Radioisotope production using lasers:From basic science to applications

The discovery of chirped pulse amplification has led to great improvements in laser technology,enabling energetic laser beams to be compressed to pulse durations of tens of femtoseconds and focused to a few micrometers.Protons with energies of tens of MeV can be accelerated using,for instance,target normal sheath acceleration and focused on secondary targets.Under such conditions,nuclear reactions can occur,with the production of radioisotopes suitable for medical application.The use of high-repetition lasers to produce such isotopes is competitive with conventional methods mostly based on accelerators.In this paper,we study the production of^(67)Cu,^(63)Zn,^(18)F,and^(11)C,which are currently used in positron emission tomography and other applications.At the same time,we study the reactions^(10)B(p,α)^(7)Be and^(70)Zn(p,4n)^(67)Ga to put further constraints on the proton distributions at different angles,as well as the reaction^(11)B(p,α)^(8)Be relevant for energy production.The experiment was performed at the 1 PW laser facility at VegaⅢin Salamanca,Spain.Angular distributions of radioisotopes in the forward(with respect to the laser direction)and backward directions were measured using a high purity germanium detector.Our results are in reasonable agreement with numerical estimates obtained following the approach of Kimura and Bonasera[Nucl.Instrum.Methods Phys.Res.,Sect.A 637,164–170(2011)].

Small heat shock protein B8:from cell functions to its involvement in diseases and potential therapeutic applications

Heat shock protein family B(small)member 8(HSPB8)is a 22 kDa ubiquitously expressed protein belonging to the family of small heat shock proteins.HSPB8 is involved in various cellular mechanisms mainly related to proteotoxic stress response and in other processes such as inflammation,cell division,and migration.HSPB8 binds misfolded clients to prevent their aggregation by assisting protein refolding or degradation through chaperone-assisted selective autophagy.In line with this function,the pro-degradative activity of HSPB8 has been found protective in several neurodegenerative and neuromuscular diseases characterized by protein misfolding and aggregation.In cancer,HSPB8 has a dual role being capable of exerting either a pro-or an anti-tumoral activity depending on the pathways and factors expressed by the model of cancer under investigation.Moreover,HSPB8 exerts a protective function in different diseases by modulating the inflammatory response,which characterizes not only neurodegenerative diseases,but also other chronic or acute conditions affecting the nervous system,such as multiple sclerosis and intracerebellar hemorrhage.Of note,HSPB8 modulation may represent a therapeutic approach in other neurological conditions that develop as a secondary consequence of other diseases.This is the case of cognitive impairment related to diabetes mellitus,in which HSPB8 exerts a protective activity by assuring mitochondrial homeostasis.This review aims to summarize the diverse and multiple functions of HSPB8 in different pathological conditions,focusing on the beneficial effects of its modulation.Drug-based and alternative therapeutic approaches targeting HSPB8 and its regulated pathways will be discussed,emphasizing how new strategies for cell and tissue-specific delivery represent an avenue to advance in disease treatments.

Lower Continental Crusts Involved in the Alpine Orogeny:New Insight from the Santa Lucia Nappe Metasediments(Corsica,France)

In the Alpine Corsica(France),the Santa Lucia Nappe represents a peculiar unit preserving the unique relicts of Paleozoic lower to medium continental crust.It consists of composite basement affected by Permian granulite facies metamorphic conditions unconformably covered by a Late Cretaceous clastic sequence(Tomboni Conglomerate and Tralonca Flysch)affected by polyphase deformation and low-grade-metamorphism.In this work,we present a new reconstruction of the deformation events registered by the Tralonca Flysch during the Alpine orogeny.The D1 phase was testified by rare isoclinal folds.The D2 phase produced a continuous foliation and a map-scale sheath-fold with a top-to-W sense of shear.The D3 phase produced E-verging non-cylindrical folds and S3 crenulation cleavage that is not associated to metamorphic blastesis.We present the first temperature-pressure-deformation(P-T-d)path for the Tralonca Flysch,demonstrating that the Santa Lucia Nappe underwent accretion and then first stage exhumation in the Alpine wedge during the D1 phase with pressure and temperature peaks both occurred under blueschist metamorphic conditions.The D2 phase occurred at lower pressure-temperature conditions during a second stage exhumation.This pressure-temperaturedeformation path is comparable with those of the Lower Units(i.e.,the subducted continental units of Alpine Corsica)suggesting a common geodynamic history.

