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Over the past decade, there has been continuous advancement in immunotherapy to improve human health. A promising technique that has emerged is chimeric antigen receptor (CAR)-T cell therapy, which presents an innovative approach to treating cancer. While CAR-T technology has shown success in treating blood cancers, it encounters challenges in addressing solid tumors. These challenges encompass the absence of dependable tumor-associated antigens, tumor heterogeneity, immunosuppressive tumor environments, and reduced T cell infiltration. To address these challenges, current research is focused on identifying dependable tumor-associated antigens and creating cost-effective, tumor microenvironment-specific CAR-T cells. These efforts aim to enhance the efficacy of CAR-T cell therapy for solid tumors. This review provides an overview of the development of CAR-T therapy for different types of tumors, encompassing both solid and hematological tumors. It outlines the challenges encountered in CAR-T cell therapy and proposes Approaches to address these obstacles.

While hundreds of cancer-associated long noncoding RNAs (lncRNAs) have been discovered, their functional role in cancer cells is still largely a mystery. An increasing number of lncRNAs are recognized to function in the cytoplasm, e.g., as modulators of translation. Here, we investigated the detailed molecular identity and functional role of EPCART, a lncRNA we previously discovered to be a potential oncogene in prostate cancer (PCa). First, we interrogated the transcript structure of EPCARTand then confirmed EPCARTto be a non-peptide-coding lncRNA using in silico methods. Pathway analysis of differentially expressed protein-coding genes in EPCARTknockout cells implied that EPCARTmodulates the translational machinery of PCa cells. EPCARTwas also largely located in the cytoplasm and at the sites of translation. With quantitative proteome analysis on EPCARTknockout cells we discovered PDCD4, an inhibitor of protein translation, to be increased by EPCARTreduction. Further studies indicated that the inhibitory effect of EPCARTsilencing on translation was mediated by reduced activation of AKT and inhibition of the mTORC1 pathway. Together, our findings identify EPCARTas a translation-associated lncRNA that functions via modulation of the PI3K/AKT/mTORC1 pathway in PCa cells. Furthermore, we provide evidence for the prognostic potential of PDCD4 in PCa tumors in connection with EPCART.

A one-step metal-catalyzed process for transforming carbon films into high-quality graphene layers for potential use in various cutting-edge technologies was developed in this study. Carbon ultrathin films grown on CoFe alloy ultrathin sublayers by filtered cathodic vacuum arc using different ion kinetic energies were subjected to thermal annealing at 650 °C for 150 s. X-ray photoelectron spectroscopy, Raman spectroscopy, and molecular dynamics simulations provided insight into phase changes and graphenization at the molecular level. Atomic force microscopy, scanning electron microscopy, and energy dispersive X-ray spectroscopy were used to characterize the surface morphology and elemental composition of the C films and the CoFe sublayer before and after thermal annealing. It was found that increasing the C+ion kinetic energy during C film deposition enhanced graphenization; however, a very high ion kinetic energy had the opposite effect. The sp3/sp2ratio in the as-deposited C films played a critical role in graphene formation during thermal annealing. Contrary to amorphization, graphenization involved a three-step process encompassing the sequential transformation of high sp3C to low sp3C, low sp3C to graphite, and, last, graphite to nanocrystalline graphite. Variations in the C+ion kinetic energy indirectly affected the dependence of graphene growth on the hybridization state of the as-deposited C films, the carbon concentration in the CoFe sublayer, and the stability and uniformity of the catalyst CoFe sublayer during thermal annealing, in this manner influencing the overall metal-catalyzed C graphenization process.

Block copolymer molecular weight is a crucial factor influencing micelle fragmentation kinetics. In particular, it is not established how block length affects the fragmentation rate, and which block is more important. In this work, we studied the separate dependence of micelle fragmentation kinetics on core and corona block lengths, with temperature-jump experiments by dynamic light scattering. Two series of 1,2-polybutadiene-b-poly(ethylene oxide) (PB-b-PEO) copolymers were prepared, both with fixed NPB(degree of polymerization of the core block) and various NPEO. In all, a total of nine narrow dispersity (D̵< 1.1) polymers were used, with PB-b-PEO block molar masses (in kDa) of (9–6), (9–9), (9–12), (9–13), (9–19), (15–10), (15–14), (15–17) and (15–22). Micelles were initially prepared using direct dissolution of PB-b-PEO in the ionic liquid 1-ethyl-3-methylimidazolium bis(trifluoromethyl sulfonyl)imide [C2MIM][TFSI], followed by fragmentation during thermal annealing at 170 °C. The relaxation time (τ) for micelle fragmentation exhibits a power-law correlation with both NPBand NPEOas τ ∼ Ncore1.4× Ncorona0.6. Micelles were also characterized before and after fragmentation, by small-angle X-ray scattering and by liquid-phase transmission electron microscopy. Both analyses confirmed that all micelles were spherical, and the mean aggregation numbers before and after fragmentation could be extracted. The stronger τ dependence on Ncoresuggests a higher core elastic free energy penalty due to core chain extension in the transition state, compared to the contribution of corona crowding. These results are apparently not captured by any available theory of micelle fragmentation.

