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This research paper seeks to investigate and categorize previous studies to understand better the role of energy generation technology in promoting sustainable development of a country country. The primary aim of this review is to identify and emphasize key issues related to energy sustainability. The study employs a systematic review approach, drawing on academic publications from the Web of Science and Scopus database. The analysis reveals five key issues: the nexus between energy generation and greenhouse gas emissions, energy generation and employment, the impact of energy generation and land use intensity, the association between energy generation and water footprint, and the nexus between energy generation and human health. This study delves into the theoretical dimensions of research concerning the interplay between energy sustainability and various aspects of energy generation technologies. Furthermore, it contributes to the existing body of knowledge concerning Sustainable Development Goal 7, with the overarching goal of enhancing both human well-being and economic prosperity through advancements in energy generation technologies. The study comprehensively explores the subject matter, offering an in-depth analysis of energy sustainability. Its unique contribution lies in its extensive examination of multiple facets of energy sustainability, making it a significant addition to the field of research.

Abstract Background Full‐body skin examination (FSE) is fundamental to the diagnosis of cutaneous malignancy but may not always include concealed site examination (CSE). Objectives To determine the approach of international dermatologists to CSE during FSE and examine influencing factors, barriers and attitudes toward CSE. Methods Members of the International Dermoscopy Society were surveyed using an online 12‐question survey disseminated via email. Results There were 706 completed responses among 1249 unique clicks to the survey, representing a completion rate of 56.5%. Fifty‐four percent of respondents reported always examining the breasts, while 52.8%, 18.8%, and 11.8% always examined the scalp, oral, and anogenital mucosa, respectively. The most frequent reason for examining concealed sites was patient concern, whilst common reasons for not examining concealed sites included low incidence of pathology and concern regarding allegations of sexual misconduct. Conclusions Our findings allude to the need for international consensus guidelines regarding the conduct and inclusion of concealed or sensitive sites in routine FSE. This is essential to define clinician responsibilities, inform patient expectations of care, and thereby mitigate potential medicolegal repercussions.

Objective To investigate the histological and biochemical alterations in the pancreas associated with statin-induced toxicity using a rat model. Methodology A one-year laboratory-based experimental control trial conducted at department of anatomy of a public sector medical college in Rawalpindi, in collaboration with the National Institute of Health (NIH) Islamabad and Armed Forces Institute of Pathology (AFIP) Rawalpindi. Twenty male Sprague-Dawley rats were assigned to the control group and another twenty to the experimental group. For a duration of 12 weeks, the experimental group was given 60 mg/kg/day of simvastatin orally, whereas the control group was given water and a conventional diet. The following characteristics were measured: body weight, pancreatic weight, biochemical parameters (cytokines, enzymes), and histological alterations (congestion, necrosis, fibrosis). Version 23 of the Statistical Package for the Social Sciences (SPSS) program was used to analyze the data. Qualitative variables were expressed as percentages and frequencies. The statistical significance was defined as P < 0.05. Chi-square analyses contrasted the qualitative factors among the groups. Results Compared to controls, the simvastatin group showed significantly increased mean pancreatic weight (p=0.043), congestion (55% vs 0%, p

Introduction: Being able to recognize high-risk facial basal cell carcinoma (BCC) may lead to fewer incomplete excisions and inappropriate treatments. Objectives: We sought to investigate clinical and dermoscopic criteria for predicting facial BCC subtypes, analyze the interobserver agreement between readers, and develop a diagnostic algorithm to predict high-risk histopathological subtype. Methods: In this single-center, retrospective investigation, 6 independent readers evaluated predefined clinical and dermoscopic criteria in images of histopathologically verified primary facial BCCs including: topography, border demarcation, vessels, ulceration, white porcelain areas, shiny white blotches and strands, and pigmented structures and vessels within ulceration. Results: Overall, 297 clinical and dermoscopic image pairs were analyzed. The strongest associations with high-risk subtype were: “bumpy” topography (OR 3.8, 95% CI, 3.1-4.7), ill-defined borders (OR 3.4, 95% CI 3.1-4.7), white porcelain area (OR 3.5, 95% CI 2.8-4.5), and vessels within ulceration (OR 3.1, 95% CI 2.4-4.1). Predominantly focused vessels were a positive diagnostic criterium for either nodular (OR 1.7, 95% CI 1.3-2.2) or high-risk (OR 2.0, 95% CI 1.6-2.5) subtypes and a strong negative diagnostic criterium for superficial BCC (OR 14.0, 95% CI 9.6-20.8). Interobserver agreement ranged from fair to substantial (κ=0.36 to 0.72). A diagnostic algorithm based on these findings demonstrated a sensitivity of 81.4% (95% CI, 78.9-83.7%) and a specificity of 53.3% (95% CI, 49.7-56.9%) for predicting high-risk BCC subtype. Conclusions: Integration of both clinical and dermoscopic features (including novel features such as topography and vessels within ulceration) are essential to improve subtype prediction of facial BCCs and management decisions.

