A Current Review of Machine Learning and Deep Learning Models in Oral Cancer Diagnosis: Recent Technologies, Open Challenges, and Future Research Directions.

Cancer is a problematic global health issue with an extremely high fatality rate throughout the world. The application of various machine learning techniques that have appeared in the field of cancer diagnosis in recent years has provided meaningful insights into efficient and precise treatment decision-making. Due to rapid advancements in sequencing technologies, the detection of cancer based on gene expression data has improved over the years. Different types of cancer affect different parts of the body in different ways. Cancer that affects the mouth, lip, and upper throat is known as oral cancer, which is the sixth most prevalent form of cancer worldwide. India, Bangladesh, China, the United States, and Pakistan are the top five countries with the highest rates of oral cavity disease and lip cancer. The major causes of oral cancer are excessive use of tobacco and cigarette smoking. Many people's lives can be saved if oral cancer (OC) can be detected early. Early identification and diagnosis could assist doctors in providing better patient care and effective treatment. OC screening may advance with the implementation of artificial intelligence (AI) techniques. AI can provide assistance to the oncology sector by accurately analyzing a large dataset from several imaging modalities. This review deals with the implementation of AI during the early stages of cancer for the proper detection and treatment of OC. Furthermore, performance evaluations of several DL and ML models have been carried out to show that the DL model can overcome the difficult challenges associated with early cancerous lesions in the mouth. For this review, we have followed the rules recommended for the extension of scoping reviews and meta-analyses (PRISMA-ScR). Examining the reference lists for the chosen articles helped us gather more details on the subject. Additionally, we discussed AI's drawbacks and its potential use in research on oral cancer. There are methods for reducing risk factors, such as reducing the use of tobacco and alcohol, as well as immunization against HPV infection to avoid oral cancer, or to lessen the burden of the disease. Additionally, officious methods for preventing oral diseases include training programs for doctors and patients as well as facilitating early diagnosis via screening high-risk populations for the disease.

Advancing genome editing with artificial intelligence: opportunities, challenges, and future directions.

Clustered regularly interspaced short palindromic repeat (CRISPR)-based genome editing (GED) technologies have unlocked exciting possibilities for understanding genes and improving medical treatments. On the other hand, Artificial intelligence (AI) helps genome editing achieve more precision, efficiency, and affordability in tackling various diseases, like Sickle cell anemia or Thalassemia. AI models have been in use for designing guide RNAs (gRNAs) for CRISPR-Cas systems. Tools like DeepCRISPR, CRISTA, and DeepHF have the capability to predict optimal guide RNAs (gRNAs) for a specified target sequence. These predictions take into account multiple factors, including genomic context, Cas protein type, desired mutation type, on-target/off-target scores, potential off-target sites, and the potential impacts of genome editing on gene function and cell phenotype. These models aid in optimizing different genome editing technologies, such as base, prime, and epigenome editing, which are advanced techniques to introduce precise and programmable changes to DNA sequences without relying on the homology-directed repair pathway or donor DNA templates. Furthermore, AI, in collaboration with genome editing and precision medicine, enables personalized treatments based on genetic profiles. AI analyzes patients' genomic data to identify mutations, variations, and biomarkers associated with different diseases like Cancer, Diabetes, Alzheimer's, etc. However, several challenges persist, including high costs, off-target editing, suitable delivery methods for CRISPR cargoes, improving editing efficiency, and ensuring safety in clinical applications. This review explores AI's contribution to improving CRISPR-based genome editing technologies and addresses existing challenges. It also discusses potential areas for future research in AI-driven CRISPR-based genome editing technologies. The integration of AI and genome editing opens up new possibilities for genetics, biomedicine, and healthcare, with significant implications for human health.

Trifecta and Pentafecta Outcomes in Laparoscopic and Robotic Nephron-Sparing Surgery for Highly Complex Renal Tumors: A Propensity Score-Matched Cohort Analysis.