This study examines the behavior of a single air bubble moving through a stratified interface between two liquid phases: purified water as the denser liquid and diesel fuel as the lighter counterpart. The study investigates the impact of the upper liquid's height on bubble behavior, particularly under low gas flow rates, using high-speed video imaging. The experimental findings unveil two distinct scenarios: stable and unstable regimes. In stable conditions, the bubble follows a linear trajectory, simultaneously transferring some of the denser liquid into the lighter phase. Conversely, under unstable conditions, the bubble undergoes oscillations, navigating a zigzag or spiral path. The study also explores the correlation between the upper liquid height and the deformation and division of the dragged volume. This comprehensive investigation sheds light on the intricate interplay between liquid heights and bubble dynamics at liquid-liquid interfaces.

Objectives. This study examines the role of different machine learning (ML) algorithms to determine which socio-demographic factors and hand–forearm anthropometric dimensions can be used to accurately predict hand function. Methods. The cross-sectional study was conducted with 7119 healthy Iranian participants (3525 males and 3594 females) aged 10–89 years. Seventeen hand–forearm anthropometric dimensions were measured by JEGS digital caliper and a measuring tape. Tip-to-tip, key and three-jaw chuck pinches were measured using a calibrated pinch gauge. Subsequently, 21 features pertinent to socio-demographic factors and hand–forearm anthropometric dimensions were used for classification. Furthermore, 12 well-known classifiers were implemented and evaluated to predict pinches. Results. Among the 21 features considered in this study, hand length, stature, age, thumb length and index finger length were found to be the most relevant and effective components for each of the three pinch predictions. The k-nearest neighbor, adaptive boosting (AdaBoost) and random forest classifiers achieved the highest classification accuracy of 96.75, 86.49 and 84.66% to predict three pinches, respectively. Conclusions. Predicting pinch strength and determining the predictive hand–forearm anthropometric and socio-demographic characteristics using ML may pave the way to designing an enhanced tool handle and reduce common musculoskeletal disorders of the hand.

Spine implants are becoming increasingly diversified. Taking inspiration from other industries, three-dimensional modeling of the spinal column has helped meet the custom needs of individual patients as both en bloc replacements and pedicle screw designs. Intraoperative tailoring of devices, a common need in the operating room, has led to expandable versions of cages and interbody spacers.

Background/aim: Occupational therapists use different models and measurements for assessing children with attention-deficit/hyperactivity disorder (ADHD). One of those measurements is the Child Occupational Self-Assessment. In this study, concurrent validity of the Child Occupational Self-Assessment with Pediatric Quality of Life was tested in children with ADHD.Methods: A correlational study was conducted. The Child Occupational Self-Assessment and Pediatric Quality of Life were filled by 128 children with ADHD aged between 8 and 11 years.Findings: The results indicated that in competency subscale the highest correlation coefficient was for the total score of Pediatric Quality of Life (r= 0.56, p< 0.01) and the lowest was for social performance (r= −0.44, p< 0.01). The highest and lowest correlation coefficient in value subscale were for the total score (r= −0.46, p< 0.01) and emotional performance of Pediatric Quality of Life (r= −0.34, p< 0.01), respectively.Conclusions: The Child Occupational Self-Assessment has an acceptable concurrent validity with Pediatric Quality of Life. It can be a suitable measurement for assessing of children with ADHD.

•ERAS protocol implementation has shown significant benefits in patient outcomes.•Surgical resident education is crucial in optimizing adherence to ERAS protocol.•Combining resident education with standardized EMR order set enhances compliance.•Multidisciplinary approach in education sessions improve adherence to protocols.•Improved compliance translates to an improvement in patient outcomes.

