bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased minute ventilation-to-carbon dioxide slope during cardiopulmonary exercise test is associated with poor postoperative outcome following lung cancer resection
Authors: Rushwan Amr , Stefanou Demetrios , Tariq Javeria , Drosos Polivious , Chaudhuri Nilanjan , Milton Richard , Tcherveniakov Peter , Papagiannopoulos Kostas , Brunelli Alessandro
Published: October 2023

OBJECTIVES

Ventilatory efficiency [minute ventilation-to-carbon dioxide output slope (VE/VCO2 slope)] can be measured at sub-maximal workload during cardiopulmonary exercise test. The aim of this study is to assess the association between VE/VCO2 slope and outcome after lung cancer resections.

METHODS

Retrospective, single-centre analysis on all patients undergoing lung resection for cancer (April 2014–August 2022) and with a preoperative cardiopulmonary exercise test. VE/VCO2 slope >40 was chosen as high-risk threshold. Logistic regression analysis was used to test the association of VE/VCO2 slope and several patient- and surgery-related factors with 90-day mortality.

RESULTS

A total of 552 patients were included (374 lobectomies, 81 segmentectomies, 55 pneumonectomies and 42 wedge resections). Seventy-four percent were minimally invasive procedures. Cardiopulmonary morbidity was 32%, in-hospital/30-day mortality 6.9% and 90-day mortality 8.9%. A total of 137 patients (25%) had a slope of >40. These patients were older (72 vs 70 years, P = 0.012), had more frequently coronary artery disease (17% vs 10%, P = 0.028), lower carbon monoxide lung diffusion capacity (57% vs 68%, P < 0.001), lower body mass index (25.4 vs 27.0 kg/m2, P = 0.001) and lower peak VO2 (14.9 vs 17.0 ml/kg/min, P < 0.001) than those with a lower slope. The cardiopulmonary morbidity among patients with a slope of >40 was 40% vs 29% in those with lower slope (P = 0.019). Ninety-day mortality was 15% vs 6.7% (P = 0.002). The 90-day mortality of elderly patients with slope >40 was 21% vs 7.8% (P = 0.001). After adjusting for peak VO2 value, extent of operation and other patient-related variables in a logistic regression analysis, VE/VCO2 slope retained a significant association with 90-day mortality.

CONCLUSIONS

VE/VCO2 slope was strongly associated with morbidity and mortality following lung resection and should be included in the functional algorithm to assess fitness for surgery.
Altered Gene Expression Within the Renin–Angiotensin System in Normal Aging and Dementia
Authors: Tayler Hannah M , MacLachlan Robert , Güzel Özge , Fisher Robert A , Skrobot Olivia A , Abulfadl Mohamed A , Kehoe Patrick G , Miners J Scott
Published: October 2023

The renin–angiotensin system (RAS) is dysregulated in Alzheimer’s disease (AD). In this study, we have explored the hypothesis that an ­age-­related imbalance in brain RAS is a trigger for RAS dysregulation in AD. We characterized RAS gene expression in the frontal cortex from (i) a cohort of normal aging (n = 99, age range = 19–96 years) and (ii) a case–control cohort (n = 209) including AD (n = 66), mixed dementia (VaD + AD; n = 50), pure vascular dementia (VaD; n = 42), and age-matched controls (n = 51). The AD, mixed dementia, and age-matched controls were further stratified by Braak tangle stage (BS): BS0–II (n = 48), BSIII–IV (n = 44), and BSV–VI (n = 85). Gene expression was calculated by quantitative PCR (qPCR) for ACE1, AGTR1, AGTR2, ACE2, LNPEP, and MAS1 using the 2−∆∆Cq method, after adjustment for reference genes (RPL13 and UBE2D2) and cell-specific calibrator genes (NEUN, GFAP, PECAM). ACE1 and AGTR1, markers of classical RAS signaling, and AGTR2 gene expression were elevated in normal aging and gene expression in markers of protective downstream regulatory RAS signaling, including ACE2, MAS1, and LNPEP, were unchanged. In AD and mixed dementia, AGTR1 and AGTR2 gene expression were elevated in BSIII–IV and BSV–VI, respectively. MAS1 gene expression was reduced at BSV–VI and was inversely related to parenchymal Aβ and tau load. LNPEP gene expression was specifically elevated in VaD. These data provide novel insights into RAS signaling in normal aging and dementia.
Spatial and temporal characterization of a recurrent scalloped hammerhead shark Sphyrna lewini aggregation using drones
Authors: López N A , McAuley R B , van Elden S , Meeuwig J J
Published: October 2023

