The Clinical Outcomes of Cervical Spine Chordoma: A Nationwide Multicenter Retrospective Study.

OBJECTIVE: Chordoma, a rare malignant tumor originating from embryonal notochord remnants, exhibits high resistance to conventional treatments, making surgical resection imperative. However, the factors influencing prognosis specifically for cervical spine chordoma have not been clearly identified. We investigate the prognosis of cervical spine chordoma with factors influential in a nationwide multicenter retrospective study. METHODS: This study included all patients diagnosed with cervical spine chordoma at 7 tertiary referral centers from January 1998 to March 2023, excluding those with clivus and thoracic spine chordomas extending into the cervical spine. Local recurrence (LR) was identified through follow-up magnetic resonance imaging, either as reappearance in completely resected tumors or regrowth in residual tumors. The study assessed LR and overall survival, analyzing factors influencing LR and death. RESULTS: Forty-five patients with cervical spine chordoma had a mean age of 46.4 years. Over a median follow-up of 52 months, LR and distant metastasis were observed in 21 (46.7%) and 4 patients (8.9%), respectively, and 16 patients (36%) were confirmed dead. The 5-year and 10-year cumulative LR rates were 51.3% and 60%, respectively, while the 5-year and 10-year survival rates were 82% and 53%. Age was the only significant factor affecting mortality (hazard ratio, 1.04; 95% confidence interval, 1.04-1.07; p=0.015). Notably, the degree of resection and adjuvant therapy did not statistically significantly impact local tumor control and mortality. CONCLUSION: This study, the largest multicenter retrospective analysis of cervical spine chordoma in Korea, identified age as the only factor significantly affecting patient survival.

DGDRP: drug-specific gene selection for drug response prediction via re-ranking through propagating and learning biological network.

Introduction: Drug response prediction, especially in terms of cell viability prediction, is a well-studied research problem with significant implications for personalized medicine. It enables the identification of the most effective drugs based on individual genetic profiles, aids in selecting potential drug candidates, and helps identify biomarkers that predict drug efficacy and toxicity.A deeper investigation on drug response prediction reveals that drugs exert their effects by targeting specific proteins, which in turn perturb related genes in cascading ways. This perturbation affects cellular pathways and regulatory networks, ultimately influencing the cellular response to the drug. Identifying which genes are perturbed and how they interact can provide critical insights into the mechanisms of drug action. Hence, the problem of predicting drug response can be framed as a dual problem involving both the prediction of drug efficacy and the selection of drug-specific genes. Identifying these drug-specific genes (biomarkers) is crucial because they serve as indicators of how the drug will affect the biological system, thereby facilitating both drug response prediction and biomarker discovery.Methods: In this study, we propose DGDRP (Drug-specific Gene selection for Drug Response Prediction), a graph neural network (GNN)-based model that uses a novel rank-and-re-rank process for drug-specific gene selection. DGDRP first ranks genes using a pathway knowledge-enhanced network propagation algorithm based on drug target information, ensuring biological relevance. It then re-ranks genes based on the similarity between gene and drug target embeddings learned from the GNN, incorporating semantic relationships. Thus, our model adaptively learns to select drug mechanism-associated genes that contribute to drug response prediction. This integrated approach not only improves drug response predictions compared to other gene selection methods but also allows for effective biomarker discovery.Discussion: As a result, our approach demonstrates improved drug response predictions compared to other gene selection methods and demonstrates comparability with state-of-the-art deep learning models. Case studies further support our method by showing alignment of selected gene sets with the mechanisms of action of input drugs.Conclusion: Overall, DGDRP represents a deep learning based re-ranking strategy, offering a robust gene selection framework for more accurate drug response prediction. The source code for DGDRP can be found at: https://github.com/minwoopak/heteronet.

Healthy First-Degree Relatives From Multiplex Families vs Simplex Families Have a Higher Subclinical Intestinal Inflammation, a Distinct Fecal Microbial Signature, and Harbor a Higher Risk of Developing Crohn's Disease.

