Late effects of the treatment of childhood cancer

Excellent progress has been made in the last few decades in the cure rates of pediatric malignancies,with more than 80%of children with cancer who have access to contemporary treatment being cured.However,the therapies responsible for this survival can also produce adverse physical and psychological long-term outcomes,referred to as late effects,which appear months to years after the completion of cancer treatment.Research has shown that 60%to 90%of childhood cancer survivors(CCSs)develop one or more chronic health conditions,and 20%to 80%of survivors experience severe or life-threatening complications during adulthood.Therefore,understanding the late side effects of such treatments is important to improve the health and quality of life of the growing population of CCSs.

Pathogenesis, diagnosis, and treatment of epilepsy: electromagnetic stimulation-mediated neuromodulation therapy and new technologies

Epilepsy is a severe,relapsing,and multifactorial neurological disorder.Studies regarding the accurate diagnosis,prognosis,and in-depth pathogenesis are crucial for the precise and effective treatment of epilepsy.The pathogenesis of epilepsy is complex and involves alterations in variables such as gene expression,protein expression,ion channel activity,energy metabolites,and gut microbiota composition.Satisfactory results are lacking for conventional treatments for epilepsy.Surgical resection of lesions,drug therapy,and non-drug interventions are mainly used in clinical practice to treat pain associated with epilepsy.Non-pharmacological treatments,such as a ketogenic diet,gene therapy for nerve regeneration,and neural regulation,are currently areas of research focus.This review provides a comprehensive overview of the pathogenesis,diagnostic methods,and treatments of epilepsy.It also elaborates on the theoretical basis,treatment modes,and effects of invasive nerve stimulation in neurotherapy,including percutaneous vagus nerve stimulation,deep brain electrical stimulation,repetitive nerve electrical stimulation,in addition to non-invasive transcranial magnetic stimulation and transcranial direct current stimulation.Numerous studies have shown that electromagnetic stimulation-mediated neuromodulation therapy can markedly improve neurological function and reduce the frequency of epileptic seizures.Additionally,many new technologies for the diagnosis and treatment of epilepsy are being explored.However,current research is mainly focused on analyzing patients’clinical manifestations and exploring relevant diagnostic and treatment methods to study the pathogenesis at a molecular level,which has led to a lack of consensus regarding the mechanisms related to the disease.

Controversies around the treatment of peritoneal metastases of colorectal cancer

In this editorial we examine the article by Wu et al published in the World Journal of Gastrointestinal Oncology.Surgical resection for peritoneal metastases from colorectal cancer(CRC)has been gradually accepted in the medical oncology community.A randomized trial(PRODIGE 7)on cytoreductive surgery(CRS)with hyperthermic intraperitoneal chemotherapy(HIPEC)failed to prove any benefit of oxaliplatin in the overall survival of patients with peritoneal metastases from colorectal origin.Nevertheless,isolated systemic chemotherapy for CRC stage IV has demonstrated a reduced response in peritoneal metastases than that obtained in other metastatic sites such as the liver.Another tool is required in those patients to achieve more local control of the disease.Surgical groups in peritoneal surgery continue to use HIPEC in their procedures,using other agents than oxaliplatin for peritoneal cavity infusion,such as mitomycin C.These patients present with complex surgical issues to manage,and consequently a large burden of complications has to be anticipated.Therefore,identifying patients who will benefit from CRS with or without HIPEC would be of great interest.

Advancing treatment strategies:Insights from network meta-analysis of hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma

This study examines the pivotal findings of the network meta-analysis of Zhou et al,which evaluated the efficacy of hepatic arterial infusion chemotherapy and combination therapies for advanced hepatocellular carcinoma(HCC).This meta-analysis suggests that therapeutic combinations have greater efficacy than do standard treatments.The article highlights the key insights that have the potential to shift current clinical practice and enhance outcomes for patients with advanced HCC.Additionally,this article discusses further research that can be conducted to optimize these treatments and achieve personalized care for patients with HCC.

