Analysis of the temperature-dependent plastic deformation of single crystals of quinary, quaternary and ternary equiatomic high- and medium-entropy alloys of the Cr-Mn-Fe-Co-Ni system.

Temperature-dependent plastic deformation behaviors of single crystals of quaternary and ternary equiatomic medium-entropy alloys (MEAs) belonging to the Cr-Mn-Fe-Co-Ni system were investigated in compression at temperatures in the range 9 K to 1373 K. Their critical resolved shear stresses (CRSSs) increase with decreasing temperature below room temperature. There is also a dulling of the temperature dependence of CRSS below 77 K due to dislocation inertial effects that we attribute to a decrease in the phonon drag coefficient. These behaviors were compared with those of previously investigated single crystals of the equiatomic Cr-Co-Ni and Cr-Fe-Co-Ni MEAs, and the equiatomic Cr-Mn-Fe-Co-Ni high-entropy alloy (HEA). The temperature dependence of CRSS and the apparent activation volumes below room temperature can be well described by conventional thermal activation theories of face-centered cubic (FCC) alloys. Above 673 K, there is a small increase in CRSS, which we believe is due to elastic interactions between solutes and mobile dislocations, the so-called Portevin-Le Chatelier (PL) effect. The CRSS at 0 K was obtained by extrapolation of fitted CRSS vs. temperature curves and compared with predictions from solid solution strengthening models of HEA and MEAs.

The novelty of our work entitled 'Analysis of the temperature-dependent plastic deformation of single crystals of quinary, quaternary and ternary equiatomic high- and medium-entropy alloys of the Cr-Mn-Fe-Co-Ni system' can be summarized as follows: The temperature dependences of CRSS were experimentally deduced from bulk single crystals of the six MEAs for the first time, so that fair comparison among the FCC HEA/MEAs is made.

Effect of experimentally induced plantar pain on trunk posture during gait.

[Purpose] Plantar pain is associated with the prevalence of low back pain. Therefore, it is reasonable to assume that some kind of physical change should be occurring in the trunk due to plantar pain. However, the physical effect of plantar pain on the trunk remains unknown. We evaluated the effect of plantar pain on trunk posture during gait. [Participants and Methods] Ten healthy volunteers participated in the present study. Participants walked under two conditions: without pain and with pain. In the with pain condition, we set pain-inducing devices to the right foot to induce plantar pain during stance phase. By using 3D motion analysis system, the angles of the head, thorax, and pelvis segments, as well as the neck, trunk, bilateral hip, bilateral knee, and bilateral ankle joints, were measured. We analyzed the angle data throughout the gait cycle by using one-dimensional statistical parametric mapping. [Results] The anterior trunk tilt was observed in the right stance phase. [Conclusion] The anterior trunk tilt observed in the with pain condition may be a burden on the trunk. Our results presented one of the possible reasons for increased prevalence of low back pain in the plantar pain patients.

Knee dynamics during take-off and landing in spike jumps performed by volleyball players with patellar tendinopathy.

[Purpose] Patellar tendinopathy is a common sports injury. The risk factors for this injury can be categorized as intrinsic, extrinsic, and dynamic. We examined the dynamic factors in this study. [Participants and Methods] The participants were volleyball players who were assigned to a patient group (n=6) if they had medial patellar tendinopathy in the left knee or to a control group (n=7) otherwise. The participants performed spike jumps, and their ground reaction force and three-dimensional kinematic data were recorded. Knee angle and moment data were extracted at the peak extension moment of take-off and landing. [Results] The two groups showed no differences in knee angles. A tendency for abduction/external rotation moments at take-off and landing on both sides was observed in the control group, while the patient group showed adduction and internal rotation moments at take-off and adduction moment at landing in the left (injured) knee. [Conclusion] The observed knee joint moments in the left (injured) knee of the patient group may have been involved in the pathophysiological mechanism underlying the development of patellar tendinopathy.

