bluuebunny/crossref_metadata_2025 huggingface dataset:
The efficacy of Carbamylglutamate impacts the nutritional management of patients with N-Acetylglutamate synthase deficiency
Authors: Singh Rani H. , Bourdages Marie-Hélène , Kurtz Angela , MacLoed Erin , Norman Chelsea , Ratko Suzanne , van Calcar Sandra C. , Kenneson Aileen
Published: April 2024

Background

The autosomal recessive disorder N-acetylglutamate synthase (NAGS) deficiency is the rarest defect of the urea cycle, with an incidence of less than one in 2,000,000 live births. Hyperammonemic crises can be avoided in individuals with NAGS deficiency by the administration of carbamylglutamate (also known as carglumic acid), which activates carbamoyl phosphatase synthetase 1 (CPS1). The aim of this case series was to introduce additional cases of NAGS deficiency to the literature as well as to assess the role of nutrition management in conjunction with carbamylglutamate therapy across new and existing cases.

Methods

We conducted retrospective chart reviews of seven cases of NAGS deficiency in the US and Canada, focusing on presentation, diagnosis, medication management, nutrition management, and outcomes.

Results

Five new and two previously published cases were included. Presenting symptoms were consistent with previous reports. Diagnostic confirmation via molecular testing varied in protocol across cases, with consecutive single gene tests leading to long delays in diagnosis in some cases. All patients responded well to carbamylglutamate therapy, as indicated by normalization of plasma ammonia and citrulline, as well as urine orotic acid in patients with abnormal levels at baseline. Although protein restriction was not prescribed in any cases after carbamylglutamate initiation, two patients continued to self-restrict protein intake. One patient experienced two episodes of hyperammonemia that resulted in poor long-term outcomes. Both episodes occurred after a disruption in access to carbamylglutamate, once due to insurance prior authorization requirements and language barriers and once due to seizure activity limiting the family’s ability to administer carbamylglutamate.

Conclusions

Follow-up of patients with NAGS deficiency should include plans for illness and for disruption of carbamylglutamate access, including nutrition management strategies such as protein restriction. Carbamylglutamate can help patients with NAGS deficiency to liberalize their diets, but the maximum safe level of protein intake to prevent hyperammonemia is not yet known. Patients using this medication should still monitor their diet closely and be prepared for any disruptions in medication access, which might require immediate dietary adjustments or medical intervention to prevent hyperammonemia.
Aripiprazole-induced quasi-neuroleptic malignant syndrome: two case reports
Authors: Osman Abdelgadir Hussein M. , Wilkinson Joshua
Published: April 2024

Background

Significant elevation of creatine kinase levels (above three digits) and leucocytosis in the absence of muscle rigidity, tremors, or autonomic dysfunction can pose a real challenge in the context of antipsychotic treatment as an early herald of neuroleptic malignant syndrome.

Case presentation

We present here two cases of adult male patients of Black British heritage, ages 51 years and 28 years, respectively. Both received a diagnosis of schizoaffective disorder and presented with massive increase of creatine kinase blood level after aripiprazole depot administration, one with pernicious increase associated with silent neuroleptic malignant syndrome, and the second with asymptomatic benign enzyme elevation.

Conclusion

Though aripiprazole use is less likely to cause neuroleptic malignant syndrome, on rare occasions it can produce massive symptomatic or asymptomatic increase in serum creatine kinase enzyme levels, raising the need for close monitoring, especially at the initial doses of the drug.
First true mastodon from the Late Miocene of Iran
Authors: Yaghoubi Sadaf , Ashouri Ali Reza , Mirzaie Ataabadi Majid , Ghaderi Abbas
Published: April 2024

Amammutidis described here for the first time from the Late Miocene (MN12 equivalent) deposits of Abkhareh village, Varzeghan region, in the North-Western part of Iran. It is identified as “Mammut” cf.obliquelophusand is represented by an isolated and moderately worn upper third molar with a zygodont crown pattern typical of mammutids. In addition, two upper incisors found associated with the molar and probably belonging to the same individual are assigned asMammut. The studied material expands the geographic distribution of “Mammut”obliquelophusinto Western Asia.
Determination of drug-related problems according to PAIR criteria in dialysis patients: a cross-sectional study in tertiary care hospital
Authors: Pehlivanli Aysel , Akkan Eren Sayeste , Sengul Sule , Basgut Bilgen , Erturk Sehsuvar , Ozcelikay A. Tanju
Published: April 2024

Background

Dialysis patients are at high risk for drug-related problems (DRPs), which have significant consequences for their morbidity, mortality, and quality of life. Improved clinical outcomes can be achieved by preventing, identifying, and resolving these problems.

Methods

This is a retrospective observational study. In this study, the PAIR instrument (Pharmacotherapy Assessment in Chronic Renal Disease) was validated for use in Turkish. Validation consisted of three stages: translation back-translation with expert panel evaluation, reliability analysis using the test-retest method, and conceptual validity with both Pharmaceutical Care Network Europe (PCNE) and PAIR used to determine DRPs prevalence.

Results

In total, 104 patients (mean ± SD age, 54.1 ± 15.8 years; 53.8% male) were included in the study. An expert panel evaluated the items in the criterion based on their intelligibility, service of purpose, differentiation, and cultural suitability during the translation stage. Content validity index (CVI) score was found to be 0.95. The reliability analysis was performed by applying the test-retest method and calculating correlation coefficient on 30 randomly selected patients one month later. Correlation coefficient (p) was found to be 0.8. To evaluate conceptual validity, 104 patients’ pharmacotherapy plans were assessed using both the PAIR and PCNE criteria. The prevalence of DRPs according to PAIR criteria (100.0%) and PCNE (73.1%) were statistically significantly different (p < 0.001).