Digital twin-and extended reality-based telepresence for collaborative robot programming in the 6G perspective

In the context of Industry 4.0,a paradigm shift from traditional industrial manipulators to Collaborative Robots(CRs)is ongoing,with the latter serving ever more closely humans as auxiliary tools in many production processes.In this scenario,continuous technological advancements offer new opportunities for further innovating robotics and other areas of next-generation industry.For example,6G could play a prominent role due to its human-centric view of the industrial domains.In particular,its expected dependability features will pave the way for new applications exploiting highly effective Digital Twin(DT)-and eXtended Reality(XR)-based telepresence.In this work,a novel application for the above technologies allowing two distant users to collaborate in the programming of a CR is proposed.The approach encompasses demanding data flows(e.g.,point cloud-based streaming of collaborating users and robotic environment),with network latency and bandwidth constraints.Results obtained by analyzing this approach from the viewpoint of network requirements in a setup designed to emulate 6G connectivity indicate that the expected performance of forthcoming mobile networks will make it fully feasible in principle.

Metal-Halide Perovskite Submicrometer-Thick Films for Ultra-Stable Self-Powered Direct X-Ray Detectors

Metal-halide perovskites are revolutionizing the world of X-ray detectors,due to the development of sensitive,fast,and cost-effective devices.Self-powered operation,ensuring portability and low power consumption,has also been recently demonstrated in both bulk materials and thin films.However,the signal stability and repeatability under continuous X-ray exposure has only been tested up to a few hours,often reporting degradation of the detection performance.Here it is shown that self-powered direct X-ray detectors,fabricated starting from a FAPbBr_(3)submicrometer-thick film deposition onto a mesoporous TiO_(2)scaffold,can withstand a 26-day uninterrupted X-ray exposure with negligible signal loss,demonstrating ultra-high operational stability and excellent repeatability.No structural modification is observed after irradiation with a total ionizing dose of almost 200 Gy,revealing an unexpectedly high radiation hardness for a metal-halide perovskite thin film.In addition,trap-assisted photoconductive gain enabled the device to achieve a record bulk sensitivity of 7.28 C Gy^(−1)cm^(−3)at 0 V,an unprecedented value in the field of thin-film-based photoconductors and photodiodes for“hard”X-rays.Finally,prototypal validation under the X-ray beam produced by a medical linear accelerator for cancer treatment is also introduced.

A divergent pattern in functional connectivity: a transdiagnostic perspective

Functional magnetic resonance imaging(fMRI)is a popular tool used to investigate not only how the brain responds to specific stimuli during sensorimotor or cognitive tasks,but also brain activity at rest.The physics beyond this approach is based on the analysis of the blood oxygenation level-dependent signal.

Investigations on MoS_(2)plasma by infra-red pulsed laser irradiation in high vacuum

MoS_(2)targets were irradiated by infra-red(IR)pulsed laser in a high vacuum to determine hot plasma parameters,atomic,molecular and ion emission,and angular and charge state distributions.In this way,pulsed laser deposition(PLD)of thin films on graphene oxide substrates was also realized.An Nd:YAG laser,operating at the 1064 nm wavelength with a 5 ns pulse duration and up to a 1 J pulse energy,in a single pulse or at a 10 Hz repetition rate,was employed.Ablation yield was measured as a function of the laser fluence.Plasma was characterized using different analysis techniques,such as time-of-flight measurements,quadrupole mass spectrometry and fast CCD visible imaging.The so-produced films were characterized by composition,thickness,roughness,wetting ability,and morphology.When compared to the MoS_(2)targets,they show a slight decrease of S with respect to Mo,due to higher ablation yield,low fusion temperature and high sublimation in vacuum.The pulsed IR laser deposited Mo Sx(with 1<x<2)films are uniform,with a thickness of about 130 nm,a roughness of about 50 nm and a higher wettability than the MoS_(2)targets.Some potential applications of the pulsed IR laser-deposited Mo Sx films are also presented and discussed.

