Radiogenomic Models Using Machine Learning Techniques to Predict EGFR Mutations in Non-Small Cell Lung Cancer.

BACKGROUND: The purpose of this study was to build radiogenomics models from texture signatures derived from computed tomography (CT) and 18F-FDG PET-CT (FDG PET-CT) images of non-small cell lung cancer (NSCLC) with and without epidermal growth factor receptor (EGFR) mutations. METHODS: Fifty patients diagnosed with NSCLC between 2011 and 2015 and with known EGFR mutation status were retrospectively identified. Texture features extracted from pretreatment CT and FDG PET-CT images by manual contouring of the primary tumor were used to develop multivariate logistic regression (LR) models to predict EGFR mutations in exon 19 and exon 20. RESULTS: An LR model evaluating FDG PET-texture features was able to differentiate EGFR mutant from wild type with an area under the curve (AUC), sensitivity, specificity, and accuracy of 0.87, 0.76, 0.66, and 0.71, respectively. The model derived from CT texture features had an AUC, sensitivity, specificity, and accuracy of 0.83, 0.84, 0.73, and 0.78, respectively. FDG PET-texture features that could discriminate between mutations in EGFR exon 19 and 21 demonstrated AUC, sensitivity, specificity, and accuracy of 0.86, 0.84, 0.73, and 0.78, respectively. Based on CT texture features, the AUC, sensitivity, specificity, and accuracy were 0.75, 0.81, 0.69, and 0.75, respectively. CONCLUSION: Non-small cell lung cancer texture analysis using FGD-PET and CT images can identify tumors with mutations in EGFR. Imaging signatures could be valuable for pretreatment assessment and prognosis in precision therapy.

Outcomes of extra oral versus intraoral approach for Mandibular angle fracture reduction.

OBJECTIVE: To compare the outcomes of intraoral versus extraoral approach in the treatment of mandibular angle fracture. METHODS: The randomised controlled trail was conducted at the Department of Maxillofacial Surgery, Mayo Hospital, Lahore Pakistan, from September 2016 to March 2017, and comprised patients of mandibular angle fracture who were divided into two equal extraoral group A and intraoral group B. . Baseline and post-operative data on 1st and 7th days as well as 3 months following the surgery was collected. Data was analysed using SPSS 20. RESULTS: Of the 100 patients, there were 50(50%) in each of the two groups. Mean age of group A was 32.28±7.79 years compared to 33.72±8.13 years in group B. There were 39 (78%) males in group A and 36(72%) in group B. The mean pain score at baseline in the groups was not significantly different (p=0.795). On the 7th day and 3 months post-operation, mean pain score was significantly lower in group A (p=0.002). Nerve complication in group A was significantly high compared to group A (p=0.005). CONCLUSIONS: Extra oral approach for the management of mandibular angle fracture is better with regards to pain while intra-oral approach is less associated with nerve complications.

Odorant Item Specific Olfactory Identification Deficit May Differentiate Alzheimer Disease From Aging.

OBJECTIVES: To explore whether the ability to recognize specific odorant items is differentially affected in aging versus Alzheimer disease (AD); to refine olfactory identification deficit (OID) as a biomarker of prodromal and early AD. DESIGN: Prospective multicenter cross-sectional study with a longitudinal arm. SETTING: Outpatient memory diagnostic clinics in New York and Texas. PARTICIPANTS: Adults aged 65 and older with amnestic mild cognitive impairment (aMCI) and AD and healthy aging (HA) subjects in the comparison group. MEASUREMENTS: Participants completed the University of Pennsylvania Smell Identification Test (UPSIT) and neuropsychological testing. AD-associated odorants (AD-10) were selected based on a model of ordinal logistic regression. Age-associated odorants (Age-10) were identified using a linear model. RESULTS: For the 841 participants (234 HA, 192 aMCI, 415 AD), AD-10 was superior to Age-10 in separating HA and AD. AD-10 was associated with a more widespread cognitive deficit across multiple domains, in contrast to Age-10. The disease- and age-associated odorants clustered separately in age and AD. AD-10 predicted conversion from aMCI to AD. CONCLUSIONS: Nonoverlapping UPSIT items were identified that were individually associated with age and disease. Despite a modest predictive value of the AD-specific items for conversion to AD, the AD-specific items may be useful in enriching samples to better identify those at risk for AD. Further studies are needed with monomolecular and unilateral stimulation and orthogonal biomarker validation to further refine disease- and age-associated signals.

