Present situation and prospect of immunotherapy for unresectable locally advanced esophageal cancer during peri-radiotherapy

Four major studies(Checkmate577,Keynote-590,Checkmate649 and Attraction-4)of locally advanced esophageal cancer published in 2020 have established the importance of immunotherapy,represented by anti-programmed death protein(PD)-1 in postoperative adjuvant treatment and advanced first-line treatment of locally advanced or advanced esophageal cancer and esophagogastric junction cancer,from the aspects of proof of concept,long-term survival,overall survival rate and progression-free survival.For unresectable or inoperable nonmetastatic esophageal cancer,concurrent radiotherapy and chemotherapy is the standard treatment recommended by various guidelines.Because its curative effect is still not ideal,it is necessary to explore radical radiotherapy and chemotherapy in the future,and it is considered to be promising to combine them with immunotherapeutic drugs such as anti-PD-1.This paper mainly discusses how to combine radical concurrent radiotherapy and chemotherapy with immunotherapy for unresectable local advanced esophageal cancer.

Programmed cell death 1 inhibitor sintilimab plus concurrent chemoradiotherapy for locally advanced pancreatic adenocarcinoma

BACKGROUND Pancreatic adenocarcinoma,a malignancy that arises in the cells of the pancreas,is a devastating disease with unclear etiology and often poor prognosis.Locally advanced pancreatic cancer,a stage where the tumor has grown significantly but has not yet spread to distant organs,presents unique challenges in treatment.This article aims to discuss the current strategies,challenges,and future directions in the management of locally advanced pancreatic adenocarcinoma(LAPC).AIM To investigate the feasibility and efficacy of programmed cell death 1(PD-1)inhibitor sintilimab plus concurrent chemoradiotherapy for LAPC.METHODS Eligible patients had LAPC,an Eastern cooperative oncology group performance status of 0 or 1,adequate organ and marrow functions,and no prior anticancer therapy.In the observation group,participants received intravenous sintilimab 200 mg once every 3 wk,and received concurrent chemoradiotherapy(concurrent conventional fractionated radiotherapy with doses planning target volume 50.4 Gy and gross tumor volume 60 Gy in 28 fractions and oral S-140 mg/m2 twice daily on days 1-14 of a 21-d cycle and intravenous gemcitabine 1000 mg/m2 on days 1 and 8 of a 21-d cycle for eight cycles until disease progression,death,or unacceptable toxicity).In the control group,participants only received concurrent chemoradiotherapy.From April 2020 to November 2021,64 participants were finally enrolled with 34 in the observation group and 30 in the control group.RESULTS Thirty-four patients completed the scheduled course of chemoradiotherapy,while 32(94.1%)received sintilimab plus concurrent chemoradiotherapy with 2 patients discontinuing sintilimab in the observation group.Thirty patients completed the scheduled course of chemoradiotherapy in the control group.Based on the Response Evaluation Criteria in Solid Tumors guidelines,the analysis of the observation group revealed that a partial response was observed in 11 patients(32.4%),stable disease was evident in 19 patients(55.9%),and 4 patients(11.8%)experienced progressive disease;a partial response was observed in 6(20.0%)patients,stable disease in 18(60%),and progressive disease in 6(20%)in the control group.The major toxic effects were leukopenia and nausea.The incidence of severe adverse events(AEs)(grade 3 or 4)was 26.5%(9/34)in the observation group and 23.3%(7/30)in the control group.There were no treatment-related deaths.The observation group demonstrated a significantly longer median overall survival(22.1 mo compared to 15.8 mo)(P<0.05)and progression-free survival(12.2 mo vs 10.1 mo)(P<0.05)in comparison to the control group.The occurrence of severe AEs did not exhibit a statistically significant difference between the observation group and the control group(P>0.05).CONCLUSION Sintilimab plus concurrent chemoradiotherapy was effective and safe for LAPC patients,and warrants further investigation.