Abstract Dermatoscopy is a non-invasive and cost-efficient imaging technique augmenting clinical examination in neoplastic and non-neoplastic dermatoses. Recently, novel dermatoscopic techniques based on principles of reflectance/absorption and excited fluorescence have been developed. However, comprehensive data on their applications are sparse, and terminology is inconsistent. In this systematic review, we addressed the principles of ultraviolet (UV) imaging and proposed categorization based on spectral characteristics and signal acquisition, as well as discussed documented and potential clinical applications, safety measures during examination, and limitations associated with reflectance and fluorescence dermatoscopy. A literature search was conducted in the PubMed medical database until 2 December 2023 according to PRISMA guidelines, and 28 papers fit the scope of this review, whereas additional relevant articles were included to provide broader context regarding the chosen terminology, chromophores described, safety of sub-UV/UV, and regulations for light-emitting devices. UV and sub-UV dermatoscopy, categorized into different methods on the basis of the emitted wavelength and signal acquisition process (reflectance versus fluorescence), augment conventional dermatoscopy by optimizing safety margins in melanoma, facilitating early detection of tumor recurrence, and enhancing visualization in non-neoplastic conditions, including pigmentation disorders, intertrigo, papulo-desquamative dermatoses, and beyond. The review highlights the limitations of these techniques, including difficulty in differentiating melanin from hemoglobin, challenges in evaluating uneven surfaces, and artifacts. Although UV dermatoscopy complements conventional dermatoscopy, clinicians should be aware of their peculiarities, artifacts, limitations, and safety concerns to optimize their diagnostic accuracy and ensure patient’s safety.

Liquid Phase Exfoliation (LPE) is a very effective technique for the synthesis of few layered two dimensional (2D) nanosheets. There is a surge to find environment friendly solvents for efficient exfoliation of layered materials to produce 2D nanosheets. TiB2 is an important layered material with very little reported work on its 2D nanosheets. The present work is about successful LPE of TiB2 using deionized (DI) water as a clean, green and low cost dispersion medium to make TiB2 nanosheets. The impact of ultrasonication conditions i.e. input power and treatment duration for efficient synthesis of few layered 2D nanosheets in DI water is studied by Atomic Force Microscopy (AFM), X-Ray Diffraction (XRD) and Scanning Electron Microscopy (SEM). It is found that by increasing input power, the layer thickness is reduced from bulk to 34 nm with lateral dimensions as huge as up to 5 μm. The increased treatment duration has further reduced the layer thickness to 21 nm associated with a decrease in lateral dimensions to about 1 μm. The mechanism of variation in the aspect ratio of the 2D nanosheets with ultrasonication power and treatment duration is explained. The optimum conditions for the fabrication of high aspect ratio 2D nanosheets of TiB2 owe to a greater acoustic cavitation intensity, an optimum treatment duration and a homogenous distribution of the cavitation events while using an appropriate size of the sonotrode in the sonicated volume during ultrasonication.

Abstract Backgrounds Despite recent advances, many cancers are still detected too late for curative treatment. There is, therefore, a need for the development of new diagnostic methods and biomarkers. One approach may arise from the detection of extrachromosomal circular DNA (eccDNA), which is part of cell‐free DNA in human plasma. Aims First, we assessed and compared two methods for the purification of eccDNA from plasma. Second, we tested for an easy diagnostic application of eccDNA liquid biopsy‐based assays. Materials & Methods For the comparison we tested a solid‐phase silica purification method and a phenol/chloroform method with salt precipitation. For the diagnostic application of eccDNA we developed and tested a qPCR primer‐based SNP detection system, for the detection of two well‐established cancer‐causing KRAS mutations (G12V and G12R) on circular DNA. This investigation was supported by purifying, sequencing, and analysing clinical plasma samples for eccDNAs containing KRAS mutant alleles in 0.5 mL plasma from 16 pancreatic ductal adenocarcinoma patients and 19 healthy controls. Results In our method comparison we observed, that following exonuclease treatment a lower eccDNA yield was found for the phenol/chloroform method (15.7%–26.7%) compared with the solid‐phase purification approach (47.8%–65.9%). For the diagnostic application of eccDNA tests, the sensitivity of the tested qPCR assay only reached ~10−3 in a background of 105 wild type (wt) KRAS circular entities, which was not improved by general amplification or primer‐based inhibition of wt KRAS amplification. Furthermore, we did not detect eccDNA containing KRAS in any of the clinical samples. Discussion A potential explanation for our inability to detect any KRAS mutations in the clinical samples may be related to the general low abundance of eccDNA in plasma. Conclusion Taken together our results provide a benchmark for eccDNA purification methods while raising the question of what is required for the optimal fast and sensitive detection of SNP mutations on eccDNA with greater sensitivity than primer‐based qPCR detection.

Abstract The use of artificial intelligence (AI) has the potential to improve the assessment of lesions suspicious of melanoma, but few clinical studies have been conducted. We validated the accuracy of an open-source, non-commercial AI algorithm for melanoma diagnosis and assessed its potential impact on dermatologist decision-making. We conducted a prospective, observational clinical study to assess the diagnostic accuracy of the AI algorithm (ADAE) in predicting melanoma from dermoscopy skin lesion images. The primary aim was to assess the reliability of ADAE’s sensitivity at a predefined threshold of 95%. Patients who had consented for a skin biopsy to exclude melanoma were eligible. Dermatologists also estimated the probability of melanoma and indicated management choices before and after real-time exposure to ADAE scores. All lesions underwent biopsy. Four hundred thirty-five participants were enrolled and contributed 603 lesions (95 melanomas). Participants had a mean age of 59 years, 54% were female, and 96% were White individuals. At the predetermined 95% sensitivity threshold, ADAE had a sensitivity of 96.8% (95% CI: 91.1–98.9%) and specificity of 37.4% (95% CI: 33.3–41.7%). The dermatologists’ ability to assess melanoma risk significantly improved after ADAE exposure (AUC 0.7798 vs. 0.8161, p = 0.042). Post-ADAE dermatologist decisions also had equivalent or higher net benefit compared to biopsying all lesions. We validated the accuracy of an open-source melanoma AI algorithm and showed its theoretical potential for improving dermatology experts’ ability to evaluate lesions suspicious of melanoma. Larger randomized trials are needed to fully evaluate the potential of adopting this AI algorithm into clinical workflows.