Efficacy,safety and treatment satisfaction of transition to a regimen of insulin degludec/aspart:A pilot study

BACKGROUND There is a lack of clinical evidence on the efficacy and safety of transitioning from a thrice-daily pre-mixed insulin or basal-prandial regimen to insulin degludec/aspart(IDegAsp)therapy,with insufficient data from the Chinese population.AIM To demonstrate the efficacy,safety,and treatment satisfaction associated with the transition to IDegAsp in type 2 diabetes mellitus(T2DM).METHODS In this 12-week open-label,non-randomized,single-center,pilot study,patients with T2DM receiving thrice-daily insulin or intensive insulin treatment were transitioned to twice-daily injections of insulin IDegAsp.Insulin doses,hemoglobin A1c(HbA1c)levels,fasting blood glucose(FBG),hypoglycemic events,a Diabetes Treatment Satisfaction Questionnaire,and other parameters were assessed at baseline and 12-weeks.RESULTS This study included 21 participants.A marked enhancement was observed in the FBG level(P=0.02),daily total insulin dose(P=0.03),and overall diabetes treatment satisfaction(P<0.01)in the participants who switched to IDegAsp.There was a decrease in HbA1c levels(7.6±1.1 vs 7.4±0.9,P=0.31)and the frequency of hypoglycemic events of those who switched to IDegAsp decreased,however,there was no statistically significant difference.CONCLUSION The present findings suggest that treatment with IDegAsp enhances clinical outcomes,particularly FBG levels,daily cumulative insulin dose,and overall satisfaction with diabetes treatment.

The emerging role of mesenchymal stem cell-derived extracellular vesicles to ameliorate hippocampal NLRP3 inflammation induced by binge-like ethanol treatment in adolescence

Our previous studies have reported that activation of the NLRP3(NOD-,LRR-and pyrin domain-containing protein 3)-inflammasome complex in ethanol-treated astrocytes and chronic alcohol-fed mice could be associated with neuroinflammation and brain damage.Mesenchymal stem cell-derived extracellular vesicles(MSC-EVs)have been shown to restore the neuroinflammatory response,along with myelin and synaptic structural alterations in the prefrontal cortex,and alleviate cognitive and memory dysfunctions induced by binge-like ethanol treatment in adolescent mice.Considering the therapeutic role of the molecules contained in mesenchymal stem cell-derived extracellular vesicles,the present study analyzed whether the administration of mesenchymal stem cell-derived extracellular vesicles isolated from adipose tissue,which inhibited the activation of the NLRP3 inflammasome,was capable of reducing hippocampal neuroinflammation in adolescent mice treated with binge drinking.We demonstrated that the administration of mesenchymal stem cell-derived extracellular vesicles ameliorated the activation of the hippocampal NLRP3 inflammasome complex and other NLRs inflammasomes(e.g.,pyrin domain-containing 1,caspase recruitment domain-containing 4,and absent in melanoma 2,as well as the alterations in inflammatory genes(interleukin-1β,interleukin-18,inducible nitric oxide synthase,nuclear factor-kappa B,monocyte chemoattractant protein-1,and C–X3–C motif chemokine ligand 1)and miRNAs(miR-21a-5p,miR-146a-5p,and miR-141-5p)induced by binge-like ethanol treatment in adolescent mice.Bioinformatic analysis further revealed the involvement of miR-21a-5p and miR-146a-5p with inflammatory target genes and NOD-like receptor signaling pathways.Taken together,these findings provide novel evidence of the therapeutic potential of MSC-derived EVs to ameliorate the hippocampal neuroinflammatory response associated with NLRP3 inflammasome activation induced by binge drinking in adolescence.

Scalable Ir‑Doped NiFe_(2)O_(4)/TiO_(2)Heterojunction Anode for Decentralized Saline Wastewater Treatment and H_(2)Production

Wastewater electrolysis cells(WECs)for decentralized wastewater treatment/reuse coupled with H_(2)production can reduce the carbon footprint associated with transportation of water,waste,and energy carrier.This study reports Ir-doped NiFe_(2)O_(4)(NFI,~5 at%Ir)spinel layer with TiO_(2)overlayer(NFI/TiO_(2)),as a scalable heterojunction anode for direct electrolysis of wastewater with circumneutral pH in a single-compartment cell.In dilute(0.1 M)NaCl solutions,the NFI/TiO_(2)marks superior activity and selectivity for chlorine evolution reaction,outperforming the benchmark IrO_(2).Robust operation in near-neutral pH was confirmed.Electroanalyses including operando X-ray absorption spectroscopy unveiled crucial roles of TiO_(2) which serves both as the primary site for Cl−chemisorption and a protective layer for NFI as an ohmic contact.Galvanostatic electrolysis of NH4+-laden synthetic wastewater demonstrated that NFI/TiO_(2)not only achieves quasi-stoichiometric NH_(4)^(+)-to-N_(2)conversion,but also enhances H_(2)generation efficiency with minimal competing reactions such as reduction of dissolved oxygen and reactive chlorine.The scaled-up WEC with NFI/TiO_(2)was demonstrated for electrolysis of toilet wastewater.

