Digital image analysis and machine learning-assisted prediction of neoadjuvant chemotherapy response in triple-negative breast cancer.

BACKGROUND: Pathological complete response (pCR) is associated with favorable prognosis in patients with triple-negative breast cancer (TNBC). However, only 30-40% of TNBC patients treated with neoadjuvant chemotherapy (NAC) show pCR, while the remaining 60-70% show residual disease (RD). The role of the tumor microenvironment in NAC response in patients with TNBC remains unclear. In this study, we developed a machine learning-based two-step pipeline to distinguish between various histological components in hematoxylin and eosin (H&E)-stained whole slide images (WSIs) of TNBC tissue biopsies and to identify histological features that can predict NAC response. METHODS: H&E-stained WSIs of treatment-naïve biopsies from 85 patients (51 with pCR and 34 with RD) of the model development cohort and 79 patients (41 with pCR and 38 with RD) of the validation cohort were separated through a stratified eightfold cross-validation strategy for the first step and leave-one-out cross-validation strategy for the second step. A tile-level histology label prediction pipeline and four machine-learning classifiers were used to analyze 468,043 tiles of WSIs. The best-trained classifier used 55 texture features from each tile to produce a probability profile during testing. The predicted histology classes were used to generate a histology classification map of the spatial distributions of different tissue regions. A patient-level NAC response prediction pipeline was trained with features derived from paired histology classification maps. The top graph-based features capturing the relevant spatial information across the different histological classes were provided to the radial basis function kernel support vector machine (rbfSVM) classifier for NAC treatment response prediction. RESULTS: The tile-level prediction pipeline achieved 86.72% accuracy for histology class classification, while the patient-level pipeline achieved 83.53% NAC response (pCR vs. RD) prediction accuracy of the model development cohort. The model was validated with an independent cohort with tile histology validation accuracy of 83.59% and NAC prediction accuracy of 81.01%. The histological class pairs with the strongest NAC response predictive ability were tumor and tumor tumor-infiltrating lymphocytes for pCR and microvessel density and polyploid giant cancer cells for RD. CONCLUSION: Our machine learning pipeline can robustly identify clinically relevant histological classes that predict NAC response in TNBC patients and may help guide patient selection for NAC treatment.

Biofortification of crops with nutrients by the application of nanofertilizers for effective agriculture.

The agricultural industry is rapidly accepting daily changes and updates, and expanding to meet the basic demands of humanity. The main objective of modern agricultural practices is high profits with minimal investment, without upsetting any other form of life or abiotic factors. According to this principle, nanofertilizers are recommended for use in agriculture and are classified in different ways based on their nutritive value, functional role in the environment, chemical composition, and form of application to ensure their persistent availability in the required quantities. These nanofertilizers meet the global crop nutrient requirement of 191.8 million metric tons along with multitudes of added value, and which are highly endorsed in the agricultural field compared to other chemical fertilizers, or their usage can be reduced to less than 50% by the use of nanofertilizers. In this review, we discuss different types of nanofertilizers, their effects on crop yield, stress tolerance, and their impact on the environment. Furthermore, the different types of nanofertilizer delivery, modes of action, and toxic impacts of nanofertilizers have been discussed. Although a large number of commercially successful effects of nanofertilizers have been demonstrated, the effects of biomagnification and cellular transformation are still disputed. The effect of the biomagnification of nanofertilizers remains unclear. A suitable strategy must be developed to easily recycle nanofertilizers. It is the need of the hour to accept the use of nanofertilizers in parallel to addressing this issue.

An Analytical Approach by Tri-Combination of Gradient UFLC, Response Surface Methodology and Green Chemistry Principle for Simultaneous Quantification of Azelnidipine and Chlorthalidone in Rabbit Plasma.

