Discovery of natural-product-derived sequanamycins as potent oral anti-tuberculosis agents.

The emergence of drug-resistant tuberculosis has created an urgent need for new anti-tubercular agents. Here, we report the discovery of a series of macrolides called sequanamycins with outstanding in vitro and in vivo activity against Mycobacterium tuberculosis (Mtb). Sequanamycins are bacterial ribosome inhibitors that interact with the ribosome in a similar manner to classic macrolides like erythromycin and clarithromycin, but with binding characteristics that allow them to overcome the inherent macrolide resistance of Mtb. Structures of the ribosome with bound inhibitors were used to optimize sequanamycin to produce the advanced lead compound SEQ-9. SEQ-9 was efficacious in mouse models of acute and chronic TB as a single agent, and it demonstrated bactericidal activity in a murine TB infection model in combination with other TB drugs. These results support further investigation of this series as TB clinical candidates, with the potential for use in new regimens against drug-susceptible and drug-resistant TB.

Impact of specific electromagnetic radiation on wakefulness in mice.

Electromagnetic radiation (EMR) in the environment, particularly in the microwave range, may constitute a public health concern. Exposure to 2.4 GHz EMR modulated by 100 Hz square pulses was recently reported to markedly increase wakefulness in mice. Here, we demonstrate that a similar wakefulness increase can be induced by the modulation frequency of 1,000 Hz, but not 10 Hz. In contrast to the carrier frequency of 2.4 GHz, 935 MHz EMR of the same power density has little impact on wakefulness irrespective of modulation frequency. Notably, the replacement of the 100 Hz square-pulsed modulation by sinusoidal-pulsed modulation of 2.4 GHz EMR still allows a marked increase of wakefulness. In contrast, continuous sinusoidal amplitude modulation of 100 Hz with the same time-averaged power output fails to trigger any detectable change of wakefulness. Therefore, alteration of sleep behavior by EMR depends upon not just carrier frequency but also frequency and mode of the modulation. These results implicate biological sensing mechanisms for specific EMR in animals.

Deciphering the clinical spectrum of gastric disease in patients with Juvenile Polyposis Syndrome.

BACKGROUND AND AIMS: Juvenile Polyposis Syndrome (JPS) is a rare hereditary autosomal dominant cancer-predisposition syndrome caused by germline pathogenic variants (PV) located in SMAD4 or BMPR1A genes. Precise clinical and endoscopic presentation as the evolution of gastric lesions remain ill-known. METHODS: Clinical, endoscopic, genetic, pathological data from patients with SMAD4 or BMPR1A PVs included between 2007 and 2020 in the French network on rare digestive polyposis (RENAPOL) database were prospectively collected to address uncertainties regarding gastric involvement. RESULTS: Thirty-six patients were included: 25 (69.5%) had SMAD4 PVs, 11 had BMPR1A PVs. For SMAD4 PV carriers, median age at inclusion was 43.0 years [range 10-78]. At baseline esophagogastroduodenoscopy (EGD), 22/25 (88%) exhibited at least one gastric juvenile polyp, 5/25 (20%) had macroscopic signs of inflammatory gastritis. Early gastric disease was mostly located under the cardia, then progressed to gastric antrum and body. During a mean follow-up period of 55.0 months, 12/25 had gastric disease progression (i.e. new juvenile polyps (91.6%), diffuse gastric involvement (41.6%), inflammatory flat progression (25%)). Among 62 biopsies, low-grade dysplasia was observed in 5 (7.5%) samples from 2 patients. Nine carriers (36%) underwent gastrectomy (mean age of 47.2 years) due to diffuse gastric involvement or worsening clinical symptoms. Gastric adenocarcinoma (T1) was found in one gastrectomy specimen. Among the 11 patients with BMPR1A PVs, 2 had gastric hamartomatomas at baseline EGD, none with dysplasia or symptoms. CONCLUSION: Gastric involvement in JPS appears to be progressive during life, initiating in the cardia area, and mostly concerns SMAD4 PV carriers.

Local recurrence rates after resection of large colorectal serrated lesions with or without margin thermal ablation.