Scalloped hammerhead sharks Sphyrna lewini are threatened throughout their distribution. The species forms aggregations, which can potentially increase its vulnerability to human impacts. Identification and characterization of aggregation sites are essential to inform management and conservation. We used drones to characterize the spatial and temporal distribution of a recently documented scalloped hammerhead aggregation within the Shoalwater Islands Marine Park, in southwest Western Australia. A total of 267 drone transects were conducted across the Austral summers of 2019–2020 and 2020–2021. The presence or absence of the sharks was examined in relation to fine scale patterns in habitat type, environmental conditions, and the occurrence of human activities. Scalloped hammerhead sharks had a small spatial and temporal distribution within the study area. Their presence in the study area was higher on days associated with higher lunar illumination phases, which could indicate that the aggregation site is potentially acting as a refuge for resting and/or predatory avoidance. The extent to which human interactions affect scalloped hammerhead sharks at the aggregation site remains unclear and raises questions about the adequacy of management measures at Shoalwater Islands Marine Park. Recommendations are proposed to limit potential impacts, such as establishing spatiotemporal fishing restrictions and regulating public interactions.
Early aortic valve neocuspidization failure due to xenograft leaflet tear in a young adult
Authors: Lee Kwok Fai Lucius , Mak Ka Lun Tony , Chen Qiang , Yam Nicholson
Published: October 2023

Aortic valve neocuspidization, initially described by Ozaki and colleagues, has become an increasingly popular treatment approach for aortic valve disease in both adult and paediatric populations. We report a case of an 18-year-old man with severe aortic regurgitation who underwent the Ozaki procedure using photo-oxidized bovine pericardium. Around 5 weeks after the surgery, he developed early symptomatic valve failure due to multiple leaflet tears requiring urgent reoperation.
Optimization of the EUCAST reference broth microdilution method for echinocandin susceptibility testing of Aspergillus fumigatus
Authors: Siopi Maria , Georgiou Panagiota-Christina , Pournaras Spyros , Meletiadis Joseph
Published: October 2023

Background

Because of the high inoculum (105 cfu/mL) used in the EUCAST susceptibility testing of Aspergillus spp., determination of the minimal effective concentration (MEC) of echinocandins is challenging as the morphological differences are subtle.

Methods

The MECs of 10 WT and 4 non-WT Aspergillus fumigatus isolates were determined with the EUCAST E.Def 9.4. Plates were inoculated with increasing inocula (102–105 cfu/mL) and after 24 and 48 h of incubation, MECs were determined macroscopically (magnifying mirror) and microscopically (inverted microscope) by two observers, spectrophotometrically (OD at 405 nm) and colorimetrically (absorbance at 450/630 nm after 2 h incubation with 400 mg/L XTT/6.25 μM menadione). The interobserver (between observers)/intermethod (compared with the microscopic method) essential agreement (EA, ±1 2-fold dilution) and categorical agreement (CA) were determined for each inoculum.

Results

Echinocandin-induced microscopic hyphal alterations or macroscopic changes in turbidity were subtle with a 105 cfu/mL inoculum compared with the lower inocula of 103 and 102 cfu/mL, where more distinct changes in turbidity and formation of characteristic rosettes were obvious at the MEC after 48 h. A 105 cfu/mL inoculum resulted in wider MEC distributions (3–6 dilutions) and lower interobserver EA (69%), macroscopic–microscopic EA (26%) and CA (71%) compared with a 103 cfu/mL inoculum (2–3 dilutions, 100%, 100% and 100%, respectively). Spectrophotometric readings using a 103 cfu/mL inoculum showed good EA (57–93%) and excellent CA (86%–100%), while the XTT assay demonstrated excellent EA (93%) and CA (100%).

Conclusions

A 48 h incubation using a 103 cfu/mL inoculum improved echinocandin MEC determination for A. fumigatus with the EUCAST method, while the colorimetric assay could allow automation.
Chromogenic and Clot-Based Bivalirudin Assays for Monitoring Anticoagulation
Authors: Raghavendran Prashant , Tillman Benjamin F , Wheeler Allison P , Gailani David
Published: October 2023

Background

Direct thrombin inhibitors (DTIs) are usually monitored with the activated partial thromboplastin time (aPTT) or activated clotting time (ACT). Both are complex assays with multiple enzymatic steps, and performance may be influenced by physiologic and pathologic factors unrelated to the DTI. Simpler systems, such as clot-based dilute thrombin time (dTT) and chromogenic anti-factor IIa assays, have been developed for monitoring DTIs, but there is limited data on their performance in clinical settings.

Methods

Medical records of patients who received bivalirudin between March 2020 and April 2022 at a single institution were reviewed for demographic data and adverse outcomes. Plasma samples drawn for aPTT testing were analyzed with chromogenic anti-IIa and dTT bivalirudin assays. Results were compared to bivalirudin dosing.