In this study, a sustainable and eco-friendly method is developed to quantify azelnidipine and chlorthalidone in rabbit plasma by gradient liquid chromatography based on green chemistry principle and analytical quality by design. The separation was achieved on a Shim pack C18 (25 cm × 5 cm × 4.6 µm) column with L1 packing. The mobile phase compromised of ethanol and 50-Mm ammonium acetate buffer (pH.6) at flow rate of 0.6 mL/min with 25-min runtime. The resolution and asymmetric factor were identified as critical analytical attributes (CAAs). The screening studies employing Control Noise Experimentation revealed that mobile phase pH, flow rate and ethanol concentration at 6 and 15 min significantly affected the CAAs method. The critical method parameters were optimized using Central Composition design. Chromatogram showed peak of the drugs at retention time of 9.03 min for chlorthalidone and 16.83 min for azelnidipine. The greenness score of the analytical method was found to be 1876.43 using analytical method greenness score calculator. The validation of the developed method was done which showed linearity at the range of 16-520 ng/mL, with R2 of 0.9992 and 0.9996 for azelnidipine and chlorthalidone, respectively, furthermore accuracy, precision, recovery and stability studies are carried out.

Perceptions and attitudes towards organ donation among people seeking healthcare in tertiary care centers of coastal South India.

BACKGROUND: Organ transplantation is the most preferred treatment modality for end-stage organ diseases. The need for the transplants is higher than the availability. Prerequisites for the success of transplantation program include awareness and positive attitudes. AIM: To assess the perceptions and attitudes of the people seeking health care in tertiary care centers towards organ donation in Mangalore, India. SETTINGS AND DESIGN: This cross-sectional study included 863 people seeking general healthcare as outpatients. MATERIALS AND METHODS: Face to face interviews were carried out using pretested tools which included the socio demographic data. Data was analyzed using Statistical Package for Social Sciences version 11.5. RESULTS: Overall, 59.6% participants showed the willingness to donate organs. Females (64.1%) and participants from upper socio economic status (62.7%) had higher willingness rates for organ donations. Hindus (63.6%) and Christians (63.3%) had higher willingness rates for organ donations than Muslims (38.2%). Also, 23.7% participants showed willingness to donate eyes and 33.6% wished to donate any organ after death. Most of the participants (67%) were aware that money should not be accepted for donating organs, and 58.1% were aware that it is an offence to accept any benefit for organ donations. Forty percent participants had perceived risks associated with organ donation. Regarding donor cards, 42.3% of the participants knew about it and 3.7% already possessed it. CONCLUSION: It is apparent from the study that though there was high level of awareness about organ donation, a high proportion of the participants did not have positive attitudes towards organ donation.

Deep learning based registration of serial whole-slide histopathology images in different stains.

For routine pathology diagnosis and imaging-based biomedical research, Whole-slide image (WSI) analyses have been largely limited to a 2D tissue image space. For a more definitive tissue representation to support fine-resolution spatial and integrative analyses, it is critical to extend such tissue-based investigations to a 3D tissue space with spatially aligned serial tissue WSIs in different stains, such as Hematoxylin and Eosin (H&E) and Immunohistochemistry (IHC) biomarkers. However, such WSI registration is technically challenged by the overwhelming image scale, the complex histology structure change, and the significant difference in tissue appearances in different stains. The goal of this study is to register serial sections from multi-stain histopathology whole-slide image blocks. We propose a novel translation-based deep learning registration network CGNReg that spatially aligns serial WSIs stained in H&E and by IHC biomarkers without prior deformation information for the model training. First, synthetic IHC images are produced from H&E slides through a robust image synthesis algorithm. Next, the synthetic and the real IHC images are registered through a Fully Convolutional Network with multi-scaled deformable vector fields and a joint loss optimization. We perform the registration at the full image resolution, retaining the tissue details in the results. Evaluated with a dataset of 76 breast cancer patients with 1 H&E and 2 IHC serial WSIs for each patient, CGNReg presents promising performance as compared with multiple state-of-the-art systems in our evaluation. Our results suggest that CGNReg can produce promising registration results with serial WSIs in different stains, enabling integrative 3D tissue-based biomedical investigations.

Integrating Research into Undergraduate Medical Education Curriculum: A 20-year Experience from a Medical School in Coastal South India.