BACKGROUND & AIMS: Unaffected first-degree relatives (FDRs) from families with ≥2 affected FDRs with Crohn's disease (CD, multiplex families) have a high risk of developing CD, although the underlying mechanisms driving this risk are poorly understood. We aimed to identify differences in biomarkers between FDRs from multiplex vs simplex families and investigate the risk of future CD onset accounting for potential confounders. METHODS: We assessed the Crohn's and Colitis Canada Genetic Environmental Microbial cohort of healthy FDRs of patients with CD. Genome-wide CD-polygenic risk scores, urinary fractional excretion of lactulose-to-mannitol ratio, fecal calprotectin (FCP), and fecal 16S ribosomal RNA microbiome were measured at recruitment. Associations between CD multiplex status and baseline biomarkers were determined using generalized estimating equations models. Cox models were used to assess the risk of future CD onset. RESULTS: There were 4051 participants from simplex families and 334 from CD multiplex families. CD multiplex status was significantly associated with higher baseline FCP (P = .026) but not with baseline CD-polygenic risk scores or the lactulose-to-mannitol ratio. Three bacterial genera were found to be differentially abundant between both groups. CD multiplex status at recruitment was independently associated with an increased risk of developing CD (adjusted hazard ratio, 3.65; 95% confidence interval, 2.18-6.11, P < .001). CONCLUSION: Within FDRs of patients with CD, participants from multiplex families had a 3-fold increased risk of CD onset, a higher FCP, and an altered bacterial composition, but not genetic burden or altered gut permeability. These results suggest that putative environmental factors might be enriched in FDRs from multiplex families.

Inflammatory bowel disease associated with primary sclerosing cholangitis is associated with an altered gut microbiome and bile acid profile.

BACKGROUND: Primary sclerosing cholangitis associated with inflammatory bowel disease (IBD-PSC) carries significant morbidity compared to IBD without PSC. Alterations in microbial composition and bile acid (BA) profiles have been shown to modulate chronic inflammation in IBD, but data in IBD-PSC is scarce. We aimed to assess the differences in gut microbiome composition as well as in the BA profile and BA-related microbial functions between IBD-PSC and IBD-only. METHODS: 54 IBD-PSC and 62 IBD-only subjects were enrolled from 2012 to 2021. Baseline samples were collected for fecal DNA shotgun metagenomic sequencing, fecal and serum BA quantitation using mass spectrometry and fecal calprotectin. Liver fibrosis measured by transient elastography (TE) was assessed in the IBD-PSC group. Data was analyzed using general linear regression models and Spearman rank correlation tests. RESULTS: Patients with IBD-PSC had reduced microbial gene richness (p=0.004) and significant compositional shifts (PERMANOVA: R2=0.01, p=0.03) compared to IBD-only. IBD-PSC was associated with altered microbial composition and function, including decreased abundance of Blautia obeum, increased abundance of Veillonella atypica, Veillonella dispar and Clostridium scindens (q<0.05 for all), and increased abundance of microbial genes involved in secondary BA metabolism. Decreased serum sulfated and increased serum conjugated secondary BA were associated with IBD-PSC and increased liver fibrosis. CONCLUSION: We identified differences in microbial species, functional capacity and serum BA profiles in IBD-PSC compared with IBD-only. Our findings provide insight into the pathophysiology of IBD associated with PSC and suggest possible targets for modulating the risk and course of IBD in subjects with PSC.

Enhancing the Evaluation System of Training Hospitals for Neurosurgical Residency Training and Education in South Korea : Striving for Balanced Participation and Differentiation.

The Korean Neurosurgical Society, with its 62 years of history, has witnessed substantial growth in the field of neurosurgery, producing over 3,400 neurosurgeons, establishing 12 divisions and 9 regional branches, and advancing in clinical management, diagnostic methods and academic research. Despite these developments, the regulations governing neurosurgical training and evaluation methods for training hospitals have remained largely unchanged, necessitating comprehensive revisions in response to evolving medical environments. To provide balanced participation opportunities for neurosurgery residents, the Korean Neurosurgical Society formed the Training Status Investigation Standard Change Task Force (TF Team) under the Training Education Committee. This paper presents the TF Team's findings and proposals for revising training status investigation standards and evaluation criteria. Through the processes including a lot of team meetings, workshops, education programs, official communications with 12 division societies, benchmarking from other societies and analysis of encrypted data from the past 5 years for neurosurgical training hospitals, the TF Team created a revised training status investigation proposal, supplemented main surgery criteria. And we applied this revised proposal to the training status investigation data collected from training hospitals in 2022 for simulation. We reduced the score for main surgeries to 10 points, introduced core competency surgery standards, allocating 5 points each for brain core competency surgery and spine and peripheral core competency surgery, for a total of 10 points. We also adjusted the major surgery score to 13 points, expanding the total surgery index score to 33 points. We introduced additional definitions for main surgeries in the areas of spine, pediatrics, and functional surgery. The equipment score was reduced from 17 points to 9 points. We specified minimum requirements for resident allocation eligibility, and if a hospital meets all of these criteria, they become eligible to apply for resident allocation. We introduced a new bonus point system for hospitals performing mechanical thrombectomy or stenting and peripheral nerve. The proposed revisions aim to improve the training and education of neurosurgical residents and overall neurosurgical care in Korea by creating a balanced and differentiated evaluation system for training hospitals. Further monitoring, communication, and adjustments are crucial for successful implementation.