INTRODUCTION: Serrated lesions (SLs) including traditional serrated adenomas (TSA), large hyperplastic polyps (HP) and sessile serrated lesions (SSLs) are associated with high incomplete resection rates. Margin ablation combined with EMR (EMR-T) has become routine to reduce local recurrence while cold snare polypectomy (CSP) is becoming recognized as equally effective for large SLs. Our aim was to evaluate local recurrence rates (LRR) and the use of margin ablation in preventing recurrence in a retrospective cohort study. METHODS: Patients undergoing resection of ≥15 mm colorectal SLs from 2010-2022 were identified through a pathology database and electronic medical records search. Hereditary CRC syndromes, first follow-up > 18 months or no follow-up, surgical resection were excluded. Primary outcome was LRRs (either histologic or visual) during the first 18-month follow-up. Secondary outcomes were LRRs according to size, and resection technique. RESULTS: 191 polyps in 170 patients were resected (59.8% women; mean age, 65 years). The mean size of polyps was 22.4 mm, with 107 (56.0%) ≥20 mm. 99 polyps were resected with EMR, 39 with EMR-T, and 26 with CSP. Mean first surveillance was 8.2 mo. Overall LRR was 18.8% (36/191) (16.8% for ≥20 mm, 17.9% for ≥30 mm). LRR was significantly lower after EMR-T when compared with EMR (5.1% vs. 23.2%; p = 0.013) or CSP (5.1% vs. 23.1%; p = 0.031). There was no difference in LRR between EMR without margin ablation and CSP (p = 0.987). CONCLUSION: The local recurrence rate for SLs ≥15 mm is high with 18.8% overall recurrence. EMR with thermal ablation of the margins is superior to both no ablation and CSP in reducing LRRs.

Patient Access of Their Radiology Reports Before and After Implementation of 21st Century Cures Act Information-Blocking Provisions at a Large Multicampus Health System.

BACKGROUND. To implement provisions of the 21st Century Cures Act that address information blocking, federal regulations mandated that health systems provide patients with immediate access to elements of their electronic health information, including imaging results. OBJECTIVE. The purpose of this study was to compare patient access of radiology reports before and after implementation of the information-blocking provisions of the 21st Century Cures Act. METHODS. This retrospective study included patients who underwent outpatient imaging examinations from January 1, 2021, through December 31, 2022, at three campuses within a large health system. The system implemented policies to comply with the Cures Act information-blocking provisions on January 1, 2022. Imaging results were released in patient portals after a 36-hour embargo period before implementation versus being released immediately after report finalization after implementation. Data regarding patient report access in the portal and report acknowledgment by the ordering provider in the EMR were extracted and compared between periods. RESULTS. The study included reports for 1,188,692 examinations in 388,921 patients (mean age, 58.5 ± 16.6 [SD] years; 209,589 women, 179,290 men, eight nonbinary individuals, and 34 individuals for whom sex information was missing). A total of 77.5% of reports were accessed by the patient before implementation versus 80.4% after implementation. The median time from report finalization to report release in the patient portal was 36.0 hours before implementation versus 0.4 hours after implementation. The median time from report release to first patient access of the report in the portal was 8.7 hours before implementation versus 3.0 hours after implementation. The median time from report finalization to first patient access was 45.0 hours before implementation versus 5.5 hours after implementation. Before implementation, a total of 18.5% of reports were first accessed by the patient before being accessed by the ordering provider versus 44.0% after implementation. After implementation, the median time from report release to first patient access was 1.8 hours for patients with age younger than 60 years old versus 4.3 hours for patients 60 years old or older. CONCLUSION. After implementation of institutional policies to comply with 21st Century Cures Act information-blocking provisions, the length of time until patients accessed imaging results decreased, and the proportion of patients who accessed their reports before the ordering provider increased. CLINICAL IMPACT. Radiologists should consider mechanisms to ensure timely and appropriate communication of important findings to ordering providers.

