A clinical audit to evaluate antibiotic prescribing practice in pediatric patients admitted for enteric fever. Rationalizing antibiotic stewardship program.

To evaluate the antibiotic prescribing practice in pediatric patients for enteric fever, and to assess the need of developing and implementing the Antibiotic Stewardship Program (ASP) for the hospital. A prospective audit was completed in the pediatric ward of tertiary care hospital of Lahore for one year. Blood culture reports were collected from microbiology departed and clinical data were assessed regarding the choice of antibiotics, frequency, dosage and clinical outcome. All the statistics were analyzed using SPSS software and compared with the guidelines. Out of 157 cases hospitalized with suspicion of enteric fever, 137 cultures were positive for salmonella. Monotherapy of ceftriaxone (70%) was prescribed mostly as empirical therapy. About 20% of patients received a combination of antibiotics empirically. Susceptibility reports showed only 7 cases were of non-resistant typhoid, 15 multi-drug resistant and 115 extensively drug-resistant. Nearly 46% of patients were discharged earlier whose empirical therapy was changed either before or promptly after susceptibility reporting. Commonly used definitive antibiotics (32%) were a combination of azithromycin and meropenem. Inappropriate use of antibiotics was noted frequently as compared to the guidelines. However, recommendations themselves need to be reviewed as antibiotic resistance patterns are changing drastically.

Recent Advances in Carbon Nanotube Utilization in Perovskite Solar Cells: A Review.

Due to their exceptional optoelectronic properties, halide perovskites have emerged as prominent materials for the light-absorbing layer in various optoelectronic devices. However, to increase device performance for wider adoption, it is essential to find innovative solutions. One promising solution is incorporating carbon nanotubes (CNTs), which have shown remarkable versatility and efficacy. In these devices, CNTs serve multiple functions, including providing conducting substrates and electrodes and improving charge extraction and transport. The next iteration of photovoltaic devices, metal halide perovskite solar cells (PSCs), holds immense promise. Despite significant progress, achieving optimal efficiency, stability, and affordability simultaneously remains a challenge, and overcoming these obstacles requires the development of novel materials known as CNTs, which, owing to their remarkable electrical, optical, and mechanical properties, have garnered considerable attention as potential materials for highly efficient PSCs. Incorporating CNTs into perovskite solar cells offers versatility, enabling improvements in device performance and longevity while catering to diverse applications. This article provides an in-depth exploration of recent advancements in carbon nanotube technology and its integration into perovskite solar cells, serving as transparent conductive electrodes, charge transporters, interlayers, hole-transporting materials, and back electrodes. Additionally, we highlighted key challenges and offered insights for future enhancements in perovskite solar cells leveraging CNTs.

Comparative analysis of single-cell genome sequencing techniques toward the characterization of germline and somatic genomes in ciliated protists.

Ciliated protists contain both germline micronucleus (MIC) and somatic macronucleus (MAC) in a single cytoplasm. Programmed genome rearrangements occur in ciliates during sexual processes, and the extent of rearrangements varies dramatically among species, which lead to significant differences in genomic architectures. However, genomic sequences remain largely unknown for most ciliates due to the difficulty in culturing and in separating the germline from the somatic genome in a single cell. Single-cell whole genome amplification (WGA) has emerged as a powerful technology to characterize the genomic heterogeneity at the single-cell level. In this study, we compared two single-cell WGA, multiple displacement amplification (MDA) and multiple annealing and looping-based amplification cycles (MALBAC) in characterizing the germline and somatic genomes in ciliates with different genomic architectures. Our results showed that: 1) MALBAC exhibits strong amplification bias towards MAC genome while MDA shows bias towards MIC genome of ciliates with extensively fragmented MAC genome; 2) both MDA and MALBAC could amplify MAC genome more efficiently in ciliates with moderately fragmented MAC genome. Moreover, we found that more sample replicates could help to obtain more genomic data. Our work provides a reference for selecting the appropriate method to characterize germline and somatic genomes of ciliates.