Conclusions

As a result, PAIR criteria can identify clinically relevant DRPs in patients with CKD and is a new, validated tool to be used in Turkey, but may not be adequate for patients receiving dialysis. Therefore, it needs to be reviewed and updated for dialysis patients.
Therapeutic potential of targeting Nrf2 by panobinostat in pituitary neuroendocrine tumors
Authors: Cheng Yijun , Dai Yuting , Tang Hao , Lu Xingyu , Xie Jing , Xie Wanqun , Zhang Qianqian , Liu Yanting , Lin Shaojian , Yao Hong , Shang Hanbing , Yang Kun , Liu Hongyi , Wu Xuefeng , Zhang Jianming , Zhang Xun , Xue Li , Wu Zhe Bao
Published: April 2024

We aimed to identify the druggable cell-intrinsic vulnerabilities and target-based drug therapies for PitNETs using the high-throughput drug screening (HTS) and genomic sequencing methods. We examined 9 patient-derived PitNET primary cells in HTS. Based on the screening results, the potential target genes were analyzed with genomic sequencing from a total of 180 PitNETs. We identified and verified one of the most potentially effective drugs, which targeted the Histone deacetylases (HDACs) both in in vitro and in vivo PitNET models. Further RNA sequencing revealed underlying molecular mechanisms following treatment with the representative HDACs inhibitor, Panobinostat. The HTS generated a total of 20,736 single-agent dose responses which were enriched among multiple inhibitors for various oncogenic targets, including HDACs, PI3K, mTOR, and proteasome. Among these drugs, HDAC inhibitors (HDACIs) were, on average, the most potent drug class. Further studies using in vitro, in vivo, and isolated PitNET primary cell models validated HDACIs, especially Panobinostat, as a promising therapeutic agent. Transcriptional surveys revealed substantial alterations to the Nrf2 signaling following Panobinostat treatment. Moreover, Nrf2 is highly expressed in PitNETs. The combination of Panobinostat and Nrf2 inhibitor ML385 had a synergistic effect on PitNET suppression. The current study revealed a class of effective anti-PitNET drugs, HDACIs, based on the HTS and genomic sequencing. One of the representative compounds, Panobinostat, may be a potential drug for PitNET treatment via Nrf2-mediated redox modulation. Combination of Panobinostat and ML385 further enhance the effectiveness for PitNET treatment.
BCOR::CREBBP fusion in malignant neuroepithelial tumor of CNS expands the spectrum of methylation class CNS tumor with BCOR/BCOR(L1)-fusion
Authors: Ebrahimi Azadeh , Waha Andreas , Schittenhelm Jens , Gohla Georg , Schuhmann Martin U , Pietsch Torsten
Published: April 2024

Methylation class “CNS tumor with BCOR/BCOR(L1)-fusion” was recently defined based on methylation profiling and tSNE analysis of a series of 21 neuroepithelial tumors with predominant presence of a BCOR fusion and/or characteristic CNV breakpoints at chromosome 22q12.31 and chromosome Xp11.4. Clear diagnostic criteria are still missing for this tumor type, specially that BCOR/BCOR(L1)-fusion is not a consistent finding in these tumors despite being frequent and that none of the Heidelberger classifier versions is able to clearly identify these cases, in particular tumors with alternative fusions other than those involving BCOR, BCORL1, EP300 and CREBBP. In this study, we introduce a BCOR::CREBBP fusion in an adult patient with a right temporomediobasal tumor, for the first time in association with methylation class “CNS tumor with BCOR/BCOR(L1)-fusion” in addition to 35 cases of CNS neuroepithelial tumors with molecular and histopathological characteristics compatible with “CNS tumor with BCOR/BCOR(L1)-fusion” based on a comprehensive literature review and data mining in the repository of 23 published studies on neuroepithelial brain Tumors including 7207 samples of 6761 patients. Based on our index case and the 35 cases found in the literature, we suggest the archetypical histological and molecular features of “CNS tumor with BCOR/BCOR(L1)-fusion”. We also present four adult diffuse glioma cases including GBM, IDH-Wildtype and Astrocytoma, IDH-Mutant with CREBBP fusions and describe the necessity of complementary molecular analysis in “CNS tumor with BCOR/BCOR(L1)-alterations for securing a final diagnosis.
Exploring pottery origin by composition and technique comparison: a case study at the Daqu burial site, Beijing, China
Authors: He Xiang , Wen Jingqi , He Zhang , Go InHee , Liu Naitao , Guo Hong
Published: April 2024

Scientific analysis of excavated pottery reveals critical archaeological insights, yet data on Han Dynasty pottery remains limited. This study focuses on pottery artifacts excavated from the Daqu burial site in Beijing, renowned for their polychrome decorations and size. Utilizing optical microscopy (OM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), and X-ray Fluorescence (XRF), this study examined five substrate samples sourced from fragments of pottery towers and ellipse-shaped dishes. All samples exhibited similar inclusions and the same firing atmosphere. The mineralogical analysis indicated that quartz and feldspar are predominant components, with minor constituents like chlorite and kaolinite observed in the coarse pottery of the ellipse-shaped dish. Minor mineral variations suggest differences in firing temperatures. The resemblance between low-value pottery cups and delicate polychrome towers suggests they were crafted locally. These findings advance our understanding of ceramic materials and techniques in late Eastern Han Dynasty Beijing, providing crucial insights for future studies on ancient Chinese economy and society.
A firm-specific Malmquist productivity index model for stochastic data envelopment analysis: an application to commercial banks
Authors: Amirteimoori Alireza , Allahviranloo Tofigh , Nematizadeh Maryam
Published: April 2024