Combined endoscopic mucosal resection and full-thickness resection for large colorectal polyps: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Combined endoscopic mucosal resection (EMR) with endoscopic Full thickness resection (EFTR) is an emerging technique that has been developed to target colorectal polyps larger than 2 cm. We performed a systematic review and meta-analysis to evaluate this technique for the resection of large colorectal lesions. METHODS: We conducted a comprehensive search of multiple electronic databases from inception through August 2023, to identify studies that reported on hybrid FTR. A random-effects model was employed to calculate the overall pooled technical success, macroscopic complete resection, free vertical margins resection rate, adverse events, and recurrence on follow up. RESULTS: A total of 8 Study arms with 244 patients (30% women) were included in the analysis. The pooled technical success rate was 97% (95% CI 88%-100%, I2 = 79.93%). The pooled rate of macroscopic complete resection was achieved in 95% (95% CI 90%-99%, I2 = 49.98) with a free vertical margins resection rate 88% (95% CI, 78%-96%, I2 = 63.32). The overall adverse events rate was 2% (95% CI 0%-5%, I2 = 11.64) and recurrence rate of 6% (95% CI 2%-12%, I2=20.32). CONCLUSION: Combined EMR with EFTR is effective and safe for resecting large, and complex colorectal adenomas, offering a good alternative for high surgical risk patients. Regional heterogeneity was observed, indicating that outcomes may be impacted by differences in operator expertise and industry training certification across regions. Comparative studies that directly compare combined EMR with EFTR against alternative methods such as ESD and surgical resection are needed.

Risk factors for positive resection margins after endoscopic resection for gastrointestinal neuroendocrine tumors.

BACKGROUND: In recent years, the incidence of gastrointestinal neuroendocrine tumors (GI-NETs) has remarkably increased due to the widespread use of screening gastrointestinal endoscopy. Currently, the most common treatments are surgery and endoscopic resection. Compared to surgery, endoscopic resection possesses a higher risk of resection margin residues for the treatment of GI-NETs. METHODS: A total of 315 patients who underwent surgery or endoscopic resection for GI-NETs were included. We analyzed their resection modality (surgery, ESD, EMR), margin status, Preoperative marking and Prognosis. RESULTS: Among 315 patients included, 175 cases underwent endoscopic resection and 140 cases underwent surgical treatment. A total of 43 (43/175, 24.57%) and 10 (10/140, 7.14%) patients exhibited positive resection margins after endoscopic resection and surgery, respectively. Multivariate regression analysis suggested that no preoperative marking and endoscopic treatment methods were risk factors for resection margin residues. Among the patients with positive margin residues after endoscopic resection, 5 patients underwent the radical surgical resection and 1 patient underwent additional ESD resection. The remaining 37 patients had no recurrence during a median follow-up of 36 months. CONCLUSIONS: Compared with surgery, endoscopic therapy has a higher margin residual rate. During endoscopic resection, preoperative marking may reduce the rate of lateral margin residues, and endoscopic submucosal dissection may be preferred than endoscopic mucosal resection. Periodical follow-up may be an alternative method for patients with positive margin residues after endoscopic resection.

The role of advanced endoscopy in appendiceal polyp management and outcomes.

BACKGROUND: Appendiceal orifice lesions are often managed operatively with limited or oncologic resections. The aim is to report the management of appendiceal orifice mucosal neoplasms using advanced endoscopic interventions. METHODS: Patients with appendiceal orifice mucosal neoplasms who underwent advanced endoscopic resections between 2011 and 2021 with either endoscopic mucosal resection (EMR), endoscopic mucosal dissection (ESD), hybrid ESD, or combined endoscopic laparoscopic surgery (CELS) were included from a prospectively collected dataset. Patient and lesion details and procedure outcomes are reported. RESULTS: Out of 1005 lesions resected with advanced endoscopic techniques, 41 patients (4%) underwent appendiceal orifice mucosal neoplasm resection, including 39% by hybrid ESD, 34% by ESD, 15% by EMR, and 12% by CELS. The median age was 65, and 54% were male. The median lesion size was 20 mm. The dissection was completed piecemeal in 49% of patients. Post-procedure, one patient had a complication within 30 days and was admitted with post-polypectomy abdominal pain treated with observation for 2 days with no intervention. Pathology revealed 49% sessile-serrated lesions, 24% tubular adenomas, and 15% tubulovillous adenomas. Patients were followed up for a median of 8 (0-48) months. One patient with a sessile-serrated lesion experienced a recurrence after EMR which was re-resected with EMR. CONCLUSION: Advanced endoscopic interventions for appendiceal orifice mucosal neoplasms can be performed with a low rate of complications and early recurrence. While conventionally lesions at the appendiceal orifice are often treated with surgical resection, advanced endoscopic interventions are an alternative approach with promising results which allow for cecal preservation.

Risk of diabetes and expected years in life without diabetes among adults from an urban community in India: findings from a retrospective cohort.