Purpose: To compare the trifecta and pentafecta outcomes of laparoscopic partial nephrectomy (LPN) and robotic partial nephrectomy (RPN) in highly complex renal tumors (RENAL nephrometry score ≥10) using a matched cohort analysis. Methods: Patients undergoing LPN or RPN for renal tumors with RENAL score ≥10 between January 2014 and December 2019 were matched using 1:2 propensity score match analysis based on age, body mass index, gender, laterality of tumor, RENAL score, and American Society of Anesthesiologists (ASA) score. The two groups were compared for trifecta and pentafecta outcomes. Results: Thirty patients undergoing LPN (Group A) were matched with 60 patients undergoing RPN (Group B). The mean age (standard deviation) was 53.7 (12.9) years. The median (interquartile range) RENAL score was 10 (10-11). In comparison, the mean warm ischemia time in Group A was significantly longer than that in Group B (26.2 vs 23.0 minutes, p = 0.013). The overall complication rate was 36.7% in Group A as compared with 20% in Group B (p = 0.440). The trifecta outcomes could be achieved in 11 patients (36.7%) in Group A compared with 40 patients (66.7%) in Group B (p = 0.012). Moreover, 10 patients (33.3%) in Group A and 28 patients (46.7%) in Group B achieved pentafecta outcomes (p = 0.227). Conclusions: In a matched cohort of patients undergoing nephron-sparing surgery for highly complex renal tumors (RENAL score ≥10), the robotic approach offers a superior advantage in the achievement of trifecta outcomes as compared with the laparoscopic approach. However, both LPN and RPN can achieve similar pentafecta outcomes.

The Bioactive Potential of Culturable Fungal Endophytes Isolated From the Leaf of Catharanthus roseus (L.) G. Don.

INTRODUCTION: Endophyte is considered a source of natural bioactive secondary metabolites that provides an array of bioactive lead compounds. The present study was aimed to determine the antimicrobial and anti-inflammatory potential of fungal endophytes isolated from Catharanthus roseus. METHODS: A total of seven fungal endophytes crude extract were screened against bacterial pathogens. Of these, Curvularia geniculata CATDLF7 crude extract exhibited the most potent inhibitory activity against bacterial pathogens. Hence, CATDLF7 crude extract was subjected to chromatographic separation. This purification leads to the isolation of six pure compounds (1PS - 6PS). Of these, 3PS was found to be a major constituent and most effective against clinical isolates of methicillin- resistant Staphylococcus aureus (MRSA) with minimum inhibitory concentration (MIC) values ranging from 100 to 200 µg/ml. Based on the spectroscopic data, 3PS was characterized as α,ß- dehydrocurvularin. This compound also showed synergistic interaction with norfloxacin and reduced its MIC up to 32-folds with a fractional inhibitory concentration index (FICI) of 0.09. RESULTS: To understand the possible antibacterial mechanism of action, α,ß-dehydrocurvularin alone (100 µg/ml) exhibited efflux pump inhibitory potential by 0.84 fold decreasing in ethidium bromide (EtBr) fluorescence. In addition, α,ß-dehydrocurvularin inhibited inflammatory cytokines TNF-α and IL-6 production, which is further validated by molecular docking scores -4.921 and -5.641, respectively, for understanding orientation and binding affinity. CONCLUSION: Overall, the results highlighted identifying bioactive compound α,ß-dehydrocurvularin, which could be used as an antimicrobial and anti-inflammatory agent.

Role of laparoscopy in the era of robotic surgery in urology in developing countries.

With the rapid expansion of robotic platforms in urology, there is an urgent and unmet need to review its cost and benefits in comparison to the traditional laparoscopy, especially in reference to a developing country. A nonsystematic review of the literature was conducted to compare the outcomes of pure laparoscopic and robot-assisted urologic procedures. Available literature over the past 30 years was reviewed. Robot-assisted surgery and laparoscopy were found to have similar outcomes in the areas of radical prostatectomy, partial and radical nephrectomy, radical cystectomy, retroperitoneal lymph node (LN) dissection, inguinal LN dissection, donor nephrectomy, and kidney transplantation. Robot-assisted surgery was found to be significantly costlier than pure laparoscopy. In the absence of a clear advantage of robot-assisted surgery over pure laparoscopy, lack of widespread availability and the currently prohibitive cost of robotic technology, laparoscopic urological surgery has a definite role in the developing world.

Establishing a Robot-Assisted Kidney Transplant Program: Independent Evaluation of the Learning Curve and Surgical Nuances.

