed. We documented a significant amelioration in CPET and other laboratory parameters (sST2), as well as a consistent reverse remodeling of the left heart chambers and a significant reduction in MR grade. Conclusions We described a case of significant left heart chambers reverse remodeling and disease regression in a patient with end–stage CKD presenting with HFrEF treated with off–label optimized HF medical therapy. Further studies on hemodialyzed HF patients will be needed.

This study reports the treatment feasibility and efficacy of a novel multiagent intensive treatment program for young patients with desmoplastic small round cell tumor. This small series includes three patients and should be seen as a first suggestion of integration of the dose density and the maintenance chemotherapy concept. The IrIVA regimen (irinotecan, ifosfamide, vincristine, and actinomycin-D) is added—used at a short interval between chemotherapy administrations—at more classic intensive ifosfamide–based regimens. The vinorelbine and low-dose oral cyclophosphamide maintenance therapy is added at the end of conventional chemotherapy to achieve an antiangiogenic effect.

To evaluate the phrenic nerve compound muscle action potential (CMAP) in rats after diabetes mellitus (DM) induction.Twenty DM animals (intravenous streptozotocin, 45 mg.kgAmplitude (mV) progressively declined in DM group after 30 (Mean difference (MD): -0.915, 95 % Confidence interval (CI) -1.580 to -0.250, p 0.01), 60 (MD: -1.122, 95 % CI -1.664 to -0.581, p 0.001) and 90 days (MD: -2.226, 95 % CI -3.059 to -1.393, p 0.001); as well as the area (mV.ms) after 30 (MD: -3.19, 95 % CI -5.94 to -0.44, p 0.05), 60 (MD: -3.94, 95 % CI -6.24 to -1.64, p 0.001) and 90 days (MD: -8.64, 95 % CI -12.08 to -5.21, p 0.001). Transient differences were observed in latency and duration at 60 days.The progressive changes in phrenic nerve CMAP observed during DM suggest a decrement in axonal function rather than substantial demyelination.

Background and aim Near infra-red/indocyanine green imaging fluorescence (NIR/ICG) technology is showing promising results in several fields of surgical oncology. However, the clinical value of NIR/ICG technology in the surgical treatment of advanced gastric cancer (AGC) is not clearly established. Indeed, although lymphadenectomy is one of the main steps in curative-intent surgery for gastric cancer and lymph node status is the most important prognostic factor for survival, several questions have risen in literature on considering the overall number of harvested lymph nodes as the best indicator of the NIR/ICG technology clinical value. At present, no data exist regarding the ability of NIR/ICG technology to modify the surgical conduct at the moment of lymphadenectomy. Methods This is the ‘iGreenGO’ (indocyanine Green Gastric Observation) study protocol: an international, prospective, multicentre study. Study population will be a cohort of Western patients undergoing preoperative upper gastrointestinal endoscopy with submucosal peritumoral ICG injection followed by curative-intent minimally invasive gastrectomy with D2 lymphadenectomy for locally AGC. High-volume western academic and non-academic hospitals will be allowed to participate in the study. The primary endpoint will be the ‘change of the surgical conduct’ (CSC) at the moment of intraoperative NIR/ICG technology activation after completing a D2 lymphadenectomy ‘with the naked eye’. Key secondary endpoints will be the identification of preoperative clinical variables potentially associated with CSC, the number of additional LNs retrieved and pTNM stage migration using NIR/ICG technology, abdominal fluorescence location according to patient’s and tumor’s characteristics. Results The sample size was calculated by considering the estimated incidence of intraoperative change of the surgical conduct when using NIR/ICG technology. Data from the literature indirectly suggest an approximate rate of such event around 17%. A sample size of 350 patients will be necessary to obtain a measurement with an estimated precision of 4% with a confidence level of 1-alfa = 95%. Conclusion The iGreenGO study will be the first western study to investigate the intraoperative clinical role of NIR/ICG technology in surgical treatment of AGC in a large cohort of Western patients. Results from the present study can further clarify the role of the NIR/ICG technology in helping the surgeon during lymphadenectomy for AGC.

Optical communications, imaging, and biomedicine require efficient detection of infrared radiation. Growing demand pushes for the integration of such detectors on chips. It is a challenge for conventional semiconductor devices to meet these specs due to spectral limitations arising from their finite band gap, as well as material incompatibilities. Single layer graphene (SLG) is compatible with complementary metal-oxide-semiconductor (CMOS) Si technology, while its broadband (UV to THz) absorption makes the SLG/Si junction a promising platform for photodetection. Here we model the thermionic operation of SLG/Si Schottky photodetectors, considering SLG’s absorption, heat capacity, and carrier cooling dependence on temperature and carrier density. We self-consistently solve coupled rate equations involving electronic and lattice temperatures, and nonequilibrium carrier density under light illumination. We use as an example the infrared photon energy of 0.4 eV, below the threshold for direct photoemission over the Schottky barrier, to study the photothermionic response as a function of voltage bias, input power, pulse width, electronic injection, and relaxation rates. We find that device and operation parameters can be optimized to reach responsivities competitive with the state of the art for any light frequency, unlike conventional semiconductor-based devices. Our results prove that the SLG/Si junction is a broadband photodetection platform.

