Cingulate dynamics track depression recovery with deep brain stimulation.

Deep brain stimulation (DBS) of the subcallosal cingulate (SCC) can provide long-term symptom relief for treatment-resistant depression (TRD)1. However, achieving stable recovery is unpredictable2, typically requiring trial-and-error stimulation adjustments due to individual recovery trajectories and subjective symptom reporting3. We currently lack objective brain-based biomarkers to guide clinical decisions by distinguishing natural transient mood fluctuations from situations requiring intervention. To address this gap, we used a new device enabling electrophysiology recording to deliver SCC DBS to ten TRD participants (ClinicalTrials.gov identifier NCT01984710). At the study endpoint of 24 weeks, 90% of participants demonstrated robust clinical response, and 70% achieved remission. Using SCC local field potentials available from six participants, we deployed an explainable artificial intelligence approach to identify SCC local field potential changes indicating the patient's current clinical state. This biomarker is distinct from transient stimulation effects, sensitive to therapeutic adjustments and accurate at capturing individual recovery states. Variable recovery trajectories are predicted by the degree of preoperative damage to the structural integrity and functional connectivity within the targeted white matter treatment network, and are matched by objective facial expression changes detected using data-driven video analysis. Our results demonstrate the utility of objective biomarkers in the management of personalized SCC DBS and provide new insight into the relationship between multifaceted (functional, anatomical and behavioural) features of TRD pathology, motivating further research into causes of variability in depression treatment.

Mutation in protein disulfide isomerase A3 causes neurodevelopmental defects by disturbing endoplasmic reticulum proteostasis.

Recessive gene mutations underlie many developmental disorders and often lead to disabling neurological problems. Here, we report identification of a homozygous c.170G>A (p.Cys57Tyr or C57Y) mutation in the gene coding for protein disulfide isomerase A3 (PDIA3, also known as ERp57), an enzyme that catalyzes formation of disulfide bonds in the endoplasmic reticulum, to be associated with syndromic intellectual disability. Experiments in zebrafish embryos show that PDIA3C57Y expression is pathogenic and causes developmental defects such as axonal disorganization as well as skeletal abnormalities. Expression of PDIA3C57Y in the mouse hippocampus results in impaired synaptic plasticity and memory consolidation. Proteomic and functional analyses reveal that PDIA3C57Y expression leads to dysregulation of cell adhesion and actin cytoskeleton dynamics, associated with altered integrin biogenesis and reduced neuritogenesis. Biochemical studies show that PDIA3C57Y has decreased catalytic activity and forms disulfide-crosslinked aggregates that abnormally interact with chaperones in the endoplasmic reticulum. Thus, rare disease gene variant can provide insight into how perturbations of neuronal proteostasis can affect the function of the nervous system.

Traumatic Thoracic Aortic Coarctation after Blunt Thoracic Aortic Injury Mandates Emergent Thoracic Endovascular Aortic Repair.

OBJECTIVE: This study sought to elucidate clinical and imaging findings predictive for malperfusion syndrome after blunt thoracic aortic injury (BTAI). SUMMARY BACKGROUND DATA: There is limited literature on malperfusion syndrome after BTAI and the timing of thoracic endovascular aortic repair (TEVAR) in patients with this condition has not been defined. METHODS: A retrospective analysis of prospectively collected data of patients with BTAI treated between January 2021 and October 2023. Clinical and thoracic aortic (TA) imaging data, time to TEVAR, in-hospital death, and malperfusion/reperfusion sequelae (paraplegia, renal/visceral/limb ischemia, and compartment syndromes) were assessed. Correlations between clinical and imaging findings, time to TEVAR, and outcomes were evaluated. RESULTS: Of the 19,203 trauma patients evaluated, 13,717 (71%) had blunt injuries and 77 (0.6%) had BTAI. The majority (67.5%) were male with a median age of 40 years (IQR:33-55). TEVAR was performed in 42 (54.5%) patients. Seven (9.1%) patients presented with clinical and TA imaging criteria for traumatic thoracic aortic coarctation (TTAC), including diminished/absent femoral pulses and TA luminal narrowing of 50-99%. The median time to TEVAR was 9 (IQR:5-32), 11, and 4 hours for all non-TTAC and TTAC BTAI patients, respectively (P=0.037). Only TTAC patients presented/developed malperfusion/reperfusion sequelae. In-hospital mortality rates were 7.8%, 5.8%, and 29% for all non-TTAC and TTAC BTAI patients, respectively (P=0.09). Aortic-related mortality occurred in only two (2.6%) TTAC patients.. CONCLUSIONS: Patients with clinical and TA imaging manifestations of TTAC are predisposed to malperfusion/reperfusion sequelae if TEVAR is delayed. We recommend the emergent repair of all BTAIs with TTAC.