Canada’s national rail network plays a vital role in moving goods and people, transferring $320 billion worth of goods and over 100 million passengers annually. Severe train occurrences are rare events. But they have the potential to cause fatalities and injuries, as well as environmental and property damage. Recent severe incidents, such as Burlington in 2012 and Lac-Mégantic in 2013, have shown that there is still a need for increased awareness and enhanced risk assessment. This work focuses on risk assessment on the Canadian railway system using the Safety Risk Model (SRM). The study applied a customized Canadian SRM (C-SRM) to two groups of hazardous events: main-track derailments and collisions with fatality and injury consequences, calibrated for data between 2007 and 2017. The model used Fault Tree Analysis (FTA) and Event Tree Analysis (ETA) to identify the risks of hazardous events. The individual risks of the hazardous events were then evaluated for three groups of people: passengers, employees, and members of the public (MOP). Finally, the effectiveness of introducing a new control measure, Enhanced Train Control (ETC), was assessed. The results of the study showed that the collective risk of main-track derailments is higher than main-track collisions. Moreover, the risk to MOP and employees form the most significant proportion of individual risk. Finally, risk reduction analysis of the ETC revealed that developing this system reduced the risk of main-track derailments and collisions. This new control measure thus has the potential to make Canadian railways safer.

Caspian kutum, Rutilus kutumKamensky 1901, is a commercially important fish species in the southern basins of the Caspian Sea. In spite of the popularity and consumption of the gonads, muscles, and viscera of kutum as edible parts in the region, there is no report on concentrations of trace elements (TE) in its gonads. In this study, some 51 specimens of R. kutumcaught from five different fishing regions (Astara, Anzali, Kiashahr, Sari, and Gorgan) in the southern shoreline of the Caspian Sea from September 2017 to January 2018. An inductively coupled plasma optical emission spectrometry (ICP-OES) was used to assay 36 element concentrations in fish gonads, but only 26 elements were detected and statistically analyzed. The concentration of elements in gonads (except for Ca, Sn, and Sr) did not exhibit significant differences between the eastern and western parts (p< 0.05) of the Caspian Sea. The Ca and Sr concentrations were higher in western parts (Astara, Anzali, and Kiashahr) than in eastern parts (Sari and Gorgan), while Sn showed higher levels in eastern as compared to western parts. In total, the element concentrations in this study were not higher than thresholds permitted by FAO/WHO and USFDA and pose no threat to human health.

Laser beam shaping offers remarkable possibilities to control and optimise process stability and tailor material properties and structure in laser-based welding and additive manufacturing. However, little is known about the influence of laser beam shaping on the complex melt-pool behaviour, solidified melt-track bead profile and microstructural grain morphology in laser material processing. A simulation-based approach is utilised in the present work to study the effects of laser beam intensity profile and angle of incidence on the melt-pool behaviour in conduction-mode laser melting of stainless steel 316L plates. The present high-fidelity physics-based computational model accounts for crucial physical phenomena in laser material processing such as complex laser–matter interaction, solidification and melting, heat and fluid flow dynamics, and free-surface oscillations. Experiments were carried out using different laser beam shapes and the validity of the numerical predictions is demonstrated. The results indicate that for identical processing parameters, reshaping the laser beam leads to notable changes in the thermal and fluid flow fields in the melt pool, affecting the melt-track bead profile and solidification microstructure. The columnar-to-equiaxed transition is discussed for different laser-intensity profiles.

For arteriovenous fistula (AVF) presence of a venous segment with adequate diameter is essential which is lacking in many patients. To find the optimal augmentation technique in patients with small-caliber cephalic vein (i.e., cephalic vein diameter <3 mm), studies compared primary balloon angioplasty (PBA) versus hydrostatic dilation (HD); however, it remained debatable. This systematic review seeks to determine which technique is preferable.

Background/AimsChildren with leukaemia are less able to perform activities of daily living and participate in leisure activities compared to typically developing children, which can affect their occupational competency. The aim of this study was to compare occupational competency and values between typically developing children and children with leukaemia.MethodsIn this pilot cross-sectional study, 102 children (52 typically developing children and 50 children with leukaemia) aged 7 to 13 years were assessed using the Child Occupational Self-Assessment tool, which includes occupational competency and occupational value scales for each item.ResultsThe independent t-test analysis demonstrated that there was a significant difference between the two groups on the competency scale (P=0.02). However, there was no significant difference between the two groups in the value scale (P=0.07).ConclusionsChildren with leukaemia feel less competent in carrying out everyday activities than typically developing children. Occupational competency interventions should be prioritised in occupational therapy services.