BACKGROUND: Diabetes prevalence has increased over the past few decades, and the shift of the burden of diabetes from the older population to the younger population has increased the exposure of longer durations in a morbid state. The study aimed at ascertaining the likelihood of progression to diabetes and to estimate the onset of diabetes within the urban community of Mumbai. METHODS: This study utilized an observational retrospective non-diabetic cohort comprising 1629 individuals enrolled in a health security scheme. Ten years of data were extracted from electronic medical records, and the life table approach was employed to assess the probability of advancing to diabetes and estimate the expected number of years lived without a diabetes diagnosis. RESULTS: The study revealed a 42% overall probability of diabetes progression, with age and gender variations. Males (44%) show higher probabilities than females (40%) of developing diabetes. Diabetes likelihood rises with age, peaking in males aged 55-59 and females aged 65-69. Males aged 30-34 exhibit a faster progression (10.6 years to diagnosis) compared to females (12.3 years). CONCLUSION: The study's outcomes have significant implications for the importance of early diabetes detection. Progression patterns suggest that younger cohorts exhibit a comparatively slower rate of progression compared to older cohorts.

al-BERT: a semi-supervised denoising technique for disease prediction.

BACKGROUND: Medical records are a valuable source for understanding patient health conditions. Doctors often use these records to assess health without solely depending on time-consuming and complex examinations. However, these records may not always be directly relevant to a patient's current health issue. For instance, information about common colds may not be relevant to a more specific health condition. While experienced doctors can effectively navigate through unnecessary details in medical records, this excess information presents a challenge for machine learning models in predicting diseases electronically. To address this, we have developed 'al-BERT', a new disease prediction model that leverages the BERT framework. This model is designed to identify crucial information from medical records and use it to predict diseases. 'al-BERT' operates on the principle that the structure of sentences in diagnostic records is similar to regular linguistic patterns. However, just as stuttering in speech can introduce 'noise' or irrelevant information, similar issues can arise in written records, complicating model training. To overcome this, 'al-BERT' incorporates a semi-supervised layer that filters out irrelevant data from patient visitation records. This process aims to refine the data, resulting in more reliable indicators for disease correlations and enhancing the model's predictive accuracy and utility in medical diagnostics. METHOD: To discern noise diseases within patient records, especially those resembling influenza-like illnesses, our approach employs a customized semi-supervised learning algorithm equipped with a focused attention mechanism. This mechanism is specifically calibrated to enhance the model's sensitivity to chronic conditions while concurrently distilling salient features from patient records, thereby augmenting the predictive accuracy and utility of the model in clinical settings. We evaluate the performance of al-BERT using real-world health insurance data provided by Taiwan's National Health Insurance. RESULT: In our study, we evaluated our model against two others: one based on BERT that uses complete disease records, and another variant that includes extra filtering techniques. Our findings show that models incorporating filtering mechanisms typically perform better than those using the entire, unfiltered dataset. Our approach resulted in improved outcomes across several key measures: AUC-ROC (an indicator of a model's ability to distinguish between classes), precision (the accuracy of positive predictions), recall (the model's ability to find all relevant cases), and overall accuracy. Most notably, our model showed a 15% improvement in recall compared to the current best-performing method in the field of disease prediction. CONCLUSION: The conducted ablation study affirms the advantages of our attention mechanism and underscores the crucial role of the selection module within al-BERT.

Detrimental effects of electromagnetic radiation emitted from cell phone on embryo morphokinetics and blastocyst viability in mice.

Electromagnetic radiation (EMR) has deleterious effects on sperm motility and viability, as well as oocyte membrane and organelle structure. The aim was to assess the effects of cell phone radiation on preimplantation embryo morphokinetics and blastocyst viability in mice. For superovulation, 20 female mice were treated with intraperitoneal (IP) injections of 10 IU pregnant mare's serum gonadotropin (Folligon® PMSG), followed by 10 IU of human chorionic gonadotropin (hCG) after 48 h. The zygotes (n = 150) from the control group were incubated for 4 days. The experimental zygotes (n = 150) were exposed to a cell phone emitting EMR with a frequency range 900-1800 MHz for 30 min on day 1. Then, all embryos were cultured in the time-lapse system and annotated based on time points from the 2-cell stage (t2) to hatched blastocyst (tHDyz), as well as abnormal cleavage patterns. Blastocyst viability was assessed using Hoechst and propidium iodide staining. Significant increases (P < 0.05) were observed in the cleavage division time points of t2, t8, t10, and t12 of the experimental group compared with the controls. In terms of blastocyst formation parameters, a delay in embryo development was observed in the experimental group compared with the controls. Data analysis of the time intervals between the two groups showed a significant difference in the s3 time interval (P < 0.05). Also, the rates of fragmentation, reverse cleavage, vacuole formation, and embryo arrest were significantly higher in the experimental group (P < 0.05). Furthermore, the cell survival rate in the experimental group was lower than the control group (P < 0.05). Exposure to EMR has detrimental consequences for preimplantation embryo development in mice. These effects can manifest as defects in the cleavage stage and impaired blastocyst formation, leading to lower cell viability.