Disentangling brain PrP^(C)proteoforms and their roles in physiology and disease

The cellular prion protein(PrPC),a cell surface glycoprotein of 209 amino acids,has been considerably studied over the decades mainly due to its critical involvement in transmissible spongiform encephalopathies,or prion diseases.Indeed,it is the misfolding and aggregation of PrPC into pathological assemblies-named PrPSc-that constitute prions,the agents causing these unusual neurodegenerative diseases affecting humans and animals(Prusiner,1982).Furthermore,increasing evidence support its relevance also in other neurodegenerative diseases(NDDs),such as Alzheimer’s and Parkinson’s diseases(Corbett et al.,2020).

How dopamine tunes parvalbumin interneurons in the hippocampus:new experimental observations in Alzheimer's disease

Despite decades of dedicated resea rch,Alzheimer's disease (AD) is an age-related and progressive neurodegenerative disorder for which the mechanisms of onset are sti unc ear.AD is cha racterized by featured histological alterations including amyloid-beta (AB) plaque deposition,accumulation of neurofibrillary to ngles of hyperphosphorylated-tau,and neuronal loss,accompanied by progressive cognitive decline and behavioral changes.

Multifaceted superoxide dismutase 1 expression in amyotrophic lateral sclerosis patients:a rare occurrence?

Amyotrophic lateral sclerosis(ALS)is a neuromuscular condition resulting from the progressive degeneration of motor neurons in the cortex,brainstem,and spinal cord.While the typical clinical phenotype of ALS involves both upper and lower motor neurons,human and animal studies over the years have highlighted the potential spread to other motor and non-motor regions,expanding the phenotype of ALS.Although superoxide dismutase 1(SOD1)mutations represent a minority of ALS cases,the SOD1 gene remains a milestone in ALS research as it represents the first genetic target for personalized therapies.Despite numerous single case reports or case series exhibiting extramotor symptoms in patients with ALS mutations in SOD1(SOD1-ALS),no studies have comprehensively explored the full spectrum of extramotor neurological manifestations in this subpopulation.In this narrative review,we analyze and discuss the available literature on extrapyramidal and non-motor features during SOD1-ALS.The multifaceted expression of SOD1 could deepen our understanding of the pathogenic mechanisms,pointing towards a multidisciplinary approach for affected patients in light of new therapeutic strategies for SOD1-ALS.

A chaotic hierarchical encryption/watermark embedding scheme for multi-medical images based on row-column confusion and closed-loop bi-directional diffusion

Security during remote transmission has been an important concern for researchers in recent years.In this paper,a hierarchical encryption multi-image encryption scheme for people with different security levels is designed,and a multiimage encryption(MIE)algorithm with row and column confusion and closed-loop bi-directional diffusion is adopted in the paper.While ensuring secure communication of medical image information,people with different security levels have different levels of decryption keys,and differentiated visual effects can be obtained by using the strong sensitivity of chaotic keys.The highest security level can obtain decrypted images without watermarks,and at the same time,patient information and copyright attribution can be verified by obtaining watermark images.The experimental results show that the scheme is sufficiently secure as an MIE scheme with visualized differences and the encryption and decryption efficiency is significantly improved compared to other works.

Artificial intelligence in detection of small bowel lesions and their bleeding risk:A new step forward

The present letter to the editor is related to the study with the title“Automatic detection of small bowel(SB)lesions with different bleeding risk based on deep learning models”.Capsule endoscopy(CE)is the main tool to assess SB diseases but it is a time-consuming procedure with a significant error rate.The development of artificial intelligence(AI)in CE could simplify physicians’tasks.The novel deep learning model by Zhang et al seems to be able to identify various SB lesions and their bleeding risk,and it could pave the way to next perspective studies to better enhance the diagnostic support of AI in the detection of different types of SB lesions in clinical practice.

Long COVID and gut candidiasis:What is the existing relationship?