Reporting Quality of Observational Studies in Plastic Surgery Needs Improvement: A Systematic Review.

INTRODUCTION: Our objective was to determine the compliance of observational studies in plastic surgery with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement checklist. METHODS: All cohort, cross-sectional, and case-control studies published in five major plastic surgery journals in 2013 were assessed for their compliance with the STROBE statement. RESULTS: One hundred thirty-six studies were identified initially and 94 met the inclusion criteria. The average STROBE score was 12.4 (range, 2-20.1) with a standard deviation of 3.36. The most frequent reporting deficiencies were not reporting the study design in the title and abstract 30% compliance; describing the setting, locations, and relevant dates, including periods of recruitment, exposure, follow-up, and data collection (24%); describing efforts to address sources of bias (20%); reporting numbers of individuals at each stage of the study (20%); and discussing limitations (40%). CONCLUSIONS: The reporting quality of observational studies in Plastic Surgery needs improvement. We suggest ways this could be improved including better education, awareness among all stakeholders, and hardwiring compliance through electronic journal submission systems.

Fibromatosis of infratemporal space.

Fibromatosis is a rare benign mesenchymal neoplasm which primarily originates in the muscle, connective tissue, fascial sheaths, and musculoaponeurotic structures. It is commonly seen as abdominal tumour but in maxillofacial region, the occurrence of these tumours is very rare and exceedingly rare in infratemporal space. Often misdiagnosed due to its varied clinical behaviour, fibromatosis is benign, slow-growing, infiltrative tumour without any metastatic potential, but is locally aggressive causing organ dysfunction along with high recurrence rate. We report a case of fibromatosis involving the left infratemporal space in a 35-year-old female who presented with chief complaint of limited mouth opening for the preceding 4 years.

Effective killing of leukemia cells by the natural product OSW-1 through disruption of cellular calcium homeostasis.

3ß,16ß,17α-Trihydroxycholest-5-en-22-one 16-O-(2-O-4-methoxybenzoyl-ß-D-xylopyranosyl)-(1→3)-2-O-acetyl-α-L-arabinopyranoside (OSW-1) is a natural product with potent antitumor activity against various types of cancer cells, but the exact mechanisms of action remain to be defined. In this study, we showed that OSW-1 effectively killed leukemia cells at subnanomolar concentrations through a unique mechanism by causing a time-dependent elevation of cytosolic Ca(2+) prior to induction of apoptosis. A mechanistic study revealed that this compound inhibited the sodium-calcium exchanger 1 on the plasma membrane, leading to an increase in cytosolic Ca(2+) and a decrease in cytosolic Na(+). The elevated cytosolic Ca(2+) caused mitochondrial calcium overload and resulted in a loss of mitochondrial membrane potential, release of cytochrome c, and activation of caspase-3. Furthermore, OSW-1 also caused a Ca(2+)-dependent cleavage of the survival factor GRP78. Inhibition of Ca(2+) entry into the mitochondria by the uniporter inhibitor RU360 or by cyclosporin A significantly prevented the OSW-1-induced cell death, indicating the important role of mitochondria in mediating the cytotoxic activity. The extremely potent activity of OSW-1 against leukemia cells and its unique mechanism of action suggest that this compound may be potentially useful in the treatment of leukemia.

Comparison of the efficacy of single volar subcutaneous digital block and the dorsal two injections block.