Relationship between Trace Element in Tumor and Prognosis in Lung Cancer Patients.

Background and Objectives: This study aimed to observe the relationship between trace element concentrations in lung tissue from lung non-small cell lung carcinoma (NSCLC) patients and prognosis. Materials and Methods: The concentrations of various trace elements in the lung tissues were measured by a particle-induced X-ray emission (PIXE) system, and the results were analyzed for statistical significance. Eight essential trace elements, Cr, Mn, Fe, Co, Cu, Zn, Se, and Mo, were analyzed. We investigated the relationship between trace element concentrations and disease-free survival (DFS) and overall survival (OS) in NSCLC patients. Results: A total of 129 NSCLC patients and 20 control patients were included in this study. As for DFS, Co was the only element that showed a significant difference, and the high Co group had better DFS (HR: 0.352, 95% CI = 0.128-0.97). No significant difference was observed for Cr, Mn, Fe, Se, or Mo, but DFS tended to be better in the high trace element group. No significant difference was observed for Cu and Zn, but DFS tended to be good in the low trace element group. As for OS, Cr was the only element that showed a significant difference, and the high Cr element group had better OS (HR: 0.477, 95% CI = 0.128-0.97). Conclusions: This study suggests that the prognosis is good in lung cancer cases with high intratumoral concentrations of Co and Cr. The dynamics of trace elements in body and in tumor tissue have not been well established, and we consider that more research is necessary in the future.

Human cytomegalovirus downregulates SLITRK6 expression through IE2.

Congenital human cytomegalovirus (HCMV) infection causes sensorineural hearing loss (SNHL) and other neurological disorders, although the neuropathogenesis of HCMV infection is not well understood. Here, we show that the expression of SLITRK6, one of causative genes for hereditary SNHL, was robustly downregulated by HCMV infection in cultured neural cells. We also show that HCMV-encoded immediate-early 2 (IE2) proteins mediate this downregulation and their carboxy-terminal region, especially amino acid residue Gln548, has a critical role. These findings suggest that the downregulation of SLITRK6 expression by IE2 may have a role in HCMV-induced SNHL and other neurological disorders.

Inkjet printing of single-crystal films.

The use of single crystals has been fundamental to the development of semiconductor microelectronics and solid-state science. Whether based on inorganic or organic materials, the devices that show the highest performance rely on single-crystal interfaces, with their nearly perfect translational symmetry and exceptionally high chemical purity. Attention has recently been focused on developing simple ways of producing electronic devices by means of printing technologies. 'Printed electronics' is being explored for the manufacture of large-area and flexible electronic devices by the patterned application of functional inks containing soluble or dispersed semiconducting materials. However, because of the strong self-organizing tendency of the deposited materials, the production of semiconducting thin films of high crystallinity (indispensable for realizing high carrier mobility) may be incompatible with conventional printing processes. Here we develop a method that combines the technique of antisolvent crystallization with inkjet printing to produce organic semiconducting thin films of high crystallinity. Specifically, we show that mixing fine droplets of an antisolvent and a solution of an active semiconducting component within a confined area on an amorphous substrate can trigger the controlled formation of exceptionally uniform single-crystal or polycrystalline thin films that grow at the liquid-air interfaces. Using this approach, we have printed single crystals of the organic semiconductor 2,7-dioctyl[1]benzothieno[3,2-b][1]benzothiophene (C(8)-BTBT) (ref. 15), yielding thin-film transistors with average carrier mobilities as high as 16.4 cm(2) V(-1) s(-1). This printing technique constitutes a major step towards the use of high-performance single-crystal semiconductor devices for large-area and flexible electronics applications.

Brainstem control of locomotion and muscle tone with special reference to the role of the mesopontine tegmentum and medullary reticulospinal systems.