ImportanceUse of prognostic gene expression profile (GEP) testing in cutaneous melanoma (CM) is rising despite a lack of endorsement as standard of care.ObjectiveTo develop guidelines within the national Melanoma Prevention Working Group (MPWG) on integration of GEP testing into the management of patients with CM, including (1) review of published data using GEP tests, (2) definition of acceptable performance criteria, (3) current recommendations for use of GEP testing in clinical practice, and (4) considerations for future studies.Evidence reviewThe MPWG members and other international melanoma specialists participated in 2 online surveys and then convened a summit meeting. Published data and meeting abstracts from 2015 to 2019 were reviewed.FindingsThe MPWG members are optimistic about the future use of prognostic GEP testing to improve risk stratification and enhance clinical decision-making but acknowledge that current utility is limited by test performance in patients with stage I disease. Published studies of GEP testing have not evaluated results in the context of all relevant clinicopathologic factors or as predictors of regional nodal metastasis to replace sentinel lymph node biopsy (SLNB). The performance of GEP tests has generally been reported for small groups of patients representing particular tumor stages or in aggregate form, such that stage-specific performance cannot be ascertained, and without survival outcomes compared with data from the American Joint Committee on Cancer 8th edition melanoma staging system international database. There are significant challenges to performing clinical trials incorporating GEP testing with SLNB and adjuvant therapy. The MPWG members favor conducting retrospective studies that evaluate multiple GEP testing platforms on fully annotated archived samples before embarking on costly prospective studies and recommend avoiding routine use of GEP testing to direct patient management until prospective studies support their clinical utility.Conclusions and relevanceMore evidence is needed to support using GEP testing to inform recommendations regarding SLNB, intensity of follow-up or imaging surveillance, and postoperative adjuvant therapy. The MPWG recommends further research to assess the validity and clinical applicability of existing and emerging GEP tests. Decisions on performing GEP testing and patient management based on these results should only be made in the context of discussion of testing limitations with the patient or within a multidisciplinary group.

Standard assessment of immune infiltration of biopsies is not sufficient to accurately predict response to immunotherapy. Here, the authors show that reflectance confocal microscopy can be used to quantify dynamic vasculature and inflammatory features to better predict treatment response in skin cancers.

Sodium-induced potassium (K+) deficiency is more prevalent in salt-affected soils. Plants experience K+ starvation thus cytosolic K+/Na+ ratio is lowered, which is a prerequisite for their survival. K+ enrichment in crops can be acquired via K-solubilizing bacteria as a sustainable green agriculture approach. This study was conducted to explore potent K-solubilizing bacteria from the rhizosphere of wheat, rice, and native flora grown in salt-affected soils in two distinct regions of Pakistan. The aim of this work was to evaluate the contribution of microbial consortiums to the improvement of K+ assimilation and cytosolic K+/Na+ ratios in rice crops under saline-sodic conditions. Among 250 bacterial isolates, 9 were selected based on their salt (11% NaCl) and alkali (9) tolerance and K-solubilization indices (1.57–5.67). These bacterial strains were characterized for their plant growth-promoting traits and identified based on 16S rRNA gene sequencing. A consortium of five strains, namely, Enterobacter hormaechei, Citrobacter braakii, Pseudomonas putida, Erwinia iniecta, and Pantoea agglomerans, was used as a bio-inoculant to evaluate its role in K+ assimilation, cytosolic K+/Na+ ratio, and subsequent yield enhancement in rice grown under saline-sodic conditions. The impact of applied consortium on rice was assessed under variable salt levels (Control, 40, 80, and 120 mM) in a pot experiment and under natural saline-sodic conditions in the field. Plant agronomical parameters were significantly higher in the bacterial consortium-treated plants, with a concomitant increase in K+-uptake in root and shoot (0.56 and 0.35 mg g−1 dry wt.) of the salt-tolerant rice variety Shaheen. The root K+/Na+ ratio was significantly improved (200% in 40 mM and 126% in 80 mM NaCl) and in the shoot (99% in 40 mM and 131% in 80 mM) too. A similar significant increase was also observed in the salt-susceptible variety Kainat. Moreover, grain yield (30.39 g/1,000 grains wt.) and biomass (8.75 g) of the rice variety Shaheen, grown in field conditions, were also improved. It can be concluded that K-solubilizing bacteria can be used as bio-inoculants, contributing to growth and yield increment via enhanced K-assimilation and cytosolic K+/Na+ ratio in rice crops under salt stress.

Introduction: Melanoma of the lentigo maligna (LM) type is challenging. There is lack of consensus on the optimal diagnosis, treatment, and follow-up. Objectives: To obtain general consensus on the diagnosis, treatment, and follow-up for LM. Methods: A modified Delphi method was used. The invited participants were either members of the International Dermoscopy Society, academic experts, or authors of published articles relating to skin cancer and melanoma. Participants were required to respond across three rounds using a 4-point Likert scale). Consensus was defined as >75% of participants agreeing/strongly agreeing or disagreeing/strongly disagreeing. Results: Of the 31 experts invited to participate in this Delphi study, 29 participants completed Round 1 (89.9% response rate), 25/31 completed Round 2 (77.5% response rate), and 25/31 completed Round 3 (77.5% response rate). Experts agreed that LM diagnosis should be based on a clinical and dermatoscopic approach (92%) followed by a biopsy. The most appropriate primary treatment of LM was deemed to be margin-controlled surgery (83.3%), although non-surgical modalities, especially imiquimod, were commonly used either as alternative off-label primary treatment in selected patients or as adjuvant therapy following surgery; 62% participants responded life-long clinical follow-up was needed for LM. Conclusions: Clinical and histological diagnosis of LM is challenging and should be based on macroscopic, dermatoscopic, and RCM examination followed by a biopsy. Different treatment modalities and follow-up should be carefully discussed with the patient.