Background: Robot-assisted kidney transplantation (RAKT) is a technically challenging procedure and there has been limited reporting of its learning curve (LC), mostly by a single surgical working group. The aim of the current study was to perform an independent analysis of LC and describe our modifications in the technique of RAKT. Materials and Methods: All consecutive cases performed at our center from April 2016 to March 2020 were reviewed. LC was analyzed by using the cumulative summation method for total anastomosis time (technical outcome) and serum creatinine at days 7 and 30 (functional outcome). Patient safety was assessed by using Shewhart control charts, and a comparison of safety outcomes before and after achieving LC was done by using Chi-square or Fischer exact test as appropriate. A descriptive review of technical modifications made during our experience was conducted. Results: Ninety patients underwent robot-assisted renal transplant during the study period. LC was crossed at 24 cases (total anastomosis time) and 15 to 25 cases (serum creatinine). Shewhart control charts showed that total anastomosis time remained below alert/alarm line in 94.4%/98.9% cases, with the alert line being crossed a significantly greater number of times before the LC. Serum creatinine values remained below alert/alarm line in 85.5%/90% cases at day 7 and 92.2%/96.7% cases at day 30, with no difference made due to LC. Key technical modifications included arterial and ureteric spatulation at bench, use of polypropylene 5 to 0 holding stitch in graft vessels to facilitate intraoperative handling, keeping anterior arterial wall smaller to visualize posterior arterial wall anastomosis, and leaving a small amount of fatty tissue on the supero-lateral surface of the kidney for handling after jacket removal. Conclusion: Our LC of RAKT was crossed at 24 cases (technical outcome) and 15 to 25 cases (functional outcome). We have also detailed valuable technical modifications in the procedure.

Chemical composition, bactericidal kinetics, mechanism of action, and anti-inflammatory activity of Isodon melissoides (Benth.) H. Hara essential oil.

Present study was aimed to investigate the antibacterial activity, bactericidal mechanism of action, killing kinetics and anti-inflammatory activity of Isodon melissoides (Benth.) H. Hara essential oil. The gas chromatography-flame ionization detector (GC-FID) and gas chromatography-mass spectrometry (GC-MS) analysis revealed the presence of carvacrol (45.4%), p-cymene (11.6%) and thymol (11.3%) as major constituents of the oil. The oil displayed broad spectrum significant antibacterial activity (MIC: 0.13-8.33 ppm; MBC: 0.13->33.34 ppm) against test strains. The oil exhibited a time and dose-dependent bactericidal effect. The oil disrupted the cell membrane by changing the cell membrane permeability. The essential oil significantly decreased the overproduction of proinflammatory cytokines in LPS-induced inflammation in HaCaT cells without any cytotoxic effect. I. melissoides essential oil can be a promising alternative antimicrobial agent for the control of methicillin resistant staphylococci and other pathogenic bacteria tested, and also useful for the topical anti-inflammatory properties.

Comparative analysis of outcomes and long-term follow-up of robot-assisted pediatric kidney transplantation, with open counterpart.

How does the robotic kidney transplant fare against the open technique, in pediatric patients? No one knows. To address this question, this study compares the outcomes of robotic kidney transplants, with those of open transplant in these patients. This study was a retrospective analysis of outcomes (renal function and complications), of all pediatric patients (<18 years of age), who underwent kidney transplant at our institute, after 2014, till their last follow-up. Fisher's exact test was used to compare proportions. Continuous variables were analyzed using Mann-Whitney test. P value of <.05 was considered significant. Of the twenty-five patients included, 21 belonged to open group, and 4 to the robotic group. Patients in the robotic group had significantly higher Re-WIT (P value .002) and had lower analgesia requirement (P value .04). Median follow-up period was 31 months. Both groups were comparable in terms of length of hospital stay, blood transfusion, and renal function post-operatively till their last follow-up. Three patients in the open group had surgical site infection as compared to none in the robotic group. All the patients had functioning grafts till their last follow-up. Robotic transplant is safe and delivers functional results similar to open technique, with lesser pain and better cosmesis. Longer Re-WIT in robotic transplant has no impact on post-operative renal function. Ours is the first known effort to compare robotic technology with the established open technique of transplant in this population. A prospective randomized controlled trial should refine the results of the present study.

Primary Bladder Neck Obstruction in a Young Woman: A Novel Technique of Bladder Neck Incision Using Holmium Laser.