The lateral part of the mesopontine tegmentum contains functionally important structures involved in the control of posture and gait. Specifically, the mesencephalic locomotor region, which may consist of the cuneiform nucleus and pedunculopontine tegmental nucleus (PPN), occupies the interest with respect to the pathophysiology of posture-gait disorders. The purpose of this article is to review the mechanisms involved in the control of postural muscle tone and locomotion by the mesopontine tegmentum and the pontomedullary reticulospinal system. To make interpretation and discussion more robust, the above issue is considered largely based on our findings in the experiments using decerebrate cat preparations in addition to the results in animal experimentations and clinical investigations in other laboratories. Our investigations revealed the presence of functional topographical organizations with respect to the regulation of postural muscle tone and locomotion in both the mesopontine tegmentum and the pontomedullary reticulospinal system. These organizations were modified by neurotransmitter systems, particularly the cholinergic PPN projection to the pontine reticular formation. Because efferents from the forebrain structures as well as the cerebellum converge to the mesencephalic and pontomedullary reticular formation, changes in these organizations may be involved in the appropriate regulation of posture-gait synergy depending on the behavioral context. On the other hand, abnormal signals from the higher motor centers may produce dysfunction of the mesencephalic-reticulospinal system. Here we highlight the significance of elucidating the mechanisms of the mesencephalic-reticulospinal control of posture and locomotion so that thorough understanding of the pathophysiological mechanisms of posture-gait disorders can be made.

Estimation of center of pressure information by smartphone sensors for postural control training.

Postural control training based on physical information is a common rehabilitation training method for patients with movement disorder. This research aims to verify the feasibility of using one smartphone embedded sensors to estimate CoP (Center of Pressure) displacement to take postural control training. We tested the reliability of smartphone sensor by motion capture system based on the following two CoP calculation models: (1) one-link inverted pendulum model; (2) two-link inverted pendulum model. We compared the estimation results with real CoP values measured by force plate. Sway training experiment was conducted under two tasks conditions: feet apart and feet together. The results show that data obtained from smartphone sensors is capable of representing human body CoM (Center of Mass) information. These two models can roughly estimate CoP displacement; and the results suggested that the two-link model performed better than one-link model. The estimation error between smartphone and real value is 0.70 - 2.01 cm in feet apart task and 1.03 - 1.12 cm in feet together task with two-link model.Clinical Relevance- This study verified the performance of smartphone in estimating CoP displacement for postural control training.

Effect of Sway Frequency on the Joint Angle and Center of Pressure in Voluntary Sway.

Voluntary sway is the periodic movement of one's body back and forth. The study aimed to clarify the effects of sway frequency on center of pressure and joint angle during voluntary sway. We measured 10 unrestricted voluntary sway conditions with different frequencies and natural pace conditions. The frequencies ranged from 0.1 to 1 Hz in 0.1-Hz increments. The joint angles and centers of pressure during voluntary sway were compared between the conditions. The joint angle amplitude of the trunk and knee were greater in the slow frequency condition than in the fast frequency condition. The trunk and knee joint angles during voluntary sway were considered to change according to the sway frequency.

Analysis of abnormal posture in patients with Parkinson's disease using a computational model considering muscle tones.

Patients with Parkinson's disease (PD) exhibit distinct abnormal postures, including neck-down, stooped postures, and Pisa syndrome, collectively termed "abnormal posture" henceforth. In the previous study, when assuming an upright stance, patients with PD exhibit heightened instability in contrast to healthy individuals with disturbance, implying that abnormal postures serve as compensatory mechanisms to mitigate sway during static standing. However, limited studies have explored the relationship between abnormal posture and sway in the context of static standing. Increased muscle tone (i.e., constant muscle activity against the gravity) has been proposed as an underlying reason for abnormal postures. Therefore, this study aimed to investigate the following hypothesis: abnormal posture with increased muscle tone leads to a smaller sway compared with that in other postures, including normal upright standing, under the sway minimization criterion. To investigate the hypothesis, we assessed the sway in multiple postures, which is determined by joint angles, including cases with bended hip joints. Our approach involved conducting forward dynamics simulations using a computational model comprising a musculoskeletal model and a neural controller model. The neural controller model proposed integrates two types of control mechanisms: feedforward control (representing muscle tone as a vector) and feedback control using proprioceptive and vestibular sensory information. An optimization was performed to determine the posture of the musculoskeletal model and the accompanied parameters of the neural controller model for each of the given muscle tone vector to minimize sway. The optimized postures to minimize sway for the optimal muscle tone vector of patients with PD were compared to the actual postures observed in these patients. The results revealed that on average, the joint-angle differences between these postures was <4°, which was less than one-tenth of the typical joint range of motion. These results suggest that patients with PD exhibit less sway in the abnormal posture than in other postures. Thus, adopting an abnormal posture with increased muscle tone can potentially serve as a valid strategy for minimizing sway in patients with PD.