Implications of recent neoadjuvant clinical trials on the future practice of radiotherapy in locally advanced rectal cancer

Over the last two decades, the standard treatment for locally advanced rectal cancer(LARC) has been neoadjuvant chemoradiotherapy plus total mesorectal excision followed by adjuvant chemotherapy. Total neoadjuvant treatment(TNT) and immunotherapy are two major issues in the treatment of LARC. In the two latest phase Ⅲ randomized controlled trials(RAPIDO and PRODIGE23), the TNT approach achieved higher rates of pathologic complete response and distant metastasis-free survival than conventional chemoradiotherapy. Phase I/II clinical trials have reported promising response rates to neoadjuvant(chemo)-radiotherapy combined with immunotherapy. Accordingly, the treatment paradigm for LARC is shifting toward methods that increase the oncologic outcomes and organ preservation rate. However, despite the progress of these combined modality treatment strategies for LARC, the radiotherapy details in clinical trials have not changed significantly. To guide future radiotherapy for LARC with clinical and radiobiological evidence, this study reviewed recent neoadjuvant clinical trials evaluating TNT and immunotherapy from a radiation oncologist’s perspective.

Stereotactic body radiotherapy in pancreatic adenocarcinoma

Background:Stereotactic body radiotherapy(SBRT)in pancreatic cancer allows high delivery of radiation doses on tumors without affecting surrounding tissue.This review aimed at the SBRT application in the treatment of pancreatic cancer.Data sources:We retrieved articles published in MEDLINE/PubMed from January 2017 to December 2022.Keywords used in the search included:“pancreatic adenocarcinoma”OR“pancreatic cancer”AND“stereotactic ablative radiotherapy(SABR)”OR“stereotactic body radiotherapy(SBRT)”OR“chemoradiotherapy(CRT)”.English language articles with information on technical characteristics,doses and fractionation,indications,recurrence patterns,local control and toxicities of SBRT in pancreatic tumors were included.All articles were assessed for validity and relevant content.Results:Optimal doses and fractionation have not yet been defined.However,SBRT could be the standard treatment in patients with pancreatic adenocarcinoma in addition to CRT.Furthermore,the combination of SBRT with chemotherapy may have additive or synergic effect on pancreatic adenocarcinoma.Conclusions:SBRT is an effective modality for patients with pancreatic cancer,supported by clinical practice guidelines as it has demonstrated good tolerance and good disease control.SBRT opens a possibility of improving outcomes for these patients,both in neoadjuvant treatment and with radical intent.

Chemotherapy-free radiotherapy combined with immune checkpoint inhibitors:a new regimen for locally advanced non-small cell lung cancer?

Maintenance immunotherapy after concurrent chemoradiotherapy remains the standard therapeutic approach in patients with unresectable locally advanced non-small cell lung cancer(LA-NSCLC).The efficacy of pembrolizumab without chemotherapy in stage IV NSCLC has incited interest in similar approaches for LA-NSCLC.Several recent investigations involving the synergistic potential of immunotherapy combined with radiotherapy(i RT)have generated encouraging results.This review discusses the existing studies and prospective directions of chemotherapy-free i RT strategies in unresectable LA-NSCLC.Although the initial findings of chemotherapy-free i RT strategies have shown promising efficacy,we must consider the methodologic limitations of current studies and the myriad of challenges that accompany the implementation of chemotherapy-free i RT.These challenges include determining the optimal dose and fractionation,precise target volume delineation,and identification of additional suitable patient cohorts.Furthermore,the feasibility of chemotherapy-free i RT as a novel treatment modality for select patients with LA-NSCLC is contingent upon validation through randomized phase III trials.

Genome-wide investigation to assess copy number variants in the Italian local chicken population

Background Copy number variants(CNV)hold significant functional and evolutionary importance.Numerous ongoing CNV studies aim to elucidate the etiology of human diseases and gain insights into the population structure of livestock.High-density chips have enabled the detection of CNV with increased resolution,leading to the identification of even small CNV.This study aimed to identify CNV in local Italian chicken breeds and investigate their distribution across the genome.Results Copy number variants were mainly distributed across the first six chromosomes and primarily associated with loss type CNV.The majority of CNV in the investigated breeds were of types 0 and 1,and the minimum length of CNV was significantly larger than that reported in previous studies.Interestingly,a high proportion of the length of chromosome 16 was covered by copy number variation regions(CNVR),with the major histocompatibility complex being the likely cause.Among the genes identified within CNVR,only those present in at least five animals across breeds(n=95)were discussed to reduce the focus on redundant CNV.Some of these genes have been associated to functional traits in chickens.Notably,several CNVR on different chromosomes harbor genes related to muscle development,tissue-specific biological processes,heat stress resistance,and immune response.Quantitative trait loci(QTL)were also analyzed to investigate potential overlapping with the identified CNVR:54 out of the 95 gene-containing regions overlapped with 428 QTL associated to body weight and size,carcass characteristics,egg production,egg components,fat deposition,and feed intake.Conclusions The genomic phenomena reported in this study that can cause changes in the distribution of CNV within the genome over time and the comparison of these differences in CNVR of the local chicken breeds could help in preserving these genetic resources.