Adaptations of green technologies to counter abiotic stress, including salinity for crops like wheat by using halotolerant microbes, is a promising approach. The current study investigated 17 salt-affected agroecological zones from the Punjab and Sindh provinces of Pakistan to explore the potential of indigenous microbial flora, with their multiple biochemical characteristics in addition to plant growth promoting (PGP) traits, for enhanced wheat production in saline areas. Initially, 297 isolated pure bacterial colonies were screened for salt tolerance, biochemical, and PGP traits. Three bacterial strains belonging to Pantoea spp. and Erwinia rhaphontici with possession of multiple characteristics were selected for the development of the halotolerant bacterial consortium. Inoculation of two local wheat varieties, Faisalabad 2008 and Galaxy 2013, with the consortium for in vitro seed germination assay and sand microcosm experiments exhibited significant improvement of selected plant growth parameters like germination percentage and root structure. Two previously reported PGP fungal strains of Trichoderma harzianum and T. viridae were also used as fungal consortium separately for pot experiments and field trials. The pot experiments exhibited a positive correlation of consortia with metabolic viz. catalase, peroxidase, and proline and agronomical parameters including shoot length, dry weight, number of spikes, spike length, and 100 grain weight. To evaluate their performance under natural environmental conditions, field trials were conducted at three salt-affected sites. Agronomical attributes including days of flowering and maturity, flag leaf weight, length and width, shoot length, number of spikes, spike length, spike weight, number of seeds spike−1, 1,000 grain weight, and plot yield indicated the efficiency of these microbes to enhance wheat growth. Concisely, the bacterial consortium showed better performance and Faisalabad 2008 was a more resistant variety as compared to Galaxy 2013. Initial promising results indicate that further extensive research on indigenous microbes might lead to the development of Pakistan’s first saline-specific biofertilizers and sustainable eco-friendly agriculture practices.

ObjectiveTo identify risk factors associated with nonmelanoma skin cancer (NMSC) occurrence and survival in children.Study designThis was a multicenter, retrospective, case-control study of patients 12 months prior to diagnosis and 49% of patients were diagnosed with ≥2 skin cancers. At last follow-up, 5% (6 of 124) of patients with NMSC died. Voriconazole exposure was noted in 7 cases and associated with worse 3-year overall survival (P = .001).ConclusionsNMSC in children and young adults is often associated with a predisposing condition or iatrogenic exposure. High-risk patients should be identified early to provide appropriate counseling and management.

Recent progress in the treatment of advanced melanoma has led to unprecedented improvements in overall survival and, as these new melanoma treatments have been developed and deployed in the clinic, much has been learned about the natural history of the disease. Now is the time to apply that knowledge toward the design and clinical evaluation of new chemoprevention agents. Melanoma chemoprevention has the potential to reduce dramatically both the morbidity and the high costs associated with treating patients who have metastatic disease. In this work, scientific and clinical melanoma experts from the national Melanoma Prevention Working Group, composed of National Cancer Trials Network investigators, discuss research aimed at discovering and developing (or repurposing) drugs and natural products for the prevention of melanoma and propose an updated pipeline for translating the most promising agents into the clinic. The mechanism of action, preclinical data, epidemiological evidence, and results from available clinical trials are discussed for each class of compounds. Selected keratinocyte carcinoma chemoprevention studies also are considered, and a rationale for their inclusion is presented. These data are summarized in a table that lists the type and level of evidence available for each class of agents. Also included in the discussion is an assessment of additional research necessary and the likelihood that a given compound may be a suitable candidate for a phase 3 clinical trial within the next 5 years.

Objective: To study the effect of aloe vera extract on glycosylated haemoglobin (HbA1C) and blood glucose levels in albino rats. Study Design: Laboratory-based experimental study. Place and Duration of Study: Army Medical College, Rawalpindi and National Institute of Health, Islamabad Pakistan, from Oct 2018 to Mar 2019. Methodology: Ninety male Sprague Dawley rats, aged 10-12 weeks, weighing 250±50 grams, were divided into three Groups. In Group-A, non-diabetic rats were given a standard lasb diet. In Groups B and C, diabetic rats were given a standard laboratory diet. In Group-C, an extract of Aloe Vera at 300mg/kg body weight was also given once daily. Before the commencement of the experiment, blood glucose was measured, and then after injection, STZ on the fourth-day record of blood glucose was taken. At the end of the experiment, a blood sample was taken from the tail vein to analyze glycosylated haemoglobin levels and blood glucose. Results: The difference in blood glucose levels at the start of the experiment was significant statistically (p-value