Analysis of the Relationship Between Muscle Tones and Abnormal Postures in a Computational Model.

Patients with Parkinson's disease (PD), a neurodegenerative disorder, exhibit a characteristic posture known as a forward flexed posture. Increased muscle tone is suggested as a possible cause of this abnormal posture. For further analysis, it is necessary to measure muscle tone, but the experimental measurement of muscle tone during standing is challenging. The aim of this study was to examine the hypothesis that "In patients with PD, abnormal postures are those with a small sway at increased muscle tones" using a computational model. The muscle tones of various magnitudes were estimated using the computational model and standing data of patients with PD. The postures with small sway at the estimated muscle tones were then calculated through an optimization method. The postures and sway calculated using the computational model were compared to those of patients with PD. The results showed that the differences in posture and sway between the simulation and experimental results were small at higher muscle tones compared to those considered plausible in healthy subjects by the simulations. This simulation result indicates that the reproduced sway at high muscle tones is similar to that of actual patients with PD and that the reproduced postures with small sway locally at high muscle tones in the simulations are similar to those of patients with PD. The result is consistent with the hypothesis, reinforcing the hypothesis.Clinical relevance- This study implies that improving the increased muscle tone in patients with PD may lead to an improved abnormal posture.

A Neural Controller Model Considering the Vestibulospinal Tract in Human Postural Control.

Humans are able to control their posture in their daily lives. It is important to understand how this is achieved in order to understand the mechanisms that lead to impaired postural control in various diseases. The descending tracts play an important role in controlling posture, particularly the reticulospinal and the vestibulospinal tracts (VST), and there is evidence that the latter is impaired in various diseases. However, the contribution of the VST to human postural control remains unclear, despite extensive research using neuroscientific methods. One reason for this is that the neuroscientific approach limits our understanding of the relationship between an array of sensory information and the muscle outputs. This limitation can be addressed by carrying out studies using computational models, where it is possible to make and validate hypotheses about postural control. However, previous computational models have not considered the VST. In this study, we present a neural controller model that mimics the VST, which was constructed on the basis of physiological data. The computational model is composed of a musculoskeletal model and a neural controller model. The musculoskeletal model had 18 degrees of freedom and 94 muscles, including those of the neck related to the function of the VST. We used an optimization method to adjust the control parameters for different conditions of muscle tone and with/without the VST. We examined the postural sway for each condition. The validity of the neural controller model was evaluated by comparing the modeled postural control with (1) experimental results in human subjects, and (2) the results of a previous study that used a computational model. It was found that the pattern of results was similar for both. This therefore validated the neural controller model, and we could present the neural controller model that mimics the VST.

[Control of Posture and Gait by the Basal Ganglia: Pathophysiological Mechanisms Implicated in Parkinson's Disease].

