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Chemical modification of RNAs is important for posttranscriptional gene regulation. The METTL3-METTL14 complex generates most N6-methyladenosine (m6A) modifications in messenger RNAs (mRNAs), and dysregulated methyltransferase expression has been linked to cancers. Here we show that a changed sequence context for m6A can promote oncogenesis. A gain-of-function missense mutation from patients with cancer, METTL14R298P, increases malignant cell growth in culture and transgenic mice without increasing global m6A levels in mRNAs. The mutant methyltransferase preferentially modifies noncanonical sites containing a GGAU motif, in vitro and in vivo. The m6A in GGAU context is detected by the YTH family of readers similarly to the canonical sites but is demethylated less efficiently by an eraser, ALKBH5. Combining the biochemical and structural data, we provide a model for how the cognate RNA sequences are selected for methylation by METTL3-METTL14. Our work highlights that sequence-specific m6A deposition is important and that increased GGAU methylation can promote oncogenesis.

Objective: To assess the tolerability and efficacy of endoscopic sphenopalatine artery cauterization (ESPAC) under local anesthesia (LA) in managing posterior epistaxis. Methods: It was a prospective, cohort study, conducted in the Otorhinolaryngology Department of a tertiary-level hospital. Patients aged 18 years or above with posterior epistaxis who underwent ESPAC under LA were included. The tolerability of the procedure was reflected by the intraoperative pain measured using an 11-point numerical rating scale while the rebleed rate up to three months postoperatively denoted its efficacy. Results: A total of 35 patients, 23 males and 12 females, aged 31 to 86 years (mean 57.42 ± 12.94) were included. Five out of 35 (14.2%) patients needed additional procedures besides ESPAC; 82.8% (29/35) had pterygopalatine fossa (PPF) block before ESPAC. The numerical rating scale reflecting the intraoperative pain ranged from 1 to 7 with a mean of 3.6 (± 1.7). The mean score was slightly higher in females than in males. Similarly, those who did not receive PPF block had a higher mean score than those who received it; however, the differences were not statistically significant. Meanwhile, the mean score was the same (3.6) irrespective of any additional procedure besides ESPAC. Amongst the 30 patients who completed the three-month follow-up, two patients rebled, so the overall success rate amounted to 93.3% in three months. Conclusion: Based on the outcome of this study, ESPAC under LA for posterior epistaxis is well tolerated and is as efficacious as under general anesthesia.

ABSTRACTTyphoid fever is a significant public health concern with most of the sufferers between 15 and 25 y of age in Nepal. We undertook this study to demonstrate Vi polysaccharide conjugated with diphtheria toxoid (Vi-DT) conjugate vaccine which is non-inferior to Typbar typhoid conjugate vaccine, a Vi polysaccharide vaccine conjugated with tetanus toxoid (Vi-TT) with a focus on the adult population from Dhulikhel Hospital which was one of the total four sites in Nepal. In this study, we assigned the eligible participants in 1:1:1:1 ratio by block randomization, and stratified into three age groups (6 months to less than 2 y, 2 y to less than 18 y, and 18 y to 45 y), allotted to Group A, B, C, and D. Group A, B, and C received 25 μg (0.5 mL) of Vi-DT study vaccine and participants in Group D received 25 μg (0.5 mL) Vi-TT vaccine. We descriptively analyzed safety in all the participants receiving one dose of the investigational vaccine. The anti-Vi-IgG seroconversion rate in Vi-DT recipients was 99.71% (97.5% CI 98.04–99.96; 344 of 345 participants) and 99.13% (94.27–99.87; 114 of 115) in Vi-TT recipients which indicates that Vi-DT vaccine is non-inferior to Vi-TT vaccine. In safety aspect, 16.81% of total subject had at least one solicited adverse reaction and 22.61% of the Vi-TT participants experienced at least one solicited adverse reaction with most of them being local adverse reactions. None of the enrolled participants reported serious adverse events. Our study shows that a single dose of the Vi-DT vaccine is immunogenic, safe to administer and non-inferior to the Vi-TT vaccine four weeks after vaccination.

Erythema Multiforme Major (EMM) is a rare hypersensitivity reaction that primarily affects the skin and mucosa, typically self-limiting. This case discusses a patient who developed severe EMM lesions after consuming nimesulide, a non-steroidal anti-inflammatory drug (NSAID), for abdominal discomfort. Patient was admitted to the hospital, the drug was discontinued, and supportive measures such as pain management and fluid replacement were initiated. This case, being the first to identify nimesulide as a possible trigger for EMM, aims to contribute to the growing body of knowledge on this topic. It emphasizes the need for vigilance and swift intervention for unusual drug reactions.