Introduction: Among the various widely recognized basal cell carcinoma (BCC) clinical patterns, linear basal cell carcinoma (LBCC) is an uncommon morphologic variant of BCC. Objective: Describe the clinical and dermoscopic characteristics of LBCC. Methods: Retrospective study including LBCC cases from 5 dermatology centers in North and South America. Biopsy-proven primary BCCs, that presented with at least 3:1 length:width ratio on physical examination, irrespective of tumor subtype or location, were included. Clinical and dermoscopic analysis were performed by 2 experts in dermoscopy. Results: Eighteen cases of LBCC met our inclusion criteria and were included in the study. Median age at diagnosis was 86.0 years, 10 patients (58.8%) were males. Regarding anatomic location, 11/18 (61.1%) were located on the head and neck, 5/18 (27.7%) cases were found on the trunk, and 2 on lower extremities (11.1%). Under dermoscopy, 15/18 (83.3%) of LBCC were pigmented. All tumors displayed at least one of the BCC-specific dermoscopic criteria the most common being blue-grey globules (72.2%). Conclusions: Dermoscopy might be useful in the differentiation of LBCC from other diagnoses presenting as linear lesions such as scars, scratches/erosions, and tattoos, among others. Some of these lesions might be confused by naked eye examination alone.

Simple Summary: Patients with skin lesions suspicious for skin cancer or atypical melanocytic nevi of uncertain malignant potential often present to dermatologists, who may have variable dermoscopy triage clinical experience. We evaluated the clinical utility of a digital dermoscopy image-based artificial intelligence algorithm (DDI-AI device) on the diagnosis and management of skin cancers. Thirty-six United States board-certified dermatologists evaluated 50 cases with clinical images and DDI of the same skin lesions (25 malignant and 25 benign), first without and then with knowledge of the DDI-AI device output. We identified that when using the DDI-AI device, management sensitivity, management specificity, diagnostic sensitivity, and diagnostic specificity all increased over baseline use of clinical images and dermoscopy images. Hence, the use of the DDI-AI device may quickly, safely, and effectively improve dermoscopy performance, skin cancer diagnosis, and management when used by dermatologists, independent of training and experience. Background: Patients with skin lesions suspicious for skin cancer or atypical melanocytic nevi of uncertain malignant potential often present to dermatologists, who may have variable dermoscopy triage clinical experience. Objective: To evaluate the clinical utility of a digital dermoscopy image-based artificial intelligence algorithm (DDI-AI device) on the diagnosis and management of skin cancers by dermatologists. Methods: Thirty-six United States board-certified dermatologists evaluated 50 clinical images and 50 digital dermoscopy images of the same skin lesions (25 malignant and 25 benign), first without and then with knowledge of the DDI-AI device output. Participants indicated whether they thought the lesion was likely benign (unremarkable) or malignant (suspicious). Results: The management sensitivity of dermatologists using the DDI-AI device was 91.1%, compared to 84.3% with DDI, and 70.0% with clinical images. The management specificity was 71.0%, compared to 68.4% and 64.9%, respectively. The diagnostic sensitivity of dermatologists using the DDI-AI device was 86.1%, compared to 78.8% with DDI, and 63.4% with clinical images. Diagnostic specificity using the DDI-AI device increased to 80.7%, compared to 75.9% and 73.6%, respectively. Conclusion: The use of the DDI-AI device may quickly, safely, and effectively improve dermoscopy performance, skin cancer diagnosis, and management when used by dermatologists, independent of training and experience. [ABSTRACT FROM AUTHOR]

This research paper seeks to investigate and categorize previous studies to understand better the role of energy generation technology in promoting sustainable development of a country country. The primary aim of this review is to identify and emphasize key issues related to energy sustainability. The study employs a systematic review approach, drawing on academic publications from the Web of Science and Scopus database. The analysis reveals five key issues: the nexus between energy generation and greenhouse gas emissions, energy generation and employment, the impact of energy generation and land use intensity, the association between energy generation and water footprint, and the nexus between energy generation and human health. This study delves into the theoretical dimensions of research concerning the interplay between energy sustainability and various aspects of energy generation technologies. Furthermore, it contributes to the existing body of knowledge concerning Sustainable Development Goal 7, with the overarching goal of enhancing both human well-being and economic prosperity through advancements in energy generation technologies. The study comprehensively explores the subject matter, offering an in-depth analysis of energy sustainability. Its unique contribution lies in its extensive examination of multiple facets of energy sustainability, making it a significant addition to the field of research. [ABSTRACT FROM AUTHOR]

Darchini (Cinnamomum zeylanicum) is a bark of a cinnamon plant that belongs to the Lauraceae family. Cinnamon is a rich tasting and aromatic spice used by different cultures worldwide. Recently, many phytochemicals were discovered and obtained from Darchini. Numerous experimental research using these phytochemical components have established several therapeutic actions. In addition, it possesses useful medicinal properties and is considered a remedy for indigestion, flatulency, depletion of innate heat, respiratory diseases, diabetes, cardiovascular diseases, and neurological disorders. A manual literature search of classical Unani manuscripts was carried out to acquire information on temperament (Mizaj), pharmacological activities and medicinal applications of Darchini. In addition, all accessible material on phytochemical, physiochemical and pharmacological studies have been collected using an extensive review of internet sources such PubMed, Google Scholar and Science Direct. The aim of this review article is to further highlight the discovered pharmacological effect and medicinal values of Cinnamomum zeylanicum as per the Unani literature as well as scientific research. Based on scientific studies regarding its phytochemical components, it is beneficial for various ailments. Darchini also has a beneficial effect on some gynaecological disorders such as amenorrhoea, dysmenorrhoea, leucorrhoea, menorrhagia, prolapse, and vaginosis. However, there is need to conduct experimental and clinical study to validate their effectiveness and safety in humans. [ABSTRACT FROM AUTHOR]