In the data envelopment analysis (DEA) literature, productivity change captured by the Malmquist productivity index, especially in terms of a deterministic environment and stochastic variability in inputs and outputs, has been somewhat ignored. Therefore, this study developed a firm-specific, DEA-based Malmquist index model to examine the efficiency and productivity change of banks in a stochastic environment. First, in order to estimate bank-specific efficiency, we employed a two-stage double bootstrap DEA procedure. Specifically, in the first stage, the technical efficiency scores of banks were calculated by the classic DEA model, while in the second stage, the double bootstrap DEA model was applied to determine the effect of the contextual variables on bank efficiency. Second, we applied a two-stage procedure for measuring productivity change in which the first stage included the estimation of stochastic technical efficiency and the second stage included the regression of the estimated efficiency scores on a set of explanatory variables that influence relative performance. Finally, an empirical investigation of the Iranian banking sector, consisting of 120 bank-year observations of 15 banks from 2014 to 2021, was performed to measure their efficiency and productivity change. Based on the findings, the explanatory variables (i.e., the nonperforming loan ratio and the number of branches) indicated an inverse relationship with stochastic technical efficiency and productivity change. The implication of the findings is that, in order to improve the efficiency and productivity of banks, it is important to optimize these factors.
Anesthetic management in pregnant women with Fontan circulation: a case series
Authors: Fujita Ai , Shirozu Kazuhiro , Higashi Midoriko , Yamaura Ken
Published: April 2024

Background

Given the advances in medicine, women with Fontan circulation are now reaching childbearing age. However, data on the mode of delivery and anesthetic management of these patients are limited. We report the cases of five pregnant women with Fontan circulation.

Case presentation

The mean age at delivery was 28 ± 3 years, and the mean gestational period was 34 weeks and 3 days. Anticoagulation therapy was switched from warfarin and aspirin to continuous intravenous heparin. The modes of delivery were scheduled cesarean section (C/S) in one, emergency C/S in three, and vaginal delivery with epidural labor analgesia in one patient. Three patients underwent C/S under regional anesthesia; one received general anesthesia. The perinatal complications were heart failure, worsening valve regurgitation, and postoperative hematoma in three, four, and two patients, respectively.

Conclusions

For C/S in women with Fontan circulation, regional anesthesia should be considered. Epidural labor analgesia can help prevent the decrease in pulmonary blood flow due to straining. We initiated labor analgesia or C/S with regional anesthesia at the appropriate time in four patients.
Genome editing iPSC to purposing enhancement of induce CD8 killer T cell function for regenerative immunotherapy
Authors: Kurihara Sota , Ishikawa Akihiro , Kaneko Shin
Published: April 2024

In recent years, immunotherapy has become a standard cancer therapy, joining surgery, chemotherapy, and radiation therapy. This therapeutic approach involves the use of patient-derived antigen-specific T cells or genetically modified T cells engineered with chimeric antigen receptors (CAR) or T cell receptors (TCR) that specifically target cancer antigens. However, T cells require ex vivo stimulation for proliferation when used in therapy, and the resulting “exhaustion,” which is characterized by a diminished proliferation capacity and anti-tumor activity, poses a significant challenge. As a solution, we reported “rejuvenated” CD8 + T cells that possess high proliferation capacity from induced pluripotent stem cells (iPSCs) in 2013. This review discusses the status and future developments in immunotherapy using iPSC-derived T cells, drawing insights from our research to overcome the exhaustion associated with antigen-specific T cell therapy.
Application of EEUC-based inter aircraft ultraviolet communication network algorithm in energy consumption optimization of drone swarm
Authors: Yue Kun
Published: April 2024

With the widespread application of drone technology, energy management of drone swarms has become a key challenge in ensuring sustained and efficient operations. To optimize the energy consumption of drone swarms, researchers have proposed the energy balance plane routing algorithm. This algorithm uses ultraviolet light for low visibility communication and has shown promising results in managing the energy of drone swarms. To address the issues of uneven cluster head distribution and reduced energy consumption in other algorithms, an improved non-uniform clustering energy balancing routing algorithm is proposed. Compared to existing algorithms, the improved non-uniform clustering energy balancing routing algorithm achieved the lowest average communication consumption among 5 nodes and prolonged node failure time. The performance of the research method has been verified through simulation experiments, which is of great significance in maintaining energy consumption balance and can improve the energy efficiency and sustainability of the network. This study can provide more effective solutions for the development and application of drone technology, promoting its widespread application and promotion in various fields.
The Full Non-linear Vortex Tube-Vorton Method: the pre-stall condition
Authors: Pimentel-Garcia Jesus Carlos
Published: April 2024

The present hybrid vortex tube-vorton method is based entirely on the Full Multi-wake Vortex Lattice Method (FMVLM) concepts, which means detaching vorticity with precise vortex strength and orientation along all separation lines between each discretized element of a shell-body, including all external edges. Since the classic Vortex Particle Method (VPM) is unstable by itself because it does not conserve the total amount of circulation as time evolves (Kelvin’s circulation theorem), an isolated Vortex (regularized) Filament Method (VFM) approach is implemented to obtain advection of vorticity, while the induced velocity field is obtained through its corresponding full vorton cloud. Further, a novel vortex squeezing/stretching scheme for such a vortex cylinder-sphere approach is proposed based on variation in time for vortex volumes in order to precisely (zero residual) conserve both circulation and vorticity at each time step (for each detached vortex element), while the viscous effect can be accounted for via the Core Spreading Method (CSM).
Evaluating the impact of a UK recovery college on mental well-being: pre- and post-intervention study
Authors: Allard Jon , Pollard Adam , Laugharne Richard , Coates Jamie , Wildfire-Roberts Julia , Millward Michelle , Shankar Rohit
Published: April 2024

Background

Recovery colleges provide personalised educational mental health support for people who self-refer. The research evidence supporting them is growing, with key components and the positive experiences of attendees reported. However, the quantitative outcome evidence and impact on economic outcomes is limited.