Research is the key to advancement in medical science. Medical school can nurture the skill of research right from the under graduation. Research forms an integral part of the medical curriculum in western countries. We attempted the same in our medical school in India. We developed a structured research methodology program, which was implemented in the undergraduate (UG) curriculum in two phases. Phase I focuses on research methodology and Phase II on manuscript writing. With the implementation of a competency-based medical education curriculum (CBME), we have extended the research methodology program with manuscript writing and introduction to systematic reviews, which is being offered as electives to UG medical students in the third professional year. Our experience in training students at an UG level has been immensely satisfying. We hope that this article will help other medical schools to adopt a similar method of training UG medical students in research methodology and scientific medical writing.

Reversible neuropathy after chemotherapy for metastatic adenocarcinoma from an unknown primary tumor to the sural nerve.

Adenocarcinomas and other various tumors are known to metastasize to various locations without any significant predilection and the metastasis could be the first presentation of the malignancy by the patient. Involvement of peripheral nerves without the central nervous system involvement has been rarely reported. Perineural tumor spread has been infrequently reported with soft tissue tumors without central nervous system involvement. Here we present an unusual case of an elderly gentleman presenting with symptoms consistent with peripheral neuropathy involving multiple nerves. After failure of symptomatic therapy, electromyogram, and nerve conduction study showed severe bilateral carpal tunnel syndrome. Interestingly, symptoms worsened in the left hand after bilateral release surgery. Due to persistence of significant lifestyle-limiting symptoms, biopsy of the sural nerve was done that showed metastatic poorly differentiated adenocarcinoma cells. A complete surveillance for the primary lesion has been negative so far. The peripheral neuropathy was considered to be arising from the involvement of the perineural sheaths by the metastatic tumor lesions. The patient was then started on gemcitabine therapy and after just 2 cycles of chemotherapy, the patient has shown notable improvement of his symptoms. After completion of the duration of chemotherapy, he has been symptom-free for more than 6 months. Metastatic lesions to the peripheral nervous system should be considered in patients who have persisting neuropathic symptoms because treatment of those lesions can results in improvement of symptoms.

Hand-foot hyperpigmentation skin lesions associated with combination gemcitabine-carboplatin (GemCarbo) therapy.

Gemcitabine (Gemzar) is a nucleoside analogue used as a cytotoxic agent for the treatment of various carcinomas: pancreatic cancer, bladder cancer, breast cancer, and non-small-cell-lung cancer. Carboplatin, a DNA alkylating agent, is used alongside with gemcitabine in a regimen known as GemCarbo chemotherapy to treat several different types of cancer, most commonly lung cancer. We report an unusual case of hand-foot hyperpigmentation after the use of GemCarbo therapy on a man with stage IV non-small cell lung carcinoma. Physical examination revealed hyperpigmented lesions that were approximately 1-2 mm in diameter, of brown/purple discoloration localized to the palmar surface of his hands and the dorsum of his feet. A rapid plasma reagin blood test, used for the screening of syphilis was nonreactive. Discontinuation of both agents resulted in the dramatic disappearance of the lesions over the course of 2 weeks. In this report, we describe, to our knowledge, the first case of hand-foot hyperpigmentation that has been reported with the use of either of these 2 agents.

Perceptions and practices regarding use of personal listening devices among medical students in coastal south India.

UNLABELLED: Today's generation enjoys having music at their fingertips. This has led to an increase in the usage of personal listening devices (PLDs) over the past decade. There are significant concerns regarding harmful effects of PLD use. To find out the perception and practice of medical students regarding use of PLDs. Cross-sectional study was carried out in Mangalore, Coastal south India. Data were collected using a 31 item semi structured questionnaire that was distributed among 570 medical students, of which 485 completed questionnaire were received giving an overall response rate of 86.14%. The study was approved by the departmental review board. STATISTICAL ANALYSIS USED: data were analyzed using SPSS Version 11.5, Chi-square test for association was used and P<0.05 was considered statistically significant. Of the total study participants, 83.1% of them used PLDs regularly, of whom 77.7% used it for more than 1 h a day. Overall, 18.0% of the study population was aware that prolonged use of PLDs could be harmful to their health. Majority of the study subjects (72.4%) felt that the safe duration of listening to PLDs is 3 to 5 h. Among the subjects using PLDs ≥ 1 h, 60.1% preferred ear phones and among those using PLDs <1 h, 44.1% preferred earphones. Overall, 12.4% experienced temporary hearing loss on usage of PLDs. The use of PLDs among the medical students is on the rise, and they should be made more aware of the harmful effects associated with its use.