Predictive model and risk analysis for coronary heart disease in people living with HIV using machine learning.

OBJECTIVE: This study aimed to construct a coronary heart disease (CHD) risk-prediction model in people living with human immunodeficiency virus (PLHIV) with the help of machine learning (ML) per electronic medical records (EMRs). METHODS: Sixty-one medical characteristics (including demography information, laboratory measurements, and complicating disease) readily available from EMRs were retained for clinical analysis. These characteristics further aided the development of prediction models by using seven ML algorithms [light gradient-boosting machine (LightGBM), support vector machine (SVM), eXtreme gradient boosting (XGBoost), adaptive boosting (AdaBoost), decision tree, multilayer perceptron (MLP), and logistic regression]. The performance of this model was assessed using the area under the receiver operating characteristic curve (AUC). Shapley additive explanation (SHAP) was further applied to interpret the findings of the best-performing model. RESULTS: The LightGBM model exhibited the highest AUC (0.849; 95% CI, 0.814-0.883). Additionally, the SHAP plot per the LightGBM depicted that age, heart failure, hypertension, glucose, serum creatinine, indirect bilirubin, serum uric acid, and amylase can help identify PLHIV who were at a high or low risk of developing CHD. CONCLUSION: This study developed a CHD risk prediction model for PLHIV utilizing ML techniques and EMR data. The LightGBM model exhibited improved comprehensive performance and thus had higher reliability in assessing the risk predictors of CHD. Hence, it can potentially facilitate the development of clinical management techniques for PLHIV care in the era of EMRs.

Measuring Emergency Department Workload Perception Using Electronic Medical Record Measures of Patient Volume and Acuity.

BACKGROUND: Workload in the emergency department (ED) fluctuates and there is no established model for measurement of clinician-level ED workload. OBJECTIVE: The aim of this study was to measure perceived ED workload and assess the relationship between perceived workload and objective measures of workload from the electronic medical record (EMR). METHODS: This study was conducted at a tertiary care, academic ED from July 1, 2020 through April 13, 2021. Attending workload perceptions were collected using a 5-point scale in three care areas with variable acuity. We collected eight EMR measures thought to correlate with perceived workload. EMR values were compared across areas of the department using ANOVA and correlated with attending workload ratings using linear regression. RESULTS: We collected 315 unique workload ratings, which were normally distributed. For the entire department, there was a weak positive correlation between reported workload perception and mean percentage of inpatient admissions (r = 0.23; p < 0.001), intensive care unit admissions (r = 0.2; p < 0.001), patient arrivals per shift (r = 0.14; p = 0.017), critical care billed visits (r = 0.22; p < 0.001), cardiopulmonary resuscitation code activations (r = 0.2; p < 0.001), and level 5 visits (r = 0.13; p = 0.02). There was weak negative correlation for ED discharges (r = -0.23; p < 0.001). Several correlations were stronger in individual care areas, including percent admissions in the lowest-acuity area (r = 0.43; p = 0.033) and patient arrivals in the highest-acuity area (r = 0.44; p < .01). No significant correlation was found in any area for observation admissions or trauma activations. CONCLUSIONS: In this study, EMR measures of workload were not closely correlated with ED attending physician workload perception. Future study should examine additional factors contributing to physician workload outside of the EMR.

Upregulation of EMR1 (ADGRE1) by Tumor-Associated Macrophages Promotes Colon Cancer Progression by Activating the JAK2/STAT1,3 Signaling Pathway in Tumor Cells.