Background: Management of primary bladder neck obstruction (PBNO) in women is difficult. Surgical treatment in the form of bladder neck incision (BNI) is indicated in many cases. There is no defined consensus on the best surgical technique of BNI in women. We present a novel technique of BNI in such cases using pediatric cystoscope and holmium laser, which is a promising alternative to the existing management techniques. Case Presentation: A 28-year-old lady complained of obstructive lower urinary tract symptoms. Serum biochemistry revealed azotemia. Further investigation utilizing a micturating cystourethrogram showed a closed bladder neck, and urodynamic studies revealed a high bladder outlet obstruction index suggestive of PBNO. BNI was effectively performed using pediatric cystoscope and holmium laser at 3, 9, and 12 o'clock positions. Postoperatively the patient had improving renal function and clinical improvement. Conclusion: Use of pediatric cystoscope with holmium laser for BNI in females is a novel technique that offers the advantage of higher maneuverability in the female urethra, precise incision with protection of external sphincter from thermal damage, and avoidance of the complication of vesicovaginal fistula caused by posterior incisions.

Urethral metastasis with neuroendocrine differentiation in a patient with prostate cancer treated with hormone deprivation.

Adenocarcinoma prostate treated with hormone deprivation may evolve into a neuroendocrine differentiated tumor. Usually visceral metastasis are seen in neuroendocrine tumors. We present a case of neuroendocrine differentiated urethral metastasis from a hormone deprived prostate cancer.

Essential oil from waste leaves of Curcuma longa L. alleviates skin inflammation.

BACKGROUND: Curcuma longa L. is an important industrial crop used by medicinal and cosmetic industries in the world. Its leaves are a waste material after harvesting rhizomes. The aim of the study was to evaluate the chemical and pharmacological profile of essential oil from waste leaves of Curcuma longa (EOCl) against skin inflammation. METHODS: EOCl was subjected to gas chromatography (GC) analysis for identification of essential oil constituents and its anti-inflammatory evaluation through in vitro and in vivo models. RESULTS: Chemical fingerprinting using GC and GC-MS analysis of EOCl revealed the presence of 11 compounds, representing 90.29% of the oil, in which terpinolene (52.88%) and α-phellandrene (21.13%) are the major components. In the in vitro testing EOCl inhibited the production of pro-inflammatory cytokines (TNF-α, IL-6, IL-1ß) in lipopolysaccharide (LPS) and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation in the human keratinocyte cell line (HaCaT). Topical application of EOCl produced anti-inflammatory effects by reducing ear thickness, ear weight and ameliorating the level of pro-inflammatory cytokines (TNF-α, IL-6, IL-1ß) at protein and mRNA levels as well as regulating the overproduction of oxidative markers and restoring the histopathological damage in a TPA-induced mouse model of inflammation. CONCLUSION: These findings of topical anti-inflammatory properties of EOCl provide a scientific basis for medicinal use of this plant material against inflammatory disorders.

Structure and specificity of the Type VI secretion system ClpV-TssC interaction in enteroaggregative Escherichia coli.

The Type VI secretion system (T6SS) is a versatile machine that delivers toxins into either eukaryotic or bacterial cells. It thus represents a key player in bacterial pathogenesis and inter-bacterial competition. Schematically, the T6SS can be viewed as a contractile tail structure anchored to the cell envelope. The contraction of the tail sheath propels the inner tube loaded with effectors towards the target cell. The components of the contracted tail sheath are then recycled by the ClpV AAA+ ATPase for a new cycle of tail elongation. The T6SS is widespread in Gram-negative bacteria and most of their genomes carry several copies of T6SS gene clusters, which might be activated in different conditions. Here, we show that the ClpV ATPases encoded within the two T6SS gene clusters of enteroaggregative Escherichia coli are not interchangeable and specifically participate to the activity of their cognate T6SS. Here we show that this specificity is dictated by interaction between the ClpV N-terminal domains and the N-terminal helices of their cognate TssC1 proteins. We also present the crystal structure of the ClpV1 N-terminal domain, alone or in complex with the TssC1 N-terminal peptide, highlighting the commonalities and diversities in the recruitment of ClpV to contracted sheaths.

Adrenocortical carcinoma with inferior vena cava thrombus: Renal preserving surgery.