Study of finger print patterns in children with acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) is a malignant disease of an unknown origin. The present case control study was intended to compare the finger print patterns between the children diagnosed with ALL and a control group. A total of 24 children with established ALL were included in the study. Fingerprints of the affected children were analyzed in both hands and compared with the finger print patterns of 24 age and sex matched controls. The study indicated an increase in frequency of whorls and a decreased frequency of loops in children suffering from ALL. Radial loops, double loops, central pocket loops and tented arches are found to be proportionately less frequent in cases than controls. On quantitative analysis of patterns, mean pattern intensity index (PII) was found to be higher in cases than controls; however, a significant overlapping was evident. Most of the cases (n = 10, 41.7%) had a PII of 16-20, while a PII of 11-15 is reported among most children in the control group (n = 16, 66.7%). The findings of the study are suggestive of a possible trend and an association of finger print patterns with children suffering from ALL. The present research emphasizes the significance of the application of forensic science in medicine and pathology.

Comparative analysis of splice site regions by information content.

We have applied concepts from information theory for a comparative analysis of donor (gt) and acceptor (ag) splice site regions in the genes of five different organisms by calculating their mutual information content (relative entropy) over a selected block of nucleotides. A similar pattern that the information content decreases as the block size increases was observed for both regions in all the organisms studied. This result suggests that the information required for splicing might be contained in the consensus of approximately 6-8 nt at both regions. We assume from our study that even though the nucleotides are showing some degrees of conservation in the flanking regions of the splice sites, certain level of variability is still tolerated, which leads the splicing process to occur normally even if the extent of base pairing is not fully satisfied. We also suggest that this variability can be compensated by recognizing different splice sites with different spliceosomal factors.

1/f correlations in viral genomes--a Fast-Fourier Transformation (FFT) Study.

We have studied the presence of long-range correlations in the complete genomes of ten different dsDNA viruses and Saccharomyces cerevisiae (bakers' yeast) chromosome I. We have also studied the correlation between the distribution of the gene length and the domain of "1/f region" of their genomes. Linear regression analysis was done for the power-law region of these organisms and the slope values obtained were approximately -1, which signify the existence of "1/f noise" in the low and medium (intermediate) frequency regions. This suggests the presence of long-range correlations in their genomes. The presence of 1/f noise in a given frequency interval indicates the existence of a fractal (self-similar) structure in the corresponding range of wavelengths. The results of our study suggest that genes have correlations within themselves, and the correlations appear to be related with the scaling exponent alpha.

Vibrational spectroscopic, molecular docking and density functional theory studies on 2-acetylamino-5-bromo-6-methylpyridine.

Conformational and molecular docking analysis of 2-acetylamino-5-bromo-6-methylpyridine molecule was carried out and the vibrational spectral analysis was also carried out using experimental and theoretical methods. The calculated and experimentally observed vibrational frequencies of the molecule were assigned and compared. The pyridine ring CH stretching and CH3 stretching vibrational modes were shifted towards higher wavenumber (blue shift). The C=O stretching vibrational frequency was shifted towards lower wavenumber (red shift). Ultraviolet-visible spectrum of the molecule simulated theoretically was further validated experimentally. Molecular reactivity and stability were investigated using the frontier molecular orbital analysis and the related quantum chemical molecular properties. Natural bond orbital analysis and the structure activity relations were also studied to confirm the bioactivity of the molecule. Anticancer activity was examined based on molecular docking analysis and it has been identified that the AABMP molecule can act as a good inhibitor against lung cancer.