Impact of sex on outcome after pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension.

BACKGROUND: The impact of sex on long-term outcomes after pulmonary endarterectomy (PEA) for chronic thromboembolic pulmonary hypertension (PH) remains unclear. We therefore examined the early and long-term outcome after PEA to determine whether sex had an impact on the risk of residual PH and need for targeted PH medical therapy. METHODS: Retrospective study of 401 consecutive patients undergoing PEA at our institution between August 2005 and March 2020 was performed. Primary outcome was the need for targeted PH medical therapy postoperatively. Secondary outcomes included survival and measures of hemodynamic improvement. RESULTS: Females (N = 203, 51%) were more likely to have preoperative home oxygen therapy (29.6% vs 11.6%, p < 0.01), and to present with segmental and subsegmental disease compared to males (49.2% vs 21.2%, p < 0.01). Despite similar preoperative values, females had higher postoperative pulmonary vascular resistance (final total pulmonary vascular resistance after PEA, 437 Dynes∙s∙cm-5 vs 324 Dynes∙s∙cm-5 in males, p < 0.01). Although survival at 10 years was not significantly different between sexes (73% in females vs 84% in males, p = 0.08), freedom from targeted PH medical therapy was lower in females (72.9% vs 89.9% in males at 5 years, p < 0.001). Female sex remained an independent factor affecting the need for targeted PH medical therapy after PEA in multivariate analysis (HR 2.03, 95%CI 1.03-3.98, p = 0.04). CONCLUSIONS: Although outcomes are excellent for both sexes, females had greater need for targeted PH medical therapy in the long-term. Early reassessment and long-term follow-up of these patients are important. Further investigations into possible mechanisms to explain the differences are warranted.

An Improved COVID-19 Detection using GAN-Based Data Augmentation and Novel QuNet-Based Classification.

COVID-19 is a fatal disease caused by the SARS-CoV-2 virus that has caused around 5.3 Million deaths globally as of December 2021. The detection of this disease is a time taking process that have worsen the situation around the globe, and the disease has been identified as a world pandemic by the WHO. Deep learning-based approaches are being widely used to diagnose the COVID-19 cases, but the limitation of immensity in the publicly available dataset causes the problem of model over-fitting. Modern artificial intelligence-based techniques can be used to increase the dataset to avoid from the over-fitting problem. This research work presents the use of various deep learning models along with the state-of-the-art augmentation methods, namely, classical and generative adversarial network- (GAN-) based data augmentation. Furthermore, four existing deep convolutional networks, namely, DenseNet-121, InceptionV3, Xception, and ResNet101 have been used for the detection of the virus in X-ray images after training on augmented dataset. Additionally, we have also proposed a novel convolutional neural network (QuNet) to improve the COVID-19 detection. The comparative analysis of achieved results reflects that both QuNet and Xception achieved high accuracy with classical augmented dataset, whereas QuNet has also outperformed and delivered 90% detection accuracy with GAN-based augmented dataset.

Central venoarterial extracorporeal membrane oxygenation as a bridge to recovery after pulmonary endarterectomy in patients with decompensated right heart failure.