Aims

To evaluate the impact of attending a UK recovery college for students who receive a full educational intervention.

Method

This is a pre- and post-intervention study, with predominantly quantitative methods. Participants recruited over an 18-month period (01.2020–07.2021) completed self-reported well-being (Short Warwick–Edinburgh Mental Wellbeing Scale (SWEMWBS)) and recovery (Process of Recovery (QPR)) surveys, and provided details and evidence of employment and educational status. Descriptive statistics for baseline data and Shapiro–Wilk, Wilcoxon signed-rank and paired t-tests were used to compare pre- and post-intervention scores, with Hedges’ g-statistic as a measure of effect size. Medical records were reviewed and a brief qualitative assessment of changes reported by students was conducted.

Results

Of 101 student research participants, 84 completed the intervention. Well-being (mean SWEMWBS scores 17.3 and 21.9; n = 80) and recovery (mean QPR scores 27.2 and 38.8; n = 75) improved significantly (P < 0.001; Hedges’ g of 1.08 and 1.03). The number of economically inactive students reduced from 53 (69%) to 19 (24.4%). No research participants were referred for specialist mental health support while students. ‘Within-self’ and ‘practical’ changes were described by students following the intervention.

Conclusions

Findings detail the largest self-reported pre–post data-set for students attending a recovery college, and the first data detailing outcomes of remote delivery of a recovery college.
Methodology for Using Real-World Data From Electronic Health Records to Assess Chemotherapy Administration in Women With Breast Cancer
Authors: Bhimani Jenna , O'Connell Kelli , Ergas Isaac J. , Foley Marilyn , Gallagher Grace B. , Griggs Jennifer J. , Heon Narre , Kolevska Tatjana , Kotsurovskyy Yuriy , Kroenke Candyce H. , Laurent Cecile A. , Liu Raymond , Nakata Kanichi G. , Persaud Sonia , Rivera Donna R. , Roh Janise M. , Tabatabai Sara , Valice Emily , Bowles Erin J.A. , Bandera Elisa V. , Kushi Lawrence H. , Kantor Elizabeth D.
Published: April 2024

PURPOSE

Identification of patients' intended chemotherapy regimens is critical to most research questions conducted in the real-world setting of cancer care. Yet, these data are not routinely available in electronic health records (EHRs) at the specificity required to address these questions. We developed a methodology to identify patients' intended regimens from EHR data in the Optimal Breast Cancer Chemotherapy Dosing (OBCD) study.

METHODS

In women older than 18 years, diagnosed with primary stage I-IIIA breast cancer at Kaiser Permanente Northern California (2006-2019), we categorized participants into 24 drug combinations described in National Comprehensive Cancer Network guidelines for breast cancer treatment. Participants were categorized into 50 guideline chemotherapy administration schedules within these combinations using an iterative algorithm process, followed by chart abstraction where necessary. We also identified patients intended to receive nonguideline administration schedules within guideline drug combinations and nonguideline drug combinations. This process was adapted at Kaiser Permanente Washington using abstracted data (2004-2015).

RESULTS

In the OBCD cohort, 13,231 women received adjuvant or neoadjuvant chemotherapy, of whom 10,213 (77%) had their intended regimen identified via the algorithm, 2,416 (18%) had their intended regimen identified via abstraction, and 602 (4.5%) could not be identified. Across guideline drug combinations, 111 nonguideline dosing schedules were used, alongside 61 nonguideline drug combinations. A number of factors were associated with requiring abstraction for regimen determination, including: decreasing neighborhood household income, earlier diagnosis year, later stage, nodal status, and human epidermal growth factor receptor 2 (HER2)+ status.

CONCLUSION

We describe the challenges and approaches to operationalize complex, real-world data to identify intended chemotherapy regimens in large, observational studies. This methodology can improve efficiency of use of large-scale clinical data in real-world populations, helping answer critical questions to improve care delivery and patient outcomes.
Transcriptome-Based Prognostic and Predictive Biomarker Analysis of ENACT: A Randomized Controlled Trial of Enzalutamide in Men Undergoing Active Surveillance
Authors: Ross Ashley E. , Iwata Kenneth K. , Elsouda Dina , Hairston John , Russell David , Davicioni Elai , Proudfoot James A. , Shore Neal D. , Schaeffer Edward M.
Published: April 2024

PURPOSE

Few studies have explored the potential for pharmacological interventions to delay disease progression in patients undergoing active surveillance (AS). This preplanned transcriptomic analysis of patient samples from the ENACT trial aims to identify biomarkers in patients on AS who are at increased risk for disease progression or who may derive the greatest benefit from enzalutamide treatment.

PATIENTS AND METHODS

In the phase II ENACT (ClinicalTrials.gov identifier: NCT02799745 ) trial, patients on AS were randomly assigned 1:1 to 160 mg orally once daily enzalutamide monotherapy or continued AS for 1 year. Transcriptional analyses were conducted on biopsies collected at trial screening, year 1, and year 2. Three gene expression signatures were evaluated in samples collected at screening and in available samples from patients on AS at any time during surveillance (expanded cohort): Decipher genomic classifier, androgen receptor activity (AR-A) score, and Prediction Analysis of Microarray 50 (PAM50) cell subtype signature.

RESULTS

The Decipher genomic classifier score was prognostic; higher scores were associated with disease progression in the expanded cohort and AS arm of the expanded cohort. Patients with higher Decipher scores had greater positive treatment effect from enzalutamide as measured by time to secondary rise in prostate-specific antigen >25% above baseline. In patients treated with enzalutamide, higher AR-A scores and PAM50 luminal subtypes were associated with a greater likelihood of negative biopsy incidence at year 2.