Radiotherapy for hyoid bone metastasis from lung adenocarcinoma:A case report

BACKGROUND Metastasis to the hyoid bone is an exceptionally rare occurrence,with documented cases limited to breast,liver,colon,skin,lung,and prostate cancers.This report highlights an unusual case involving the metastasis of lung adenocarcinoma to the hyoid bone,accompanied by a distinctive headache.Previous documentation involved surgical resection of the hyoid mass.We present a case displaying the benefits of palliative radiotherapy.CASE SUMMARY A 72-year-old non-smoking,non-alcoholic woman,initially under investigation for a year-long elevation in absolute lymphocyte count,presented with a monthlong history of intermittent throat pain.Despite negative findings in gastroenterological and otolaryngologic examinations,a contrast-enhanced chest computed tomography scan revealed a mediastinal mass and questionable soft tissue thickening in her left anterolateral neck.Subsequent imaging and biopsies confirmed the presence of lung adenocarcinoma metastasis to the hyoid bone.The patient was treated with platinum-based chemo-immunotherapy along with pembrolizumab.Ultimately,the lung cancer was unresponsive.Our patient opted for palliative radiation therapy instead of surgical resection to address her throat pain.As a result,her throat pain was alleviated,and it also incidentally resolved her chronic headaches.This is the second documented case of lung adenocarcinoma metastasizing to the hyoid bone.CONCLUSION Palliative radiotherapy may add to the quality of life in symptomatic patients with cancer metastatic to the hyoid bone.

Deep brain implantable microelectrode arrays for detection and functional localization of the subthalamic nucleus in rats with Parkinson’s disease

The subthalamic nucleus(STN)is considered the best target for deep brain stimulation treatments of Parkinson’s disease(PD).It is difficult to localize the STN due to its small size and deep location.Multichannel microelectrode arrays(MEAs)can rapidly and precisely locate the STN,which is important for precise stimulation.In this paper,16-channel MEAs modified with multiwalled carbon nanotube/poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate)(MWCNT/PEDOT:PSS)nanocomposites were designed and fabricated,and the accurate and rapid identification of the STN in PD rats was performed using detection sites distributed at different brain depths.These results showed that nuclei in 6-hydroxydopamine hydrobromide(6-OHDA)-lesioned brains discharged more intensely than those in unlesioned brains.In addition,the MEA simultaneously acquired neural signals from both the STN and the upper or lower boundary nuclei of the STN.Moreover,higher values of spike firing rate,spike amplitude,local field potential(LFP)power,and beta oscillations were detected in the STN of the 6-OHDA-lesioned brain,and may therefore be biomarkers of STN localization.Compared with the STNs of unlesioned brains,the power spectral density of spikes and LFPs synchronously decreased in the delta band and increased in the beta band of 6-OHDA-lesioned brains.This may be a cause of sleep and motor disorders associated with PD.Overall,this work describes a new cellular-level localization and detection method and provides a tool for future studies of deep brain nuclei.