Results

Results of aPTT assays from 32 patients were compared with the chromogenic (n = 136) and dTT (n = 120) bivalirudin assays. Correlations between the aPTT and the chromogenic and dTT assays were poor (Spearman coefficients 0.55 and 0.62, respectively). There was a stronger correlation when results of the chromogenic and dTT assays were compared to each other (Spearman coefficient 0.92). When assay results were compared to bivalirudin dose, there were stronger correlations with the chromogenic and dTT assays than with the aPTT (Spearman coefficients 0.51, 0.63 and 0.22, respectively).

Conclusions

There was considerable variation between results of specific bivalirudin assays and the aPTT. While bivalirudin assay results correlated better with administered drug dose, suggesting improving reliability, more studies are needed to determine if there is correlation between testing and clinical outcomes.
Effects of ensiling sugarcane tops with bacteria-enzyme inoculants on growth performance, nutrient digestibility, and the associated rumen microbiome in beef cattle
Authors: Tang Qingfeng , He Renchun , Huang Feng , Liang Qimei , Zhou Zhiyang , Zhou Junhua , Wang Qizhi , Zou Caixia , Gu Qichao
Published: October 2023

Major challenges when ensiling sugarcane tops include fermentation that results in high quantities of alcohol and decrease in nutrient digestibility due to the accumulation of fiber components. Increased efforts to apply bacteria-enzyme inoculants in silage have the potential to improve nutrient digestibility. This study aimed to evaluate the effects of ensiling sugarcane tops with bacteria-enzyme inoculants or mixed bacterial inoculants on growth performance, nutrient digestibility, and rumen microbiome in beef cattle. Chopped sugarcane tops were ensiled in plastic bags for 60 d after application of 1) no inoculant (control check, CK); 2) bacteria-enzyme inoculants containing Pediococcus acidilactici, Saccharomyces cerevisiae, cellulase, and xylanase (T1, viable colony-forming units of each bacterial strain ≥108 CFU/g; enzyme activity of each enzyme ≥200 U/g); or 3) mixed bacterial inoculants containing Lactobacillus plantarum, Bacillus subtilis, and Aspergillus oryzae (T2, viable colony-forming units of each bacterial strain ≥107 CFU/g). Silages were fed to eighteen Holstein bull calves (n = 6/treatment) weighing 163.83 ± 7.13 kg to determine intake in a 49-d experimental period. The results showed that beef cattle-fed T1 silage or T2 silage had a significantly higher (P < 0.05) average daily gain than those fed CK silage, but the difference in dry matter intake was not significant (P > 0.05). The apparent digestibility of crude protein (CP) and acid detergent fiber (ADF) were higher (P < 0.05) for beef cattle-fed T1 silage or T2 silage than for those fed CK silage. The rumen bacterial community of beef cattle-fed T1 silage or T2 silage had a tendency to increase (P > 0.05) abundance of Firmicutes and Rikenellaceae_RC9_gut_group than those fed CK silage. Rumen fungal communities of beef cattle-fed T1 or T2 silage had a tendency to increase (P > 0.05) abundance of Mortierellomycota and of Mortierella than those fed CK silage. Spearman’s rank correlation coefficient showed that the apparent digestibility of ADF for beef cattle was positively correlated with unclassified_p_Ascomycota of the fungal genera (P < 0.05). Neocalimastigomycota of the fungal phyla was strongly positively correlated with the apparent digestibility of neutral detergent fiber (NDF) (P < 0.05). Ruminococcus was positively correlated with the apparent digestibility of CP (P < 0.05). It was concluded that both T1 and T2 improved the growth performance of beef cattle by improving the ruminal apparent digestibility of CP and ADF, and had no significant impact on major rumen microbial communities in beef cattle.
The SH3 binding site in front of the WH1 domain contributes to the membrane binding of the BAR domain protein endophilin A2
Authors: Sim Pei Fang , Chek Min Fey , Nguyen Nhung Thi Hong , Nishimura Tamako , Inaba Takehiko , Hakoshima Toshio , Suetsugu Shiro
Published: October 2023