CONCLUSION

This analysis suggests that the Decipher genomic classifier may be prognostic for disease progression in AS patients with low- to intermediate-risk prostate cancer. Higher Decipher and AR-A scores, as well as PAM50 luminal subtypes, may also serve as biomarkers for treatment response.
Implementation of a Three-Way Comparability Assessment for a Bioanalytical Anti-Drug Antibody Method
Authors: Kwok Rosanna S. , Nijem Ihsan , Brady Ann , Hendricks Robert
Published: April 2024

Immunogenicity evaluation is a critical part of drug development. Regulatory guidelines from multiple health agencies provide recommendations for the development and validation of anti-drug antibody (ADA) assays to assess immunogenicity in clinical trials. These recommendations primarily describe an ADA method run in one bioanalytical laboratory supporting a biotherapeutic molecule; however, there are increasing instances that may necessitate the support of the ADA method being run in more than one laboratory. A program can rapidly expand into multiple clinical studies within one or multiple countries, where the most appropriate way to support the program is by having multiple laboratories perform ADA sample analysis. In addition, there may be certain country-specific challenges that may make it infeasible to transport samples outside of the country for analysis. China for example has a lengthy sample exportation process that has potential to negatively impact study timelines. If multiple laboratories analyze samples using the same ADA method, comparable method performance should be established. Here, we describe a three-way assessment of ADA assay comparability between two US-based bioanalytical laboratories and one based in China.

Graphical Abstract
Obesity, Inflammation, and Clinical Outcomes in COVID-19: A Multicenter Prospective Cohort Study
Authors: Hutten Christina G , Padalia Kishan , Vasbinder Alexi , Huang Yiyuan , Ismail Anis , Pizzo Ian , Machado Diaz Kristen , Catalan Tonimarie , Presswalla Feriel , Anderson Elizabeth , Erne Grace , Bitterman Brayden , Blakely Pennelope , Giamarellos-Bourboulis Evangelos J , Loosen Sven H , Tacke Frank , Chalkias Athanasios , Reiser Jochen , Eugen-Olsen Jesper , Banerjee Mousumi , Pop-Busui Rodica , Hayek Salim S
Published: April 2024

Context

Obesity is a risk factor for coronavirus disease 2019 (COVID-19)-related outcomes; however, the mechanism remains unclear.

Objective

The objective of this analysis was to determine whether inflammation mediates the association between obesity and COVID-19 outcomes.

Methods

The International Study of Inflammation in COVID-19 (ISIC): A Prospective Multi-Center Observational Study Examining the Role of Biomarkers of Inflammation in Predicting Covid-19 Related Outcomes in Hospitalized Patients, was conducted at 10 hospitals in the United States and Europe. Participants were adults hospitalized specifically for COVID-19 between February 1, 2020, through October 19, 2022. Inflammatory biomarkers, including soluble urokinase plasminogen activator receptor (suPAR), were measured at admission. Associations were examined between body mass index (BMI, kg/m2) and a composite of death, need for mechanical ventilation, and renal replacement therapy, stratified by pre- and post-Omicron variants. The contribution of inflammation to the relationship between obesity and outcomes was assessed.

Results

Among 4644 participants (mean age 59.3, 45.6% male, 21.8% BMI ≥ 35), those with BMI > 40 (n = 485) had 55% higher odds of the composite outcome (95% CI, 1.21-1.98) compared with nonobese individuals (BMI < 30, n = 2358) in multivariable analysis. In multiple mediation analysis, only suPAR remained a significant mediator between BMI and composite outcome. Associations were amplified for participants younger than 65 years and with pre-Omicron variants.

Conclusion

Obesity is associated with worse outcomes in COVID-19, notably in younger participants and in the pre-Omicron era. Inflammation, as measured by suPAR, is a significant mediator of the association between obesity and COVID-19 outcomes.
Genetic Underpinnings of Fasting and Oral Glucose-stimulated Based Insulin Sensitivity Indices
Authors: Suleman Sufyan , Madsen Anne L , Ängquist Lars H , Schubert Mikkel , Linneberg Allan , Loos Ruth J F , Hansen Torben , Grarup Niels
Published: April 2024

Context

Insulin sensitivity (IS) is an important factor in type 2 diabetes (T2D) and can be estimated by many different indices.

Objective

We aimed to compare the genetic components underlying IS indices obtained from fasting and oral glucose-stimulated plasma glucose and serum insulin levels.

Methods

We computed 21 IS indices, classified as fasting, OGTT0,120, and OGTT0,30,120 indices, using fasting and oral glucose tolerance test (OGTT) data in 2 cohorts. We used data from a family cohort (n = 313) to estimate the heritability and the genetic and phenotypic correlations of IS indices. The population cohort, Inter99 (n = 5343), was used to test for associations between IS indices and 426 genetic variants known to be associated with T2D.

Results

Heritability estimates of IS indices ranged between 19% and 38%. Fasting and OGTT0,30,120 indices had high genetic (ρG) and phenotypic (ρP) pairwise correlations (ρG and ρP: 0.88 to 1) The OGTT0,120 indices displayed a wide range of pairwise correlations (ρG: 0.17-1.00 and ρP: 0.13-0.97). We identified statistically significant associations between IS indices and established T2D-associated variants. The PPARG rs11709077 variant was associated only with fasting indices and PIK3R rs4976033 only with OGTT0,30,120 indices. The variants in FAM63A/MINDY1, GCK, C2CD4A/B, and FTO loci were associated only with OGTT0,120 indices.