Simple Summary: Early detection of melanoma and differentiation from benign nevi can be challenging even for the most experienced dermatologists. To improve melanoma detection, artificial intelligence algorithms incorporating dermoscopy have been developed, but lack transparency and therefore have limited training value for healthcare providers. To address this, an automated approach utilizing imaging biomarker cues (IBCs), logical features extracted from images that mimic expert dermatologists' dermoscopic pattern recognition skills, was developed. This study excluded deep learning approaches to which IBCs are complementary or alternative. Ten participants assessed 78 dermoscopic images (39 melanomas and 39 nevi) first without IBCs and then with IBCs. Using IBCs significantly improved diagnostic accuracy: sensitivity increased significantly from 73.69% to 81.57% (p = 0.0051) and specificity increased from 60.50% to 67.25% (p = 0.059). These results indicate that incorporating IBCs can significantly enhance melanoma diagnosis, with potential implications for improved screening practices. Further research is needed to confirm these findings across a variety of healthcare providers. Incorporation of dermoscopy and artificial intelligence (AI) is improving healthcare professionals' ability to diagnose melanoma earlier, but these algorithms often suffer from a "black box" issue, where decision-making processes are not transparent, limiting their utility for training healthcare providers. To address this, an automated approach for generating melanoma imaging biomarker cues (IBCs), which mimics the screening cues used by expert dermoscopists, was developed. This study created a one-minute learning environment where dermatologists adopted a sensory cue integration algorithm to combine a single IBC with a risk score built on many IBCs, then immediately tested their performance in differentiating melanoma from benign nevi. Ten participants evaluated 78 dermoscopic images, comprised of 39 melanomas and 39 nevi, first without IBCs and then with IBCs. Participants classified each image as melanoma or nevus in both experimental conditions, enabling direct comparative analysis through paired data. With IBCs, average sensitivity improved significantly from 73.69% to 81.57% (p = 0.0051), and the average specificity improved from 60.50% to 67.25% (p = 0.059) for the diagnosis of melanoma. The index of discriminability (d′) increased significantly by 0.47 (p = 0.002). Therefore, the incorporation of IBCs can significantly improve physicians' sensitivity in melanoma diagnosis. While more research is needed to validate this approach across other healthcare providers, its use may positively impact melanoma screening practices. [ABSTRACT FROM AUTHOR]

Abstract Background Reproducible detection of inherited variants with whole genome sequencing (WGS) is vital for the implementation of precision medicine and is a complicated process in which each step affects variant call quality. Systematically assessing reproducibility of inherited variants with WGS and impact of each step in the process is needed for understanding and improving quality of inherited variants from WGS. Results To dissect the impact of factors involved in detection of inherited variants with WGS, we sequence triplicates of eight DNA samples representing two populations on three short-read sequencing platforms using three library kits in six labs and call variants with 56 combinations of aligners and callers. We find that bioinformatics pipelines (callers and aligners) have a larger impact on variant reproducibility than WGS platform or library preparation. Single-nucleotide variants (SNVs), particularly outside difficult-to-map regions, are more reproducible than small insertions and deletions (indels), which are least reproducible when > 5 bp. Increasing sequencing coverage improves indel reproducibility but has limited impact on SNVs above 30×. Conclusions Our findings highlight sources of variability in variant detection and the need for improvement of bioinformatics pipelines in the era of precision medicine with WGS.

Abstract Background Accurate detection of somatic mutations is challenging but critical in understanding cancer formation, progression, and treatment. We recently proposed NeuSomatic, the first deep convolutional neural network-based somatic mutation detection approach, and demonstrated performance advantages on in silico data. Results In this study, we use the first comprehensive and well-characterized somatic reference data sets from the SEQC2 consortium to investigate best practices for using a deep learning framework in cancer mutation detection. Using the high-confidence somatic mutations established for a cancer cell line by the consortium, we identify the best strategy for building robust models on multiple data sets derived from samples representing real scenarios, for example, a model trained on a combination of real and spike-in mutations had the highest average performance. Conclusions The strategy identified in our study achieved high robustness across multiple sequencing technologies for fresh and FFPE DNA input, varying tumor/normal purities, and different coverages, with significant superiority over conventional detection approaches in general, as well as in challenging situations such as low coverage, low variant allele frequency, DNA damage, and difficult genomic regions

Extrachromosomal circular DNA (eccDNA) of chromosomal origin is common in eukaryotic cells. Amplification of oncogenes on large eccDNA (ecDNA) can drive biological processes such as tumorigenesis, and identification of eccDNA by sequencing after removal of chromosomal DNA is therefore important for understanding their impact on the expressed phenotype. However, the circular mitochondrial DNA (mtDNA) might challenge the detection of eccDNA because the average somatic cell has hundreds of copies of mtDNA. Here we show that 61.2–99.5% of reads from eccDNA-enriched samples correspond to mtDNA in mouse tissues. We have developed a method to selectively remove mtDNA from total circular DNA by CRISPR/Cas9 guided cleavage of mtDNA with one single-guide RNA (sgRNA) or two sgRNAs followed by exonuclease degradation of the linearized mtDNA. Sequencing revealed that mtDNA reads were 85.9% ± 12.6% removed from eccDNA of 9 investigated mouse tissues. CRISPR/Cas9 cleavage also efficiently removed mtDNA from a human HeLa cell line and colorectal cancer samples. We identified up to 14 times more, and also larger eccDNA in CRISPR/Cas9 treated colorectal cancer samples than in untreated samples. We foresee that the method can be applied to effectively remove mtDNA from any eukaryotic species to obtain higher eccDNA yields.

