Investigating the Association between the Autophagy Markers LC3B, SQSTM1/p62, and DRAM and Autophagy-Related Genes in Glioma.

High-grade gliomas are extremely fatal tumors, marked by severe hypoxia and therapeutic resistance. Autophagy is a cellular degradative process that can be activated by hypoxia, ultimately resulting in tumor advancement and chemo-resistance. Our study aimed to examine the link between autophagy markers' expression in low-grade gliomas (LGGs) and high-grade gliomas (HGGs). In 39 glioma cases, we assessed the protein expression of autophagy markers LC3B, SQSTM1/p62, and DRAM by immunohistochemistry (IHC) and the mRNA expression of the autophagy genes PTEN, PI3K, AKT, mTOR, ULK1, ULK2, UVRAG, Beclin 1, and VPS34 using RT-qPCR. LC3B, SQSTM1/p62, and DRAM expression were positive in 64.1%, 51.3%, and 28.2% of glioma cases, respectively. The expression of LC3B and SQSTM1/p62 was notably higher in HGGs compared to LGGs. VPS34 exhibited a significant differential expression, displaying increased fold change in HGGs compared to LGGs. Additionally, it exhibited robust positive associations with Beclin1 (rs = 0.768), UVRAG (rs = 0.802), and ULK2 (rs = 0.786) in HGGs. This underscores a potential association between autophagy and the progression of gliomas. We provide preliminary data for the functional analysis of autophagy using a cell culture model and to identify potential targets for therapeutic interventions.

Differential Regulation of Innate Lymphoid Cells in Human and Murine Oral Squamous Cell Carcinoma.

Oral squamous cell carcinomas (OSCC) remain a major healthcare burden in Asian countries. In Pakistan alone, it is the most common cancer in males and second only to breast cancer in females. Alarmingly, treatment options for OSCC remain limited. With this context, investigations made to explore the inflammatory milieu of OSCC become highly relevant, with the hope of practicing immunotherapeutic approaches to address this highly prevalent tumor. We investigated the newly identified innate lymphoid cells (ILCs) and associated cytokines in well-defined human oral squamous cell carcinoma (OSCC) as well as in a 7,12-dimethylbenz[a]anthracene (DMBA)-induced murine model of OSCC using flow cytometry and quantitative real-time polymerase chain reaction (qPCR). We further went on to explore molecular circuitry involved in OSCC by developing a murine model of OSCC and using an α-Thy1 antibody to inhibit ILCs. Amongst the ILCs that we found in human OSCC, ILC3 (23%) was the most abundant, followed by ILC2 (17%) and ILC1 (1%). Mice were divided into four groups: DMBA (n = 33), DMBA+antibody (Ab) (n = 30), acetone (n = 5), and control (n = 5). In murine OSCC tissues, ILC1 and ILC3 were down-infiltrated, while ILC2 remained unchanged compared to controls. Interestingly, compared to the controls (DMBA group), mice treated with the α-Thy1 antibody showed fewer numbers of large tumors, and a larger percentage of these mice were tumor-free at this study's end point. We present novel data on the differential expansion/downsizing of ILCs in OSCC, which provides a pivotal basis to dive deeper into molecular circuitry and the OSCC tumor niche to devise novel diagnostic, therapeutic, and prognostic strategies to prevent/treat oral cancers.

Expressional variations of Kaiso: an association with pathological characteristics and field cancerization of OSCC.

BACKGROUND: A group of genetically altered cells that have not transformed into a clinical or histologically identifiable state of malignancy but contains a higher risk of transforming into one is known as the field of cancerization. Numerous molecules are being investigated for their significance in the development of this phenomenon. One such protein of this family is Kaiso also known as ZBTB33 (Zinc Finger and BTB Domain containing 33). This protein belongs to the POZ-ZF family of transcription factors and may have functional tasks similar to its other siblings such as the growth and development of vertebrates and the pathogenesis of neoplastic diseases. Nevertheless, its role in the pathogenesis, progression, epithelial mesenchyal transition and field cancerization in case of oral cancer still needs exploration. Hence, this study was designed to explore the expressional differences between the mucosa of controls and those diagnosed with oral squamous cell carcinoma (OSCC). METHODS: Soft tissue samples were obtained from the main tumor, tumor periphery and opposite buccal mucosa of 50 oral cancer patients, whereas normal mucosa was taken from 50 volunteers undergoing elective tooth removal. The acquired samples were subjected to Immunohistochemical exploration for expression of Kaiso and E-Cadherin. The expression was measured using Image-J IHC profiler and summed as Optical density. The Optical density values were then subjected to statistical analysis. RESULTS: Results revealed a significant differential expression of Kaiso between the mucosal tissues taken from oral cancer patients and controls (p-value: < 0.0001), showing almost 50% down-regulation of Kaiso in all three tissue samples taken from oral cancer patients as compared to normal mucosa. CONCLUSION: Kaiso has a significant difference of expression in the mucosa of oral cancer patients as compared to the mucosa of normal patients, making it a probable contributor to disease pathogenesis and field cancerization.