Adrenocortical carcinoma with tumor thrombus extending via an adrenal vein into the inferior vena cava is uncommon. We describe a left side kidney-preserving surgery in such a patient where, after transection of the main renal vein at the point of insertion of the adrenal vein, the left kidney was being drained by lumbar and gonadal veins.

Unusual presentation of tuberculosis in the form of a bilateral renal pseudotumor.

Genitourinary tuberculosis (TB) is a common form of extrapulmonary tuberculosis. The kidneys are usually affected by hematogenous seeding at the time of primary pulmonary infection. Genitourinary TB has non-specific clinical presentations and variable radiographic appearances. We are reporting a case of genitourinary TB presenting as bilateral renal mass. The patient underwent computed tomography-guided kidney biopsy that showed a granulomatous lesion. Then, the patient was put on anti-tuberculous treatment with a good response. We feel that patients having multiple bilateral kidney lesions should undergo biopsy to determine the nature of the lesion before any surgical intervention.

Diarylheptanoids from Alnus nepalensis attenuates LPS-induced inflammation in macrophages and endotoxic shock in mice.

Diarylheptanoids, a group of plant secondary metabolites are increasingly recognized as potential therapeutic agents. The aim of study was to ascertain the anti-inflammatory profile of diarylheptanoids from Alnus nepalensis against lipopolysaccharide (LPS)-induced inflammation in macrophages and endotoxic shock in mice. Extracts prepared from dried leaves of A. nepalensis using standard solvents were tested against LPS-induced inflammation in macrophages. Among all, butanol extract (ANB) has shown most significant inhibition of pro-inflammatory cytokines without any cytotoxicity. HPLC analysis of ANB showed the presence of diarylheptanoids. The diarylheptanoids were further isolated and tested in-vitro for anti-inflammatory activity. Treatment of isolated diarylheptanoids (HOG, ORE and PLS) was able to reduce the production and mRNA level of pro-inflammatory cytokines (TNF-α and IL-6). Furthermore, we demonstrated that it inhibited the expression of NF-kB protein in LPS-induced inflammation in macrophages. In-vivo efficacy and safety profile of ANB revealed that oral treatment of ANB was able to improve the survival rate, and inhibited the production of pro-inflammatory cytokines in serum, attenuated vital organ injury in a dose dependent manner without any toxic effect at higher dose in mice. The results suggest that diarylheptanoids from A. nepalensis can be considered as potential therapeutic candidates for the management of inflammation related diseases.

AIDS orphans and vulnerable children in India: problems, prospects, and concerns.

This article reviews and discusses the problems, responses, and concerns of orphans and vulnerable children in India. The article shows that HIV/AIDS programs and interventions are vital for survival and welfare of orphan and vulnerable children, but they have reached only to a small fraction of the most vulnerable children. The article suggests a number of measures that government and civil society could take to address the problems and emphasizes the need to learn from other countries' experience and initiatives in developing appropriate policy and programmes for orphan and vulnerable children.

Urethrocutaneous fistula after hypospadias repair: outcome of three types of closure techniques.

OBJECTIVE: To evaluate the outcomes of three surgical techniques for the closure of urethrocutaneous fistula (UCF) after hypospadias repair. MATERIALS AND METHODS: Fifty-one patients (mean age 6.5 years) who underwent UCF closure between June 1998 and February 2008 were divided in to three groups depending on fistula size; group I had <2 mm and (n = 17, 33.4%), group II had 2-4 mm (n = 21, 41.2%) and group III had >4 mm or multiple fistulas (n = 13, 25.4%). Group I patients were treated by excision and simple closure. Patients in group II and III were treated with flip flap technique along with the wrapping of repaired area with scrotal dartos flap and tunneled tunica vaginalis flap (TVF), respectively. RESULTS: Mean surgical time was 45 min (range 30-55), 60 min (range 50-75) and 80 min (range 60-100) in three techniques, respectively. The mean follow-up was 3.5 years (range 6 months-10 years). No patient had recurrence of fistula in group III, while 2 (9.5%) and 4 (25.4%) patients in groups II and I, respectively, had recurrent UCF. No postoperative complications were encountered in the testis or the scrotum. No patient had torsion or deviation of penis. CONCLUSION: Simple fistula closure carries a higher risk of recurrence even in small sized fistulas. The application of scrotal dartos or TVF for wrapping the repaired area gives excellent results and they are easy to harvest with no harmful effects on the scrotum or testis.