Gender preferences among antenatal women: a cross-sectional study from coastal South India.

BACKGROUND: A balanced sex ratio is essential for a stable society. OBJECTIVE: The main objective of the present research was to study the perceptions of women attending the antenatal care (ANC) facility regarding their gender preferences and family composition. METHOD: In this cross-sectional study 132 antenatal women were interviewed in their preferred language using a predesigned semi-structured questionnaire. The collected information was analyzed using SPSS version 11.5. RESULTS: The mean age of the study participants was 27.2 ± 4.1 years. The majority of the antenatal women (60.6%, n=80) did not have any gender preferences. Among those who had a gender preference (39.4%, n=52), male and female preference was reported by 55.7% (n=29) and 44.3% (n=23) of the participants respectively. The overall son preference index was observed to be 1.3. No consistent relationship could be established between the socio-demographic factors and the preference for gender. The mean preferred family size in our study was 1.85±0.531 and more than half of the participants had a balanced gender preference. The majority of the participants were aware that the adverse sex ratio can lead to fall in the number of brides and that it would bring about a social imbalance. CONCLUSION: As a developed society we need to ensure that both the genders get equal respect and are free from any sort of preferences and prejudices. To achieve this, more and more people need to be made aware of the consequences of gender imbalance and adverse sex ratio in a society.

Medical students' research - facilitators and barriers.

BACKGROUND: Undergraduate research in medicine is important to expose and encourage the students towards the newer advances and research practices. The present study was taken up in a medical institute to assess the perception of the medical faculty about research undertaken by the medical undergraduates, and identifying the barriers faced by them in training undergraduate students for research. MATERIALS AND METHODS: A questionnaire on perceptions, barriers and limitations towards undergraduate research was distributed to 105 participants included in the study. The responses of the participants were collected on a five point Likert scale and analysed using spss version 11.5. RESULTS: There was a strong agreement among the faculty about students' interest in carrying out research (95.1%), and that they had gained knowledge to design, conduct, present and publish their research from the projects undertaken by them (90.2%). Among the barriers for training undergraduate research, time consumption was perceived as a barrier by the participating medical teachers (37.7%) followed by lack of motivation and commitment among students (19.7%). Time constraint was the commonest reason for the faculty in not guiding undergraduate research (39.0%). A larger proportion of medical teachers suggested that incentives for students and teachers (62.7%) and frequent workshops for students related to undergraduate research (61.8%) are likely to encourage the students and teachers and thus, improve the scenario. CONCLUSION: It is suggested to address certain important issues like reducing the workload of faculty engaged in undergraduate research, and conducting frequent research methodology workshops for the under graduate students to improvise the standards of undergraduate research.

Compliance with iron-folic acid (IFA) therapy among pregnant women in an urban area of south India.

BACKGROUND: Anaemia is highly prevalent among pregnant women and iron deficiency is the most important cause. Like many other countries, India has policies to give pregnant women iron supplements. Non-compliance is one important challenging factor in combating anaemia. OBJECTIVE: To estimate the compliance for IFA tablets among pregnant women and to study the social factors influencing it. METHODOLOGY: This study included 190 pregnant women seeking ante-natal care in tertiary health Centres in the Mangalore city in South India. After Institutional Ethics Committee (IEC) approval, data was collected by personal interview. Missing ≥2 doses consecutively was considered non-compliance. The data was analyzed using SPSS (Statistical Package for Social Sciences) version 11.5. RESULTS: The mean age of the study population was 25.8 years (SD: 4.1). Majority of the subjects consumed mixed diet and 72.1% belonged to lower socioeconomic status. Overall, compliance with IFA tablets was 64.7%. Compliance increased with the increase in age, birth order and single daily dose. Forgetfulness and both perceived as well as experienced side effects of IFA therapy were the important factors for non-compliance. CONCLUSION: There was a moderate level of Compliance towards IFA tablets with key social and demographic factors playing important role.

Perceptions and practices of medical practitioners towards ethics in medical practice - a study from coastal South India.