Subgenomic sequence analysis reveals emergence of new circulating recombinant forms of HIV-1 in Pakistan.

Background and Objective: Pakistan has witnessed a dramatic change in the increasing prevalence and emergence of HIV subtypes for more than two decades. Pakistani population is increasingly engaged in high-risk practices, and the prescribed drugs are potentially causing resistance. There are chances that these resistant strains are beginning to circulate from high-risk to the general population. Methods: The study was conducted at the section of Molecular Pathology Lab of Dow Diagnostic and Research Laboratory, Dow University of Health Sciences (DUHS) Karachi. In this study, we analyzed gene sequences of HIV for drug resistance and molecular epidemiology., along with amino acid sequence variability. Furthermore, we undertook phylogenetic analysis for possible geographic linkages of Pakistani HIV strains. Results: Our results demonstrate that A1 is the leading HIV subtype circulating in the country, whereas other emerging subtypes and recombinant forms, including subtype B, CRF02_AG, CRF10_CD CRF35_AD, and CRF11_cpx were also observed. Our sequences cluster with the Middle East, African, and a few European sequences according to geographical distribution. These sequences showed high-level resistance per drug resistance pattern, with 62.5% of patients exhibiting resistance to NNRTI drugs and 60% mutation at E138A and K103N, respectively, against NNRTI drugs. About 75% sequences showed resistance mutation at M184V against NRTI drugs. The antiretroviral drugs are now causing H-LR to the patients with no effect. Our results also revealed that certain regions of RT exhibited high sequence variability, especially at Amino Acids positions p.119, p.130, p.157, p.164. Conclusion: We hereby report major novel mutations and several minor mutations that may have a drastic change in the drug resistance pattern.

Differential Immune Landscape of Hepatocellular Carcinoma Suggests Potential role of Macrophages in Hepatocarcinogenesis.

OBJECTIVES: To investigate immune cell densities in tumor microenvironment of hepatocellular carcinoma. METHODS: This cross-sectional study was conducted during 2017-2019 at the Dow University of Health Sciences Karachi. A total of 42 subsequent patients undergoing liver biopsy/resection and diagnosed with hepatocellular carcinoma were included in the study. Moreover, a total of 10 control tissues were also included. In order to investigate immune cells densities in hepatocellular carcinoma, immunohistochemistry was performed using antibodies including α-MPO(neutrophils), α-CD-68(macrophages), α-CD-3(T-cells), α-CD-20(B-cells), α-CD-4(CD4+ T-cells) and α-CD-8(CD8+ T-cells). Quantification of immune cells/mm2 was performed as per the College of American Pathologists' guidelines. Data were analyzed using SPSS version 21. A p-value of 0.05 was considered significant at all times. RESULTS: We report significantly increased infiltration of macrophages (mean macrophages= 306.57/mm2, p-value <0.05), moderately significant infiltration of neutrophils (p-value=0.06) and B-cells (p-value=0.07) while no significant infiltration of CD4+T-cells (p- value=0.31), and CD8+T-cells (p-value=0.39) in tumour microenvironment of patients with hepatocellular carcinoma. CONCLUSION: We provide evidence for increased macrophage infiltration in liver cancer microenvironment suggesting a potential role of these cells in hepatocarcinogenesis.

Quantitative Analyses of Skin Cancer Research in Pakistan.