The Bin–Amphiphysin–Rvs (BAR) domain of endophilin binds to the cell membrane and shapes it into a tubular shape for endocytosis. Endophilin has a Src-homology 3 (SH3) domain at their C-terminal. The SH3 domain interacts with the proline-rich motif (PRM) that is found in proteins such as neural Wiskott–Aldrich syndrome protein (N-WASP). Here, we re-examined the binding sites of the SH3 domain of endophilin in N-WASP by machine learning-based prediction and identified the previously unrecognized binding site. In addition to the well-recognized PRM at the central proline-rich region, we found a PRM in front of the N-terminal WASP homology 1 (WH1) domain of N-WASP (NtPRM) as a binding site of the endophilin SH3 domain. Furthermore, the diameter of the membrane tubules in the presence of NtPRM mutant was narrower and wider than that in the presence of N-WASP and in its absence, respectively. Importantly, the NtPRM of N-WASP was involved in the membrane localization of endophilin A2 in cells. Therefore, the NtPRM contributes to the binding of endophilin to N-WASP in membrane remodeling.
The impact of client-overlap hiring on PSF client embeddedness
Authors: Kim Yeongsu Anthony , Skaggs Bruce C
Published: October 2023

Professional service firms (PSFs) are commonly perceived to attain success through the acquisition of new clients. However, these firms are not solely reliant on this strategy as PSFs may also achieve competitive advantage by improving their relationships with existing clients. Despite the significance of these established client relationships, limited information exists regarding how PSFs can effectively enhance and utilize them. This study examines how a PSF’s client-related knowledge can be obtained and developed through its hiring practices in order to strengthen relationships with existing clients. Results reveal that when hiring from other PSFs who share similar clients (i.e., client-overlapping PSFs), that this has a positive impact on the firm’s overall relationships with its clients, with the effect being impacted by the firm’s level of practice overlap with the new hires and the degree of co-mobility of the hires.
SoyMD: a platform combining multi-omics data with various tools for soybean research and breeding
Authors: Yang Zhiquan , Luo Chengfang , Pei Xinxin , Wang Shengbo , Huang Yiming , Li Jiawei , Liu Baohui , Kong Fanjiang , Yang Qing-Yong , Fang Chao
Published: October 2023

Advanced multi-omics technologies offer much information that can uncover the regulatory mechanisms from genotype to phenotype. In soybean, numerous multi-omics databases have been published. Although they cover multiple omics, there are still limitations when it comes to the types and scales of omics datasets and analysis methods utilized. This study aims to address these limitations by collecting and integrating a comprehensive set of multi-omics datasets. This includes 38 genomes, transcriptomes from 435 tissue samples, 125 phenotypes from 6686 accessions, epigenome data involving histone modification, transcription factor binding, chromosomal accessibility and chromosomal interaction, as well as genetic variation data from 24 501 soybean accessions. Then, common analysis pipelines and statistical methods were applied to mine information from these multi-omics datasets, resulting in the successful establishment of a user-friendly multi-omics database called SoyMD (https://yanglab.hzau.edu.cn/SoyMD/#/). SoyMD provides researchers with efficient query options and analysis tools, allowing them to swiftly access relevant omics information and conduct comprehensive multi-omics data analyses. Another notable feature of SoyMD is its capability to facilitate the analysis of candidate genes, as demonstrated in the case study on seed oil content. This highlights the immense potential of SoyMD in soybean genetic breeding and functional genomics research.
Yeast ribosome biogenesis factors Puf6 and Nog2 and ribosomal proteins uL2 and eL43 act in concert to facilitate the release of nascent large ribosomal subunits from the nucleolus
Authors: LaPeruta Amber J , Hedayati Stefanie , Micic Jelena , Fitzgerald Fiona , Kim David , Oualline Grace , Woolford John L
Published: October 2023

Large ribosomal subunit precursors (pre-LSUs) are primarily synthesized in the nucleolus. At an undetermined step in their assembly, they are released into the nucleoplasm. Structural models of yeast pre-LSUs at various stages of assembly have been collected using cryo-EM. However, which cryo-EM model is closest to the final nucleolar intermediate of the LSU has yet to be determined. To elucidate the mechanisms of the release of pre-LSUs from the nucleolus, we assayed effects of depleting or knocking out two yeast ribosome biogenesis factors (RiBi factors), Puf6 and Nog2, and two ribosomal proteins, uL2 and eL43. These proteins function during or stabilize onto pre-LSUs between the late nucleolar stages to early nucleoplasmic stages of ribosome biogenesis. By characterizing the phenotype of these four mutants, we determined that a particle that is intermediate between the cryo-EM model State NE1 and State NE2 likely represents the final nucleolar assembly intermediate of the LSU. We conclude that the release of the RiBi factors Nip7, Nop2 and Spb1 and the subsequent stabilization of rRNA domains IV and V may be key triggers for the release of pre-LSUs from the nucleolus.
SORC: an integrated spatial omics resource in cancer
Authors: Zhou Weiwei , Su Minghai , Jiang Tiantongfei , Yang Qingyi , Sun Qisen , Xu Kang , Shi Jingyi , Yang Changbo , Ding Na , Li Yongsheng , Xu Juan
Published: October 2023