Variations in quantifying patient reported outcome measures to estimate treatment effect

In the practice of healthcare,patient-reported outcomes(PROs)and PRO measures(PROMs)are used as an attempt to observe the changes in complex clinical situations.They guide us in making decisions based on the evidence regarding patient care by recording the change in outcomes for a particular treatment to a given condition and finally to understand whether a patient will benefit from a particular treatment and to quantify the treatment effect.For any PROM to be usable in health care,we need it to be reliable,encapsulating the points of interest with the potential to detect any real change.Using structured outcome measures routinely in clinical practice helps the physician to understand the functional limitation of a patient that would otherwise not be clear in an office interview,and this allows the physician and patient to have a meaningful conver-sation as well as a customized plan for each patient.Having mentioned the rationale and the benefits of PROMs,understanding the quantification process is crucial before embarking on management decisions.A better interpretation of change needs to identify the treatment effect based on clinical relevance for a given condition.There are a multiple set of measurement indices to serve this effect and most of them are used interchangeably without clear demarcation on their differences.This article details the various quantification metrics used to evaluate the treatment effect using PROMs,their limitations and the scope of usage and implementation in clinical practice.

Fluctuations of Single-Mode Laser Driven by Two Different Kinds of Colored Noise

A single-mode laser with coupling between additive and multiplicative noise terms is investigated when the multiplicative noise and the coupling between two noise terms are colored fluctuations with finite correlation times T1 and T2. Combining the unified colored noise approximation （UCNA） and the functional analysis, the stationary probability distribution （SPD） and the variance of the laser intensity is derived. It is found that the colored nature of multiplicative noise and the coupling strength between two noise terms can affect both the structure and the height of the SPD, while the colored nature of the coupling between two noise terms can only affect the height of the SPD. The multiplicative noise can enhance the intensity fluctuations while the additive noise can reduce the fluctuations in a laser system. Numerical simulations are presented and consistent to the analytical results.

Experimental demonstration of single-mode fiber coupling using adaptive fiber coupler

Coupling plane wave into a single-mode fiber （SMF） with high and steady coupling efficiency is crucial for fiber- based free-space laser systems, where random angular jitters are the main influencing factors of fiber coupling. In this paper, we verified a new adaptive-optic device named adaptive fiber coupler （AFC） which could compensate angular jitters and improve the SMF coupling efficiency in some degree. Experiments of SMF coupling under the angular jitter situation using AFC have been achieved. Stochastic parallel gradient descent （SPGD） algorithm is employed as the control strategy, of which the iteration rate is 625 Hz. In closed loop, the coupling efficiency keeps above 65% when angular errors are below 80/3tad. The compensation bandwidth is 35 Hz at sine-jitter of 15 ~rad amplitude with average coupling efficiency of above 60%. Also, experiments with simulated turbulence have been studied. The average coupling efficiency increases from 31.97% in open loop to 61.33% in closed loop, and mean square error （MSE） of coupling efficiency drops from 7.43% to 1.75%.

Stable single-mode operation of 894.6 nm VCSEL at high temperatures for Cs atomic sensing

In this paper, stable single-mode operation at high temperatures is produced by the surface-relief-integrated vertical cavity surface emitting laser（VCSEL）. The gain-cavity mode detuning technique is employed to realize high operating temperatures for the VCSEL. The surface relief is etched in the centre of the top side as a mode discriminator for the fundamental mode output, and the threshold current minimum is 1.94 mA at high temperatures by the gain-cavity mode detuning technique. Maximum single-fundamental-mode output power of 0.45 mW at 80℃ is obtained, and the side mode suppression ratios（SMSRs） are more than 30 dB with increasing temperature and current, respectively.