In order to investigate the current status of skin cancer research output in Pakistan, International (PubMed) and national (PakMediNet) scientific databases were searched using variety of keywords to retrieve relevant publications. A strict inclusion criterion was applied to select skin cancer publications for final analyses. Data were recorded by two authors and consistent data were entered into SPSS and Microsoft Excel and analyzed for annual growth rate and frequencies. Of 116 articles that were finally included in the study, 74 were original articles, 24 were case-reports, 10 were review articles, three were editorials, two were research communications and one each of case-series, correspondence and response to letter to the editor. The first article on skin cancer from Pakistan was published in 1976 whereas the last article included in our study was published in December 2018. Excluding Karachi, most of the cities have no contribution in the field of skin cancer. Since 1976 to date, the average number of publications per year has been low, with only 2.7 publications per year. Skin cancer research is alarmingly scarce in Pakistan. This calls for immediate attention by all concerned to contribute and devise appropriate measures towards skin cancer research in Pakistan.

Serologic Evidence of Severe Fever with Thrombocytopenia Syndrome Virus and Related Viruses in Pakistan.

We describe the seroprevalence of severe fever with thrombocytopenia syndrome virus (SFTSV) and the association of antibody occurrence with location, sex, and age among the human population in Pakistan. Our results indicate substantial activity of SFTSV and SFTSV-related viruses in this country.

Common Cancers in Karachi, Pakistan: 2010-2019 Cancer Data from the Dow Cancer Registry.

OBJECTIVES: To present 2010-2019 cancer data from the Dow Cancer Registry representing all districts of Karachi (~17.4 million). METHODS: The study was conducted at the Dow University of Health Sciences. After ethical approval, the Dow Cancer Registry was established at the largest government-run diagnostic and reference center of Karachi (Dow Labs). All cancers registered during 2010-2019 were analyzed. Patients >18years of age were labeled as adults while those with ages ≤18years were classified as children/young adults. RESULTS: During 2010-2019, a total of 22,858 cancers were registered. Of these, 9,112(39.9%) cancers were diagnosed in males while 13,746(60.1%) in females. Incidence rates for all cancers (all ages) were 108/1,00,000 for males and 188.6/1,00,000 for females. In adult males, cancer of lip and oral cavity was the most frequently diagnosed cancer (33.6%), followed by non-melanoma -skin-cancer (NMSC) (7.2%), oesophagus (6.8%), colorectum (6.7%) and stomach (4.9%). In adult females, breast cancer was the most frequently recorded malignancy (53.2%), followed by cancers of lip and oral cavity (10.4%), oesophagus (5.3%), colorectum (3.3%) and NMSC (3%). In children, most common malignancy was that of brain and nervous system (15.3%), followed by Hodgkin's lymphoma (14.2%), colorectum (8.1%), endocrine-&-related organs (8%) and non-Hodgkin's lymphoma (7.8%). CONCLUSION: Cancers of lip and oral cavity and breast cancer were the most common malignancies in males and females respectively. In paediatric group, cancers of brain and nervous system were most common. Alarmingly, Karachi males have highest ASR of cancers of lip and oral cavity compared to any other city of Pakistan.

Spectrum of Preneoplastic and Neoplastic lesions of intestine in a Tertiary Care Hospital of Karachi, Pakistan.

OBJECTIVES: To present 7 years data mentioning the spectrum of preneoplastic & neoplastic cases of intestine received at Dow Diagnostic Research and Reference Laboratory. METHODS: All the cases of preneoplastic & neoplastic lesions of intestine received during 2009 - 2015 were reviewed. The data obtained were subjected to descriptive statistical analysis using SPSS version 22. Furthermore, the association of diagnosis was seen with various other variables including age, gender & site of the lesion. A p-value of < 0.05 was considered as significant. RESULTS: The total samples were 486, out of which 33 cases were of premalignant and 453 were of malignant lesions. Out of total 33 cases of premalignant lesions of intestine, it consisted adenomatous polyp = 39.4% (n=13), dysplasia = 36.4% (n=12) and adenoma = 24.2% (n=8). From the total of 453 cases diagnosed as malignant lesions; adenocarcinoma as Grade-I were 14.2% (n=64), Grade-II were 7.6% (n=260) and Grade-III were 22% (n=99). Squamous cell carcinoma Grade-I were 0.4% (n=2), Grade-II 1.6% (n=7) and Grade-III 0.9% (n=4). 2.4% (n=11) cases were of metastatic adoncarcinoma, 0.9% (n=4) were diagnosed as neuroendocrine tumors and 0.4% (n=2) as lymphoma. A significant association was seen between site of the tumor and diagnosis, rectum was the commonest site for adenocarcinomas (p=0.001). Moderately differentiated adenocarcinoma was predominantly present in young age (p=0.001). CONCLUSION: Colorectal carcinoma is on rise in Pakistan, predominantly in young males, and rectum being the commonest site. In our study, all the lesions showed male predominance with adenomatous polyp as the commonest premalignant lesion & Grade-II adenocarcinoma the most common malignancy of intestine.