BACKGROUND: Digital nerve blocks are commonly used as effective techniques of anaesthesia to allow a variety of surgical procedures performed on digits. This study was conducted to compare the efficacy of volar subcutaneous single injection block and the traditional dorsal two injections digital block. METHODS: This randomized controlled trial was conducted at Plastic and Reconstructive Surgery Department, Hayatabad Medical Complex Peshawar from December. 2009-10. A total of 126 patients with pathology distal to the first palmer digital crease divided into two equal groups. Group A received volar subcutaneous digital block while group B dorsal two injections block. Efficacy of digital block was measured in terms of time of onset of anaesthesia, which was the total time duration after administering local anaesthetic to loss of pinprick sensation and total duration of anaesthesia, which was defined as the time period from onset of block (loss of pinprick sensation) till the appearance of pain which required additional local anaesthetic or postoperative analgesia. RESULTS: A total of 126 patients were studied, 63 in each group. Of the total patients, 102 (81%) were male and 24 (19%) female with a mean age of 27 ± 4.2 years (range 17-60 years). The mean time of onset of anaesthesia from injection till the loss of pin prick sensation was 3.32 ± 0.42 minutes for volar single injection group and 4.53 minutes ± 0.57 minutes for dorsal two injections group (p = 0.049). Similarly the mean total duration of anaesthesia for the volar subcutaneous group was 271.9 ± 29.34 minutes while for the dorsal two injections group, it was 229.52 ± 28.82 minutes (p = 0.415). CONCLUSION: Single injection volar subcutaneous digital block provides faster onset of anaesthesia, produces predictable, consistent dense anaesthesia of all of the fingers with the help of single injection prick.

A novel dataset of date fruit for inspection and classification.

Date fruit grading and inspection is a challenging and crucial process in the industry. The grading process requires skilled and experienced labour. Moreover, the labour turnover in the date processing industries has been increased regularly. Therefore, due to the lack of trained labour, the quality of date fruit is often compromised. It leads to fruit wastage and instability of fruit prices. Currently, deep learning algorithms have achieved the research community's attention in solving the problems in the agriculture sector. The pre-trained models like VGG16 and VGG19 have been applied for the classification of date fruit [1,2]. Furthermore, machine learning techniques like K-Nearest Neighbors, Support Vector Machine, Random Forest and a few others [3], [4], [5], [6] have been used for grading of date fruit. Therefore, classification and sorting of date fruit problems have become common in the industry. The classification and grading of date fruit needed a neat and clean dataset. In this article, an indigenous and state-of-the-art dataset of date fruit is offered. The dataset contains images of four date fruit varieties. It consists of 3004 pre-processed images of different classes and grades. Moreover, images have been sorted based on size as large, medium, and small. Additionally, it is graded based on the quality as grade 1, grade 2, and grade 3. This dataset is separated into eighteen different directories for the facilitation of the researchers. It may contribute to develop an intelligent system to grade and inspect date fruit. This system may add value to the sustainable economic growth of fruit processing industries and farmers locally and internationally.

Da Vinci Robotic Surgical System: Early Experience from Pakistan.

OBJECTIVE: To determine the outcomes of robotic surgeries using the Da Vinci robotic surgical system (DVSS) at Pakistan's largest urological tertiary healthcare system. STUDY DESIGN: Descriptive study. Place and Duration of the Study: Department of Minimally Invasive and Robotic Surgery, Division of Urology, Sindh Institute of Urology and Transplantation, Karachi, Pakistan, from March 2017 to December 2021. METHODOLOGY: Hospital records of patients who underwent robotic urological surgeries were assessed for their outcomes in terms of blood loss, mortality, system malfunction, and conversion to open surgery. Descriptive statistics were determined. RESULTS: A total of 550 procedures were performed. The mean age recorded was 39.58±16.83 years. The mean blood loss recorded was 255.611±353.57 ml; there were 3 cases of malfunction. Forty cases were converted to open surgery, and the mortality rate was 1.1%. CONCLUSION: Minimally invasive surgical techniques have high precision, fewer complications, and lower morbidity rates. Using DVSS for surgical interventions is both effective and safe. KEY WORDS: Minimally invasive surgery, Da Vinci robotic surgical system, Robotic surgery.

A comprehensive review on Gossypium hirsutum resistance against cotton leaf curl virus.