Degassing 4-tert-Butylpyridine in the Spiro-MeOTAD Film Improves the Thermal Stability of Perovskite Solar Cells.

The organic molecular 2,2',7,7'-tetrakis(4,4'-dimethoxy-3-methyldiphenylamino)-9,9'-spirobifluorene (Spiro-MeOTAD) is known as a typical hole transport material in the development of an all-solid-state perovskite solar cell (PSC). Spiro-MeOTAD requires additives of lithium bifurflimide (LiTFSI) and 4-tert-butylpyridine (tBP) to increase the conductivity and solubility for enhancing the photovoltaic performance of PSCs. However, those additives have an adverse effect on the thermal stability. We report on the origin of instability of additive-containing Spiro-MeOTAD at 85 °C and the methodology to solve the thermal instability. We have found that the interaction of LiTFSI with the underneath perovskite surface facilitated by diffusive tBP is responsible for thermal degradation. Degasification of tBP from the Spiro-MeOTAD film is found to be the key to achieving thermally stable PSCs, where the optimal degassing process achieves 90% of the initial power conversion efficiency (PCE) at 85 °C after 1000 h.

Generation of an induced pluripotent stem cell line from a patient with arrhythmogenic right ventricular cardiomyopathy harboring a TMEM43 splice-site variant.

Arrhythmogenic cardiomyopathy (ACM) is a cardiomyopathy that is predominantly inherited and characterized by cardiac arrhythmias and structural abnormalities. TMEM43 (transmembrane protein 43) is one of the well-known genetic culprits behind ACM. In this study, we successfully generated an induced pluripotent stem cell (iPSC) line, YCMi010-A, derived from a male patient diagnosed with ACM. Although these iPSCs harbored a heterozygous intronic splice variant, TMEM43 c.443-2A > G, they still displayed normal cellular morphology and were confirmed to express pluripotency markers. YCMi010-A iPSC line is a promising model for investigating the pathomechanisms associated with ACM and exploring potential therapeutic strategies.

Environmental Factors Associated With Risk of Crohn's Disease Development in the Crohn's and Colitis Canada - Genetic, Environmental, Microbial Project.

BACKGROUND & AIMS: To date, it is unclear how environmental factors influence Crohn's disease (CD) risk and how they interact with biological processes. This study investigates the association between environmental exposures and CD risk and evaluates their association with pre-disease biomarkers. METHODS: We studied 4289 healthy first-degree relatives (FDRs) of patients with CD from the Crohn's and Colitis Canada - Genetic, Environmental, Microbial (CCC-GEM) project. Regression models identified environmental factors associated with future CD onset and their association with pre-disease biological factors, including altered intestinal permeability measured by urinary fractional excretion of lactulose to mannitol ratio (LMR); gut inflammation via fecal calprotectin (FCP) levels; and fecal microbiome composition through 16S rRNA sequencing. RESULTS: Over a 5.62-year median follow-up, 86 FDRs developed CD. Living with a dog between ages 5 and 15 (hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.40-0.96; P = .034), and living with a large family size in the first year of life (HR, 0.43; 95% CI, 0.21-0.85; P = .016) were associated with decreased CD risk, whereas having a bird at the time of recruitment (HR, 2.78; 95% CI, 1.36-5.68; P = .005) was associated with an increased CD risk. Furthermore, living with a dog was associated with reduced LMR, altered relative abundance of multiple bacterial genera, and increased Chao1 diversity, whereas bird owners had higher FCP levels. Large family during participants' first year of life was associated with altered microbiota composition without affecting FCP or LMR. CONCLUSION: This study identifies environmental variables associated with CD risk. These variables were also associated with altered barrier function, subclinical inflammation, and gut microbiome composition shifts, suggesting potential roles in CD pathogenesis.