Conclusion

Even though the IS indices mostly share a common genetic background, notable differences emerged between OGTT0,120 indices. The fasting and OGTT-based indices have distinct associations with T2D risk variants. This work provides a basis for future large-scale genetic investigations into the differences between IS indices.
Drug-Induced Atypical Lipodystrophy
Authors: Rajakumar Priyadarshini , Mahadevan Shriraam , Asirvatham Adlyne Reena , Ranjan Asha
Published: April 2024

We describe a case of an Asian-Indian female patient who presented to us with abnormal fat accumulations in the torso and upper arms following indiscriminate use of corticosteroid and anabolic steroids for about 7 years. Despite prolonged steroid use, the patient did not display cushingoid phenotype or metabolic decompensation. Bone density, echocardiography, and ultrasonogram of the liver were also normal with no evidence of excess pericardial fat, hepatic steatosis, or peliosis hepatis. Concurrent use of anabolic androgen is thought to be protective against the ill effects of steroids, especially on the muscle and bone. This phenomenon has been observed in children and adolescents with Cushing syndrome where the adrenal androgen excess and increased physical activity have shown to reasonably reduce protein catabolism and help in preserving muscle and bone mass. The patient was withdrawn from the drugs and was put on replacement hydrocortisone that was gradually tapered over the next few weeks and planned for surgical correction. This case highlights the fact that medical providers should be aware that a combination of anabolic steroids and glucocorticoids are still used for weight-building purposes, and these patients may present with atypical signs/symptoms as a result of this combination of drugs.
Female Self-Attack and Suicide in Tayeb Salih’s Season of Migration to the North and Liana Badr’s The Eye of the Mirror
Authors: Hamamra Bilal , Mleitat Ayman , Qabaha Ahmad
Published: April 2024

Drawing on psychoanalytic and sociocultural theories of suicide and self-harm, this article argues that Hosna’s suicide in Tayeb Salih’s Season of Migration to the North (1969) and Aisha’s self-harm in Liana Badr’s The Eye of the Mirror (1994) delineate two psychological modes of the protagonists’ coping with patriarchal oppression. While Aisha’s self-harm is therapeutic and cathartic, Hosna’s suicide is revolutionary on societal levels. Although both acts stem from the destructive patriarchal practice of forced marriage, they vary in their extremity and significance. While Aisha temporarily acts out her internal distress and communicates her discontent by cutting off her hair, Hosna’s suicide embodies a feminist agenda based on self-esteem and resistance and threatens the sovereignty of the whole patriarchal structure.
The scaling of metabolic traits differs among larvae and juvenile colonies of scleractinian corals
Authors: Bean Nina K. , Edmunds Peter J.
Published: April 2024

Body size profoundly affects organism fitness and ecosystem dynamics through the scaling of physiological traits. This study tested for variation in metabolic scaling and its potential drivers among corals differing in life history strategies and taxonomic identity. Data were compiled from published sources and augmented with empirical measurements of corals in Moorea, French Polynesia. The data compilation revealed metabolic isometry in broadcasted larvae, but size-independent metabolism in brooded larvae; empirical measurements of Pocillopora acuta larvae also supported size-independent metabolism in brooded coral larvae. In contrast, for juvenile colonies (i.e. 1–4 cm diameter), metabolic scaling was isometric for Pocillopora spp., and negatively allometric for Porites spp. The scaling of biomass with surface area was isometric for Pocillopora spp., but positively allometric for Porites spp., suggesting the surface area to biomass ratio mediates metabolic scaling in these corals. The scaling of tissue biomass and metabolism were not affected by light treatment (i.e. either natural photoperiods or constant darkness) in either juvenile taxa. However, biomass was reduced by 9–15% in the juvenile corals from the light treatments and this coincided with higher metabolic scaling exponents, thus supporting the causal role of biomass in driving variation in scaling. This study shows that metabolic scaling is plastic in early life stages of corals, with intrinsic differences between life history strategy (i.e. brooded and broadcasted larvae) and taxa (i.e. Pocillopora spp. and Porites spp.), and acquired differences attributed to changes in area-normalized biomass.
Impact of hindlimb length variation on jumping dynamics in the Longshanks mouse
Authors: Bradley-Cronkwright Madison , Moore Sarah , Hou Lily , Cote Susanne , Rolian Campbell
Published: April 2024

Distantly related mammals (e.g. jerboa, tarsiers, kangaroos) have convergently evolved elongated hindlimbs relative to body size. Limb elongation is hypothesized to make these species more effective jumpers by increasing their kinetic energy output (through greater forces or acceleration distances), thereby increasing take-off velocity and jump distance. This hypothesis, however, has rarely been tested at the population level, where natural selection operates. We examined the relationship between limb length, muscular traits and dynamics using Longshanks mice, which were selectively bred over 22 generations for longer tibiae. Longshanks mice have approximately 15% longer tibiae and 10% longer femora compared with random-bred Control mice from the same genetic background. We collected in vivo measures of locomotor kinematics and force production, in combination with behavioral data and muscle morphology, to examine how changes in bone and muscle structure observed in Longshanks mice affect their hindlimb dynamics during jumping and clambering. Longshanks mice achieved higher mean and maximum lunge-jump heights than Control mice. When jumping to a standardized height (14 cm), Longshanks mice had lower maximum ground reaction forces, prolonged contact times and greater impulses, without significant differences in average force, power or whole-body velocity. While Longshanks mice have longer plantarflexor muscle bodies and tendons than Control mice, there were no consistent differences in muscular cross-sectional area or overall muscle volume; improved lunge-jumping performance in Longshanks mice is not accomplished by simply possessing larger muscles. Independent of other morphological or behavioral changes, our results point to the benefit of longer hindlimbs for performing dynamic locomotion.
Association of Hospital Market Competition with Outcomes of Complex Cancer Surgery
Authors: Munir Muhammad Musaab , Woldesenbet Selamawit , Endo Yutaka , Dillhoff Mary , Tsai Susan , Pawlik Timothy M.
Published: April 2024

Background

The association of hospital market competition, financial costs, and quality of oncologic care has not been well-defined. This study sought to evaluate variations in patient outcomes and financial expenditures after complex cancer surgery across high- and low-competition markets.