Objective: Older adults typically experience higher rates of severe disease and mortality than the general population after contracting an infectious disease. Vaccination is critical for preventing disease and severe downstream outcomes; however, vaccination rates among older adults are suboptimal. We assessed predictors associated with pneumococcal and seasonal influenza vaccination among older women.Methods: We used data from the Women’s Health Initiative, a nationwide cohort of women. We ascertained seasonal influenza and pneumococcal vaccination status through a questionnaire administered in 2013. We limited analyses to women aged ≥65 years at questionnaire administration. We used logistic regression to estimate associations between demographic, lifestyle, and health-related factors and vaccination and explored stratification by race.Results: Of participants who responded to each question, 84.3% (n = 60 578) reported being vaccinated for influenza and 85.5% (n = 59 015) for pneumonia. The odds of reporting influenza vaccination were significantly lower among non-Hispanic Black participants than among non-Hispanic White participants (odds ratio [OR] = 0.53; 95% CI, 0.49-0.58), women with no health insurance versus private health insurance (OR = 0.61; 95% CI, 0.54-0.68), and women living in rural versus urban settings (OR = 0.84; 95% CI, 0.73-0.96). Current smoking, lower education levels, and having comorbid conditions were associated with lower likelihood of being vaccinated for influenza (than not); past pneumonia diagnosis and being currently married were associated with a higher likelihood. We observed similar associations for pneumococcal vaccination coverage.Conclusions: These findings reinforce the need to enact policy and implement programs to improve access to, education and awareness about, and provider recommendations for these critical disease-prevention tools. Results from our study should guide strategies for SARS-CoV-2 vaccination.

We successfully demonstrated the improvement and stabilization of the electrical properties of a graphene field effect transistor by fabricating a sandwiched amorphous boron nitride (a-BN)/graphene (Gr)/a-BN using a directly grown a-BN film. The a-BN film was grown vialow-pressure chemical vapor deposition (LPCVD) at a low growth temperature of 250 °C and applied as a protection layer in the sandwiched structure. Both structural and chemical states of the as-grown a-BN were verified by various spectroscopic and microscopic analyses. We analyzed the Raman spectra of Gr/SiO2and a-BN/Gr/a-BN structures to determine the stability of the device under exposure to ambient air. Following exposure, the intensity of the 2D/G-peak ratio of Gr/SiO2decreased and the position of the G and 2D peaks red-shifted due to the degradation of graphene. In contrast, the peak position of encapsulated graphene is almost unchanged. We also confirmed that the mobility of a-BN/Gr/a-BN structure is 17,941 cm2/Vs. This synthetic strategy could provide a facile way to synthesize uniform a-BN film for encapsulating various van der Waals materials, which is beneficial for future applications in nanoelectronics.

Relapse infection usually results from resistance to the antibiotic, acquired genes, or persister cells. Persister cells are formed through mutation, reduced activity or metabolically inactive pathways induced by antibiotics, harassing conditions, low ATP, and malnutrition. These factors provide the ground for bacteria to grow slowly. Such a slow growth rate makes traditional antibiotics ineffective against persister cells. Staphylococcus aureus (S. aureus), in addition to this form, can be observed in Small Colony Variants (SCVs), L-forms, and dormant, all of which are characterized by at least one feature, i.e., slow growth. Despite their slow growth, they are metabolically active in terms of stringent SOS and cell wall stress responses. The stress response involves resistance against harassing conditions, and it survives until it is reactivated later. The present study aims to discuss the mechanisms of all persister cell formations, circumstances involved, gene mutation, and adoptable strategies against it.

Today, the wheel-rail dynamic forces (WRDFs) is one of the criteria for reliable evaluation of running stability, track loading, and vibration behaviour of railway systems. Over-limit dynamic forces, with the creation and growth of wheel and rail defects, are the cause of the derailment, accidents, and damage, and must be constantly monitored. In the present paper, after modelling and validating a passenger rail system, the effects of changes in train speed, track irregularities, and wheel flats on the WRDFs, derailment coefficient, and wheel-rail dynamic impact factor are evaluated. One of the results showed that by changing the train speed in different track irregularities, the WRDFs has changed significantly and the maximum force has increased with increasing speed. For example, in class 5 and class 6 of irregularity, by changing the train speed from 20 km/h to 100 km/h, the WRDFs is increased about 32% and 27%, respectively.

Evaluating and predicting the possibility of derailment at turnouts is important in operation and maintenance. In addition, wheel flat defect is one of the sources of infrastructure damage due to the occurrence of severe impact forces. In this paper, the dynamic and safety studies of a freight train with a defective wheel when passing through turnouts are investigated. After modelling and validation, the evaluation of the wheel-rail dynamic forces and derailment coefficient at turnout has been done using the multibody dynamic universal mechanism (UM), and the effect of the wheel flat depth on these items has been evaluated. The results indicate that the depth of the wheel flat, as well as the train speed, strongly affect the dynamic forces and derailment coefficient at the turnout. Excessive dynamic forces, with the creation and growth of wheel and rail defects, are the cause of derailment, accidents, and destruction, and must be continuously monitored.