Inhibition of TBL1 cleavage alleviates doxorubicin-induced cardiomyocytes death by regulating the Wnt/ß-catenin signal pathway.

AIMS: Doxorubicin (DOX) is a widely used anthracycline anticancer agent; however, its irreversible effects on the heart can result in DOX-induced cardiotoxicity (DICT) after cancer treatment. Unfortunately, the pathophysiology of DICT has not yet been fully elucidated, and there are no effective strategies for its prevention or treatment. In this investigation, the novel role of transducin beta-like protein 1 (TBL1) in developing and regulating DICT was explored. METHODS AND RESULTS: We observed a reduction in TBL1 protein expression levels as well as cleavage events in the transplanted cardiac tissues of patients diagnosed with Dilated Cardiomyopathy and DICT. It was revealed that DOX selectively induces TBL1 cleavage at caspase-3 preferred sites-D125, D136, and D215. Interestingly, overexpression of the uncleaved TBL1 mutant (TBL1uclv) variant reduced apoptosis, effectively preventing DOX-induced cell death. We confirmed that cleaved TBL1 cannot form a complex with ß-catenin. As a result, Wnt reporter activity and Wnt target gene expression collectively indicate a decrease in Wnt/ß-catenin signalling, leading to DICT progression. Furthermore, the cleaved TBL1 triggered DOX-induced abnormal electrophysiological features and disrupted calcium homeostasis. However, these effects were improved in TBL1uclv-overexpressing human-induced pluripotent stem cell-derived cardiomyocytes. Finally, in a DICT mouse model, TBL1uclv overexpression inhibited the DICT-induced reduction of cardiac contractility and collagen accumulation, ultimately protecting cardiomyocytes from cell death. CONCLUSION: Our findings reveal that the inhibition of TBL1 cleavage not only mitigates apoptosis but also enhances cardiomyocyte function, even in the context of DOX administration. Consequently, this study's results suggest that inhibiting TBL1 cleavage may be a novel strategy to ameliorate DICT.

Exploring the link between pediatric headaches and environmental noise exposure.

BACKGROUND: Headaches are the most common neurologic symptoms in the pediatric population. Most primary headache in children and adolescents focuses on associated factors, including noise. Auditory discomfort is related to recognizing the pain. We aimed to analyze the headache profile of pediatric populations and the connection between noise exposure and head pain in children and adolescents. METHODS: We reviewed retrospectively medical records of the pediatric population with headaches in Gyeongsang National University Changwon Hospital from January 2022 to April 2023. Personal headache profiling from self-questionnaires and environmental noise data from the National Noise Information System (NNIS) were used to analyze each variable, and chi-square tests and linear regression models by SAS were used to analyze the statistical correlation. RESULTS: Of the 224 participants, 125 were clinically diagnosed with headaches. Of the 104 pubertal subjects, 56.7% were diagnosed with headaches, compared to 60% in the prepubertal group. Both daytime and nighttime noise was significantly higher in the diagnosed headache group than in the non-diagnosed group. Headache duration increased by daytime and nighttime noise with statistical significance in age-adjusted models. CONCLUSION: We found that noise exposure is correlated to headaches in children and adolescents. Daytime and nighttime environmental noise exposure was significantly associated with the duration of headaches through our data. Therefore, we assume that noise exposure is vitally relevant to prolonged headaches in the pediatric population. Further research is needed to improve our data.

Discovery of N-(1-(2-hydroxyethyl)quinolin-2-one)-N'-(1-phenyl-1H-pyrazol-5-yl)methyl) urea as Mode-Selective TRPV1 antagonist.