Numerical study on local scour characteristics around submarine pipelines in the Yellow River Delta silty sandy soil under waves and currents

Due to their high reliability and cost-efficiency,submarine pipelines are widely used in offshore oil and gas resource engineering.Due to the interaction of waves,currents,seabed,and pipeline structures,the soil around submarine pipelines is prone to local scour,severely affecting their operational safety.With the Yellow River Delta as the research area and based on the renormalized group(RNG)k-εturbulence model and Stokes fifth-order wave theory,this study solves the Navier-Stokes(N-S)equation using the finite difference method.The volume of fluid(VOF)method is used to describe the fluid-free surface,and a threedimensional numerical model of currents and waves-submarine pipeline-silty sandy seabed is established.The rationality of the numerical model is verified using a self-built waveflow flume.On this basis,in this study,the local scour development and characteristics of submarine pipelines in the Yellow River Delta silty sandy seabed in the prototype environment are explored and the influence of the presence of pipelines on hydrodynamic features such as surrounding flow field,shear stress,and turbulence intensity is analyzed.The results indicate that(1)local scour around submarine pipelines can be divided into three stages:rapid scour,slow scour,and stable scour.The maximum scour depth occurs directly below the pipeline,and the shape of the scour pits is asymmetric.(2)As the water depth decreases and the pipeline suspension height increases,the scour becomes more intense.(3)When currents go through a pipeline,a clear stagnation point is formed in front of the pipeline,and the flow velocity is positively correlated with the depth of scour.This study can provide a valuable reference for the protection of submarine pipelines in this area.

Local dose-dense chemotherapy for triple-negative breast cancer via minimally invasive implantation of 3D printed devices

Dose-dense chemotherapy is the preferred first-line therapy for triple-negative breast cancer(TNBC),a highly aggressive disease with a poor prognosis.This treatment uses the same drug doses as conventional chemotherapy but with shorter dosing intervals,allowing for promising clinical outcomes with intensive treatment.However,the frequent systemic administration used for this treatment results in systemic toxicity and low patient compliance,limiting therapeutic efficacy and clinical benefit.Here,we report local dose-dense chemotherapy to treat TNBC by implanting 3D printed devices with timeprogrammed pulsatile release profiles.The implantable device can control the time between drug releases based on its internal microstructure design,which can be used to control dose density.The device is made of biodegradable materials for clinical convenience and designed for minimally invasive implantation via a trocar.Dose density variation of local chemotherapy using programmable release enhances anti-cancer effects in vitro and in vivo.Under the same dose density conditions,device-based chemotherapy shows a higher anticancer effect and less toxic response than intratumoral injection.We demonstrate local chemotherapy utilizing the implantable device that simulates the drug dose,number of releases,and treatment duration of the dose-dense AC(doxorubicin and cyclophosphamide)regimen preferred for TNBC treatment.Dose density modulation inhibits tumor growth,metastasis,and the expression of drug resistance-related proteins,including p-glycoprotein and breast cancer resistance protein.To the best of our knowledge,local dose-dense chemotherapy has not been reported,and our strategy can be expected to be utilized as a novel alternative to conventional therapies and improve anti-cancer efficiency.

Cooperative Anti-Jamming and Interference Mitigation for UAV Networks: A Local Altruistic Game Approach

To improve the anti-jamming and interference mitigation ability of the UAV-aided communication systems, this paper investigates the channel selection optimization problem in face of both internal mutual interference and external malicious jamming. A cooperative anti-jamming and interference mitigation method based on local altruistic is proposed to optimize UAVs’ channel selection. Specifically, a Stackelberg game is modeled to formulate the confrontation relationship between UAVs and the jammer. A local altruistic game is modeled with each UAV considering the utilities of both itself and other UAVs. A distributed cooperative anti-jamming and interference mitigation algorithm is proposed to obtain the Stackelberg equilibrium. Finally, the convergence of the proposed algorithm and the impact of the transmission power on the system loss value are analyzed, and the anti-jamming performance of the proposed algorithm can be improved by around 64% compared with the existing algorithms.

Hemostatic radiotherapy for bleeding gastrointestinal

Hemostatic radiotherapy is a non-invasive treatment for bleeding gastrointestinal(GI)tumors,promoting tumor shrinkage,blood supply reduction,and fibrotic tissue formation.It is effective in cases where traditional interventions are insufficient or contraindicated and can prevent recurrent bleeding in patients with GI bleeding histories.Hypofractionation schedules are also effective for tumor control and patient compliance.