Acute pancreatitis associated with pembrolizumab-induced hypertriglyceridemia.

INTRODUCTION: Acute pancreatitis (AP) following drug-induced hypertriglyceridemia is a rare clinical phenomenon. Immune checkpoint inhibitors have revolutionized treatment for a variety of solid organ and hematological malignancies. Pembrolizumab is a programmed cell death receptor-1 (PD-1) inhibitor that has shown promising responses in many advanced cancers. However, a constellation of immune-related adverse events has also been described. There are reports of pembrolizumab-induced hypertriglyceridemia, but AP as a result of this side effect remains an exceedingly rare clinical sequela. CASE REPORT: We delineate a case of a patient with stage IVB non-small-cell lung cancer who developed progressive abdominal pain and nausea following administration of pembrolizumab for four months. Laboratory studies revealed increased serum lipase and triglyceride levels at 12,562 IU/L and 16,901 mg/dL, respectively. The diagnosis of AP was made based on the revised Atlanta classification criteria. After ruling out alternative causes, pembrolizumab-induced hypertriglyceridemia was considered the likely etiology of AP. MANAGEMENT AND OUTCOME: The patient was transferred to the medical intensive care unit for close monitoring. Treatment was initiated with intravenous fluids, pain medications, and an insulin infusion. However, her hypertriglyceridemia levels remained persistently elevated, necessitating therapeutic apheresis. She recovered well with no complications after triglyceride apheresis. DISCUSSION: AP following pembrolizumab-associated hypertriglyceridemia remains a rare clinicopathologic entity. Given the widespread clinical use of immune checkpoint inhibitors, knowledge of such rare adverse events is crucial. Evaluation of serum triglyceride levels before and after initiating pembrolizumab therapy may be mandated, especially in patients with metabolic comorbidities.

Making Science Computable Using Evidence-Based Medicine on Fast Healthcare Interoperability Resources: Standards Development Project.

BACKGROUND: Evidence-based medicine (EBM) has the potential to improve health outcomes, but EBM has not been widely integrated into the systems used for research or clinical decision-making. There has not been a scalable and reusable computer-readable standard for distributing research results and synthesized evidence among creators, implementers, and the ultimate users of that evidence. Evidence that is more rapidly updated, synthesized, disseminated, and implemented would improve both the delivery of EBM and evidence-based health care policy. OBJECTIVE: This study aimed to introduce the EBM on Fast Healthcare Interoperability Resources (FHIR) project (EBMonFHIR), which is extending the methods and infrastructure of Health Level Seven (HL7) FHIR to provide an interoperability standard for the electronic exchange of health-related scientific knowledge. METHODS: As an ongoing process, the project creates and refines FHIR resources to represent evidence from clinical studies and syntheses of those studies and develops tools to assist with the creation and visualization of FHIR resources. RESULTS: The EBMonFHIR project created FHIR resources (ie, ArtifactAssessment, Citation, Evidence, EvidenceReport, and EvidenceVariable) for representing evidence. The COVID-19 Knowledge Accelerator (COKA) project, now Health Evidence Knowledge Accelerator (HEvKA), took this work further and created FHIR resources that express EvidenceReport, Citation, and ArtifactAssessment concepts. The group is (1) continually refining FHIR resources to support the representation of EBM; (2) developing controlled terminology related to EBM (ie, study design, statistic type, statistical model, and risk of bias); and (3) developing tools to facilitate the visualization and data entry of EBM information into FHIR resources, including human-readable interfaces and JSON viewers. CONCLUSIONS: EBMonFHIR resources in conjunction with other FHIR resources can support relaying EBM components in a manner that is interoperable and consumable by downstream tools and health information technology systems to support the users of evidence.