Design and analysis of a novel single-mode single-polarization photonic crystal fibre based on polarization-dependent coupling and absorption effect

A novel single-mode single-polarization （SMSP） photonic crystal fibre has been proposed and analysed based on the polarization-dependent coupling and absorption effect via a full-vector finite element method with perfectly matched layers. The numerical results predict that very efficient SMSP operation can be achieved with both high bandwidth and high extinction ratio at low loss penalty. Effects of the fibre structural parameters on the SMSP bandwidth and extinction ratio have been explored, which will provide useful guide for the design and fabrication of the fibre. The results obtained will be instructive for the realization of new SMSP fibres with high performance.

Laser patterning of large-scale perovskite single-crystal-based arrays for single-mode laser displays

Lead halide perovskites have attracted considerable attention as potential candidates for high-performance nano/microlasers,owing to their outstanding optical properties.However,the further development of perovskite microlaser arrays(especially based on polycrystalline thin films)produced by the conventional processing techniques is hindered by the chemical instability and surface roughness of the perovskite structures.Herein,we demonstrate a laser patterning of large-scale,highly crystalline perovskite single-crystal films to fabricate reproducible perovskite single-crystal-based microlaser arrays.Perovskite thin films were directly ablated by femtosecond-laser in multiple low-power cycles at a minimum machining line width of approximately 300 nm to realize high-precision,chemically clean,and repeatable fabrication of microdisk arrays.The surface impurities generated during the process can be washed away to avoid external optical loss due to the robustness of the single-crystal film.Moreover,the high-quality,large-sized perovskite single-crystal films can significantly improve the quality of microcavities,thereby realizing a perovskite microdisk laser with narrow linewidth(0.09 nm)and low threshold(5.1µJ/cm2).Benefiting from the novel laser patterning method and the large-sized perovskite single-crystal films,a high power and high color purity laser display with single-mode microlasers as pixels was successfully fabricated.Thus,this study may offer a potential platform for mass-scale and reproducible fabrication of microlaser arrays,and further facilitate the development of highly integrated applications based on perovskite materials.

Stochastic Resonance in Linear Region of a Single-Mode Laser: Effects of Amplitude Modulation of Signal

A single-mode laser noise model driven by quadratic colored pump noise and amplitude modulation signal is proposed. The real and imaginary parts of the pump noise are assumed to be cross-correlation. The effect of cross- correlation of noise and amplitude modulation of signal on laser statistical properties is studied by using the linearized approximation. The analytic expression of signal-to-noise ratio （SNR） is calculated. It is found that the phenomena of stochastic resonance （SR） respectively exist in the curves of the SNR versus the noise cross-correlation coefficient λ and the SNR versus the pump parameter a, as well as the SNR versus the signal frequency ω in our model. It is shown that there are three different typies of SR in the model： the conventional form of SR, the SR in the broad sense, and the bona fide SR.

Wavelength dependent loss of splice of single-mode fibers

After reviewing three different definitions of mode field diameter of single-mode fibers, coupled efficiency calculation methods associated with lateral offset, longitude separation and wavelength, the effects produced by them, and the influences of splicing defects were discussed in detail. The regularities of the effects were studied according to the first order derivation of couple efficiency formula, and a simplified formula for couple efficiency calculation was presented under the circumstance of slight misalignment, with respect to wavelength, 2, and in a good agreement with the theoretical model. The simplified formula provides a new but simple approach to evaluate wavelength dependent couple efficiency of single-mode fibers. Theoretical analyses and numerical calculations show that, when those defects exist, the wavelength produces additional effects on the couple loss that growth of wavelength causes an increase on the couple efficiency for the lateral offset or longitude separation whereas lessens the couple efficiency due to angular misalignment or mode fields mismatching, and that the wavelength degrades the couple efficiency distinctly when λ≥2.5 μm whereas it distorts the couple slightly in range of λ≤2λ≤2 μm.

Entropy squeezing for a V-type three-level atom interacting with a single-mode field and passing through the amplitude damping channel with weak measurement

The entropy squeezing of a V-type three-level atom interacting with a single-mode field and passing through the amplitude damping channel is investigated in detail. Our results show that when coupled to the single-mode field, the atom in appropriate initial states can not only generate obvious entropy squeezing but also keep in the optimal squeezing state,while passing through the amplitude damping channel, the atom can generate entropy squeezing under the control of the weak measurement. Besides, it is proved again that as a measurement method for atomic squeezing, the entropy squeezing is precise and effective. Therefore our work is instructive for experiments in preparing three-level system information resource with ultra-low quantum noise.