INTRODUCTION: Patients with chronic thromboembolic pulmonary hypertension (CTEPH) and decompensated right heart failure (DRHF) have worse outcomes after pulmonary endarterectomy (PEA). We reviewed the role of central veno-arterial extracorporeal membrane oxygenation (VA-ECMO) as a bridge to recovery after PEA in these patients. METHODS: Of 388 consecutive patients undergoing PEA, 40 (10.3%) were admitted with DRHF before PEA. This group was compared to the remaining 348 patients undergoing PEA (elective group). We also compared 2 periods: 2005-2013 (n = 120) and 2014-2019 (n = 268) after which early central VA-ECMO was introduced as a strategy to manage difficulty weaning from cardiopulmonary bypass (CPB). RESULTS: The proportion of patients with DRHF remained similar between the first and second period (13% vs 9%, p = .2). The number of VA-ECMO bridge to recovery increased from 0.8% in 2005-2013 to 6.3% in 2014-2019 (p = .02). In the second period, 29% of DRHF patients were transitioned intraoperatively from CPB to central VA-ECMO for a median duration of 3 (2-7) days. After the introduction of central VA-ECMO as a bridge to recovery, the hospital mortality in patients with DRHF dropped from 31% in 2005-2013 to 4% in 2014-2019 (p = .03). In the long-term, the functional recovery and survival after discharged from hospital was similar between the DRHF group and the elective group. However, at 5 years, DRHF patients more frequently required PH targeted medical therapy (45% vs 20% in the elective group, p = .002). CONCLUSIONS: Central VA-ECMO as a bridge to recovery is an important treatment strategy that can decrease hospital mortality in patients with DRHF and lead to excellent long-term outcome.

Pseudo Heparin Resistance After Pulmonary Endarterectomy: Role of Thrombus Production of Factor VIII.

Pulmonary endarterectomy (PEA) is the main treatment for chronic thromboembolic pulmonary hypertension (CTEPH). Postoperative unfractionated heparin dosing can be monitored by activated partial thromboplastin time (APTT) or by anti-factor Xa activity (anti-Xa). In pseudo heparin resistance, APTT response to heparin is blunted due to elevated Factor VIII (FVIII) which can underestimate anticoagulation. We examined possible pseudo heparin resistance after PEA and assessed the impact of FVIII. APTT response to heparin before and after operation was determined in 13 PEA patients anticoagulated with unfractionated heparin. APTT and anti-Xa concordance was analyzed from paired postoperative samples, and antithrombin, fibrinogen and FVIII levels were measured. Single-cell RNA sequencing was used to characterize FVIII gene expression in PEA specimens of 5 patients. APTT response to heparin was blunted after PEA. APTT and anti-Xa were discordant in 36% of postoperative samples and most common discordant patterns were subtherapeutic APTT with therapeutic (16%) or supratherapeutic (11%) anti-Xa. Overall, APTT underestimated anticoagulation relative to anti-Xa in one-third of the samples. FVIII levels were elevated before surgery, increased substantially 1 and 3 days (median 4.32 IU/mL) after PEA, and were higher in discordant than concordant samples. Single-cell RNA sequencing showed FVIII gene expression in PEA specimen endothelial cells. Pseudo heparin resistance is common after PEA likely due to highly elevated postoperative FVIII levels indicating that anti-Xa reflects postoperative heparinization better than APTT in these patients. FVIII production by the pulmonary artery endothelium may participate in local prothrombotic processes important for CTEPH pathogenesis.

BTLA+CD200+ B cells dictate the divergent immune landscape and immunotherapeutic resistance in metastatic vs. primary pancreatic cancer.

Response to cancer immunotherapy in primary versus metastatic disease has not been well-studied. We found primary pancreatic ductal adenocarcinoma (PDA) is responsive to diverse immunotherapies whereas liver metastases are resistant. We discovered divergent immune landscapes in each compartment. Compared to primary tumor, liver metastases in both mice and humans are infiltrated by highly anergic T cells and MHCIIloIL10+ macrophages that are unable to present tumor-antigen. Moreover, a distinctive population of CD24+CD44-CD40- B cells dominate liver metastases. These B cells are recruited to the metastatic milieu by Muc1hiIL18hi tumor cells, which are enriched >10-fold in liver metastases. Recruited B cells drive macrophage-mediated adaptive immune-tolerance via CD200 and BTLA. Depleting B cells or targeting CD200/BTLA enhanced macrophage and T-cell immunogenicity and enabled immunotherapeutic efficacy of liver metastases. Our data detail the mechanistic underpinnings for compartment-specific immunotherapy-responsiveness and suggest that primary PDA models are poor surrogates for evaluating immunity in advanced disease.