Previously, we reported that epidermal growth factor-like module-containing mucin-like hormone receptor-like 1 (EMR1/ADGRE1) is abnormally expressed in colon cancer (CC) and is a risk factor for lymph node metastasis (LNM) and poor recurrence-free survival in patients with abundant tumor-associated macrophages (TAMs). However, the signaling pathways associated with EMR1 expression in CC progression remain unclear. In this study, we aimed to explore the role of EMR1 and its signaling interactions with macrophages in CC progression. Spatial transcriptomics of pT3 microsatellite unstable CC tissues revealed heightened Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling in EMR1-HL CC with LNM compared to EMR1-N CC without LNM. Through in vitro coculture of CC cells with macrophages, EMR1 expression by CC cells was found to be induced by TAMs, ultimately interacting with upregulated JAK/STAT signaling, increasing cell proliferation, migration, and motility, and reducing apoptosis. JAK2/STAT3 inhibition decreased the levels of EMR1, JAK2, STAT1, and STAT3, significantly impeded the proliferation, migration, and mobility of cells, and increased the apoptosis of EMR1+ CC cells compared to their EMR1KO counterparts. Overall, TAMs-induced EMR1 upregulation in CC cells may promote LNM and CC progression via JAK2/STAT1,3 signaling upregulation. This study provides further insights into the molecular mechanisms involving macrophages and intracellular EMR1 expression in CC progression, suggesting its clinical significance and offering potential interventions to enhance patient outcomes.

The effect of electronic medical records on medication errors, workload, and medical information availability among qualified nurses in Israel- a cross sectional study.

BACKGROUND: Errors in medication administration by qualified nursing staff in hospitals are a significant risk factor for patient safety. In recent decades, electronic medical records (EMR) systems have been implemented in hospitals, and it has been claimed that they contribute to reducing such errors. However, systematic research on the subject in Israel is scarce. This study examines the position of the qualified nursing staff regarding the impact of electronic medical records systems on factors related to patient safety, including errors in medication administration, workload, and availability of medical information. METHODS: This cross-sectional study examines three main variables: Medication errors, workload, and medical information availability, comparing two periods- before and after EMR implementation based on self-reports. A final sample of 591 Israeli nurses was recruited using online private social media groups to complete an online structured questionnaire. The questionnaires included items assessing workload (using the Expanding Nursing Stress Scale), medical information availability (the Carrington-Gephart Unintended Consequences of Electronic Health Record Questionnaire), and medical errors (the Medical Error Checklists). Items were assessed twice, once for the period before the introduction of electronic records and once after. In addition, participants answered open-ended questions that were qualitatively analyzed. RESULTS: Nurses perceive the EMR as reducing the extent of errors in drug administration (mean difference = -0.92 ± 0.90SD, p < 0.001), as well as the workload (mean difference = -0.83 ± 1.03SD, p < 0.001) by ∼ 30% on average, each. Concurrently, the systems are perceived to require a longer documentation time at the expense of patients' treatment time, and they may impair the availability of medical information by about 10% on average. CONCLUSION: The results point to nurses' perceived importance of EMR systems in reducing medication errors and relieving the workload. Despite the overall positive attitudes toward EMR systems, nurses also report that they reduce information availability compared to the previous pen-and-paper approach. A need arises to improve the systems in terms of planning and adaptation to the field and provide appropriate technical and educational support to nurses using them.

Effects of non-ionizing radio frequency electromagnetic radiation on the development and behavior of early embryos of Danio rerio.

Biological effects of radio frequency electromagnetic radiation (RF-EMR) in the range of 900-1800 MHz emerging from the mobile phone were investigated and were found to influence the locomotor pattern when exposure was initiated from 1 hour post fertilization (hpf) in zebrafish embryos (ZE), Danio rerio. Mobile phones and other wireless devices offer tremendous advantages. However, on the flipside they are leading to an increased electromagnetic energy in the environment, an excess of which could be termed as electromagnetic pollution. Herein, we tried to understand the effects of RF-EMR emerging from the mobile phone, on the development and behavior of ZE, exposed to RF-EMR (specific absorption rate of 1.13 W/kg and 1800 MHz frequency) 1 hr daily, for 5 days. To understand if there could be any developmental stage-specific vulnerability to RF-EMR, the exposure was initiated at three different time points: 1hpf, 6hpf and 24hpf of ZE development. Observations revealed no significant changes in the survival rate, morphology, oxidative stress or cortisol levels. However, statistically significant variations were observed in the batch where exposure started at 1hpf, with respect to locomotion patterns (distance travelled: 659.1 ± 173.1 mm Vs 963.5 ± 200.4 mm), which could be correlated to anxiety-like behavior; along with a corresponding increase in yolk consumption (yolk sac area: 0.251 ± 0.019 mm2 Vs 0.225 ± 0.018 mm2). Therefore, we conclude that RF-EMR exposure influences the organism maximally during the earliest stage of development, and we also believe that an increase in the time of exposure (corresponding to the patterns of current usage of mobile phones) might reveal added afflictions.