The evaluation of bacterial-augmented floating treatment wetlands for concomitant removal of phenol and chromium from contaminated water.

Contamination of aquatic ecosystems with organic and inorganic contaminants is a global threat due to their hazardous effects on the environment and human health. Floating treatment wetland (FTW) technology is a cost-effective and sustainable alternative to existing treatment approaches. It consists of a buoyant mat in which wetland plants can grow and develop their roots in a suspended manner and can be implemented to treat stormwater, municipal wastewater, and industrial effluents. Here we explored the potential of bacterial-augmented FTWs for the concurrent remediation of phenol and hexavalent chromium (Cr6+) contaminated water and evaluated treated water toxicity using Triticum aestivum L. (wheat) as a test plant. The FTWs carrying Phragmites australis L. (common reed) were inoculated with a consortium of four bacterial strains (Burkholderia phytofirmans PsJN, Acinetobacter lwofii ACRH76, Pseudomonas aeruginosa PJRS20, Bacillus sp. PJRS25) and evaluated for their potential to simultaneously remove phenol and chromium (Cr) from contaminated water. Results revealed that the FTWs efficiently improved water quality by removing phenol (86%) and Cr (80%), with combined use of P. australis and bacterial consortium after 50 days. The phytotoxicity assay demonstrated that the germination of wheat seed (96%) was significantly higher where bacterial-augmented FTWs treated water was used compared to untreated water. This pilot-scale study highlights that the combined application of wetland plants and bacterial consortium in FTWs is a promising approach for concomitant abatement of phenol and Cr from contaminated water, especially for developing countries like Pakistan where the application of advanced and expensive technologies is limited.

This pilot-scale research provides new interventions and information required for establishing a large-scale remediation framework for the effective, sustainable and eco-friendly remediation of phenol and Cr co-contaminated aquatic ecosystems, using bacterial augmented floating wetlands technology (FTWs).

Exploring the potential of bacterial-augmented floating treatment wetlands for the remediation of detergent-contaminated water.

Due to industrialization and urbanization, the use of detergents inadvertently led to contamination of aquatic environments, thus posing potential threat to aquatic organisms and human health. One of the main components of detergents is linear alkylbenzene sulfonate (LAS), which can cause toxic effects on living organisms, particularly aquatic life in the environment. In this study, floating treatment wetlands (FTWs) mesocosms were developed and augmented with LAS-degrading bacteria. The plant species, Brachiaria mutica (Para grass), was vegetated to establish FTWs and bacterial consortium (1:1:1:1) of Pseudomonas aeruginosa strain PJRS20, Bacillus sp. BRRH60, Acinetobacter sp. strain CYRH21, and Burkholderia phytofirmans Ps.JN was augmented (free or immobilized) in these mesocosms. Results revealed that the FTWs removed LAS from the contaminated water and their augmentation with bacteria slightly increased LAS removal during course of the experiment. Maximum reduction in LAS concentration (94%), chemical oxygen demand (91%), biochemical oxygen demand (93%), and total organic carbon (91%) was observed in the contaminated water having FTWs augmented with bacterial consortium immobilized on polystyrene sheet. This study highlights that the FTWs supported with immobilized bacteria on polystyrene sheets can provide an eco-friendly and sustainable solution for the remediation of LAS-bearing water, especially for developing countries like Pakistan.

This pilot-scale study provided insights to resolve the detergent-contaminated wastewater issue, using floating treatment wetlands (FTWs) augmented with bacteria. The FTWs augmented with bacteria immobilized on a polystyrene sheet and vegetated with Brachiaria mutica led to high degradation of LAS, a toxic compound of detergent, from the contaminated water.

Special Issue "Emerging AI+X-Based Sensor and Networking Technologies including Selected Papers from ICGHIT 2022-2023".

This Special Issue is a collection of selected papers from the 10th and 11th International Conferences on Green and Human Information Technology (ICGHITs) [...].

Oxyphenbutazone ameliorates carfilzomib induced cardiotoxicity in rats via inhibition of oxidative free radical burst and NF-κB/IκB-α pathway.