Genetic transformation of many plant species relies on in vitro tissue culture-based approaches. This can be a labor-intensive process, requiring aseptic conditions and regenerating often recalcitrant species from tissue culture. Here, we have optimized an in planta transformation protocol to rapidly transform commercial citrus cultivars, bypassing the need for tissue culture. As a proof of concept, we used in planta transformation to introduce CRISPR/Cas9 constructs into Limoneira 8A Lisbon lemon and Pineapple sweet orange, cultivars that are challenging to transform with conventional techniques. Using our optimized protocol, the regeneration rate was significantly increased from 4.8% to over 95%, resulting in multiple gene-edited lines in lemon. We also successfully recovered gene-edited Pineapple sweet orange lines using this protocol; the transformation efficiency for these cultivars ranged between 0.63% and 4.17%. Remarkably, these lines were obtained within three months, making this in planta protocol a rapid methodology to obtain transformed citrus plants. This approach can rapidly and effectively introduce key genetic changes into a wide variety of citrus cultivars.

Uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a rare uterine neoplasm of uncertain histogenesis, with presence of ovarian sex cord-like elements. These tumours typically occur in perimenopausal and postmenopausal women, and are considered to behave in an indolent fashion in most of the cases. However, recurrences and metastases have also been reported. We report a case of a 37 year old female who presented with lower abdominal pain and abnormal uterine bleeding, and underwent hysterectomy following a clinical and radiological suspicion of a submucosal uterine fibroid. Macroscopically the tumor resembled a Leiomyoma. However, the diagnosis of UTROSCT was made after histopathological examination and immunohistochemical studies. Clinicians and pathologists need to be aware of this diagnosis, given the rarity of this condition and potential aggressive clinical course.

Gallbladder neuroendocrine carcinoma is a rare neoplasm thought to arise in the background of chronic inflammation triggered by cholelithiasis. The symptoms of this tumor overlap with those of cholecystitis and other carcinomas of the gall bladder. The imaging findings with fine needle aspiration cytology help in the pre-operative diagnosis. However, the gold standard for diagnosis is histopathology evaluation with immunohistochemistry. We report a case of a 76-year female who was clinically diagnosed with acute calculus cholelithiasis and underwent surgery. The histopathology and immunohistochemistry of the gallbladder revealed neuroendocrine carcinoma.

Yellow rust, caused by Puccinia striiformis f. sp. tritici (Pst), is a devastating fungal disease threatening much of global wheat production. Race-specific resistance (R)-genes are used to control rust diseases, but the rapid emergence of virulent Pst races has prompted the search for a more durable resistance. Here, we report the cloning of Yr15, a broad-spectrum R-gene derived from wild emmer wheat, which encodes a putative kinase-pseudokinase protein, designated as wheat tandem kinase 1, comprising a unique R-gene structure in wheat. The existence of a similar gene architecture in 92 putative proteins across the plant kingdom, including the barley RPG1 and a candidate for Ug8, suggests that they are members of a distinct family of plant proteins, termed here tandem kinase-pseudokinases (TKPs). The presence of kinase-pseudokinase structure in both plant TKPs and the animal Janus kinases sheds light on the molecular evolution of immune responses across these two kingdoms.

Mitochondrial dysfunction is a hallmark of cancer cachexia (CC). Mitochondrial reactive oxygen species (ROS) are elevated in muscle shortly after tumor onset. Targeting mitochondrial ROS may be a viable option to prevent CC. The aim of this study was to evaluate the efficacy of a mitochondria-targeted antioxidant, SkQ1, to mitigate CC in both biological sexes. Male and female Balb/c mice were injected bilaterally with colon 26 adenocarcinoma (C26) cells (total 1 × 106 cells) or PBS (equal volume control). SkQ1 was dissolved in drinking water (∼250 nmol/kg body wt/day) and administered to mice beginning 7 days following tumor induction, whereas control groups consumed normal drinking water. In vivo muscle contractility of dorsiflexors, deuterium oxide-based protein synthesis, mitochondrial respiration and mRNA content of mitochondrial, protein turnover, and calcium channel-related markers were assessed at endpoint (25 days following tumor induction). Two-way ANOVAs, followed by Tukey's post hoc test when interactions were significant (P ≤ 0.05), were performed. SkQ1 attenuated cancer-induced atrophy, promoted protein synthesis, and abated Redd1 and Atrogin induction in gastrocnemius of C26 male mice. In female mice, SkQ1 decreased muscle mass and increased catabolic signaling in the plantaris of tumor-bearing mice, as well as reduced mitochondrial oxygen consumption, regardless of tumor. However, in females, SkQ1 enhanced muscle contractility of the dorsiflexors with concurrent induction of Ryr1, Serca1, and Serca2a in TA. In conclusion, the mitochondria-targeted antioxidant SkQ1 may attenuate CC-induced muscle loss in males, while improving muscle contractile function in tumor-bearing female mice, suggesting sexual dimorphism in the effects of this mitochondrial therapy in CC. NEW & NOTEWORTHY: Herein, we assess the efficacy of the mitochondria-targeted antioxidant SkQ1 to mitigate cancer cachexia (CC) in both biological sexes. We demonstrate that SkQ1 administration attenuates muscle wasting induced by C26 tumors in male, but not female, mice. Conversely, we identify that in females, SkQ1 improves muscle contractility. These phenotypic adaptations to SkQ1 are aligned with respective responses in muscle protein synthesis, mitochondrial respiration, and mRNA content of protein turnover, as well as mitochondrial and calcium handling-related markers. [ABSTRACT FROM AUTHOR]