Since the beginning of the coronavirus disease(COVID)2019 pandemic,thou-sands of articles on the topic have been published,and although there is a growing trend of research on another associated condition,long coronavirus disease,important points still remain to be clarified in this respect.Robust evidence has suggested a relevant link between new clinical discoveries and molecular mechanisms that could be associated with the manifestations of different signs and symptoms involving cases of long COVID.However,one of the existing gaps that requires further investigation concerns a possible rela-tionship between gut candidiasis and long COVID.While recent studies also suggest an interplay between the occurrence of these two conditions,it is not yet fully clear how this may happen,as well as the specifics regarding the possible pathophysiological mechanisms involved.In this connection and with the advent of a potential strengthening of the body of evidence supporting the hypothesis of a link between gut candidiasis and long COVID,a better understanding of the clinical presentation,pathophysiology and clinical management of such a relationship should be essential and useful for both,additional advances towards more targeted research and appropriate case management.Knowing more about the signs,symptoms,and complications associated with cases of long COVID is essential in order to more effectively mitigate the related burden and provide a higher quality of care and life for the affected population.In light of this and the need for better outcomes,here we review and discuss the content on different aspects of long COVID,including its pathophysiology and the existing evidence of a potential relationship between such a condition and gut candidiasis,as well as suggest propositions for future related research.INTRODUCTION Long coronavirus disease(COVID)is a condition characterized by the emergence of new symptoms or the persistence of existing symptoms for at least two months,three months after the initial infection[1].Although such a condition has initially been extensively studied,there are still many contradictions between the findings and methodologies of different related research articles[2,3].Within this context and since the middle of the COVID-19 pandemic,important studies have been published in the literature reporting the occurrence of fungal infections among COVID-19 patients[4,5],including mucormycosis,and oral candidiasis[6].On the other hand,evidence on a possible relationship between gut candidiasis and long COVID is still recent[7].Indeed,a marked gastrointestinal(GI)fungal dysbiosis together with perturbation of the lung-gut axis has been observed in severe COVID-19 patients.This combined with neutrophilia and an exacerbated worsening of the inflammatory response,which can be implicated in the acute and chronic immunopathology of such a viral disease[7,8].Furthermore,persistent changes in the immune system may also occur,resulting in a possible relationship with the occurrence of long COVID[7].However,more targeted evidence is still scarce and the specific topic related to gut candidiasis has been the subject of little discussion.In response to this,in this article we discuss general aspects of long COVID,the inherent pathophysiology and current evidence of a potential relationship between this condition and gut candidiasis,in addition to providing recommendations for future research.ACKNOWLEDGEMENTS Tovani-Palone MR thanks the Saveetha Institute of Medical and Technical Sciences for supporting this study.

Machine learning applications on lunar meteorite minerals:From classification to mechanical properties prediction

Amid the scarcity of lunar meteorites and the imperative to preserve their scientific value,nondestructive testing methods are essential.This translates into the application of microscale rock mechanics experiments and scanning electron microscopy for surface composition analysis.This study explores the application of Machine Learning algorithms in predicting the mineralogical and mechanical properties of DHOFAR 1084,JAH 838,and NWA 11444 lunar meteorites based solely on their atomic percentage compositions.Leveraging a prior-data fitted network model,we achieved near-perfect classification scores for meteorites,mineral groups,and individual minerals.The regressor models,notably the KNeighbor model,provided an outstanding estimate of the mechanical properties—previously measured by nanoindentation tests—such as hardness,reduced Young’s modulus,and elastic recovery.Further considerations on the nature and physical properties of the minerals forming these meteorites,including porosity,crystal orientation,or shock degree,are essential for refining predictions.Our findings underscore the potential of Machine Learning in enhancing mineral identification and mechanical property estimation in lunar exploration,which pave the way for new advancements and quick assessments in extraterrestrial mineral mining,processing,and research.

Management of cerebral amyloid angiopathy and atrial fibrillation:We are still far from precision medicine

The use of anticoagulation therapy could prove to be controversial when trying to balance ischemic stroke and intracranial bleeding risks in patients with concurrent cerebral amyloid angiopathy(CAA)and atrial fibrillation(AF).In fact,CAA is an age-related cerebral vasculopathy that predisposes patients to intracerebral hemorrhage.Nevertheless,many AF patients require oral systemic dose-adjusted warfarin,direct oral anticoagulants(such as factor Xa inhibitors)or direct thrombin inhibitors to control often associated with cardioembolic stroke risk.The prevalence of both CAA and AF is expected to rise,due to the aging of the population.This clinical dilemma is becoming increasingly common.In patients with coexisting AF and CAA,the risks/benefits profile of anticoagulant therapy must be assessed for each patient individually due to the lack of a clear-cut consensus with regard to its risks in scientific literature.This review aims to provide an overview of the management of patients with concomitant AF and CAA and proposes the implementation of a risk-based decision-making algorithm.