Regulation of posture-gait control by the basal ganglia (BG) plays a critical role in the acquisition of automatically executed context-dependent learned motor acts, technically referred to as habit formation. Patients with Parkinson's disease (PD) show posture-gait disturbances and progressively lose habitual behaviors. Injury to dopamine (DA) neurons in the midbrain is implicated as the primary pathophysiological mechanism underlying PD; therefore, DA actions in the BG play a pivotal role in optimal BG function. In this commentary, we discuss the mechanism underlying BG-modulated regulation of cognitive posture-gait control by the cerebral cortex through the cortico-BG loop and the basic posture-gait mechanisms underlying the actions of the brainstem and spinal cord via the BG-brainstem projection. The BG primarily regulates excitability of the cerebral cortex and brainstem through its DA-mediated inhibitory action. Based on these considerations, we describe the pathophysiological mechanisms that contribute to posture-gait disturbances in PD. Recent clinical studies suggest that posture-gait disturbances may be attributable to functional disconnection between the BG and the cerebral cortex and brainstem. Injury to various neurotransmitter systems in addition to the DA system and significant alpha-synuclein (Lewy body)-induced degeneration of the brainstem neurons may worsen posture-gait control impairment in PD.

Increase in muscle tone promotes the use of ankle strategies during perturbed stance.

BACKGROUND: To maintain an upright standing posture against external disturbances, the human body mainly employs two types of postural control strategies: "ankle strategy" and "hip strategy." While it has been reported that the magnitude of the disturbance alters the use of postural control strategies, it has not been elucidated how the level of muscle tone, one of the crucial parameters of bodily function, determines the use of each strategy. We have previously confirmed using forward dynamics simulations of human musculoskeletal models that an increased muscle tone promotes the use of ankle strategies. The objective of the present study was to experimentally evaluate a hypothesis: an increased muscle tone promotes the use of ankle strategies. RESEARCH QUESTION: Do changes in the muscle tone affect the use of ankle strategies? METHODS: Participants were asked to maintain their standing posture on a movable platform sliding horizontally at several accelerations. Postural reactions for support surface translations were examined under three instructions with or without handgrips: relax state, squeezing a handgrip, and an increased muscle tone of the whole body. Surface-electromyography and marker locations of joints were measured to calculate the index of muscle tone and postural control strategies. The relationship of the indexes was evaluated based on correlation coefficients. RESULTS: In half of the conditions, weak negative correlations were noted between the muscle tone index and postural control strategy index. In other words, an increased muscle tone rather promoted the use of the ankle strategy than the hip strategy. These findings are consistent with our previous simulation results. SIGNIFICANCE: The results recognized a positive response to the research question. This suggests that it is crucial to take muscle tone into account to understand postural control strategies.

Evaluation of Postural Sway in Post-stroke Patients by Dynamic Time Warping Clustering.

Post-stroke complications are the second most frequent cause of death and the third leading cause of disability worldwide. The motor function of post-stroke patients is often assessed by measuring the postural sway in the patients during quiet standing, based on sway measures, such as sway area and velocity, which are obtained from temporal variations of the center of pressure. However, such approaches to establish a relationship between the sway measures and patients' demographic factors have hardly been successful (e.g., days after onset). This study instead evaluates the postural sway features of post-stroke patients using the clustering method of machine learning. First, we collected the stroke patients' multi-variable motion-capture standing-posture data and processed them into t s long data slots. Then, we clustered the t-s data slots into K cluster groups using the dynamic-time-warping partition-around-medoid (DTW-PAM) method. The DTW measures the similarity between two temporal sequences that may vary in speed, whereas PAM identifies the centroids for the DTW clustering method. Finally, we used a post-hoc test and found that the sway amplitudes of markers in the shoulder, hip, knee, and center-of-mass are more important than their sway frequencies. We separately plotted the marker amplitudes and frequencies in the medial-lateral direction during a 5-s data slot and found that the post-stroke patients' postural sway frequency lay within the bandwidth of 0.5-1.5 Hz. Additionally, with an increase in the onset days, the cluster index of cerebral hemorrhage patients gradually transits in a four-cluster solution. However, the cerebral infarction patients did not exhibit such pronounced transitions over time. Moreover, we found that the postural-sway amplitude increased in clusters 1, 3, and 4. However, the amplitude of cluster 2 did not follow this pattern, owing to age effects related to the postural sway changes with age. A rehabilitation doctor can utilize these findings as guidelines to direct the post-stroke patient training.