The interactions between tumor cells and the microenvironment play pivotal roles in the initiation, progression and metastasis of cancer. The advent of spatial transcriptomics data offers an opportunity to unravel the intricate dynamics of cellular states and cell–cell interactions in cancer. Herein, we have developed an integrated spatial omics resource in cancer (SORC, http://bio-bigdata.hrbmu.edu.cn/SORC), which interactively visualizes and analyzes the spatial transcriptomics data in cancer. We manually curated currently available spatial transcriptomics datasets for 17 types of cancer, comprising 722 899 spots across 269 slices. Furthermore, we matched reference single-cell RNA sequencing data in the majority of spatial transcriptomics datasets, involving 334 379 cells and 46 distinct cell types. SORC offers five major analytical modules that address the primary requirements of spatial transcriptomics analysis, including slice annotation, identification of spatially variable genes, co-occurrence of immune cells and tumor cells, functional analysis and cell–cell communications. All these spatial transcriptomics data and in-depth analyses have been integrated into easy-to-browse and explore pages, visualized through intuitive tables and various image formats. In summary, SORC serves as a valuable resource for providing an unprecedented spatially resolved cellular map of cancer and identifying specific genes and functional pathways to enhance our understanding of the tumor microenvironment.
Physician, patient, and caregiver support for a formal certification in pediatric neuro-oncology: A survey-based report from the SNO pediatrics working group
Authors: Lindsay Holly B , Cheng Sylvia , Fisher Paul Graham , Peters Katherine B , Walsh Kyle M , Ashley David M , Huang Annie
Published: October 2023

Background

Although CNS tumors are the most common pediatric cancer in the United States, most physicians caring for these patients are not formally certified in the subspecialty. To determine support for developing a formal certification process in pediatric neuro-oncology, the Society for Neuro-Oncology’s Pediatrics Special Interest Track Training and Credentialing working group performed a cross-sectional survey-based study of physicians and patients/caregivers of children with a CNS tumor history.

Methods

Surveys were built in Survey Monkey and were available for 3 months. The physician survey had 34 questions and was open to doctors currently caring for pediatric neuro-oncology patients. The patient/caregiver survey had 13 questions. Both surveys were completed anonymously.

Results

The physician survey was completed by 193 participants, the majority of whom self-identified as oncologists. Only 5.6% of survey participants had ever been board-certified in neuro-oncology; the majority of participating physicians were either unaware that this certification existed or thought they were not eligible due to training in pediatrics rather than neurology or internal medicine. Almost half of the self-identified pediatric neuro-oncologists had not completed any specific clinical neuro-oncology training. Over 75% of physicians were supportive of the implementation of a formal certification process in pediatric neuro-oncology. A total of 30 participants completed the patient/caregiver survey. Although the majority of survey participants were highly satisfied with their oncologist, 70% would have been more comfortable if their oncologist had been specifically certified in pediatric neuro-oncology.

Conclusions

There is support from physicians, patients, and caregivers to establish a formal certification process in pediatric neuro-oncology.
Spectral analysis of the Galactic supernova remnant Kesteven 69 with Suzaku
Authors: Yamauchi Shigeo , Pannuti Thomas G
Published: October 2023

The results of a Suzaku observation of the supernova remnant (SNR) Kesteven 69 = G21.8−0.6 are presented. To estimate the sky background precisely, we conducted a simultaneous fit of the source region spectrum with the background region spectrum and found that the SNR spectrum is well represented by a two-component ionizing plasma model composed of a low-temperature plasma at kTe = 0.80 ± 0.11 keV and a high-temperature plasma at kTe = 1.5 ± 0.4 keV. The existence of a low-ionized Fe K line at 6.49 ± 0.07 keV was confirmed. The center energy of the line is consistent with those of type Ia SNRs.
Platelet rich plasma could replace tranexemic acid in total knee replacement? A comparative study between their postoperative- bleeding hemostatic effects
Authors: Fahmy Mahmoud , Yasin Ebeed
Published: October 2023

Background:

The aim of the study is to detect whether platelet rich plasma (PRP) is equal to tranexemic acid (TXA) in reducing blood loss and transfusion rates following total knee arthroplasty (TKA), and compare clinical outcomes, complications, and cost effectiveness between the two groups. This is one of the first randomized, controlled trials that compare both materials in elective knee arthroplasty.

Methods:

120 patients were randomized. Postoperative blood loss was determined and compared by measuring the total drainage suction together with the hemoglobin level and blood transfusion rate. Thromboembolic complications and knee society score were recorded.

Results:

The mean total drain output was 469 mL in the TXA group compared with 698 mL in the PRP group, with statistical significance. There were significant differences in reduction of hemoglobin level (TXA: 1.21 vs. PRP: 2.08). The rate of deep vein thrombosis (DVT) in patients given TXA was higher than those given PRP, however, there were no significant differences. No transfusions were required in either group, and no significant differences were found in the length of hospital stay, pain assessment and knee society score.