Heterostructured nickel-cobalt metal alloy and metal oxide nanoparticles as a polysulfide mediator for stable lithium-sulfur full batteries with lean electrolyte

Batteries that utilize low-cost elemental sulfur and light metallic lithium as electrodes have great potential in achieving high energy density.However,building a lithium-sulfur(Li-S)full battery by controlling the electrolyte volume generally produces low practical energy because of the limited electrochemical Li-S redox.Herein,the high energy/high performance of a Li-S full battery with practical sulfur loading and minimum electrolyte volume is reported.A unique hybrid architecture configured with Ni-Co metal alloy(NiCo)and metal oxide(NiCoO_(2))nanoparticles heterogeneously anchored in carbon nanotube-embedded selfstanding carbon matrix is fabricated as a host for sulfur.This work demonstrates the considerable improvement that the hybrid structure's high conductivity and satisfactory porosity promote the transport of electrons and lithium ions in Li-S batteries.Through experimental and theoretical validations,the function of NiCo and NiCoO_(2) nanoparticles as an efficient polysulfide mediator is established.These particles afford polysulfide anchoring and catalytic sites for Li-S redox reaction,thus improving the redox conversion reversibility.Even at high sulfur loading,the nanostructured Ni-Co metal alloy and metal oxide enable to have stable cycling performance under lean electrolyte conditions both in half-cell and full-cell batteries using a graphite anode.

Hepatitis C virus eradication in people living with human immunodeficiency virus:Where are we now?

Hepatitis C virus(HCV)/human immunodeficiency virus(HIV)co-infection still involves 2.3 million patients worldwide of the estimated 37.7 million living with HIV,according to World Health Organization.People living with HIV(PLWH)are six times greater affected by HCV,compared to HIV negative ones;the greater prevalence is encountered among people who inject drugs and men who have sex with men:the risk of HCV transmission through sexual contact in this setting can be increased by HIV infection.These patients experience a high rate of chronic hepatitis,which if left untreated progresses to end-stage liver disease and hepato-cellular carcinoma(HCC)HIV infection increases the risk of mother to child vertical transmission of HCV.No vaccination against both infections is still available.There is an interplay between HIV and HCV infections.Treatment of HCV is nowadays based on direct acting antivirals(DAAs),HCV treatment plays a key role in limiting the progression of liver disease and reducing the risk of HCC development in mono-and coinfected individuals,especially when used at an early stage of fibrosis,reducing liver disease mortality and morbidity.Since the sustained virological response at week 12 rates were observed in PLWH after HCV eradication,the AASLD has revised its simplified HCV treatment algorithm to also include individuals living with HIV.HCV eradication can determine dyslipidemia,since HCV promotes changes in serum lipid profiles and may influence lipid metabolism.In addition to these apparent detrimental effects on the lipid profile,the efficacy of DAA in HCV/HIV patients needs to be considered in light of its effects on glucose metabolism mediated by improvements in liver function.The aim of the present editorial is to describe the advancement in HCV treatment among PLWH.

An Unconventional Divergence Preserving Finite-Volume Discretization of Lagrangian Ideal MHD

