Drug synergy model for malignant diseases using deep learning.

Drug synergy has emerged as a viable treatment option for malignancy. Drug synergy reduces toxicity, improves therapeutic efficacy, and overcomes drug resistance when compared to single-drug doses. Thus, it has attained significant interest from academics and pharmaceutical organizations. Due to the enormous combinatorial search space, it is impossible to experimentally validate every conceivable combination for synergistic interaction. Due to advancement in artificial intelligence, the computational techniques are being utilized to identify synergistic drug combinations, whereas prior literature has focused on treating certain malignancies. As a result, high-order drug combinations have been given little consideration. Here, DrugSymby, a novel deep-learning model is proposed for predicting drug combinations. To achieve this objective, the data is collected from datasets that include information on anti-cancer drugs, gene expression profiles of malignant cell lines, and screening data against a wide range of malignant cell lines. The proposed model was developed using this data and achieved high performance with f1-score of 0.98, recall of 0.99, and precision of 0.98. The evaluation results of DrugSymby model utilizing drug combination screening data from the NCI-ALMANAC screening dataset indicate drug combination prediction is effective. The proposed model will be used to determine the most successful synergistic drug combinations, and also increase the possibilities of exploring new drug combinations.

A Primary Extracutaneous Presentation of Merkel Cell Carcinoma.

Merkel cell carcinoma (MCC) is a rare aggressive cutaneous neuroendocrine malignancy with a mortality rate of around 33%. The presence of advanced disease at the time of diagnosis is associated with poor prognosis. Twofold etiologies have been described in the pathogenesis of Merkel cell carcinoma: chronic exposure to ultraviolet (UV) light and Merkel cell polyomavirus (MCPvY). MCC usually affects sun-exposed skin areas, and the presence of cutaneous nodules is the hallmark of the disease. However, there have been case reports in the literature where the diagnosis of MCC was made in the absence of any cutaneous findings. We present a case report of Merkel cell carcinoma that is unique in its presentation because of the presence of pulmonary and hepatic nodules and the absence of cutaneous lesions.

Otological Assessment in Head Injury Patients: A Prospective Study and Review of Literature.

Head injuries constitute a tragic problem invariably in under-developed, developed and developing countries. The concomitant otological injuries often go unnoticed. The purpose of this study was to assess the various otological manifestations following head injuries. Prospective study with review of literature using PubMed database was done. All the patients were evaluated for their presenting symptoms and signs. Audiological investigations including PTA (Pure tone audiometry), OAE (Otoacoustic emission), Impedance-Audiometry and BERA were done. HRCT temporal bone was advised in cases of suspicion. Relevant literature was reviewed to calculate the pooled prevalence rates. Random-effects model to synthesize overall effects was used. Heterogeneity was evaluated with the I2 statistic. Of 53 patients enrolled in the study, RTA was the most common mode of injury. The audiometric findings showed SNHL, CHL and mixed HL in 34, 20 and 18% of patients respectively. HRCT showed Longitudinal fracture (n = 17; 53.12%); isolated mastoid bone fracture (n = 9; 28.12%), transverse (n = 3; 9.37%) and isolated EAC fracture in (n = 3; 9.37%) patients. The pooled prevalence (n = 1106 patients) of SNHL, CHL, Mixed HL and Normal hearing were-35% (95%CI, 18-55%; I2 = 95.20%; P < 0.00), 24% (95%CI, 16-33%; I2 = 80.01%; P < 0.00), 15%(95%CI, 9-23%; I2 = 79.64%; P < 0.00) and 30% (95%CI, 3-66%; I2 = 98.71%; P < 0.00) respectively. The pooled prevalence (n = 4191 patients) of longitudinal, Transverse, mixed and other fractures were-44% (95%CI, 3-66%;I2 = 99.48%; P < 0.00), 9% (95% CI, 4-16%; I2 = 95.95%; P < 0.00), 4% (95%CI, 1-8%; I2 = 94.13%; P < 0.00) and 1% (95%CI, 0-4%; I2 = 90.37%; P < 0.00) respectively. In patients with head injury coordination between the trauma-surgeon, neurosurgeon and otologist is must to improve the long-term outcomes.

Artificial intelligence techniques for prediction of drug synergy in malignant diseases: Past, present, and future.