Conclusions:

Though the blood loss was significantly bigger in the custom-made PRP group, no transfusions were required. Meanwhile, the rate of DVT in the PRP group tends to be lower than those in TXA group. We concluded that PRP was not superior to TXA in reducing perioperative blood loss, however further large-scale randomized trials are crucial to confirm these results to be added to the calling literature.
Surveillance With Serial Imaging and CA 19-9 Tumor Marker Testing After Resection of Pancreatic Cancer
Authors: Nong Minerva Z. , Dove Devanshi , Fischer Dawn A. , Hourdequin Kathryn C. , Ripple Gregory H. , Amin Manik A. , McGrath Elizabeth B. , Zaki Bassem I. , Smith Kerrington D. , Brooks Gabriel A.
Published: October 2023

Objectives:

Most patients receiving curative-intent surgery for pancreatic cancer will experience cancer recurrence. However, evidence that postoperative surveillance testing improves survival or quality of life is lacking. We evaluated the use and characteristics of surveillance with serial imaging and CA 19-9 tumor marker testing at an NCI-designated comprehensive cancer center.

Methods:

We conducted a retrospective cohort study of patients who entered surveillance after curative-intent resection of pancreatic adenocarcinoma. We abstracted information from the electronic medical record about oncology office visits, surveillance testing (cross-sectional imaging and CA 19-9 tumor marker testing), and pancreatic cancer recurrence, with follow-up through 2 years after pancreatectomy. We conducted analyses to describe the use of surveillance testing and to characterize the sensitivity and specificity of CA 19-9 tumor marker testing for the identification of cancer recurrence.

Results:

We identified 90 patients entering surveillance after pancreatectomy. CA 19-9 was the most frequently used surveillance test, followed by CT imaging. Forty-seven patients (52.2%) experienced recurrence within two years of pancreatectomy. Recurrence risk was 58.8% versus 31.8% in patients with elevated versus normal CA 19-9 at diagnosis (P=0.03). Elevated CA 19-9 at any point during surveillance was significantly associated with 2-year recurrence risk (P<0.001). Elevated CA 19-9 had a sensitivity of 83% (95% CI 0.72–0.95) and specificity of 87% (0.76–0.98) for identification of recurrence within 2 years of pancreatectomy.

Conclusions:

CA 19-9 demonstrates clinical validity for identifying recurrence of pancreatic cancer during surveillance. Surveillance approaches with reduced reliance on imaging should be prospectively evaluated.
Association of Late Potentials With Fatal Arrhythmic Events in Patients With Brugada Syndrome—A Meta-analysis
Authors: Bazoukis George , Letsas Konstantinos P. , Liu Tong , Tse Gary , Alsheikh-Ali Alawi
Published: October 2023

Risk stratification of patients with Brugada syndrome (BrS) remains challenging. Signal-averaged electrocardiogram (SAECG) is a noninvasive tool that can be used to identify the electrophysiologic substrate potentially underlying fatal ventricular arrhythmias. The aim of this meta-analysis is to summarize the existing evidence about the role of late potentials (LP) as a predictor for arrhythmic events in patients with BrS. A systematic search in the MedLine database through to June 2022 without any limitations was performed. Ten studies were included in the quantitative synthesis (1431 patients with BrS, mean age 47.4 years, males 86%). Of these, 1220 patients underwent SAECG evaluation (53.2% had positive LP, and 20.6% had a fatal arrhythmic event). There was a nonsignificant association between positive LPs and fatal arrhythmic events [RR: 2.06 (0.98–4.36), P = 0.06, I2 = 82%]. By including only studies with patients without a history of fatal arrhythmia, the association between LP with arrhythmic events remained nonsignificant [RR: 1.29 (0.67–2.48), P = 0.44, I2 = 54%]. In conclusion, there is a possible association between LP and fatal arrhythmic events in patients with BrS, but the literature remains inconclusive. Large cohort studies using a multiparametric approach for risk stratification purposes are needed to improve the risk stratification of BrS and to optimize the selection of BrS patients that should be referred for implantable cardioverter-defibrillator.
Free Flap Failure and Complications in Acute Burns: A Systematic Review and Meta-analysis
Authors: Kasmirski Julia A. , Alessandri-Bonetti Mario , Liu Hilary , Corcos Alain C. , Ziembicki Jenny A. , Stofman Guy M. , Egro Francesco M.
Published: October 2023

Background:

Severe acute burn injuries represent a challenge to the reconstructive surgeon. Free flap reconstruction might be required in cases of significant critical structure exposure and soft tissue deficits, when local options are unavailable. This study aimed to determine the free flap complication rate in acute burn patients.