Optically powered gas monitoring system using single-mode fibre for underground coal mines

We present an optically powered,intrinsically safe gas monitoring system to measure four essential environmental gases(CH_(4),CO_(2),CO and O_(2)),together with ambient temperature and pressure,for underground mines.The system is based on three key technologies developed at UNSW:(1)power-over-fbre(PoF)at 1550 nm using a single industry-standard,low-cost single-mode fbre(SMF)for both power delivery and information transmission,(2)liquid–crystal-based optical transducers for optical telemetry,and(3)ultra-low power consumption design of all electronics.Together,this approach allows each gas monitoring station to operate with less than 150 mW of optical power,meeting the intrinsic safety requirements specifed by the IEC60079-28 standard.A 2-month feld trial at BMA’s Broadmeadow underground mine proved the cabling compatibility to the mine’s existing optical network and the stability of the system performance.Compared with conventional electrically powered gas sensors,this technology bypasses the usual roadblocks of underground gas monitoring where electrical power is either unsafe or unavailable.Furthermore,using one fbre for both power delivery and communication enables longer distance coverage,reduces optical cabling and increases multiplexing possibilities and data throughput for better awareness of underground environment.

Time-Delayed Feedback Control in a Single-Mode Laser System

The effects of time-delayed feedback control in a single-mode laser system is investigated.Using the smalltime delay approximation,the analytic expression of the stationary probability distribution function of the laser field isobtained.The mean,normalized variance and skewness of the steady-state laser intensity are calculated.It is found thatthe time-delayed feedback control can suppress the intensity fluctuation of the laser system.The numerical simulationsare in good agreement with the approximate analytic results.

Stochastic resonance in a single-mode laser driven by frequency modulated signal and coloured noises

By adding frequency modulated signals to the intensity equation of gain noise model of the single-mode laser driven by two coloured noises which are correlated, this paper uses the linear approximation method to calculate the power spectrum and signal-to-noise ratio （SNR） of the laser intensity. The results show that the SNR appears typical stochastic resonance with the variation of intensity of the pump noise and quantum noise. As the amplitude of a modulated signal has effects on the SNR, it shows suppression, monotone increasing, stochastic resonance, and multiple stochastic resonance with the variation of the frequency of a carrier signal and modulated signal.

Combination treatment of inflammatory bowel disease:Present status and future perspectives

The treatment of patients with inflammatory bowel disease(IBD),especially those with severe or refractory disease,represents an important challenge for the clinical gastroenterologist.It seems to be no exaggeration to say that in these patients,not only the scientific background of the gastroenterologist is tested,but also the abundance of“gifts”that he should possess(insight,intuition,determ-ination,ability to take initiative,etc.)for the successful outcome of the treatment.In daily clinical practice,depending on the severity of the attack,IBD is treated with one or a combination of two or more pharmaceutical agents.These combin-ations include not only the first-line drugs(e.g.,mesalazine,corticosteroids,antibiotics,etc)but also second-and third-line drugs(immunosuppressants and biologic agents).It is a fact that despite the significant therapeutic advances there is still a significant percentage of patients who do not satisfactorily respond to the treatment applied.Therefore,a part of these patients are going to surgery.In recent years,several small-size clinical studies,reviews,and case reports have been published combining not only biological agents with other drugs(e.g.,immunosuppressants or corticosteroids)but also the combination of two biologi-cal agents simultaneously,especially in severe cases.In our opinion,it is at least a strange(and largely unexplained)fact that we often use combinations of drugs in a given patient although studies comparing the simultaneous administration of two or more drugs with monotherapy are very few.As mentioned above,there is a timid tendency in the literature to combine two biological agents in severe cases unresponsive to the applied treatment or patients with severe extraintestinal manifestations.The appropriate dosage,the duration of the administration,the suitable timing for checking the clinical and laboratory outcome,as well as the treatment side-effects,should be the subject of intense clinical research shortly.In this editorial,we attempt to summarize the existing data regarding the already applied combination therapies and to humbly formulate thoughts and suggestions for the future application of the combination treatment of biological agents in a well-defined category of patients.We suggest that the application of biomarkers and artificial intelligence could help in establishing new forms of treatment using the available modern drugs in patients with IBD resistant to treatment.