To discover mode-selective TRPV1 antagonists as thermoneutral drug candidates, the previous potent antagonist benzopyridone 2 was optimized based on the pharmacophore A- and C-regions. The structure activity relationship was investigated systematically by modifying the A-region by incorporating a polar side chain on the pyridone and then by changing the C-region with a variety of substituted pyridine and pyrazole moieties. The 3-t-butyl and 3-(1-methylcyclopropyl) pyrazole C-region analogs provided high potency as well as mode-selectivity. Among them, 51 and 54 displayed potent and capsaicin-selective antagonism with IC50 = 2.85 and 3.27 nM to capsaicin activation and 28.5 and 31.5 % inhibition at 3 µM concentration toward proton activation, respectively. The molecular modeling study of 51 with our homology model indicated that the hydroxyethyl side chain in the A-region interacted with Arg557 and Glu570, the urea B-region engaged in hydrogen bonding with Tyr511 and Thr550, respectively, and the pyrazole C-region made two hydrophobic interactions with the receptor. Optimization of antagonist 2, which has full antagonism for activators of all modes, lead to mode-selective antagonists 51 and 54. These observations will provide insight into the future development of clinical TRPV1 antagonists without target-based side effects.

Quantitative Analysis of the Effect of Stereotactic Radiosurgery for Postoperative Residual Cervical Dumbbell Tumors: A Multicenter Retrospective Cohort Study.

OBJECTIVE: Stereotactic radiosurgery (SRS) has been performed for spinal tumors. However, the quantitative effect of SRS on postoperative residual cervical dumbbell tumors remains unknown. This study aimed to quantitatively evaluate the efficacy of SRS for treating postoperative residual cervical dumbbell tumors. METHODS: We retrospectively reviewed cases of postoperative residual cervical dumbbell tumors from 1995 to 2020 in 2 tertiary institutions. Residual tumors underwent SRS (SRS group) or were observed with clinical and magnetic resonance imaging (MRI) follow-up (observation group). Tumor regrowth rates were compared between the SRS and observation groups. Additionally, risk factors for tumor regrowth were analyzed. RESULTS: A total of 28 cervical dumbbell tumors were incompletely resected. Eight patients were in the SRS group, and 20 in the observation group. The mean regrowth rate was not significantly lower (p = 0.784) in the SRS group (0.18 ± 0.29 mm/mo) than in the observation group (0.33 ± 0.40 mm/mo). In the multivariable Cox regression analysis, SRS was not a significant variable (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.18-1.79; p = 0.336). CONCLUSION: SRS did not significantly decrease the tumor regrowth rate in our study. We believe that achieving maximal resection during the initial operation is more important than postoperative adjuvant SRS.

Chiral recognition and discrimination studies of tyrosine enantiomers on (-)-18-crown-6-tetracarboxylic acid as a chiral selector by nuclear magnetic resonance spectroscopy and docking simulations.

Considering the substantial significance of chiral biomolecules, such as amino acids, in our daily routines, we performed chiral recognition and discrimination of tyrosine (Tyr) enantiomers on (-)-(18-crown-6)-2,3,11,12-tetracarboxylic acid [(-)-18-C-6-TA] as crown-ether type chiral selector (CS) by nuclear magnetic resonance (NMR) spectroscopy and docking simulations. In this study, successful discrimination of the enantiomers of Tyr was achieved, as evidenced by the proton chemical shift differences (ΔΔδ) of Tyr enantiomers observed in the 1 H NMR spectra with (-)-18-C-6-TA CS. We compared the results of these two techniques with the findings obtained from high performance liquid chromatography (HPLC) investigations. In both NMR and HPLC experimental and docking simulation studies, a stronger interaction between the L-Tyr enantiomer with (-)-18-C-6-TA CS than the D-Tyr was consistently observed. Also, the binding energy differences (ΔΔEL-D ) found in simulation data that correspond to enantioselectivity aligned well with the NMR experimental result.

Development of a novel prediction model for differential diagnosis between spinal myxopapillary ependymoma and schwannoma.