Methods

Medicare 100% Standard Analytic Files were used to identify patients with lung, esophageal, gastric, hepatopancreaticobiliary, or colorectal cancer who underwent surgical resection between 2018 and 2021. Data were merged with the annual hospital survey database, and the hospital market Herfindahl–Hirschman index was used to categorize hospitals into low- and high-concentration markets. Multi-level, multivariable regression models adjusting for patient characteristics (i.e., age, sex, comorbidities, and social vulnerability), year of procedure, and hospital factors (i.e., case volume, nurse-bed ratio, and teaching status) were used to assess the association between hospital market competition and outcomes.

Results

Among 117,641 beneficiaries who underwent complex oncologic surgery, the mean age was 73.8 ± 6.1 years, and approximately one-half of the cohort was male (n = 56,243, 47.8%). Overall, 63.8% (n = 75,041) of the patients underwent care within a high-competition market. Notably, there was marked geographic variation relative to market competition. High versus low market-competition hospitals were more likely to be in high social vulnerability areas (35.1 vs 27.5%; p < 0.001), as well as care for racial/ethnic minority individuals (13.8 vs 7.7%; p < 0.001), and patients with more comorbidities (≥ 2 Elixhauser comorbidities: 63.1 vs 61.1%; p < 0.001). In the multivariable analysis, treatment at hospitals in high- versus low-competition markets was associated with lower odds of achieving a textbook outcome (odds ratio, 0.95; 95% confidence interval, 0.91–0.99; p = 0.009). Patients at high-competition hospitals had greater mean index hospitalization costs ($19,462.2 [16211.9] vs $18,844.7 [14994.7]) and 90-day post-discharge costs ($7807.8 [15431.3] vs $7332.8 [14038.2]) (both p < 0.001) than individuals at low-competition hospitals.

Conclusions

Hospital market competition was associated with poor achievement of an optimal postoperative outcome and greater hospitalization costs.
PACRAT: Pathogen detection with aptamer-detected cascaded recombinase polymerase amplification-in vitro transcription
Authors: Khan Pavana , Aufdembrink Lauren , Adamala Katarzyna P , Engelhart Aaron
Published: April 2024

The SARS-CoV-2 pandemic underscored the need for early, rapid, and widespread pathogen detection tests that are readily accessible. Many existing rapid isothermal detection methods employ the recombinase polymerase amplification (RPA), which exhibits PCR-like sensitivity, specificity, and even higher speed. However, coupling RPA to other enzymatic reactions has proven difficult. For the first time, we demonstrate that with tuning of buffer conditions and optimization of reagent concentrations, RPA can be cascaded into an in vitro transcription reaction, enabling detection using fluorescent aptamers in a one-pot reaction. We show that this reaction, which we term PACRAT (Pathogen detection with Aptamer-detected Cascaded Recombinase polymerase Amplification-in vitro Transcription) can be used to detect SARS-CoV-2 with single-copy detection limits and 10-minute detection times. Further demonstrating the utility of our one-pot, cascaded amplification system, we show PACRAT can be employed for multiplexed detection of the pathogens SARS-CoV-2 and E. coli, along with multiplexed detection of two variants of SARS-CoV-2.
Η εφαρμογή της τεχνητής νοημοσύνης στoν τραπεζικό κλάδο
Authors: Ζιοβίρης Γεώργιος
Published: April 2024