Carfilzomib (CFZ), a chemotherapeutic agent used for multiple myeloma treatments reported to cause high incidence of cardiac events either new onset and/or exacerbate formerly diagnosed heart failure with ventricular and myocardial dysfunction. Purpose: Current research designed to explore and examine the preventive effect of oxyphenbutazone in the CFZ -instigated cardiotoxicity. Methodology: Female Wistar Rats weighing 200-250 g selected randomly and grouped as follows: Group 1 designated as the Normal control and receive normal saline only. Group 2 served toxic control and exposed to CFZ (4 mg/kg, intraperitoneally [i.p.]). Group 3 & 4 served as treatment groups and administered with CFZ concomitantly orally fed with oxyphenbutazone at doses of 35 and 70 mg/kg/three times a week, respectively. The total duration of experimental protocol was of 21 days. After completion of the experiments animals subjected to blood collection using light ether anesthesia and serum was separated for biochemical analysis further. The serum levels of Mg+2, Ca+2 and cardiac enzymes (aspartate transaminase (AST), lactate dehydrogenase (LDH), creatine kinase (CK) and creatine kinase-MB (CK-MB) levels were estimated. Later animals sacrificed and heart tissue isolated for further examinations. Intracellular proteins NFkB and IkBα were estimated by western blot. Results: The serum analysis revealed that CFZ administration significantly elevated the levels of LDH, CK and CKMB in CFZ exposed animals when compared to normal animals while administration of oxyphenbutazone significantly reduced these biochemical changes, Intracellular antioxidant enzymes and NF-kB in treatment groups as compared to disease control animals. Conclusion: Findings of the research protocol suggests significant injuries to cardiac tissues when animals exposed to CFZ and Oxyphenbutazone protected the cardiac tissues.

Formulation and characterization of polymeric nanoparticle of Rivastigmine for effective management of Alzheimer's disease.

Memory loss or dementia is a progressive disorder, and one of its common forms is Alzheimer's disease (AD), effecting mostly middle aged and older adults. In the present study, we developed Rivastigmine (RIV) nanoparticles using poly(lactic-co-glycolic acid) (RIV-loaded PLGA NPs) and polyvinyl alcohol (PVA). The prepared RIV-PLGA nanoparticles was evaluated for the management of Alzheimer's disease (AD). The nanoparticles were prepared by the slightly modified nano-precipitation technique. The developed formulations were evaluated for particle size, zeta potential (ZP), polydispersibility index (PDI) and surface morphology and drug content. The experimental result revealed that prepared RIV-loaded PLGA NPs (F1) was optimized having particle size (61.2 ± 4.6 nm), PDI (0.292), ZP (-11.2 ± 1.2). SEM study confirms the prepared nanoparticles depicted non-aggregated as well smooth surface particles without any fracture. This formulation (F1) was further assessed for in vivo studies on animal model. A pharmacological screening on an animal model of Alzheimer's disease revealed that RIV-loaded PLGA NPs formulations treat CNS disorders like Alzheimer's effectively. In addition to that, an in-vivo brain cholinesterase estimation study found that, animals treated with optimized formulation significantly (p < 0.01) reduced brain cholinesterase activity when compared to scopolamine-treated animals. According to the above results, it can be concluded that RIV-loaded PLGA NPs are ideal carriers for delivering the drug at a specific target site in the brain, thus may treat Alzheimer's disease efficiently and improve patient compliance.

Comparison of risk factors for Methicillin Resistant Staphylococcus aureus (MRSA) colonization in healthy newborns, born to mothers with and without MRSA colonization.