BackgroundDermoscopy is commonly used for the evaluation of pigmented lesions, but agreement between experts for identification of dermoscopic structures is known to be relatively poor. Expert labeling of medical data is a bottleneck in the development of machine learning (ML) tools, and crowdsourcing has been demonstrated as a cost- and time-efficient method for the annotation of medical images. ObjectiveThe aim of this study is to demonstrate that crowdsourcing can be used to label basic dermoscopic structures from images of pigmented lesions with similar reliability to a group of experts. MethodsFirst, we obtained labels of 248 images of melanocytic lesions with 31 dermoscopic “subfeatures” labeled by 20 dermoscopy experts. These were then collapsed into 6 dermoscopic “superfeatures” based on structural similarity, due to low interrater reliability (IRR): dots, globules, lines, network structures, regression structures, and vessels. These images were then used as the gold standard for the crowd study. The commercial platform DiagnosUs was used to obtain annotations from a nonexpert crowd for the presence or absence of the 6 superfeatures in each of the 248 images. We replicated this methodology with a group of 7 dermatologists to allow direct comparison with the nonexpert crowd. The Cohen κ value was used to measure agreement across raters. ResultsIn total, we obtained 139,731 ratings of the 6 dermoscopic superfeatures from the crowd. There was relatively lower agreement for the identification of dots and globules (the median κ values were 0.526 and 0.395, respectively), whereas network structures and vessels showed the highest agreement (the median κ values were 0.581 and 0.798, respectively). This pattern was also seen among the expert raters, who had median κ values of 0.483 and 0.517 for dots and globules, respectively, and 0.758 and 0.790 for network structures and vessels. The median κ values between nonexperts and thresholded average–expert readers were 0.709 for dots, 0.719 for globules, 0.714 for lines, 0.838 for network structures, 0.818 for regression structures, and 0.728 for vessels. ConclusionsThis study confirmed that IRR for different dermoscopic features varied among a group of experts; a similar pattern was observed in a nonexpert crowd. There was good or excellent agreement for each of the 6 superfeatures between the crowd and the experts, highlighting the similar reliability of the crowd for labeling dermoscopic images. This confirms the feasibility and dependability of using crowdsourcing as a scalable solution to annotate large sets of dermoscopic images, with several potential clinical and educational applications, including the development of novel, explainable ML tools.

Introduction: A wide range of descriptive terms have been used for dermoscopic findings in intraepidermal carcinoma (IEC) and the clinical diagnostic accuracy of IEC can be challenging. Furthermore, dermoscopic findings in IEC have only rarely been evaluated in fair-skinned populations. Objectives: To measure the interobserver agreement between dermatologists for dermoscopic findings in IEC. Furthermore, to describe the frequency of these findings in a predominantly fair-skinned population. Methods: One hundred dermoscopic images of histopathologically verified IECs were collected. The 11 most common dermoscopic findings described in previous studies were re-defined in a new terminology in a pre-study consensus meeting. Images were assessed by eight experienced international dermoscopists. The frequency of findings and the interobserver agreement was analyzed. Results: Scales (83%), dotted/glomerular vessels (77%), pinkish-white areas (73%) and hemorrhage (46%) were the most commonly present dermoscopic findings. Pigmented structures were found in 32% and shiny white structures (follicular or stromal) in 54% of the IEC. Vascular structures (vessels and/or hemorrhage) could be seen in 89% of the lesions. Overall, the interobserver agreement for the respective dermoscopic findings was poor to moderate, with the highest kappa values noted for scales (0.55) and hemorrhage (0.54) and the lowest for pinkish-white areas (0.015). Conclusion: Our results confirm those of previous studies on dermoscopy in IEC, including the frequency of pigmented structures despite the fair-skinned population. The interobserver agreement was relatively low. The proposed new terminology and our findings can hopefully serve as a guideline for researchers, teachers and students on how to identify IEC.

Abstract Background Genomic structural variations (SV) are important determinants of genotypic and phenotypic changes in many organisms. However, the detection of SV from next-generation sequencing data remains challenging. Results In this study, DNA from a Chinese family quartet is sequenced at three different sequencing centers in triplicate. A total of 288 derivative data sets are generated utilizing different analysis pipelines and compared to identify sources of analytical variability. Mapping methods provide the major contribution to variability, followed by sequencing centers and replicates. Interestingly, SV supported by only one center or replicate often represent true positives with 47.02% and 45.44% overlapping the long-read SV call set, respectively. This is consistent with an overall higher false negative rate for SV calling in centers and replicates compared to mappers (15.72%). Finally, we observe that the SV calling variability also persists in a genotyping approach, indicating the impact of the underlying sequencing and preparation approaches. Conclusions This study provides the first detailed insights into the sources of variability in SV identification from next-generation sequencing and highlights remaining challenges in SV calling for large cohorts. We further give recommendations on how to reduce SV calling variability and the choice of alignment methodology.