Methods:

A systematic review and meta-analysis were conducted and reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines and registered on the International Prospective Register of Systematic Reviews database (CRD42023404478). The following databases were accessed: Embase, PubMed, Web of Science, and Cochrane Library. The primary outcome was the free flap failure rate.

Results:

The study identified 31 articles for inclusion. A total of 427 patients (83.3% men, 16.7% women) accounting for 454 free flaps were included. The mean patient age was 36.21 [95% confidence interval (CI), 31.25–41.16]. Total free flap loss rate was 9.91% [95% CI, 7.48%–13.02%], and partial flap loss was 4.76% [95% CI, 2.66%–8.39%]. The rate of venous thrombosis was 6.41% [95% CI, 3.90%–10.36%] and arterial thrombosis was 5.08% [95% CI, 3.09%–8.26%]. Acute return to the operating room occurred in 20.63% [16.33%–25.71%] of cases. Stratified by body region, free flaps in the lower extremity had a failure rate of 8.33% [95% CI, 4.39%–15.24%], whereas in the upper extremity, the failure rate was 6.74% [95% CI, 3.95%–11.25%].

Conclusion:

This study highlights the high risk of free flap complications and failure in acute burn patients.
Angiotensin-converting enzyme 2: virus accomplice or host defender?
Authors: Wang Jiyan , Chang Hongkai , Qiao Yaya , Sun Huanran , Li Xichuan , Yuan Shuofeng , Zhang Shuai , Shan Changliang
Published: October 2023

Objective:

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to social disruptions, mainly because we know too little about SARS-CoV-2.

Methods and Results:

In this study, we integrated RNA sequencing results and found that SARS-CoV-2 infection alters aerobic glycolysis, the oxidative pentose phosphate pathway (oxiPPP), and DNA replication in lung tissues and cells. However, the direction of metabolic flux and DNA replication are dominated by angiotensin-converting enzyme 2 (ACE2), a host cell-expressed viral receptor protein. More interestingly, although hosts with a high expression of ACE2 are more likely to be infected with SARS-CoV-2, the invading virus cannot perform nucleic acid replication well due to the restriction of glucose metabolism, eventually resulting in a prolonged infection cycle or infection failure.

Conclusion:

Our findings preliminarily explain the reasons for the emergence of asymptomatic infections at an early stage, which will provide assistance for the development of detection methods for diagnosing COVID-19.
Cerebral Spinal Fluid Parameters Following CD19-Targeted Therapies in Children and Young Adults
Authors: Leib Shiran , Bielorai Bella , Vernitsky Helly , Aharony-Tevet Yarden , Toren Amos , Jacoby Elad
Published: October 2023

The presence of leukocytes in the cerebral spinal fluid (CSF) of patients with acute lymphoblastic leukemia may indicate a relapse in the central nervous system. CD19-directed immunotherapy may increase the blood-brain barrier permeability, leading to neurologic toxicity and infiltrate the CNS. We studied the CSF cell and protein content in 71 consecutive patients who received either CD19 chimeric antigen receptor T cells or blinatumomab. Responding patients had an incidence of 66% and 61% of pleocytosis following blinatumomab or chimeric antigen receptor T cells, respectively. CSF parameters did not correlate with toxicity or prior CNS disease. Routine CSF flow cytometry following immunotherapy to distinguish T-cell infiltration from CNS relapse should be considered.
Suicide and Self-Harm in Adolescents During the COVID-19 Pandemic: A U.S. Virtual Pediatric Systems, LLC, Database Study of PICU Admissions, 2016–2021
Authors: McCluskey Casey K. , Black Tyler R. , Zee-Cheng Janine , Klein Margaret J. , Lin Anna , Rogerson Colin M. , Carroll Christopher L. , Remy Kenneth E. , Scanlon Matthew C. , Shein Steven L. , Wright Melvin , Rotta Alexandre T.
Published: October 2023

OBJECTIVES:

To characterize the epidemiology of suicide and self-harm among adolescents admitted to PICUs during the first 2 years of the COVID-19 pandemic in the United States.

DESIGN:

Descriptive analysis of a large, multicenter, quality-controlled database (Virtual Pediatric Systems [VPS]), and of a national public health dataset (U.S. Centers for Disease Control and Prevention web-based Wide-ranging ONline Data for Epidemiology Research [CDC WONDER]).

SETTING:

The 69 PICUs participating in the VPS database that contributed data for the entire the study period, January 1, 2016, to December 31, 2021.

PATIENTS:

Adolescents older than 12 years to younger than 18 years old admitted to a participating PICU during the study period with a diagnosis involving self-harm or a suicide attempt (VPS sample), or adolescent suicide deaths over the same period (CDC WONDER sample).