Cotton (Gossypium hirsutum L.) is a significant fiber crop. Being a major contributor to the textile industry requires continuous care and attention. Cotton is subjected to various biotic and abiotic constraints. Among these, biotic factors including cotton leaf curl virus (CLCuV) are dominant. CLCuV is a notorious disease of cotton and is acquired, carried, and transmitted by the whitefly (Bemisia tabaci). A cotton plant affected with CLCuV may show a wide range of symptoms such as yellowing of leaves, thickening of veins, upward or downward curling, formation of enations, and stunted growth. Though there are many efforts to protect the crop from CLCuV, long-term results are not yet obtained as CLCuV strains are capable of mutating and overcoming plant resistance. However, systemic-induced resistance using a gene-based approach remained effective until new virulent strains of CLCuV (like Cotton Leaf Curl Burewala Virus and others) came into existence. Disease control by biological means and the development of CLCuV-resistant cotton varieties are in progress. In this review, we first discussed in detail the evolution of cotton and CLCuV strains, the transmission mechanism of CLCuV, the genetic architecture of CLCuV vectors, and the use of pathogen and nonpathogen-based approaches to control CLCuD. Next, we delineate the uses of cutting-edge technologies like genome editing (with a special focus on CRISPR-Cas), next-generation technologies, and their application in cotton genomics and speed breeding to develop CLCuD resistant cotton germplasm in a short time. Finally, we delve into the current obstacles related to cotton genome editing and explore forthcoming pathways for enhancing precision in genome editing through the utilization of advanced genome editing technologies. These endeavors aim to enhance cotton's resilience against CLCuD.

Capacity building for pediatric neuro-oncology in Pakistan- a project by my child matters program of Foundation S.

Introduction: Initiated in June 2019, this collaborative effort involved 15 public and private sector hospitals in Pakistan. The primary objective was to enhance the capacity for pediatric neuro-oncology (PNO) care, supported by a My Child Matters/Foundation S grant. Methods: We aimed to establish and operate Multidisciplinary Tumor Boards (MTBs) on a national scale, covering 76% of the population (185.7 million people). In response to the COVID-19 pandemic, MTBs transitioned to videoconferencing. Fifteen hospitals with essential infrastructure participated, holding monthly sessions addressing diagnostic and treatment challenges. Patient cases were anonymized for confidentiality. Educational initiatives, originally planned as in-person events, shifted to a virtual format, enabling continued implementation and collaboration despite pandemic constraints. Results: A total of 124 meetings were conducted, addressing 545 cases. To augment knowledge, awareness, and expertise, over 40 longitudinal lectures were organized for healthcare professionals engaged in PNO care. Additionally, two symposia with international collaborators and keynote speakers were also held to raise national awareness. The project achieved significant milestones, including the development of standardized national treatment protocols for low-grade glioma, medulloblastoma, and high-grade glioma. Further protocols are currently under development. Notably, Pakistan's first pediatric neuro-oncology fellowship program was launched, producing two graduates and increasing the number of trained pediatric neuro-oncologists in the country to three. Discussion: The initiative exemplifies the potential for capacity building in PNO within low-middle income countries. Success is attributed to intra-national twinning programs, emphasizing collaborative efforts. Efforts are underway to establish a national case registry for PNO, ensuring a comprehensive and organized approach to monitoring and managing cases. This collaborative initiative, supported by the My Child Matters/Foundation S grant, showcases the success of capacity building in pediatric neuro-oncology in low-middle income countries. The establishment of treatment protocols, fellowship programs, and regional tumor boards highlights the potential for sustainable improvements in PNO care.

Commentary: Consensus Guidelines on the Appropriate Use of Brand-Name and Generic Anti-Seizure Medication for the Management of Epilepsy in the Gulf Region.

INTRODUCTION: The clinical, social, and economic burden of epilepsy is undeniable. Local guidance on epilepsy management is limited and needed to address the both use of anti-seizure medication (ASM) and switching practices which influence clinical outcomes. AREAS COVERED: An expert panel composed of practicing neurologists and epileptologists from countries of the Gulf Cooperation Council (GCC) met in 2022 to discuss local challenges in the management of epilepsy and formulate recommendations for clinical practice. Published literature on the outcomes of ASM switching was reviewed along with clinical practice/gaps, international guidelines, and local treatment availabilities. EXPERT OPINION: Improper ASM use and inappropriate brand-name-to-generic or generic-to-generic switching can contribute to worsening clinical outcomes in epilepsy. ASMs should be used for the management of epilepsy based on patient clinical profile, underlying epilepsy syndrome, and drug availability to ensure optimal and sustainable treatment. Both first-generation and newer ASMs can be considered; appropriate use is recommended from the beginning of treatment. It is critical to avoid inappropriate ASM switching to avoid breakthrough seizures. All generic ASMs should fulfill strict regulatory requirements. If needed, ASM changes should always be approved by the treating physician. ASM switching (brand-name-to-generic, generic-to-generic, generic-to-brand-name) should be avoided in epilepsy patients who have achieved control but can be considered for those uncontrolled on current medication.