Abstract Conventional tissue sampling can lead to misdiagnoses and repeated biopsies. Additionally, tissue processed for histopathology suffers from poor nucleic acid quality and/or quantity for downstream molecular profiling. Targeted micro-sampling of tissue can ensure accurate diagnosis and molecular profiling in the presence of spatial heterogeneity, especially in tumors, and facilitate acquisition of fresh tissue for molecular analysis. In this study, we explored the feasibility of performing 1–2 mm precision biopsies guided by high-resolution reflectance confocal microscopy (RCM) and optical coherence tomography (OCT), and reflective metallic grids for accurate spatial targeting. Accurate sampling was confirmed with either histopathology or molecular profiling through next generation sequencing (NGS) in 9 skin cancers in 7 patients. Imaging-guided 1–2 mm biopsies enabled spatial targeting for in vivo diagnosis, feature correlation and depth assessment, which were confirmed with histopathology. In vivo 1-mm targeted biopsies achieved adequate quantity and high quality of DNA for next-generation sequencing. Subsequent mutational profiling was confirmed on 1 melanoma in situ and 2 invasive melanomas, using a 505-gene mutational panel called Memorial Sloan Kettering-Integrated mutational profiling of actionable cancer targets (MSK-IMPACT). Differential mutational landscapes, in terms of number and types of mutations, were found between invasive and in situ melanomas in a single patient. Our findings demonstrate feasibility of accurate sampling of regions of interest for downstream histopathological diagnoses and molecular pathology in both in vivo and ex vivo settings with broad diagnostic, therapeutic and research potential in cutaneous diseases accessible by RCM-OCT imaging.

Soil salinization and heavy metal (HM) contamination are major challenges facing agricultural systems worldwide. Determining how soil microbial communities respond to these stress factors and identifying individual phylotypes with potential to tolerate these conditions while promoting plant growth could help prevent negative impacts on crop productivity. This study used amplicon sequencing and several bioinformatic programs to characterize differences in the composition and potential functional capabilities of soil bacterial, fungal, and archaeal communities in five agricultural fields that varied in salinity and HM concentrations within the Indus basin region of Pakistan. The composition of bacteria with the potential to fix atmospheric nitrogen (N) and produce the enzyme 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase were also determined. Microbial communities were dominated by: Euryarchaeota (archaea), Actinobacteria, Proteobacteria, Planctomycetota, Firimicutes, Patescibacteria and Acidobacteria (bacteria), and Ascomycota (fungi), and all soils contained phylotypes capable of N-fixation and ACC-deaminase production. Salinity influenced bacterial, but not archaeal or fungal communities. Both salinity and HM altered the relative abundance of many phylotypes that could potentially promote or harm plant growth. These stress factors also appeared to influence the potential functional capabilities of the microbial communities, especially in their capacity to cycle phosphorous, produce siderophores, and act as symbiotrophs or pathotrophs. Results of this study confirm that farms in this region are at risk due to salinization and excessive levels of some toxic heavy metals, which could negatively impact crop and human health. Changes in soil microbial communities and their potential functional capabilities are also likely to affect several critical agroecosystem services related to nutrient cycling, pathogen suppression, and plant stress tolerance. Many potentially beneficial phylotypes were identified that appear to be salt and HM tolerant and could possibly be exploited to promote these services within this agroecosystem. Future efforts to isolate these phylotypes and determine whether they can indeed promote plant growth and/or carry out other important soil processes are recommended. At the same time, identifying ways to promote the abundance of these unique phylotypes either through modifying soil and crop management practices, or developing and applying them as inoculants, would be helpful for improving crop productivity in this region.

Introduction: In patients with multiple nevi, sequential imaging using total body skin photography (TBSP) coupled with digital dermoscopy (DD) documentation reduces unnecessary excisions and improves the early detection of melanoma. Correct patient selection is essential for optimizing the efficacy of this diagnostic approach. Objectives: The purpose of the study was to identify, via expert consensus, the best indications for TBSP and DD follow-up. Methods: This study was performed on behalf of the International Dermoscopy Society (IDS). We attained consensus by using an e-Delphi methodology. The panel of participants included international experts in dermoscopy. In each Delphi round, experts were asked to select from a list of indications for TBSP and DD. Results: Expert consensus was attained after 3 rounds of Delphi. Participants considered a total nevus count of 60 or more nevi or the presence of a CDKN2A mutation sufficient to refer the patient for digital monitoring. Patients with more than 40 nevi were only considered an indication in case of personal history of melanoma or red hair and/or a MC1R mutation or history of organ transplantation. Conclusions: Our recommendations support clinicians in choosing appropriate follow-up regimens for patients with multiple nevi and in applying the time-consuming procedure of sequential imaging more efficiently. Further studies and real-life data are needed to confirm the usefulness of this list of indications in clinical practice.

Introduction: In image interpretation education, many educators have shifted away from traditional methods that involve passive instruction and fragmented learning to interactive ones that promote active engagement and integrated knowledge. By training pattern recognition skills in an effective manner, these interactive approaches provide a promising direction for dermoscopy education. Objectives: A narrative review of the literature was performed to probe emerging directions in medical image interpretation education that may support dermoscopy education. This article represents the second of a two-part review series. Methods: To promote innovation in dermoscopy education, the International Skin Imaging Collaboration (ISIC) assembled an Education Working Group that comprises international dermoscopy experts and educational scientists. Based on a preliminary literature review and their experiences as educators, the group developed and refined a list of innovative approaches through multiple rounds of discussion and feedback. For each approach, literature searches were performed for relevant articles. Results: Through a consensus-based approach, the group identified a number of theory-based approaches, as discussed in the first part of this series. The group also acknowledged the role of motivation, metacognition, and early failures in optimizing the learning process. Other promising teaching tools included gamification, social media, and perceptual and adaptive learning modules (PALMs). Conclusions: Over the years, many dermoscopy educators may have intuitively adopted these instructional strategies in response to learner feedback, personal observations, and changes in the learning environment. For dermoscopy training, PALMs may be especially valuable in that they provide immediate feedback and adapt the training schedule to the individual’s performance.