Objective: To compare the risk factors for MRSA colonization in healthy newborns, born of mothers with and without MRSA colonization. Methods: This case control study was conducted in post-natal unit of Lady Willingdon Hospital, affiliated with King Edward Medical University/Mayo Hospital, Lahore from January to June 2017. The vaginal and anterior nares swabs for MRSA culture were collected from mothers within six hours before planned delivery and the neonatal anterior nares swabs for MRSA culture were taken within one hour of birth. All the samples were cultured in Paediatric Microbiology laboratory in Mayo Hospital. Data were analyzed through SPSS 20.0 and logistic regression was applied for risk factors analysis. Results: Out of total 80 mothers and their newborns, 15 (18.75%) mothers and 16 neonates (20%) were MRSA colonized. The frequency of MRSA colonization in mothers' anterior nares and vaginal swab was 17.5% and 1.25% respectively. The significant risk factors were prolonged rupture of membranes for >18 hours (p-value 0.02, odds ratio 11.85, 95% CI 1.41-99.3), birth weight <2500 grams (p-value 0.01, odds ratio 5.39, 95% CI 1.35-21.4), history of presence of meconium (p-value 0.006, odds ratio 7.30, 95% CI 1.78-29.8). The non-significant factors were age of mother (p-value 0.682, odds ratio 0.765, 95% CI 1.0.212-2.76), parity (p-value 0.185, odds ratio 3.82, 95% CI 0.46-31.66) , gestation (p-value 0.615, odds ratio 0.797, 95% CI 0.714-0.89) , mode of delivery (p-value 0.576, odds ratio 0.543, 95% CI 0.062-4.76), sex of baby (p-value 0.546, odds ratio 0.683, 95% CI 0.196-2.37) and presentation of baby at birth (p-value 0.47, odds ratio 0.795, 95% CI 0.71-0.89). Conclusion: The presence of meconium, prolonged rupture of membranes and low birth weight were the significant risk factors for MRSA colonization in healthy new-borns, born to mothers with and without MRSA colonization.

Altered contractility, Ca2+ transients, and cell morphology seen in a patient-specific iPSC-CM model of Ebstein's anomaly with left ventricular noncompaction.

Patients with two congenital heart diseases (CHDs), Ebstein's anomaly (EA) and left ventricular noncompaction (LVNC), suffer higher morbidity than either CHD alone. The genetic etiology and pathogenesis of combined EA/LVNC remain largely unknown. We investigated a familial EA/LVNC case associated with a variant (p.R237C) in the gene encoding Kelch-like protein 26 (KLHL26) by differentiating induced pluripotent stem cells (iPSCs) generated from affected and unaffected family members into cardiomyocytes (iPSC-CMs) and assessing iPSC-CM morphology, function, gene expression, and protein abundance. Compared with unaffected iPSC-CMs, CMs containing the KLHL26 (p.R237C) variant exhibited aberrant morphology including distended endo(sarco)plasmic reticulum (ER/SR) and dysmorphic mitochondria and aberrant function that included decreased contractions per minute, altered calcium transients, and increased proliferation. Pathway enrichment analyses based on RNASeq data indicated that the "structural constituent of muscle" pathway was suppressed, whereas the "ER lumen" pathway was activated. Taken together, these findings suggest that iPSC-CMs containing this KLHL26 (p.R237C) variant develop dysregulated ER/SR, calcium signaling, contractility, and proliferation.NEW & NOTEWORTHY We demonstrate here that iPSCs derived from patients with Ebstein's anomaly and left ventricular noncompaction, when differentiated into cardiomyocytes, display significant structural and functional changes that offer insight into disease pathogenesis, including altered ER/SR and mitochondrial morphology, contractility, and calcium signaling.

Novel algorithms improve arrhythmia detection accuracy in insertable cardiac monitors.