Demographics of basal cell carcinoma and its surgical management.

BACKGROUND: Basal cell carcinoma (BCC) is the most common, slow growing epidermal skin tumour and an increase in its incidence has been noticed in the past decades. Different treatment options include surgical and non-surgical measures. Surgical options include surgical excision, cryosurgery, curettage, electrodessication and Mohs micrographic surgery. Non-surgical treatments options are 5-flourouracil, photodynamic therapy, immunomodulation and radiotherapy. This study was conducted to determine the demographics of facial BCC and its rate of incomplete excision and recurrence. METHODS: Clinically diagnosed facial BCCs were included in this prospective descriptive study. Tumours were excised with 3-5 mm clinically palpable safe margins and were sent for histopathological confirmation and margin clearance. All patients were followed for a minimum of two years to look for any recurrence. The demographic data, site, clinical presentation, size of the lesion, excision margins, reconstructive options, complications, histopathological margin clearance and recurrence was recorded and analysed. RESULTS: A total of 139 cases were recruited in this study. Four cases were lost in follow-up. Out of remaining 135 patients including 78 males and 57 females with a mean age of 58.6 years were studied. The commonest site of involvement was nose (45.9%), followed by periocular (28.1%) and cheek (15.6%) regions. The most common clinical type was nodular (51%) followed by ulcerative (38.5%). In majority of the cases, the resulting defect after excision was reconstructed with local flaps (57.8%). Majority (77.8%) of tumours had histopathologically clear margins while 20% had tumour involvement. During 2 years follow-up period, 8.9% patients had tumour recurrence.

Bentonite clay with different nitrogen sources can effectively reduce nitrate leaching from sandy soil.

Nitrate (NO3-1) leaching from soils results in the lower soil fertility, reduced crop productivity and increased water pollution. The effects of bentonite clay mixed with various nitrogen (N) fertilizers on NO3-1 leaching from sandy soils haven't been extensively studied. Therefore, the present lysimetric study determined NO3-1 leaching from bentonite [0, 2 and 4% (m/m)] treated sandy soil under three N sources (calcium nitrate [Ca(NO3)2], ammonium chloride [NH4Cl], and urea [CO(NH2)2] at the rate of 300 kg N ha-1). Results showed that bentonite markedly reduced NO3-1 release in the leachate, while 4% bentonite retained higher NO3 in the soil. The NO3-1 leaching from sandy soil varied with N sources as Ca(NO3)2 > NH4Cl > (CO(NH2)2. At early stages of leaching, higher concentrations of NO3-1 were detected in leachate with both NH4Cl and Ca(NO3)2, but leaching of NO3-1 increased with urea at later leaching stages. The amount of total NO3-1 retained in soil was conversely related to the amount of NO3-1 in the leachate. This study indicated that soil amendment with bentonite could efficiently mitigate NO3-1 leaching from sandy soil and hence prevent N fertilizer losses and groundwater pollution.

A CRISPR way for accelerating cereal crop improvement: Progress and challenges.