HIV-1 genetic diversity, geographical linkages and antiretroviral drug resistance among individuals from Pakistan.

Worldwide antiretroviral therapy (ART) has reduced the mortality and morbidity rates in individuals with HIV infection. However, the increasing occurrence of drug resistance is limiting treatment options. In recent years, Pakistan has witnessed a concentrated epidemic of HIV. It is very important to identify geographical linkages and mutations that generate selective pressure and drive resistance of HIV in our population. The aim of this work was to identify genetic diversity and drug resistance patterns of HIV in Pakistan, using available sequences and bioinformatics tools, which may help in selecting effective combination of available drugs. A total of 755 Pakistani HIV gag, pol and env sequences were retrieved from the Los Alamos HIV database. Sequences were aligned with reference sequences of different subtypes. For geographical linkages, sequences of predominant subtypes were aligned with sequences of the same subtypes from different countries. Phylogenetic trees were constructed using the maximum-likelihood method in MEGA 7 software. For drug resistance analysis, sequences were entered into the Stanford University HIV Drug Resistance Database. Phylogenetic trees for studying genetic diversity showed that 82% of the sequences were of subtype A, while the rest of the sequences were of subtypes B (9.5%), K (2%), D (2%) and AE (1%). Moreover, trees that were constructed to examine geographical linkages showed close clustering of strains with those of the neighboring countries Afghanistan and India, as well as some African countries. A search for drug resistance mutations showed that 93% of the sequences had no major or minor mutations. The remaining 7% of the sequences contained a major mutation, Y115F, which causes the virus to exhibit low to intermediate resistance against lamivudine and emtricitabine. Our data indicate that HIV subtype A is the major subtype, while subtypes K, D and AE are also present in our country, suggesting gradual viral evolution and possible entry of different subtypes from neighboring countries. These data suggest that HIV is still sensitive to most of the antiretroviral drugs used in Pakistan.

Correction to: HIV-1 genetic diversity, geographical linkages and antiretroviral drug resistance among individuals from Pakistan.

Unfortunately, the co-author's name Nouman Mughal was incorrectly published in the original article and the same is corrected here in this erratum.

Surgical treatment for intractable pruritus in progressive familial intrahepatic cholestasis.

Progressive familial intrahepatic cholestasis (PFIC) is one of the causes of childhood end stage liver disease. It is an autosomal recessive disorder, characterized by pruritus, coagulopathy, growth retardation, jaundice, and subsequently cirrhosis and hepatic failure due to impaired bile acid transport and metabolism. Diversion of bile, internally or externally, from the terminal ileum, to decrease re-uptake, is a viable option for relieving pruritus. Four children with PFIC type1 were treated with partial internal biliary diversion (PIBD) from June 2014 To March 2017 in the Unit of Paediatric surgery, Jinnah Hospital Lahore. The ages of patients were from four months to five years. Three were girls and one was a boy. The main symptom common to all was intractable pruritus. There was relief in pruritus, observed within first week postoperatively. They had been able to sleep without pruritis associated awakening episodes. PIBD is an effective technique for relieving the most devastating symptom of pruritus in PFIC.

Management of Post-traumatic and Iatrogenic urethrocutaneous fistula in children (a case series of seven patients).

This is a retrospective study of seven patients with post-traumatic and iatrogenic urethrocutaneous fistula of penile urethra, excluding complication of hypospadias surgery. It was conducted in the Paediatric Surgery Department, Jinnah Hospital Lahore from June 2014 to January 2017. The patients ages ranged from three to twelve years. All the patients were managed by repairing the fistula in three layers electively at 3 months from the date of initial presentation. They remain well with no complaints except one with a recurrence. The complications of circumcision can be avoided by preventing circumcision by non-doctors and quacks.

Human epidermal growth factor (Her-2) in gastric and colorectal adenocarcinoma.