Randomized phase II trial of uracil/tegafur and cisplatin versus pemetrexed and cisplatin with concurrent thoracic radiotherapy for locally advanced unresectable stage III non-squamous non-small cell lung cancer: NJLCG1001.

BACKGROUND: The optimal regimen for concurrent chemoradiotherapy (CCRT) of locally advanced non-squamous non-small cell lung cancer (NSCLC) was not definitive. We conducted randomized phase II study, NJLCG0601, and chemoradiotherapy with uracil/tegafur (UFT) and cisplatin achieved promising efficacy without severe toxicities. Here, we evaluated between this regimen and pemetrexed plus cisplatin in chemoradiotherapy for stage III non-squamous NSCLC. METHODS: Patients with inoperable stage III non-squamous NSCLC were randomly assigned in a 1:1 ratio to UFT 400 mg/m2 on days 1-14 and 29-42, and cisplatin 80 mg/m2 on days 8 and 36 (UP), or cisplatin 75 mg/m2 and pemetrexed 500 mg/m2 on days 1, 22, and 43 (PP). Involved-field radiotherapy (IFRT) underwent from day 1 to a total dose of 66 Gy in 33 fractions. Consolidation chemotherapy after CCRT was prohibited for this study. The primary endpoint was defined as 2-year overall survival (OS). This trial was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN000003948). RESULTS: From November 2010 to June 2017, 86 patients were entered from 11 institutions. Median follow-up was 54 months. Of the 85 eligible patients, the 2-year OS rate was 78.6% (95% CI, 62.8-88.3%) in UP and 85.5% (95% CI, 70.5-93.2%) in PP. Median PFS and OS was 12.3 and 64.2 months in UP, 26.2 months and not reached in PP, respectively. Grade 3/4 febrile neutropenia was more frequent in the UP group (14.0% vs. 2.0%). CONCLUSIONS: Both UP and PP with IFRT achieved the expected 2-year OS. PP engendered more favorable OS and PFS compared to UP in terms.

Investigation of the effect of tonus on the change in postural control strategy using musculoskeletal simulation.

BACKGROUND: Humans use different postural control strategies depending on perturbations. The shift from an ankle strategy to a hip strategy occurs at different perturbation magnitudes for different individuals. Although such differences relate to the differences in body parameters such as muscle strength, the parameter changes that affect the strategy shift are unclear. The relationship between tonus and strategy is especially unclear, but humans control tonus, which contributes to body stability. The objective of this study was to investigate the influence of tonus on postural control strategy. RESEARCH QUESTION: Is there a trend toward the use of a hip strategy with a decrease in the magnitude of tonus? METHODS: Predictive simulations were performed for changing parameters of muscle weakness and increased sensory noise, which are considered the causes of different strategies and decreased tonus. A musculoskeletal model with 70 muscles and 15 degrees of freedom of joints was controlled using a neural controller model, and the support surface was translated backward to introduce perturbations. The parameters of the musculoskeletal and neural controller models were changed for 48 conditions of different muscle strengths, sensory noise, and tonus. The control parameters were optimized for each condition. Simulations were performed with the optimized control parameters to calculate an evaluation index to show the difference in postural control strategies (peak hip angle), and the relationship between the index and parameters was analyzed using analysis of variance and multiple regression. RESULTS: The main effects of muscle weakness and decreased tonus and their interaction were confirmed. The results recognized a positive response to the research question. SIGNIFICANCE: The study emphasizes the importance of considering tonus while investigating the postural control strategy. Furthermore, it was suggested that when the magnitude of tonus was larger than a threshold, only the ankle strategy was used, regardless of muscle strength.