Humans rely heavily on cereal grains as a key source of nutrients, hence regular improvement of cereal crops is essential for ensuring food security. The current food crisis at the global level is due to the rising population and harsh climatic conditions which prompts scientists to develop smart resilient cereal crops to attain food security. Cereal crop improvement in the past generally depended on imprecise methods like random mutagenesis and conventional genetic recombination which results in high off targeting risks. In this context, we have witnessed the application of targeted mutagenesis using versatile CRISPR-Cas systems for cereal crop improvement in sustainable agriculture. Accelerated crop improvement using molecular breeding methods based on CRISPR-Cas genome editing (GE) is an unprecedented tool for plant biotechnology and agriculture. The last decade has shown the fidelity, accuracy, low levels of off-target effects, and the high efficacy of CRISPR technology to induce targeted mutagenesis for the improvement of cereal crops such as wheat, rice, maize, barley, and millets. Since the genomic databases of these cereal crops are available, several modifications using GE technologies have been performed to attain desirable results. This review provides a brief overview of GE technologies and includes an elaborate account of the mechanisms and applications of CRISPR-Cas editing systems to induce targeted mutagenesis in cereal crops for improving the desired traits. Further, we describe recent developments in CRISPR-Cas-based targeted mutagenesis through base editing and prime editing to develop resilient cereal crop plants, possibly providing new dimensions in the field of cereal crop genome editing.

Cervical lymph node metastases in squamous cell carcinoma of tongue and floor of mouth.

Oral squamous cell carcinoma has high chances of cervical lymph node metastasis. This case series describes the distribution of cervical lymph nodes in 50 cases of squamous cell carcinoma of tongue and floor of mouth. The mean age was 47.28±10.5 years. Thirty positive metastatic lymph nodes were found; 90% occurring at level I-II mostly in T4 size but also in T1 and T2 cases. The distribution of involved lymph nodes in oral cancer affects the neck dissection extent and is, therefore, an important pre-operative feature.

Reconstruction of mandibular defects with autogenous bone grafts: a review of 30 cases.

BACKGROUND: Multitudes of options are available for reconstruction of functional and cosmetic defects of the mandible, caused by various ailments. At the present time, autogenous bone grafting is the gold standard by which all other techniques of reconstruction of the mandible can be judged. The purpose of this study was to evaluate the outcome of different osseous reconstruction options using autogenous bone grafts for mandibular reconstruction. METHODS: This Interventional study was conducted at Department of Oral and Maxillofacial Surgery, King Edward Medical University/Mayo Hospital Lahore, from January 2008 to July 2009 including one year follow-up. The study was carried out on thirty patients having bony mandibular defects. They were reconstructed with the autogenous bone grafts from different graft donor sites. On post-operative visits they were evaluated for outcome variables. RESULTS: Success rate of autogenous bone grafts in this study was 90%. Only 10% of the cases showed poor results regarding infection, resorption and graft failure. CONCLUSION: Autogenous bone grafts, non-vascularised or vascularised, are a reliable treatment modality for the reconstruction of the bony mandibular defects with predictable functional and aesthetic outcome.

Achieving network level privacy in Wireless Sensor Networks.

Full network level privacy has often been categorized into four sub-categories: Identity, Route, Location and Data privacy. Achieving full network level privacy is a critical and challenging problem due to the constraints imposed by the sensor nodes (e.g., energy, memory and computation power), sensor networks (e.g., mobility and topology) and QoS issues (e.g., packet reach-ability and timeliness). In this paper, we proposed two new identity, route and location privacy algorithms and data privacy mechanism that addresses this problem. The proposed solutions provide additional trustworthiness and reliability at modest cost of memory and energy. Also, we proved that our proposed solutions provide protection against various privacy disclosure attacks, such as eavesdropping and hop-by-hop trace back attacks.

Intrusion-aware alert validation algorithm for cooperative distributed intrusion detection schemes of wireless sensor networks.

Existing anomaly and intrusion detection schemes of wireless sensor networks have mainly focused on the detection of intrusions. Once the intrusion is detected, an alerts or claims will be generated. However, any unidentified malicious nodes in the network could send faulty anomaly and intrusion claims about the legitimate nodes to the other nodes. Verifying the validity of such claims is a critical and challenging issue that is not considered in the existing cooperative-based distributed anomaly and intrusion detection schemes of wireless sensor networks. In this paper, we propose a validation algorithm that addresses this problem. This algorithm utilizes the concept of intrusion-aware reliability that helps to provide adequate reliability at a modest communication cost. In this paper, we also provide a security resiliency analysis of the proposed intrusion-aware alert validation algorithm.