Gastrointestinal (GIT) malignancies are a substantial health concern. Most patients present to the clinics with advanced and un-resectable diseases, so it remains difficult to cure with the existing chemotherapeutic regimes. It is therefore extremely important to devise novel therapeutic targets in these neoplasms in order to improve patient's survival. One such target is human epidermal growth factor, also known as Her-2. Although Her-2 expression and the use of a-Her-2 medications in breast cancers is well established, but its expression and potential use as a therapeutic target in gastrointestinal malignancies remains controversial and heavily debated. This review was planned to summarise the available literature extracted from the United States National Library of Medicine (NLM) and Pubmed Central, related to expression of Her-2 in gastric and colorectal adenocarcinomas and their correlation with different parameters. Moreover, we also planned to discuss available data in support of using a-Her-2 in gastric and colorectal malignancies.

Frequency of Her2/neu expression in colorectal adenocarcinoma: a study from developing South Asian Country.

BACKGROUND: Human Epidermal Growth Factor (Her-2/neu) has strong therapeutic implications in certain cancers like breast and gastric cancer. Literature on its frequency in colorectal cancer is scarce. In this study, we have investigated the frequency of Her-2/neu expression in colorectal adenocarcinomas and its association with various clinicopathological variables. METHODS: A total of 95 patients who underwent colonoscopic biopsy or colectomy were studied after Institutional Ethical Approval. Hematoxylin & eosin (H&E) staining was performed on all the tissue sections. Expression of Her-2/neu was investigated by immunohistochemistry using α-Her-2 antibody. In order to quantify Her-2/neu expression, three criterias were applied that includes the pattern of staining, intensity of staining and percentage of tumor cells stained. Furthermore, its association was seen with various clinicopathological variables including age, gender, histopathological type, grade and stage of the tumor. Data was entered and analyzed using SPSS version 21. A p-value of < 0.05 was considered as significant. RESULTS: From the total of 95 cases, 75 (78.9 %) cases showed Her-2/neu expression. Pattern of Her-2/neu staining was significantly associated with the grade of colorectal cancer depicting cytoplasmic Her-2/neu expression higher in low grade (50 %) while membranous Her-2/neu expression more in high grade colorectal cancer (45 %) (P-value = 0.030). Pattern of Her-2/neu staining was also significantly associated with the type of colorectal cancer representing membranous Her-2/neu expression to be more common in mucinous type (38.5 %) while cytoplasmic Her-2/neu expression to be more frequent in non mucinous type (42.7 %) of colorectal cancer (p-value = 0.024). We observed a significant association between percentage of cells stained & tumor type, with score 3+ maximum in non mucinous type of colorectal cancer (p-value = 0.006). CONCLUSION: Her2/neu is considerably expressed in colorectal adenocarcinoma in Pakistani population. Our findings indicate a significant strong association of cytoplasmic Her-2/neu expression with low grades and membranous Her-2/neu expression with high grades of colorectal cancer. These findings add to the body of information & may help in conducting clinical trials in future to explore its therapeutic significance as well.

Use of Corticosteroids in the management of Idiopathic Pulmonary Haemosiderosis: Do we have enough evidence.

Idiopathic Pulmonary Haemosiderosis (IPH) is a rare disease commonly affecting the paediatric population with approximately 500 globally reported cases in the literature. The disease usually presentswith a symptom triad consisting of ferropenic anaemia, cough with haemoptysis and diffuse bilateral alveolar infiltrates. Therapeutic options for this disorder are not only limited but also not fully effective. Moreover, corticosteroids remain the mainstay of IPH treatment. This communication reviews the available evidence in support of corticosteriod usage in the treatment of IPH. We conclude that the use of corticosteroid in IPH treatment is unfathomed and demands further investigation.

Cytogenetic and Molecular Analyses of Philadelphia Chromosome Variants in CML (chronic myeloid leukemia) Patients from Sindh using Karyotyping and RT-PCR.

OBJECTIVE: To determine the frequency of Philadelphia chromosome (Ph) and its variants in chronic myeloid leukemia (CML) cases at a tertiary care hospital of Sindh. METHODS: The study was conducted at the Department of Pathology, Liaquat University of Medical and Health Sciences, Jamshoro and Isra University Hospital, Hyderabad during May-to-September 2014. Bone marrow and peripheral blood samples from a total of 145 diagnosed cases of CML were collected. Cytogenetic analyses were performed using karyotyping as per the International System for Human Cytogenetic Nomenclature guidelines. All karyotypic images were analyzed using the Cytovision software. In order to identify BCR-ABL transcripts, RT-PCR was performed. Statistical analysis of the data was done using SPSS-version-21.0. RESULTS: Of the 145 samples, a total of 133 (91.7%) were positive for the Ph (Ph+) while 12 (8.3%) were negative for the Ph (Ph-). Of the 133 Ph+ samples, standard karyotypes were noted in 121 (91%), simple variants in 9 (6.7%) and complex variants in 3 (2.3%) of the samples. All the Ph+ samples (n=133) showed BCR-ABL positivity. Of the 12 Ph- samples, a total of 7 (58.3%) were BCR-ABL-positive and 5 (41.6%) were BCR-ABL-negative. CONCLUSION: Frequency of the Ph was found to be of 90.9% in CML patients using a highly sensitive technique, the RT-PCR. Cytogenetic abnormalities were at a lower frequency. Cytogenetic and molecular studies must be conducted for better management of CML cases. These findings could be very useful in guiding the appropriate therapeutic options for CML patients.