Mobile phones and other wireless devices are on a rampant usage worldwide. They work by radiating low energy radiofrequency electromagnetic radiations. An excessive usage of wireless devices is leading to increased presence of these radiations in our surroundings. Since these radiations are not physically sensed by the organisms, its impact stays elusive. Nevertheless, the interaction of these radiations with biological systems may produce some unwarranted effects. When we exposed the ZE to the mobile phone radiation daily 1hr for 5days, our observations revealed that the youngest of the experimental group showed susceptibility. The effect was evident through haphazard movements and stressed behavior. So, it is important to be aware of the potential effects and take necessary precautions by following safety guidelines, especially when the organism is in its early life stage.

Effect of endoscopic mucosal resection and endoscopic submucosal dissection on postoperative wound complications in patients with gastric cancer: A meta-analysis.

Endoscopic submucosa dissection (ESD) allows complete excision of the whole lesion, which results in a higher percentage of complete excision and an improved quality of life by minimizing the amount of excision as opposed to an endoscopic mucosal resection (EMR). Although ESD is now being carried out in the majority of hospitals, ESD's possible complications (such as trauma and perforation) have given rise to doubts about ESD practices in patients with early-stage stomach cancer when deciding on therapy and reimbursement. This study was designed to evaluate the effectiveness and safety of ESD over EMR in treating early-stage stomach cancer. Four main databases have been searched, including EMBASE and published. The ROBINS-I tool suggested in the Cochrane Handbook has been applied to evaluate the quality of the chosen trials. It may better reflect the risk of bias in the included studies. The meta-analyses were carried out with ReMan 5.3, and the results were treated with endote. Seven cohort studies have been completed. Meta analysis indicated that EMR and ESD surgery did not differ significantly from each other in terms of postoperative haemorrhage (OR, 0.76; 95%CI, 0.56,1.04 p = 0.09); EMR, however, was associated with a lower rate of postoperative perforation than ESD surgery (OR, 0.36; 95%CI, 0.24,0.54 p < 0.0001). Taking into account that ESD and EMR did not differ significantly in the risk of wound bleeding, even though the risk of perforation is not likely to result in life-threatening illness. In the analysis of these data, however, the potential advantages of EMR might be greater than ESD.

Barriers and Strategies for Hepatitis B and C Elimination in Pakistan.

BACKGROUND: Pakistan has a high hepatitis burden for both hepatitis C virus (HCV) and hepatitis B virus (HBV). To achieve World Health Organization (WHO) 2030 targets for hepatitis elimination, there is a need to constitute progress in the country, find the barriers and strategies for HCV elimination, and take actions to address the gaps. METHODS: We collected data from (1) WHO estimates in 2020, (2) midterm review questionnaire of the WHO regional action plan, and (3) WHO estimates on immunization. We analyzed these data to inform (1) the burden defined as prevalence and mortality and (2) response in 3 thematic areas: governance, policy, and finance; strategic information; and service delivery. RESULTS: The prevalence of hepatitis B in the general population is 1.6% with 12 000 deaths/year. The prevalence of hepatitis C in the general population is 7.5% with 19 000 deaths and 545 000 new cases (incidence)/year. The selected indicators to monitor progress on viral hepatitis in Pakistan were governance and financing, policies and guidelines, and strategic information. The overall governance indicators are good with a focal point, a national hepatitis strategy, an operational plan, strategy for price reduction, and involvement of civil society but the costed action plan and the advocacy strategy are missing. The indicators on policies and guidelines are also adequately addressed. The hepatitis B and C testing and treatment guidelines are available, there is a policy to screen all blood donations, and there is an injection safety policy, but the policy for timely hepatitis B vaccine birth dose and hepatitis B vaccination for the vulnerable is missing. Both indicators regarding strategic information, that is measures of key hepatitis indicators and regular data review, are missing. The status of 5 key interventions in Pakistan show that the hepatitis B vaccination coverage is 74% and only 3% of newborn children are given the hepatitis B vaccine birth dose. Only 22% of HCV cases have been diagnosed and 2% have received treatment. Treatment response is 96%. Same-day testing and treatment of hepatitis C reduced the overall dropout rate and improved the cascade of care. Decentralization and task shifting are important tools to improve service delivery and reach communities. Finances to implement hepatitis elimination is a major barrier. CONCLUSIONS: Pakistan has the highest hepatitis disease burden. With the current pace, hepatitis elimination appears impossible. Introduction of the birth dose of hepatitis B vaccine and improving access and affordability of testing can improve the testing and treatment numbers. Finances need to be mobilized from within the country and outside to support disease elimination.