We construct an unconventional divergence preserving discretization of updated Lagrangian ideal magnetohydrodynamics(MHD)over simplicial grids.The cell-centered finite-volume(FV)method employed to discretize the conservation laws of volume,momentum,and total energy is rigorously the same as the one developed to simulate hyperelasticity equations.By construction this moving mesh method ensures the compatibility between the mesh displacement and the approximation of the volume flux by means of the nodal velocity and the attached unit corner normal vector which is nothing but the partial derivative of the cell volume with respect to the node coordinate under consideration.This is precisely the definition of the compatibility with the Geometrical Conservation Law which is the cornerstone of any proper multi-dimensional moving mesh FV discretization.The momentum and the total energy fluxes are approximated utilizing the partition of cell faces into sub-faces and the concept of sub-face force which is the traction force attached to each sub-face impinging at a node.We observe that the time evolution of the magnetic field might be simply expressed in terms of the deformation gradient which characterizes the Lagrange-to-Euler mapping.In this framework,the divergence of the magnetic field is conserved with respect to time thanks to the Piola formula.Therefore,we solve the fully compatible updated Lagrangian discretization of the deformation gradient tensor for updating in a simple manner the cell-centered value of the magnetic field.Finally,the sub-face traction force is expressed in terms of the nodal velocity to ensure a semi-discrete entropy inequality within each cell.The conservation of momentum and total energy is recovered prescribing the balance of all the sub-face forces attached to the sub-faces impinging at a given node.This balance corresponds to a vectorial system satisfied by the nodal velocity.It always admits a unique solution which provides the nodal velocity.The robustness and the accuracy of this unconventional FV scheme have been demonstrated by employing various representative test cases.Finally,it is worth emphasizing that once you have an updated Lagrangian code for solving hyperelasticity you also get an almost free updated Lagrangian code for solving ideal MHD ensuring exactly the compatibility with the involution constraint for the magnetic field at the discrete level.

Diazoxide toxicity in congenital hyperinsulinism:A case report

BACKGROUND Diazoxide is the sole approved drug for congenital hyperinsulinism;however,diuretic administration and vigilant monitoring are crucial to prevent and promptly identify potentially life-threatening adverse effects.This report aims to highlight a seldom-considered rare side effect of diazoxide.We believe that this brief report is of general interest to World Journal of Clinical Pediatric readership and increase the physicians’awareness of the guideline importance.Moreover,it underlines the importance of stopping immediately the drug if suspected side effects.CASE SUMMARY The manuscript describes a patient diagnosed with congenital hyperinsulinism(CHI)treated with diazoxide not overlapping with diuretic.He resulted in sudden respiratory distress and therefore was transferred to the Neonatal Intensive Care Unit.The cardiological evaluation showed pericardial effusion and left ventricular myocardial hypertrophy,absent before.In suspicion of an iatrogenic effect of diazoxide it was progressively reduced until stop while introducing diuretic treatment,with resolution of symptoms.Once clinically stabilized,an 18 fluoro-diydroxy-phenylalanine positron emission tomography/computed tomography(PET/CT)was performed to differentiate between a focal or diffuse form of CHI.The PET/CT highlighted the presence of a single focal accumulation of the tracer located in the pancreatic tail,consistent with a focal form of hyperin-sulinism.At the age of four months,the patient underwent a distal pancreatectomy with histological confirmation of a focal form of nesidioblastosis,resulting in a curative operation.CONCLUSION Diuretic administration and vigilant monitoring of diazoxide therapy are crucial to prevent and promptly identify potentially life-threatening adverse effects.

How to identify early complications in patients undergoing distal gastrectomy?

In this editorial we comment on the article by Zhang et al published in a recent issue of the World Journal of Gastrointestinal Surgery.Gastrectomy with appropriate lymph node dissection is still standard curative treatment in locally advanced gastric cancer.Several studies point out that gastric cancer surgery is a complex procedure that leads to a high risk of morbidity and mortality.Many factors can contribute to the onset of complications with consequent effects on prognosis and increased mortality.The complications can be divided in complications related to anastomosis,to motility and to surgical site infection.The study presented by Zhang B et al represent an interesting analysis on the possibility to prevent postoperative morbidity.The study was performed on 131 patients with distal gastric cancer who underwent gastrectomy with D2 lymph node dissection.Of these patients,16%developed early postoperative complications.The univariate analysis showed that prealbumin level,hypertension,diabetes,history of abdominal surgery,R0 resection,and blood transfusion were factors influencing early postoperative complications after distal gastrectomy.Moreover,the inclusion of the above significant variables in the logistic regression analysis revealed that hypertension,diabetes,a history of abdominal surgery,and blood transfusion were independent predictors of postoperative complications.In conclusion,preoperative and intraoperative factors can be used to establish an early postoperative nomogram model.The results of the study presented by Zhang et al suggest that the prediction model can be used to guide the detection of postoperative complications and has clinical reference value.