INTRODUCTION: Insertable cardiac monitors (ICMs) are commonly used to diagnose cardiac arrhythmias. False detections in the latest ICM systems remain an issue, primarily due to inaccurate R-wave sensing. New discrimination algorithms were developed and tested to reduce false detections of atrial fibrillation (AF), pause, and tachycardia episodes in ICMs. METHODS: Stored electrograms (EGMs) of AF, pause, and tachycardia episodes detected by Abbott Confirm Rx™ ICMs were extracted from the Merlin.net™ Patient Care Network, and manually adjudicated to establish independent training and testing datasets. New discrimination algorithms were developed to reject false episodes due to inaccurate R-wave sensing, P-wave identification, and R-R interval patterns. The performance of these new algorithms was quantified by false positive reduction (FPR) and true positive maintenance (TPM), relative to the existing algorithms. RESULTS: The new AF detection algorithm was trained on 5911 EGMs from 744 devices, resulting in 66.9% FPR and 97.8% TPM. In the testing data set of 1354 EGMs from 119 devices, this algorithm achieved 45.8% FPR and 97.0% TPM. The new pause algorithm was trained on 7178 EGMs from 1490 devices, resulting in 70.9% FPR and 98.7% TPM. In the testing data set of 1442 EGMs from 340 devices, this algorithm achieved 74.4% FPR and 99.3% TPM. The new tachycardia algorithm was trained on 520 EGMs from 204 devices, resulting in 57.0% FPR and 96.6% TPM. In the testing data set of 459 EGMs from 237 devices, this algorithm achieved 57.9% FPR and 96.5% TPM. CONCLUSION: The new algorithms substantially reduced false AF, pause, and tachycardia episodes while maintaining the majority of true arrhythmia episodes detected by the Abbott ICM algorithms that exist today. Implementing these algorithms in the next-generation ICM systems may lead to improved detection accuracy, in-clinic efficiency, and device battery longevity.

Direct current cardioversion practices following percutaneous left atrial appendage closure.

INTRODUCTION: Among patients with non-valvular atrial fibrillation (AF) and percutaneous left atrial appendage closure (LAAC) undergoing direct current cardioversion (DCCV), the need for and use of LAA imaging and oral anticoagulation (OAC) is unclear. OBJECTIVE: The purpose of this study is to evaluate the real-world use of transesophageal echocardiography (TEE) or cardiac computed tomography angiography (CCTA) before DCCV and use of OAC pre- and post-DCCV in patients with AF status post percutaneous LAAC. METHODS: This retrospective single center study included all patients who underwent DCCV after percutaneous LAAC from 2016 to 2022. Key measures were completion of TEE or CCTA pre-DCCV, OAC use pre- and post-DCCV, incidence of left atrial thrombus (LAT) or device-related thrombus (DRT), incidence of peri-device leak (PDL), and DCCV-related complications (stroke, systemic embolism, device embolization, major bleeding, or death) within 30 days. RESULTS: A total of 76 patients with AF and LAAC underwent 122 cases of DCCV. LAAC consisted of 47 (62%), 28 (37%), and 1 (1%) case of Watchman 2.5, Watchman FLX, and Lariat, respectively. Among the 122 DCCV cases, 31 (25%) cases were identified as "non-guideline based" due to: (1) no OAC for 3 weeks and no LAA imaging within 48 h before DCCV in 12 (10%) cases, (2) no OAC for 4 weeks following DCCV in 16 (13%) cases, or (3) both in 3 (2%) cases. Among the 70 (57%) cases that underwent TEE or CCTA before DCCV, 16 (23%) cases had a PDL with a mean size of 3.0 ± 1.1 mm, and 4 (6%) cases had a LAT/DRT on TEE resulting in cancellation. There were no DCCV-related complications within 30 days. DISCUSSION: There is a widely varied practice pattern of TEE, CCTA, and OAC use with DCCV after LAAC, with a 6% rate of LAT/DRT. LAA imaging before DCCV appears prudent in all cases, especially within 1 year of LAAC, to assess for device position, PDL, and LAT/DRT.

Protein kinase CK2 - diverse roles in cancer cell biology and therapeutic promise.

The association of protein kinase CK2 (formerly casein kinase II or 2) with cell growth and proliferation in cells was apparent at early stages of its investigation. A cancer-specific role for CK2 remained unclear until it was determined that CK2 was also a potent suppressor of cell death (apoptosis); the latter characteristic differentiated its function in normal versus malignant cells because dysregulation of both cell growth and cell death is a universal feature of cancer cells. Over time, it became evident that CK2 exerts its influence on a diverse range of cell functions in normal as well as in transformed cells. As such, CK2 and its substrates are localized in various compartments of the cell. The dysregulation of CK2 is documented in a wide range of malignancies; notably, by increased CK2 protein and activity levels with relatively moderate change in its RNA abundance. High levels of CK2 are associated with poor prognosis in multiple cancer types, and CK2 is a target for active research and testing for cancer therapy. Aspects of CK2 cellular roles and targeting in cancer are discussed in the present review, with focus on nuclear and mitochondrial functions and prostate, breast and head and neck malignancies.