Rehabilitation Therapy for a COVID-19 Patient Who Received Mechanical Ventilation in Japan.

A 65-yr-old man visited a primary care hospital with a continued fever of 38°C for 3 days. As his fever did not improve until 8 days after, he was admitted into another acute care hospital, where his respiratory condition rapidly worsened. Therefore, the patient was transferred to our hospital. On the day of transfer (day 1), he was started on mechanical ventilation. COVID-19 was diagnosed using a polymerase chain reaction assay 6 days after admission (day 6). The rehabilitation therapy was begun on day 6. The initial rehabilitation programs focused on positioning and postural drainage. The patient was extubated on day 19, and he began standing and stepping on the same day. Gait exercises began on day 22, and endurance training was initiated on day 28. The patient was discharged from our hospital on day 34 as he met the physical function milestones. One month after discharge, the Medical Research Council sum score and Barthel Index had each improved; therefore, muscle strength and daily activities had returned to normal. It was assumed that mobilization should be performed as soon as possible after the end of sedation during the acute phase of severe COVID-19 infection in patients receiving mechanical ventilation.

Postural control of a musculoskeletal model against multidirectional support surface translations.

The human body is a complex system driven by hundreds of muscles, and its control mechanisms are not sufficiently understood. To understand the mechanisms of human postural control, neural controller models have been proposed by different research groups, including our feed-forward and feedback control model. However, these models have been evaluated under forward and backward perturbations, at most. Because a human body experiences perturbations from many different directions in daily life, neural controller models should be evaluated in response to multidirectional perturbations, including in the forward/backward, lateral, and diagonal directions. The objective of this study was to investigate the validity of an NC model with FF and FB control under multidirectional perturbations. We developed a musculoskeletal model with 70 muscles and 15 degrees of freedom of joints, positioned it in a standing posture by using the neural controller model, and translated its support surface in multiple directions as perturbations. We successfully determined the parameters of the neural controller model required to maintain the stance of the musculoskeletal model for each perturbation direction. The trends in muscle response magnitudes and the magnitude of passive ankle stiffness were consistent with the results of experimental studies. We conclude that the neural controller model can adapt to multidirectional perturbations by generating suitable muscle activations. We anticipate that the neural controller model could be applied to the study of the control mechanisms of patients with torso tilt and diagnosis of the change in control mechanisms from patients' behaviors.

Elemental and mutational analysis of lung tissue in lung adenocarcinoma patients.

BACKGROUND: This study aimed to observe the association between trace element concentrations in lung tissue from lung adenocarcinoma cancer (LADC) patients and mutations in the epidermal growth factor receptor (EGFR) and KRAS genes. METHODS: LADC patients who had undergone lung resection were included in this study. Furthermore, twenty patients without lung cancer were included in this study as the control group. Samples were separately collected from both tumor and peritumor tissues. The mutational status was assessed for EGFR mutations, ALK rearrangements and KRAS mutations. Based on these analyses, patients were grouped into three groups: EGFR mutation, KRAS mutation and wild-type groups. The concentrations of various trace elements in the lung tissues were measured by a particle-induced X-ray emission (PIXE) system, and the results were analyzed for statistical significance. RESULTS: A total of 110 LADC patients were included in this study. The median age was 70 years, and 60% of the participants were female. Moreover, 18% and 20% of patients were EGFR- and KRAS-positive, respectively. Thirty-two trace elements were measured, and 18 trace elements were detectable. The concentrations of Fe, Co, Ni, Cu, Zn and Br were significantly higher in the KRAS mutation and wild-type groups than in the control group regardless of whether the samples were from tumor or peritumor tissues. For these 6 trace elements, the concentrations were significantly higher in smokers than in non-smokers. Considering the effect of smoking, differences in the trace element concentrations between each mutational group remained. CONCLUSIONS: Trace elements in the lung may play a role in development of LADC in both smokers and never-smokers. However, prospective studies with larger sample sizes are needed to support this hypothesis.