Spinal myxopapillary ependymoma (MPE) and schwannoma represent clinically distinct intradural extramedullary tumors, albeit with shared and overlapping magnetic resonance imaging (MRI) characteristics. We aimed to identify significant MRI features that can differentiate between MPE and schwannoma and develop a novel prediction model using these features. In this study, 77 patients with MPE (n = 24) or schwannoma (n = 53) who underwent preoperative MRI and surgical removal between January 2012 and December 2022 were included. MRI features, including intratumoral T2 dark signals, subarachnoid hemorrhage (SAH), leptomeningeal seeding, and enhancement patterns, were analyzed. Logistic regression analysis was conducted to distinguish between MPE and schwannomas based on MRI parameters, and a prediction model was developed using significant MRI parameters. The model was validated internally using a stratified tenfold cross-validation. The area under the curve (AUC) was calculated based on the receiver operating characteristic curve analysis. MPEs had a significantly larger mean size (p = 0.0035), higher frequency of intratumoral T2 dark signals (p = 0.0021), associated SAH (p = 0.0377), and leptomeningeal seeding (p = 0.0377). Focal and diffuse heterogeneous enhancement patterns were significantly more common in MPEs (p = 0.0049 and 0.0038, respectively). Multivariable analyses showed that intratumoral T2 dark signal (p = 0.0439) and focal (p = 0.0029) and diffuse enhancement patterns (p = 0.0398) were independent factors. The prediction model showed an AUC of 0.9204 (95% CI 0.8532-0.9876) and the average AUC for internal validation was 0.9210 (95% CI 0.9160-0.9270). MRI provides useful data for differentiating spinal MPEs from schwannomas. The prediction model developed based on the MRI features demonstrated excellent discriminatory performance.

Water Extract of Capsella bursa-pastoris Mitigates Doxorubicin-Induced Cardiotoxicity by Upregulating Antioxidant Enzymes.

Doxorubicin (DOX), an effective chemotherapeutic drug, causes cardiotoxicity in a cumulative and dose-dependent manner. The aim of this study is to investigate the effects of hot-water extract of Capsella bursa-pastoris (CBW) on DOX-induced cardiotoxicity (DICT). We utilized H9c2 rat cardiomyocytes and MDA-MB-231 human breast cancer cells to evaluate the effects of CBW on DOX-induced cell death. Superoxide dismutase (SOD) levels, reactive oxygen species (ROS) production, and oxygen consumption rate were measured in H9c2 cells. C57BL/6 mice were treated with DOX and CBW to assess their impact on various cardiac parameters. Human-induced pluripotent stem-cell-derived cardiomyocytes were also used to investigate DOX-induced electrophysiological changes and the potential ameliorative effects of CBW. UPLC-TQ/MS analysis identified seven flavonoids in CBW, with luteolin-7-O-glucoside and isoorientin as the major compounds. CBW inhibited DOX-induced death of H9c2 rat cardiomyocytes but did not affect DOX-induced death of MDA-MB-231 human breast cancer cells. CBW increased SOD levels in a dose-dependent manner, reducing ROS production and increasing the oxygen consumption rate in H9c2 cells. The heart rate, RR interval, QT, and ST prolongation remarkably recovered in C57BL/6 mice treated with the combination of DOX and CBW compared to those in mice treated with DOX alone. Administration of CBW with DOX effectively alleviated collagen accumulation, cell death in mouse heart tissues, and reduced the levels of creatinine kinase (CK) and lactate dehydrogenase (LDH) in serum. Furthermore, DOX-induced pathological electrophysiological features in human-induced pluripotent stem-cell-derived cardiomyocytes were ameliorated by CBW. CBW may prevent DICT by stabilizing SOD and scavenging ROS. The presence of flavonoids, particularly luteolin-7-O-glucoside and isoorientin, in CBW may contribute to its protective effects. These results suggest the potential of CBW as a traditional therapeutic option to mitigate DOX-induced cardiotoxicity.

Characterizing and controlling infrared phonon anomaly of bilayer graphene in optical-electrical force nanoscopy.

We, for the first time, report the nanoscopic imaging study of anomalous infrared (IR) phonon enhancement of bilayer graphene, originated from the charge imbalance between the top and bottom layers, resulting in the enhancement of E1u mode of bilayer graphene near 0.2 eV. We modified the multifrequency atomic force microscope platform to combine photo-induced force microscope with electrostatic/Kelvin probe force microscope constituting a novel hybrid nanoscale optical-electrical force imaging system. This enables to observe a correlation between the IR response, doping level, and topographic information of the graphene layers. Through the nanoscale spectroscopic image measurements, we demonstrate that the charge imbalance at the graphene interface can be controlled by chemical (doping effect via Redox mechanism) and mechanical (triboelectric effect by the doped cantilever) approaches. Moreover, we can also diagnosis the subsurface cracks on the stacked few-layer graphene at nanoscale, by monitoring the strain-induced IR phonon shift. Our approach provides new insights into the development of graphene-based electronic and photonic devices and their potential applications.