Objective: To assess the tolerability and efficacy of endoscopic sphenopalatine artery cauterization (ESPAC) under local anesthesia (LA) in managing posterior epistaxis. Methods: It was a prospective, cohort study, conducted in the Otorhinolaryngology Department of a tertiary-level hospital. Patients aged 18 years or above with posterior epistaxis who underwent ESPAC under LA were included. The tolerability of the procedure was reflected by the intraoperative pain measured using an 11-point numerical rating scale while the rebleed rate up to three months postoperatively denoted its efficacy. Results: A total of 35 patients, 23 males and 12 females, aged 31 to 86 years (mean 57.42 ± 12.94) were included. Five out of 35 (14.2%) patients needed additional procedures besides ESPAC; 82.8% (29/35) had pterygopalatine fossa (PPF) block before ESPAC. The numerical rating scale reflecting the intraoperative pain ranged from 1 to 7 with a mean of 3.6 (± 1.7). The mean score was slightly higher in females than in males. Similarly, those who did not receive PPF block had a higher mean score than those who received it; however, the differences were not statistically significant. Meanwhile, the mean score was the same (3.6) irrespective of any additional procedure besides ESPAC. Amongst the 30 patients who completed the three-month follow-up, two patients rebled, so the overall success rate amounted to 93.3% in three months. Conclusion: Based on the outcome of this study, ESPAC under LA for posterior epistaxis is well tolerated and is as efficacious as under general anesthesia. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study is to evaluate the outcomes of tubeless mini- percutaneous nephrolithotomy (PCNL) for the treatment of large (>20 mm) renal stones. Patients and Methods: This study included consecutive patients who underwent single-session tubeless mini-PCNL (tract size 16–20 F) for large (>20 mm) renal stones. Stone-free status meant complete clearance or residual fragments 20 mm). Stones located in multiple sites is the only predictor of significant residual stones.

Caneberry crops (raspberry and blackberry) are globally commercialized specialty crops with a high fresh market value. Field management of canes and harvesting of fruits can be complicated by the presence of prickles (the botanically accurate term rather than spines or thorns) on the stems, petioles, and underside of the leaves. Both field management and fruit harvesting could be simplified by the development of cultivars with prickle-free canes. Scanning electron microscopy (SEM) was used to analyze and compare prickle development in different Rubus species. Comparisons were made between prickled vs. prickle-free red raspberry (Rubus idaeus L.), black raspberry (Rubus occidentalis L.), blackberry (Rubus hybrid), complex hybrid with purple fruit (R. occidentalis × R. idaeus), and the hairy and prickled wineberry (Rubus phoenicolasius Maxim). Samples from stems and leaves with petioles attached were used for imaging. There were distinct differences between prickled vs. prickle-free phenotypes in each species. The images of prickle development suggest that prickles either develop directly from glandular trichomes (in red raspberry and wineberry) or that the signal originates from glandular trichomes (in blackberry). Black raspberry prickle development was similar to that of blackberry, suggesting that prickles developed after a developmental signal from glandular trichomes rather than as a direct development from glandular trichomes. The prickle development in the purple hybrid was unique in the presence of one-sided lumps in the trichomes, which has not been seen in any other Rubus species to date; however, both prickled and prickle-free plants exhibited simple nonglandular trichomes. Unlike previous studies, an increase in the number of simple trichomes was not specific to prickle-free plants, but rather variability among the different genotypes was observed. This study adds to the basic understanding of prickle development in the genus Rubus as a first step in the development of prickle-free versions of important cultivars through gene-editing procedures for improving the ease of field management and harvesting.