In recent years, there has been a surge of interest in the application and acceptance of Artificial Intelligence for challenges involving development, design, and prediction. Artificial Intelligence has not only changed the way we see the world, but it has also offered up new avenues for solving problems. This has been made possible by advances in technology, the availability of large amounts of data generated in various formats, the availability of increasing computational capacity in the form of GPUs and TPUs, and the reduction of costs. The advantages of applying AI in medicine have long been recognized, backed up by ongoing research from numerous institutes, hospitals, and pharmaceutical companies. Drug synergy prediction in malignant diseases is one example of a problem domain that has benefited considerably from AI breakthroughs. Traditionally, finding synergistic drug combinations for malignant diseases by experimental methods has had little success, as promising outcomes may be obtained during trials but may not be achieved during actual treatment due to the development of drug resistance over time. Experimental techniques can only be used for a restricted number of drugs because they are time demanding and expensive. Screening all necessary drug combinations is impractical due to limited resources. The goal of this research is to look at the past, present, and future of AI applications, with an emphasis on drug synergy prediction in malignant diseases using deep learning models. The benefits of utilizing AI to forecast drug synergy are discussed in this paper, as well as future research directions and challenges for applying AI techniques.

A Hybrid Oral Rehabilitation of Hypohidrotic Ectodermal Dysplasia: A Conservative Approach with Three-Year Follow-Up.

This case report presents a 19-year-old male patient with hypohidrotic ectodermal dysplasia, having a chief complaint of multiple missing teeth. Atraumatic extraction of the teeth with hopeless prognosis was done, and teeth with grade 2 mobility were submerged using cast dowel and coping. Following this, incremental increase in the vertical dimension was made using removable flexible splint of two-millimeter thickness. After facebow transfer and making appropriate eccentric bite records to program the semiadjustable articulator, wax-up was done at the desired vertical dimension (VD). The upper arch was finally restored using a long-span fixed partial denture and lower arch using bilateral attachment (Rhein 83) retained cast removable partial denture as a definitive prosthesis. Therefore, in conditions like hypodontia or oligodontia caused due to ectodermal dysplasia, attachment retained removable partial denture may prove beneficial by effectively distributing the occlusal forces. In clinical scenarios where implant is not feasible or not opted by the patient, this combination treatment may be a viable option.

Genomics-Driven Immunoproteomics: An Integrative Platform to Uncover Important Biomarkers for Human Diseases.

Genomics-driven immunoproteomics (GDI) is a platform that helps identify antigenic protein targets of mutations and other deoxyribonucleic acid (DNA) variations that are commonly associated with pathological states. This platform utilizes data generated from deep sequencing of exomic DNA or ribonucleic acid (RNA) as input to synthesize mutant peptides into microarrays, which then can be used to detect antigenic proteins that invoke immune response in patients. The technology has been used to detect antigenic targets of multiple sclerosis, an autoimmune disease [1], and cancer to identify mutant proteins that invoke immune response in breast cancer patients [2]. This technology has many potential applications to select genomic changes that are specifically recognized by the immune system in a rapid and efficient manner.

Microbial taxonomy in the era of OMICS: application of DNA sequences, computational tools and techniques.

The current prokaryotic taxonomy classifies phenotypically and genotypically diverse microorganisms using a polyphasic approach. With advances in the next-generation sequencing technologies and computational tools for analysis of genomes, the traditional polyphasic method is complemented with genomic data to delineate and classify bacterial genera and species as an alternative to cumbersome and error-prone laboratory tests. This review discusses the applications of sequence-based tools and techniques for bacterial classification and provides a scheme for more robust and reproducible bacterial classification based on genomic data. The present review highlights promising tools and techniques such as ortho-Average Nucleotide Identity, Genome to Genome Distance Calculator and Multi Locus Sequence Analysis, which can be validly employed for characterizing novel microorganisms and assessing phylogenetic relationships. In addition, the review discusses the possibility of employing metagenomic data to assess the phylogenetic associations of uncultured microorganisms. Through this article, we present a review of genomic approaches that can be included in the scheme of taxonomy of bacteria and archaea based on computational and in silico advances to boost the credibility of taxonomic classification in this genomic era.

Efficacy of Retromandibular Transparotid Approach for the Management of Extracapsular Subcondylar Mandibular Fractures Using 2-mm Titanium Miniplates: A Prospective Clinical Study.