Differential immune cell densities in ductal carcinoma In-Situ and invasive breast cancer: Possible role of leukocytes in early stages of carcinogenesis.

OBJECTIVES: To investigate immune cell densities in pre-neoplastic (DCIS), cancer (IDC) and control breast tissues. METHODS: A total of four preneoplastic, 104 cancer and 104 control samples were analyzed. Morphological classification and prognostic scoring along with quantification of immune cells/mm(2) was performed. Data were entered and analyzed using SPSS version 16. Correlation of immune cell densities with various tumour sub-types was investigated using paired t-test and ANOVA. A p-value of <0.05 was considered as significant. RESULTS: Our data show increased infiltration of lymphocytes (mean lymphocytes = 287.6cells/mm(2)) as well as myelocytes (mean lymphocytes = 117.1cells/mm(2)) in pre-neoplastic tissues. This infiltration was significantly high compared to cancer (p-value<0.001) as well as control tissues (p-value <0.001). Moreover, we report increased infiltration of lymphocytes in cancer tissues compared to controls (p-value<0.001). There was no difference in lymphocyte densities within various tumour sub-types (all p-values >0.05). CONCLUSION: Leukocytes may play a role in early stages of breast carcinogenesis.

Integration of Next Generation Sequencing, Artificial Intelligence and Machine Learning in Cancer Diagnostics: A Major Leap Forward.

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Investigation of hybrid ultrasonic machining process of Nomex honeycomb composite using a toothed disc cutter.

Nomex honeycomb composite (NHC) has been increasingly used in the automotive, aerospace and defence applications due to its excellent thermal and mechanical properties. Its complex cellular hexagonal thin-walled configuration along with heterogeneous, soft and brittle nature pose substantial processing defects such as burr formation, tearing of walls, surface roughness, dimensional inaccuracy and low machining quality during conventional machining (CM). These surface defects have a substantial influence on the operating life and functional performance of its sandwiched structural members. Hybrid ultrasonic vibration assisted machining (HUSVAM) technology has been introduced to overcome such limitations. For an in depth research on HUSVAM of NHC using ultrasonic toothed disc cutter (UTDC), three dimensional finite element model was developed and experimental validation was carried out. The numerical simulation and experimental results were found to be in good agreement with one another. The influence of various machining parameters including the ultrasonic tool vibration amplitude (UTVA), feed rate (FR), depth of cut (DoC) and spindle angular speed (SAS) on NHC cutting forces, chip formation and surface quality was investigated using both HUSVAM and CM techniques. Furthermore, stresses, deformation and forces near tool-workpiece interaction along with the surface topography and morphologies were also analysed and compared for various operating conditions. A reduction in the cutting forces was found with the increase of SAS and UTVA (up to 65.47 % and 65.74 %, respectively). Although, the cutting forces were observed to increase by increasing the DoC and FR (up to 159.45 % and 126.33 %, respectively). DoC has a greater impact on the cutting forces among all machining parameters according to 4 levels, 4 factors (L16) orthogonal experiments based on Taguchi method. The results show that the chip formation and machining quality of NHC core can be improved with HUSVAM technique using UTDC. HUSVAM also reduced the cutting forces (up to 73 %) compared to CM. The ultrasonic toothed disc cutter generated large number of burr with very short length, no tearing defects and no uncut fibers as observed from scanning electron microscopy of NHC hexagonal cell structure, walls and triple points. A burr formation of less than 10 % was realized during HUSVAM of NHC cores for Fx≤3N, while it was found up to 20 % if Fx>3N, compared to at least 40 % during CM. The finite element model developed can be used to investigate the influence of HUSVAM on modern difficult to machine materials for enhanced surface quality.