Molecular characterization of lumpy skin disease virus from recent outbreaks in Pakistan.

Lumpy skin disease (LSD) is a contagious viral transboundary disease listed as a notifiable disease by the World Organization of Animal Health (WOAH). The first case of this disease was reported in Pakistan in late 2021. Since then, numerous outbreaks have been documented in various regions and provinces across the country. The current study primarily aimed to analyze samples collected during LSD outbreaks in cattle populations in the Sindh and Punjab provinces of Pakistan. Phylogenetic analysis was conducted using partial sequences of the GPCR, p32, and RP030 genes. Collectively, the LSDV strains originating from outbreaks in Pakistan exhibited a noticeable clustering pattern with LSDV strains reported in African, Middle Eastern, and Asian countries, including Egypt, the Kingdom of Saudi Arabia, India, China, and Thailand. The precise reasons behind the origin of the virus strain and its subsequent spread to Pakistan remain unknown. This underscores the need for further investigations into outbreaks across the country. The findings of the current study can contribute to the establishment of effective disease control strategies, including the implementation of a mass vaccination campaign in disease-endemic countries such as Pakistan.

Deep learning to refine the identification of high-quality clinical research articles from the biomedical literature: Performance evaluation.

BACKGROUND: Identifying practice-ready evidence-based journal articles in medicine is a challenge due to the sheer volume of biomedical research publications. Newer approaches to support evidence discovery apply deep learning techniques to improve the efficiency and accuracy of classifying sound evidence. OBJECTIVE: To determine how well deep learning models using variants of Bidirectional Encoder Representations from Transformers (BERT) identify high-quality evidence with high clinical relevance from the biomedical literature for consideration in clinical practice. METHODS: We fine-tuned variations of BERT models (BERTBASE, BioBERT, BlueBERT, and PubMedBERT) and compared their performance in classifying articles based on methodological quality criteria. The dataset used for fine-tuning models included titles and abstracts of >160,000 PubMed records from 2012 to 2020 that were of interest to human health which had been manually labeled based on meeting established critical appraisal criteria for methodological rigor. The data was randomly divided into 80:10:10 sets for training, validating, and testing. In addition to using the full unbalanced set, the training data was randomly undersampled into four balanced datasets to assess performance and select the best performing model. For each of the four sets, one model that maintained sensitivity (recall) at ≥99% was selected and were ensembled. The best performing model was evaluated in a prospective, blinded test and applied to an established reference standard, the Clinical Hedges dataset. RESULTS: In training, three of the four selected best performing models were trained using BioBERTBASE. The ensembled model did not boost performance compared with the best individual model. Hence a solo BioBERT-based model (named DL-PLUS) was selected for further testing as it was computationally more efficient. The model had high recall (>99%) and 60% to 77% specificity in a prospective evaluation conducted with blinded research associates and saved >60% of the work required to identify high quality articles. CONCLUSIONS: Deep learning using pretrained language models and a large dataset of classified articles produced models with improved specificity while maintaining >99% recall. The resulting DL-PLUS model identifies high-quality, clinically relevant articles from PubMed at the time of publication. The model improves the efficiency of a literature surveillance program, which allows for faster dissemination of appraised research.

Cardiac magnetic resonance imaging for left atrial appendage closure planning.