Genetic transformation of many plant species relies on in vitro tissue culturebased approaches. This can be a labor-intensive process, requiring aseptic conditions and regenerating often recalcitrant species from tissue culture. Here, we have optimized an in planta transformation protocol to rapidly transform commercial citrus cultivars, bypassing the need for tissue culture. As a proof of concept, we used in planta transformation to introduce CRISPR/Cas9 constructs into Limoneira 8A Lisbon lemon and Pineapple sweet orange, cultivars that are challenging to transform with conventional techniques. Using our optimized protocol, the regeneration rate was significantly increased from 4.8% to over 95%, resulting in multiple gene-edited lines in lemon. We also successfully recovered gene-edited Pineapple sweet orange lines using this protocol; the transformation efficiency for these cultivars ranged between 0.63% and 4.17%. Remarkably, these lines were obtained within three months, making this in planta protocol a rapid methodology to obtain transformed citrus plants. This approach can rapidly and effectively introduce key genetic changes into a wide variety of citrus cultivars. [ABSTRACT FROM AUTHOR]

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The unpredictable nature of cryptocurrency markets, particularly Bitcoin, has attracted significant attention from investors, researchers, and financial institutions seeking to understand and predict price movements. This study aims to analyse the effectiveness of both transparent and opaque machine learning algorithms in predicting Bitcoin prices. Transparent algorithms, such as linear regression and decision trees, provide clear insights into the factors influencing predictions. On the other hand, opaque algorithms, like ensemble methods, offer complex, non-linear models that may capture intricate patterns in the data. The main analysis is to lower the mean absolute error and enhance the r2 square, both key indicators of forecast accuracy. The study presents that linear regression and random forest outperformed others, achieving the smallest error and highest variance explanation, suggesting their effectiveness in Bitcoin price prediction with and without outliers respectively. In contrast, the support vector machine underperforms compared to all other machine learning algorithms under consideration. This paper sheds light on the most capable machine-learning techniques for Bitcoin forecasting, aiding trader investment choices and guiding academic study in the field of prediction. [ABSTRACT FROM AUTHOR]

Morphological information on fine particles is essential for understanding their transport behavior in the ambient atmosphere and in the human respiratory system. More than 3000 transmission electron microscopy (TEM) images of fine particles were collected from ambient atmosphere and directly from various sources, such as diesel and gasoline engine exhaust, biomass burning, coal combustion, and road dust, and were then morphologically categorized into four major classes (spherical, agglomerate, polygonal, and dendrite). Pre-trained convolutional neural network (CNN) models (DenseNet169, InceptionV3, MobileNetV3Small, ResNet50, and VGG16) and traditional machine learning models (decision trees, random forests, and support vector machines) were trained using the classified particles. The fine-tuned CNN model (DenseNet169) having the deepest feature learning exhibited the best performance among the tested models, with an overall classification accuracy of 89% and an average per-class accuracy ranging from 84% to 97%. The reliable classification of thousands of images was performed within several minutes. The agglomerated class was the least misclassified because of its significantly different features from those of the other classes. The critical regions of the particles for classification decisions varied among the pre-trained models. Our results suggest that the pre-trained CNN models would be useful for the rapid morphological classification of a large number of fine particles. Copyright © 2024 American Association for Aerosol Research [ABSTRACT FROM AUTHOR]

Introduction: Foreign body is any object in a region it is not meant to be, where it can cause harm if immediate medical attention is not sought. Its removal by surgical procedure is one of the commonest surgeries done. The objective is to find out prevalence of the patients who underwent operation for foreign bodies obstruction in food passage in the Department of Otorhinolaryngology-Head and Neck Surgery in a tertiary care centre. Methods: A descriptive cross-sectional study conducted among patients operated in the Department of Otorhinolaryngology and Head and Neck Surgery of a tertiary care center from August 2014 to May 2017. Ethical approval was received from the Institutional Review Committee of the Institute. Convenience sampling method was used. Statistical Package for the Social Sciences was used for analysis. Point estimate at 95% Confidence Interval was calculated along with frequency and proportion for binary data. Results: Out of total 700 patients having operation in department, 115 (16.42%) (95% Confidence Interval = 13.67–19.16) had operation for foreign body obstruction in the food passage. Among 115 patients, 62 (53.90%) were males and 53 (46.10%) were females. Most common foreign bodies ingested in children was coin 17 (14.78%) and bone chips 40 (34.78%) in adults. Cricopharynx 90 (78.26%) is the commonest site for foreign body lodgement. Conclusions: Prevalence of the patients who underwent operation for foreign bodies obstruction in food passage in a tertiary care hospital is high. Their removal by rigid oesophagoscopy is one of the commonest surgical procedures done in tertiary care center.