PURPOSE: The aim of this study was to evaluate the long-term clinical and radiologic results of the retromandibular transparotid approach to displaced extracapsular subcondylar mandibular fractures. PATIENTS AND METHODS: A prospective cohort study was conducted over a period of 5 years on patients surgically treated for displaced extracapsular subcondylar mandibular fractures by the retromandibular transparotid approach. Variables including the type of fracture, degree of mouth opening, fracture displacement, deviation, excursive movements of the mandible, and facial nerve function were monitored before and after treatment. Appropriate statistics were computed. RESULTS: Thirty-nine patients with 47 fractures were evaluated. There were 34 subcondylar fractures (located below the sigmoid notch) (87%), and 5 fractures were located in the head region in bilateral cases. Of the fractures, 31 (79%) were unilateral and 8 (21%) were bilateral. In a multivariate study, condylar coronal displacement, coronal sagittal displacement, difference in the ramal height, maximal interincisal distance, protrusive movements, and deviation of the mandible on opening showed statistically significant differences in pretreatment and post-treatment patients (P = .001). The interincisal distance was 46.8 mm (SD, 5.2 mm) postoperatively versus 24.1 mm (SD, 6.7 mm) before treatment. The average range of protrusion was significantly lower (P = .001) in patients before treatment, at 1.9 mm (SD, 1.2 mm), when compared with 6.1 mm (SD, 2.0 mm) postoperatively. During mouth opening, deviation of the mandible is often a sign of compensatory movement of the contralateral joint due to shortening of the ascending ramal height on the affected joint. The mean deviation of the mandible from the midline was 4.2 mm (SD, 1.0 mm) in patients before treatment, with a significant difference (P = .001) in patients after treatment, with a mean of 1.9 mm (SD, 0.995 mm). Temporary injuries to the facial nerve branches were observed in 3 cases (8%) 1 week after treatment, which later resolved within 3 weeks to 3 months. CONCLUSIONS: The retromandibular transparotid approach provides good exposure and facilitates accurate reduction and fixation of the subcondylar fragment with positive outcomes, good cosmetic results, and rare major complications. Most facial nerve injuries are transient in nature after this approach. A Synthes 2-mm titanium single mini-plate (West Chester, PA) provides stable results after fixation.

A rare case report and appraisal of the literature on spontaneous tooth exfoliation associated with trigeminal herpes zoster.

BACKGROUND: Reports of post herpetic maxillofacial complications have been very rarely documented in the literature that includes periapical lesions, calcified and devitalized pulps, resorption of roots, osteonecrosis, and spontaneous exfoliation of teeth. The atypical feature of the case of concern to the dental surgeon is the rare complication of spontaneous tooth exfoliation following herpes zoster. CASE REPORT: This case reports a male patient of age 47 years who reported to the Department of Periodontology with the chief complaint of mobility in the left upper central incisor. Patient history revealed herpes zoster infection that began 11 days earlier along with underlying diabetes mellitus condition. We hereby report a known diabetic patient with history of herpes zoster infection who presented with rare complication of spontaneous tooth exfoliation involving the maxillary division of the trigeminal nerve. DISCUSSION: Limited number of cases has been reported in the literature regarding spontaneous teeth exfoliation secondary to herpes zoster. The exact pathogenesis regarding the spontaneous exfoliation of teeth in herpes zoster patient is still controversial. Thus, an oral health care provider should be aware of this rare complication while managing a case of tooth mobility with the previous history of herpes zoster of trigeminal nerve.

Neck dissection for oral squamous cell carcinoma: our experience and a review of the literature.

OBJECTIVES: This article describes our experience with neck dissection in 10 patients with oral squamous cell carcinoma. MATERIALS AND METHODS: Between January 2007 and October 2009, 10 patients underwent primary surgery for the treatment of squamous cell carcinoma of the oral cavity. For patients with N0 disease on clinical exam, selective neck dissection (SND [I-III]) was performed. In patients with palpable cervical metastases (N+), modified radical neck dissections were performed, except in one patient in whom SND (I-III) was performed. The histopathologic reports were reviewed to assess the surgical margins, the presence of extra-capsular spread, perineural invasion, and lymphatic invasion. RESULTS: On histopathologic examination, positive soft tissue margins were found in three patients, and regional lymph node metastases were present in five of the ten patients. Perineural invasion was noted in five patients, and extra nodal spread was found in four patients. Regional recurrence was seen in two patients and loco-regional recurrence plus distant metastasis to the tibia was observed in one patient. During the study period, three patients died. Seven patients remain free of disease to date. CONCLUSION: Histopathological evaluation provides important and reliable information for disease staging, treatment planning, and prognosis. The philosophy of neck dissection is evolving rapidly with regard to the selectivity with which at-risk lymph node groups are removed. The sample size in the present study is small, thus, caution should be employed when interpreting these results.