Purpose: Preclinical studies demonstrated that a DNA vaccine (pTVG-AR, MVI-118) encoding the androgen receptor ligand-binding domain (AR LBD) augmented antigen-specific CD8+ T cells, delayed prostate cancer progression and emergence of castration-resistant disease, and prolonged survival of tumor-bearing mice. This vaccine was evaluated in a multicenter phase I trial. Patients and Methods: Patients with metastatic castration-sensitive prostate cancer (mCSPC) who had recently begun androgen deprivation therapy were randomly assigned to receive pTVG-AR on one of two treatment schedules over one year, and with or without GM-CSF as a vaccine adjuvant. Patients were followed for 18 months. Primary objectives were safety and immune response. Secondary objectives included median time to PSA progression, and 18-month PSA-PFS (PPFS). Results: Forty patients were enrolled at three centers. Twenty-seven patients completed treatment and 18 months of follow-up. Eleven patients (28%) had a PSA progression event before the 18-month time point. No grade 3 or 4 adverse events were observed. Of 30 patients with samples available for immune analysis, 14 (47%) developed Th1-type immunity to the AR LBD, as determined by IFNγ and/or granzyme B ELISPOT. Persistent IFNγ immune responses were observed irrespective of GM-CSF adjuvant. Patients who developed T-cell immunity had a significantly prolonged PPFS compared with patients without immunity (HR = 0.01; 95% CI, 0.0–0.21; P = 0.003). Conclusions: pTVG-AR was safe and immunologically active in patients with mCSPC. Association between immunity and PPFS suggests that treatment may delay the time to castration resistance, consistent with preclinical findings, and will be prospectively evaluated in future trials. See related commentary by Shenderov and Antonarakis, p. 5056

Primary hypothyroidism commonly occurs after radiotherapy (RT), and coincides with increased circulating thyroid-stimulating hormone (TSH) levels.We tested therefore the protective effect of suppressing TSH with L-thyroxine during RT for medulloblastoma/PNET and Hodgkin lymphoma (HL) in a prospective cohort study. From1998 to 2001, a total of 37 euthyroid children with medulloblastoma/PNET plus 14 with HL, scheduled for craniospinal irradiation and mediastinum/neck radiotherapy, respectively, underwent thyroid ultrasound and free triiodothyronine (FT3), free thyroxine (FT4), and TSH evaluation at the beginning and end of craniospinal iiradiation. From 14 days before and up to the end of radiotherapy, patients were administered L-thyroxine checking every 3 days TSH to ensure a value < 0.3 μIU/mL. During follow-up, blood tests and ultrasound were repeated; primary hypothyroidism was considered an increased TSH level greater than normal range. Twenty-two/37 patients with medulloblastoma/PNET and all the 14 patients with HL were alive after a median 231 months from radiotherapy with 7/22 and 8/14 having correctly reached TSH levels < 0.3 μIU/mL and well matched for other variables. Twenty years on, hypothyroidism-free survival rates differed significantly, being 60% ± 15% and 15.6% ± 8.2% in TSH-suppressed vs. not-TSH suppressed patients, respectively (P = 0.001). These findings suggest that hypothyroidism could be durably prevented in two populations at risk of late RT sequelae, but it should be confirmed in a larger cohort.

Ultrafast and sensitive (noise equivalent power, This is the unedited authors' version of the article accepted for publication in Nanophotonics 2020 (Online ISSN: 2192-8614)

Resumen No existe un tratamiento medico curativo para el hallux valgus, pero el tratamiento precoz y especifico puede a veces mejorar la tolerabilidad. Con demasiada frecuencia se ignora la eficacia del tratamiento conservador: una revision de la literatura de 2015 senala efectos beneficiosos con reduccion del dolor y correccion de la deformacion, pero ningun estudio lo ha evaluado a largo plazo. Al ser cada paciente distinto y tener cada podologo sus propias practicas, el primer objetivo es definir lo que se desea corregir, compensar o modificar: las posibilidades tecnicas quedan a la libre eleccion del profesional de acuerdo con su paciente, sea cual sea la situacion clinica, es decir, no hay un tratamiento estandar. Este tratamiento paliativo solo es eficaz despues de una exploracion clinica completa, de indicaciones bien planteadas y de explicaciones claras de las soluciones buscadas. El primer tratamiento medico para un hallux valgus sintomatico es aconsejar una adaptacion del calzado al volumen del pie. El origen del dolor y las molestias causadas por la deformacion guiaran al profesional en su tratamiento.