Assessment of earthquake location uncertainties for the design of local seismic networks

The ability to estimate earthquake source locations,along with the appraisal of relevant uncertainties,is paramount in monitoring both natural and human-induced micro-seismicity.For this purpose,a monitoring network must be designed to minimize the location errors introduced by geometrically unbalanced networks.In this study,we first review different sources of errors relevant to the localization of seismic events,how they propagate through localization algorithms,and their impact on outcomes.We then propose a quantitative method,based on a Monte Carlo approach,to estimate the uncertainty in earthquake locations that is suited to the design,optimization,and assessment of the performance of a local seismic monitoring network.To illustrate the performance of the proposed approach,we analyzed the distribution of the localization uncertainties and their related dispersion for a highly dense grid of theoretical hypocenters in both the horizontal and vertical directions using an actual monitoring network layout.The results expand,quantitatively,the qualitative indications derived from purely geometrical parameters(azimuthal gap(AG))and classical detectability maps.The proposed method enables the systematic design,optimization,and evaluation of local seismic monitoring networks,enhancing monitoring accuracy in areas proximal to hydrocarbon production,geothermal fields,underground natural gas storage,and other subsurface activities.This approach aids in the accurate estimation of earthquake source locations and their associated uncertainties,which are crucial for assessing and mitigating seismic risks,thereby enabling the implementation of proactive measures to minimize potential hazards.From an operational perspective,reliably estimating location accuracy is crucial for evaluating the position of seismogenic sources and assessing possible links between well activities and the onset of seismicity.

SNR and RSSI Based an Optimized Machine Learning Based Indoor Localization Approach:Multistory Round Building Scenario over LoRa Network

In situations when the precise position of a machine is unknown,localization becomes crucial.This research focuses on improving the position prediction accuracy over long-range(LoRa)network using an optimized machine learning-based technique.In order to increase the prediction accuracy of the reference point position on the data collected using the fingerprinting method over LoRa technology,this study proposed an optimized machine learning(ML)based algorithm.Received signal strength indicator(RSSI)data from the sensors at different positions was first gathered via an experiment through the LoRa network in a multistory round layout building.The noise factor is also taken into account,and the signal-to-noise ratio(SNR)value is recorded for every RSSI measurement.This study concludes the examination of reference point accuracy with the modified KNN method(MKNN).MKNN was created to more precisely anticipate the position of the reference point.The findings showed that MKNN outperformed other algorithms in terms of accuracy and complexity.

Survey of Indoor Localization Based on Deep Learning

This study comprehensively examines the current state of deep learning (DL) usage in indoor positioning.It emphasizes the significance and efficiency of convolutional neural networks (CNNs) and recurrent neuralnetworks (RNNs). Unlike prior studies focused on single sensor modalities like Wi-Fi or Bluetooth, this researchexplores the integration of multiple sensor modalities (e.g.,Wi-Fi, Bluetooth, Ultra-Wideband, ZigBee) to expandindoor localization methods, particularly in obstructed environments. It addresses the challenge of precise objectlocalization, introducing a novel hybrid DL approach using received signal information (RSI), Received SignalStrength (RSS), and Channel State Information (CSI) data to enhance accuracy and stability. Moreover, thestudy introduces a device-free indoor localization algorithm, offering a significant advancement with potentialobject or individual tracking applications. It recognizes the increasing importance of indoor positioning forlocation-based services. It anticipates future developments while acknowledging challenges such as multipathinterference, noise, data standardization, and scarcity of labeled data. This research contributes significantly toindoor localization technology, offering adaptability, device independence, and multifaceted DL-based solutionsfor real-world challenges and future advancements. Thus, the proposed work addresses challenges in objectlocalization precision and introduces a novel hybrid deep learning approach, contributing to advancing locationcentricservices.While deep learning-based indoor localization techniques have improved accuracy, challenges likedata noise, standardization, and availability of training data persist. However, ongoing developments are expectedto enhance indoor positioning systems to meet real-world demands.

Radical radiotherapy without surgical tumor resection for rectal cancer

In this editorial,I would like to comment on the article,recently published in the World Journal of Clinical Oncology.The article focuses on non-surgical treatments for locally recurrent rectal cancer,including the watch-and-wait(WW)strategy after total neoadjuvant therapy(TNT)and particle beam therapy.As treatment options for rectal cancer continue to evolve,the high complete response rate achieved with TNT has led to the development of a new non-surgical approach:WW.Chemoradiotherapy followed by consolidation chemotherapy,in particular,has a low rate of tumor growth and is a treatment aimed at achieving a cure without surgery.However,the risk of recurrence within two years is significant,necessitating careful follow-up.Establishing standardized follow-up methods that can be implemented by many physicians is essential.Carbon ion radiotherapy has demonstrated high local control with a low incidence of severe late toxicities,even after previous pelvic radiotherapy.While these new non-surgical curative treatments for rectal cancer require further investigation,future advancements in this field are anticipated.