Ethics is the application of values and moral rules to human activities. Medical practitioners are expected to not only have the skills and knowledge relevant to their field but also with the ethical and legal expectations that arise out of the standard practices. The present research was conducted with an aim to study the perceptions and practices of medical practitioners towards healthcare ethics in Indian scenario and to strengthen the evidence in the field of ethics training. A cross-sectional study was carried out in three associate hospitals of a Medical College in Southern India. Medical practitioners included in the study were administered a pre-tested, semi-structured questionnaire. Data was collected based on their responses on a 5 point Likert scale and analyzed using SPSS version 11.5. The majority of the participants mentioned that their perceptions of ethics in medical practice were based on information obtained during their undergraduate training, followed by experience at work. The medical practitioners had a positive perception on issues relating to consent in medical practice. However, the same degree of perception was not observed for issues related to confidentiality and their dealing with patients during emergency conditions. The majority of the medical practitioners agreed that ethical conduct is important to avoid legal and disciplinary actions. Among the medical practitioners, the responses of specialists and non-specialists were mostly similar with major differences of opinion for a few issues. A highest level of knowledge, awareness and understanding of ethics are expected in medical practice as it is the foundation of sound healthcare delivery system.

Sputum collection and disposal among pulmonary tuberculosis patients in coastal South India.

BACKGROUND: Safe sputum disposal practices minimise the spread of pulmonary tuberculosis (PTB). OBJECTIVES: To study the perceptions and practices of sputum disposal among PTB patients. METHODOLOGY: This study was conducted among 206 diagnosed sputum-positive TB patients registered in selected DOTS centres in Mangalore. RESULTS: Safe sputum disposal practice was followed by 50% of the subjects: it was higher among females (62%), patients of middle socio-economic status (75.5%) and those with a family history of TB (70%). Furthermore, 75% patients believed that TB was caused by several factors. CONCLUSIONS: High proportions of subjects were unaware about the causes of TB and did not practise safe disposal of sputum.

Perceptions and practices of self-medication among medical students in coastal South India.

Self-medication is a common practice worldwide and the irrational use of drugs is a cause of concern. This study assessed the prevalence of self-medication among the medical students in South India. The data was analysed using SPSS version 11.5. A total of 440 students were included in the study. The prevalence of self-medication was 78.6%. A larger number of females were self-medicating (81.2%) than males (75.3%). The majority of the students self-medicated because of the illness being too trivial for consultation (70.5%). Antipyretics were most commonly self-medicated by the participants (74.8%). Only 47% of the participants opined that self-medication was a part of self-care and it needs to be encouraged. 39.3% of the participants perceived that the supply of medicine without prescription by the pharmacist can prevent the growing trend of self-medication. Easy availability and accessibility to health care facilities remains the cornerstone for reducing the practice of self-medication.

Compliance with iron-folic acid (IFA) therapy among pregnant women in an urban area of south India.

BACKGROUND: Anaemia is highly prevalent among pregnant women and iron deficiency is the most important cause. Like many other countries, India has policies to give pregnant women iron supplements. Non-compliance is one important challenging factor in combating anaemia. OBJECTIVE: To estimate the compliance for IFA tablets among pregnant women and to study the social factors influencing it. METHODOLOGY: This study included 190 pregnant women seeking ante-natal care in tertiary health centres in the Mangalore city in south India. After Institutional Ethics Committee (IEC) approval, data was collected by personal interview. Missing >2 doses consecutively was considered non-compliance. The data was analyzed using SPSS (Statistical Package for Social Sciences) version 11.5. RESULTS: The mean age of the study population was 25.8 years (SD: 4.1). Most of the subjects consumed mixed diet and 72.1% belonged to lower socioeconomic status. Overall, compliance with IFA tablets was 64.7%. Compliance increased with the increase in age, birth order and single daily dose. Forgetfulness and both perceived as well as experienced side effects of IFA therapy were the important factors for non-compliance. CONCLUSION: There was a moderate level of compliance towards IFA tablets with key social and demographic factors playing an important role.