Identification of patients with epilepsy using automated electronic health records phenotyping.

OBJECTIVE: Unstructured data present in electronic health records (EHR) are a rich source of medical information; however, their abstraction is labor intensive. Automated EHR phenotyping (AEP) can reduce the need for manual chart review. We present an AEP model that is designed to automatically identify patients diagnosed with epilepsy. METHODS: The ground truth for model training and evaluation was captured from a combination of structured questionnaires filled out by physicians for a subset of patients and manual chart review using customized software. Modeling features included indicators of the presence of keywords and phrases in unstructured clinical notes, prescriptions for antiseizure medications (ASMs), International Classification of Diseases (ICD) codes for seizures and epilepsy, number of ASMs and epilepsy-related ICD codes, age, and sex. Data were randomly divided into training (70%) and hold-out testing (30%) sets, with distinct patients in each set. We trained regularized logistic regression and an extreme gradient boosting models. Model performance was measured using area under the receiver operating curve (AUROC) and area under the precision-recall curve (AUPRC), with 95% confidence intervals (CI) estimated via bootstrapping. RESULTS: Our study cohort included 3903 adults drawn from outpatient departments of nine hospitals between February 2015 and June 2022 (mean age = 47 ± 18 years, 57% women, 82% White, 84% non-Hispanic, 70% with epilepsy). The final models included 285 features, including 246 keywords and phrases captured from 8415 encounters. Both models achieved AUROC and AUPRC of 1 (95% CI = .99-1.00) in the hold-out testing set. SIGNIFICANCE: A machine learning-based AEP approach accurately identifies patients with epilepsy from notes, ICD codes, and ASMs. This model can enable large-scale epilepsy research using EHR databases.

Outcomes of Cold Snare Endoscopic Mucosal Resection of Nonampullary Duodenal Adenomas ≥1 cm: A Multicenter Study.

BACKGROUND AND AIMS: Endoscopic mucosal resection (EMR) with use of electrocautery (conventional EMR) has historically been used to remove large duodenal adenomas, however, use of electrocautery can predispose to adverse events including delayed bleeding and perforation. Cold snare EMR (cs-EMR) has been shown to be safe and effective for removal of colon polyps, but data regarding its use in the duodenum is limited. The aim of this study is to evaluate the efficacy and safety of cs-EMR for nonampullary duodenal adenomas ≥1 cm. METHODS: This was a multicenter retrospective study of patients with nonampullary duodenal adenomas ≥1 cm who underwent cs-EMR between October 2014 and May 2023. Patients who received any form of thermal therapy were excluded. Primary outcomes were technical success and rate of recurrent adenoma. Secondary outcomes were adverse events and predictors of recurrence. RESULTS: A total of 125 patients underwent resection of 127 nonampullary duodenal adenomas with cs-EMR. Follow up data was available in 89 cases (70.1%). The recurrent adenoma rate was 31.5% (n=28). Adverse events occurred in 3.9% (n=5) with four cases of immediate bleeding (3.1%) and one case of delayed bleeding (0.8%). There were no cases of perforation. The presence of high-grade dysplasia was found to be an independent predictor of recurrence (OR: 10.9 [95% CI: 1.1-102.1], p=0.036). CONCLUSION: This retrospective multicenter study demonstrates that cs-EMR for nonampullary duodenal adenomas is safe and technically feasible with an acceptable recurrence rate. Future prospective studies are needed to directly compare outcomes of cs-EMR with conventional and underwater EMR.