Seropositivity and Other Determinants Associated with Toxoplasmosis in Local Buffalo in Iraq

A cross-sectional study was conducted to determine the Seropositivity of Toxoplasma gondii in water buffalo in three Iraqi governorates (Baghdad, Dhi Qar, and Maysan) and to estimate the risk aspects related to infestation throughout the period from January to December 2019. A total of 430 serum samples were inspected with a commercial ELISA (Enzyme linked immunosorbent assay) kit. Indirect multi-species kit. The overall Seropositivity of T. gondii in the examined local buffalo was 7.4%, and the highest rate (9.3%) was in Baghdad Governorate. A multivariate regression analysis revealed that adult buffalo (OR = 7.10;95% CI: 0.87-57.68;P = 0.067) and young herds (OR = 8.42;95% CI: 1.07-66.02;P = 0.043) were more subject to infestation from young buffalo and large herds. Furthermore, the hazard of toxoplasmosis was increased in winter especially among animals in contact with cats. It is therefore requisite to determine risk aspects to evaluate which mitigation, control, prevention and procedures should be carried out to diminish, control and prevent infestation with T. gondii and its propagation.

Improved PSO-Extreme Learning Machine Algorithm for Indoor Localization

Wi Fi and fingerprinting localization method have been a hot topic in indoor positioning because of their universality and location-related features.The basic assumption of fingerprinting localization is that the received signal strength indication(RSSI)distance is accord with the location distance.Therefore,how to efficiently match the current RSSI of the user with the RSSI in the fingerprint database is the key to achieve high-accuracy localization.In this paper,a particle swarm optimization-extreme learning machine(PSO-ELM)algorithm is proposed on the basis of the original fingerprinting localization.Firstly,we collect the RSSI of the experimental area to construct the fingerprint database,and the ELM algorithm is applied to the online stages to determine the corresponding relation between the location of the terminal and the RSSI it receives.Secondly,PSO algorithm is used to improve the bias and weight of ELM neural network,and the global optimal results are obtained.Finally,extensive simulation results are presented.It is shown that the proposed algorithm can effectively reduce mean error of localization and improve positioning accuracy when compared with K-Nearest Neighbor(KNN),Kmeans and Back-propagation(BP)algorithms.

Phase induced localization transition

Localization phenomenon is an important research field in condensed matter physics.However,due to the complexity and subtlety of disordered systems,new localization phenomena always emerge unexpectedly.For example,it is generally believed that the phase of the hopping term does not affect the localization properties of the system,so the calculation of the phase is often ignored in the study of localization.Here,we introduce a quasiperiodic model and demonstrate that the phase change of the hopping term can significantly alter the localization properties of the system through detailed numerical simulations,such as the inverse participation ratio and multifractal analysis.This phase-induced localization transition provides valuable information for the study of localization physics.

Ab initio density response and local field factor of warm dense hydrogen

We present quasi-exact ab initio path integral Monte Carlo(PIMC)results for the partial static density responses and local field factors of hydrogen in the warm dense matter regime,from solid density conditions to the strongly compressed case.The full dynamic treatment of electrons and protons on the same footing allows us to rigorously quantify both electronic and ionic exchange–correlation effects in the system,and to compare the results with those of earlier incomplete models such as the archetypal uniform electron gas or electrons in a fixed ion snapshot potential that do not take into account the interplay between the two constituents.The full electronic density response is highly sensitive to electronic localization around the ions,and our results constitute unambiguous predictions for upcoming X-ray Thomson scattering experiments with hydrogen jets and fusion plasmas.All PIMC results are made freely available and can be used directly for a gamut of applications,including inertial confinement fusion calculations and the modeling of dense astrophysical objects.Moreover,they constitute invaluable benchmark data for approximate but computationally less demanding approaches such as density functional theory or PIMC within the fixed-node approximation.