Ο τραπεζικός τομέας βρίσκεται στα πρόθυρα ενός σημαντικού μετασχηματισμού, με την κινητήρια δύναμη πίσω από αυτόν να είναι η Τεχνητή Νοημοσύνη (ΤΝ). Νέες εφαρμογές της τεχνητής νοημοσύνης έχουν ήδη προταθεί για την αντιμετώπιση προκλήσεων σε τομείς όπως η πιστοληπτική αξιολόγηση, η αξιολόγηση κινδύνου, η βελτίωση της εμπειρίας των πελατών και η αποτελεσματική διαχείριση του χαρτοφυλακίου. Ένα από τα πιο κρίσιμα ζητήματα στον ανωτέρω τομέα είναι ο εντοπισμός απάτης σε συναλλαγές. Πρόσφατα, εισήχθησαν μοντέλα βαθιάς μάθησης για την αντιμετώπιση αυτού του προβλήματος, στοχεύοντας στον εντοπισμό και την πρόβλεψη πιθανών δόλιων ενεργειών. Ο στόχος είναι να εκτιμηθεί η άγνωστη κατανομή των κανονικών/δόλιων συναλλαγών και, στη συνέχεια, να ανιχνευθούν αποκλίσεις που μπορεί να υποδηλώνουν πιθανή απάτη. Σε αυτήν τη διατριβή, παρουσιάζουμε ένα νέο πολυεπίπεδο μοντέλο βαθιάς μάθησης που στοχεύει στην αποτελεσματική διαχείριση των εισερχομένων ροών συναλλαγών και στον εντοπισμό των δόλιων ενεργειών. Προτείνουμε τη χρήση αυτόματων κωδικοποιητών για την εκτέλεση επιλογής χαρακτηριστικών και την εκμάθηση της αναπαράστασης του κρυφού χώρου δεδομένων με βάση ένα μη γραμμικό μοντέλο βελτιστοποίησης. Στα προκαθορισμένα σημαντικά χαρακτηριστικά, εφαρμόζουμε στη συνέχεια ένα Συνελικτικό Νευρικό Δίκτυο(Convolutional Neural Network ή CNN) για τον εντοπισμό απάτης ή ένα Μοντέλο Μακράς Μνήμης με Βραχυπρόθεσμη Μνήμη (Long - Short Term Memory ή LSTM), συνδυάζοντας έτσι δύο διαφορετικά μπλοκ επεξεργασίας. Ο συνδυασμός που εφαρμόζουμε έχει ως στόχο την ανίχνευση απάτης σχετικά με την αποκαλυμμένη αναπαράσταση δεδομένων και όχι των αρχικών δεδομένων. Ένας άλλος στόχος αυτής της διατριβής είναι να παρουσιάσει μια νέα βελτίωση του αλγορίθμου L.I.M.E. που χρησιμοποιείται για την ερμηνεία μοντέλων μηχανικής μάθησης. Εκτός από τη χρήση μοντέλων για την πρόβλεψη, η δυνατότητα ερμηνείας των αποτελεσμάτων που έχει αποκτήσει ένα μοντέλο λαμβάνει αυξημένη προσοχή στη σύγχρονη έρευνα. Δεν είναι ακόμη σαφές πώς συνδέεται το ευρύ φάσμα των προτεινόμενων μεθόδων ερμηνείας και ποιες κοινές έννοιες μπορούν να χρησιμοποιηθούν για την αξιολόγησή τους. Η τεχνική που προτείνουμε χρησιμοποιεί έναν αυτόματο κωδικοποιητή για τη δημιουργία νέων δεδομένων (neighborhood) γύρω από το data point που μας ενδιαφέρει να ερμηνεύσουμε, αντί να βασιστεί σε απλή δημιουργία δεδομένων με μια κανονική κατανομή γύρω από αυτό.
A Systematic Review and Meta-Analysis of the Timing of Vasopressor Therapy in Patients with Septic Shock: Assessing Clinical Outcomes and Implication
Authors: Zaki Hany A. , Elgassim Mohamed , Shaban Eman E. , Ahmed Amina , Hashim Thamir , Mohamed Mazin Sharafeldien Elsayed , Abdelrahman Amro , Basharat Kaleem , Abdurabu Mohammed , Shaban Ahmed
Published: April 2024

Background Septic shock, is associated with a high mortality rate and increased expenses. Currently, the first-line therapy for septic shock entails administering resuscitation fluids followed by infusing vasopressors when the blood pressure goal is not achieved. The recommended first-line vasopressor is norepinephrine, followed by vasopressin, epinephrine, angiotensin II, and dopamine. There is still a controversy on when each vasopressor should be administered. Therefore, we conducted this review to determine the impact and implications of vasopressor timing in septic shock patients. Methods PubMed, Medline, Cochrane Library, Web of Science, and Google Scholar databases were comprehensively searched for potential studies until October 2023. The methodological quality and bias assessment of valid records was examined with the Newcastle Ottawa Scale and Cochrane’s risk of bias tool. Additionally, all the meta-analyses were performed with Review Manager software. Results Twelve articles were eligible for review and analysis. Pooled analyses of data from 7 of these studies demonstrated lower incidence of mortality and shorter duration to achieve target mean arterial pressure in the early vs. late epinephrine groups (OR:0.44; 95%CI: 0.35–0.55; p<0.00001 and MD:-1.17; 95%CI:-2.00– -0.34; p=0.0006). However, the length of ICU stay didn’t differ between the early and late norepinephrine group (MD:0.55; 95%CI: -0.52–1.62; p=0.31). The subgroup analyses show that early vasopressin is associated with a decreased mortality than late administration (OR:0.60; 95%CI:0.41–0.90; p=0.01). Similarly, the pooled analysis has shown that early concomitant administration of vasopressin and norepinephrine is associated with a shorter duration to achieve target MAP than norepinephrine alone (MD:-3.15; 95%CI:-4.40– -1.90;p<0.00001). Conclusion Early administration of norepinephrine has a mortality benefit and improves the duration taken to attain and sustain the goal MAP. Furthermore, early vasopressin possesses the potential to lower the fatality rate in individuals experiencing septic shock. However, further research is required to validate this finding.
A cross-sectional study on the role of computed tomography in the evaluation of oral cavity malignancies in tertiary care hospital in central India: A study protocol
Authors: Kasat Paschyanti , Kashikar Shivali
Published: April 2024

Background Oral cavity malignancies pose a significant health burden, necessitating accurate diagnostic tools for optimal treatment planning. This cross-sectional study investigates the role of Computed Tomography (CT) in evaluating oral cavity malignancies, focusing on tumor thickness and nodal staging. The study is conducted in a tertiary care hospital in Central India, aiming to enhance diagnostic precision in this region. Methods A prospective, cross-sectional design is employed over two years. Patients with clinical or biopsy-proven oral cavity carcinoma are included after obtaining informed consent. CT scans are performed using a standardized protocol, and imaging findings are correlated with histopathological staging. Statistical analyses, including descriptive statistics, bivariate analysis, correlation analysis, and multivariable modeling, are conducted using SPSS version 27.0. Expected Outcome Anticipated outcomes include a comprehensive understanding of the accuracy of CT in evaluating tumor thickness and nodal stage in oral cavity malignancies. The study aims to delineate the extent and depth of soft tissue and bony invasion, assess nodal metastases, and correlate radiologic findings with histopathological results. The expected findings will contribute valuable insights into the utility of CT in the clinical management of oral cavity malignancies, potentially influencing treatment decisions and improving patient outcomes.