BACKGROUND: Transesophageal echocardiography (TEE) and cardiac computed tomography angiography (CCTA) are currently utilized for left atrial appendage closure (LAAC) planning. During the recent global iodine contrast media shortage in 2022, cardiac magnetic resonance imaging (CMR) was utilized for the first time for LAAC planning. This study sought to assess the utility of CMR versus TEE for LAAC planning. METHODS: This single center retrospective study consisted of all patients who underwent preoperative CMR for LAAC with Watchman FLX or Amplatzer Amulet. Key measures were accuracy of LAA thrombus exclusion, ostial diameter, depth, lobe count, morphology, accuracy of predicted device size, and devices deployed per case. Bland-Altman Analysis was used to compare CMR versus TEE measurements of LAA ostial diameter and depth. RESULTS: 25 patients underwent preoperative CMR for LAAC planning. A total of 24 (96%) cases were successfully completed with 1.2 ± 0.5 devices deployed per case. Among the 18 patients who underwent intraoperative TEE, there was no significant difference between CMR versus TEE in LAA thrombus exclusion (CMR 83% vs. TEE 100% cases, p = .229), lobe count (CMR 1.7 ± 0.8 vs. TEE 1.4 ± 0.6, p = .177), morphology (p = .422), and accuracy of predicted device size (CMR 67% vs. TEE 72% cases, p = 1.000). When comparing the difference between CMR and TEE measurements, Bland-Altman analysis demonstrated no significant difference in LAA ostial diameter (CMR-TEE bias 0.7 mm, 95% CI [-1.1, 2.4], p = .420), but LAA depth was significantly larger with CMR versus TEE (CMR-TEE bias 7.4 mm, 95% CI [1.6, 13.2], p = .015). CONCLUSIONS: CMR is a promising alternative for LAAC planning in cases where TEE or CCTA are contraindicated or unavailable.

Larvicidal activity of green synthesized iron oxide nanoparticles using Grevillea robusta Cunn. leaf extract against vector mosquitoes and their characterization.

Extensive fumigation of synthetic pesticides to control the mosquito vector during each post-monsoon season in Pakistan significantly enhanced the environmental contamination and extinction of beneficial insects from the urban ecosystems. In this context, the present study examined the larvicidal efficacy of green synthesized iron nanoparticles (IONPs), using an aqueous leaf extract of Grevillea robusta against the early 2nd and 4th instar larvae of Aedes aegypti and Anopheles stephensi in Pakistan. The prepared IONPs were characterized by UV-Vis spectrum, FTIR, X-ray diffraction, scanning electron microscopy, and energy-dispersive diffraction. Larvicidal bioassay was conducted at various concentrations (80, 160, 240, 320, and 400 ppm) of IONPs prepared from leaf extract of G. robusta, and readings were taken-every 12 h for two consecutive days. In vitro, larvicidal assay, G. robusta leaf extract IONPs exhibited high mortalities of 64-96% (LC50 = 259.07 ppm; LC90 = 443.92 ppm) for the second instar and 65-98% (LC50 = 238.05 ppm; LC90 = 433.93 ppm) for the fourth instar of Ae. aegypti, while in the case of An. stephensi 56-84% (LC50 = 297.96 ppm; LC90 = 528.69 ppm) for the second and 56-88% (LC50 = 292.72 ppm; LC90 = 514.00 ppm) mortality for fourth larvae at 12-48 h post-exposure times were observed respectively. Significant (p < 0.05) dose-dependent and exposure time-dependent trends were observed among the 2nd and 4th larvalinstar of An. stephensi and Ae. aegypti. However, both species showed similar response and observed no significant (p > 0.05) difference in percentage mortality between the vector mosquitoes An. stephensi and Ae. aegypti. Overall, this study demonstrates that the larvicidal efficacy of green synthesized IONPs at low concentrations can be an ideal eco-friendly and cost-effective biocontrol of vector mosquitoes' larvae of An. stephensi and Ae. aegypti.

Acoustic scattering in lined panel cavities with membrane interfaces.

Noise control strategies are extremely important in industry. Acoustic liners and elastic membranes, which absorb or attenuate sound waves, are key components in ducting systems for active and passive noise reduction. In this article, we design and examine a reactive liner panel cavity with flexible interfaces. The lined panel cavity system is comprised of elastic membranes at the interfaces. The aim is to couple the incoming duct modes with the flexible components and then with the localized modes in the lined region. The governing equations for the lined panel cavity system are solved using a mode-matching technique that assures continuity of the normal velocities at the interfaces and can handle a range of strong coupling and higher-order edge conditions in contrast to the coupled mode theory. The aim is to investigate the effects of reactive liners and elastic membrane interfaces on wave scattering through the proposed acoustic enclosure design. The scattering performance of the proposed lined panel cavity is evaluated in terms of the reflected and transmitted energy flux as well as transmission loss. Analysis shows that the resonances at the membrane interfaces coupled to the linear cavities have a direct impact on power variations and the maximum transmission loss.