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

We identified 10,239 suicide deaths and 7,692 PICU admissions for self-harm, including 5,414 admissions in the pre-pandemic period (Q1-2016 to Q1-2020) and 2,278 in the pandemic period (Q2-2020 to Q4-2021). Compared with the pre-pandemic period, there was no increase in the median (interquartile range) number of suicide deaths per quarter (429 [399–453] vs. 416 [390–482]) or PICU admissions for self-harm per quarter (315 [289–353] vs. 310 [286–387]) during the pandemic period, respectively. There was an increase in the ratio of self-harm PICU admissions to all-cause PICU admissions per quarter during the pandemic (1.98 [1.43–2.12]) compared with the pre-pandemic period per quarter (1.59 [1.46–1.74]). We also observed a significant decrease in all-cause PICU admissions per quarter early in the pandemic compared with the pre-pandemic period (16,026 [13,721–16,297] vs. 19,607 [18,371–20,581]).

CONCLUSIONS:

The number of suicide deaths and PICU admissions per quarter for self-harm remained relatively constant during the pandemic, while the number of all-cause PICU admissions per quarter decreased compared with the pre-pandemic period. The resultant higher ratio of self-harm admissions to all-cause PICU admissions may have contributed to the perception that more adolescents required critical care for mental health-related conditions early in the pandemic.
68Ga-PSMA PET/CT Images of Multiple Cutaneous Metastases in a Patient With Prostate Carcinoma
Authors: Sivrikoz Ilknur Ak , Deveci Hakan , Ak Ali Murat , Acer Ersoy
Published: October 2023

Although distant cutaneous metastasis is an uncommon presentation of prostate cancer, it remains an important diagnostic consideration as an advanced disease and a poor prognosis. Herein we present a rare case of prostate cancer patient whose multiple cutaneous metastases were treated with177Lu-PSMA-617 radioligand treatment. To our knowledge, it is the first report in which a complete response was seen with68Ga-PSMA PET/CT scan after177Lu-PSMA-617 radioligand treatment.
Comparison of 68Ga-PSMA-HBED-CC and 18F-FDG PET/CT in the Evaluation of Adenoid Cystic Carcinoma—A Prospective Study
Authors: Shamim Shamim Ahmed , Kumar Naresh , Arora Geetanjali , Kumar Deepak , Pathak Anshika , Thakkar Alok , Sikka Kapil , Singh Chirom Amit , Kakkar Aanchal , Bhalla Ashu Seith
Published: October 2023

Purpose of Study

18F-FDG PET/CT plays a major role in diagnosis and staging of head and neck cancer; however, FDG has lower uptake in adenoid cystic carcinoma (AdCC). Prostate-specific membrane antigen (PSMA) expression is found to be associated with endothelial cells or tumor neovasculature in malignant AdCC and salivary duct carcinoma. Thus, present study is aimed to compare the role of 68Ga-PSMA and 18F-FDG PET/CT in patients with primary and/or metastatic AdCC.

Materials and Methods

Histopathologically proven AdCC patients were intravenously injected with 370 MBq (10 mCi) of 18F-FDG and 111–185 MBq (3–5 mCi) of 68Ga-PSMA. Images were acquired at 60 and 45 minutes postinjection for 18F-FDG and 68Ga-PSMA, respectively, on dedicated PET/CT scanners. Visual and semiquantitative analyses of PSMA expression in regional and metastatic sites were performed by 2 experienced nuclear medicine physicians.

Results

Seventeen patients (7 men, 10 women) having mean age of 44 ± 14.19 years were prospectively included in the study. Of 17 patients, FDG PET/CT was performed in only 14 (82%) patients. PSMA and FDG uptakes were seen at the primary site in 16 (94%) and 13 (93%) patients, respectively, whereas 1 patient was postradical tumor excision. Lung lesions (n = 7) and lymph nodes (n = 5) were detected on both FDG and PSMA PET scans. However, cerebellar and meningeal metastasis (n = 1, 6%) and bony lesions (n = 2, 12%) were detected only on PSMA PET/CT but not visualized on FDG PET/CT scan.

Conclusions

PSMA may have theranostic importance in unresectable or metastatic AdCC, besides having a role in staging/restaging.
Fine-Tuning GBS Data with Comparison of Reference and Mock Genome Approaches for Advancing Genomic Selection in Less Studied Farmed Species
Authors: Fischer Daniel , Tapio Miika , Bitz Oliver , Iso-Touru Terhi , Kause Antti , Tapio Ilma
Published: October 2023

Background

Diversifying animal cultivation demands efficient genotyping for enabling genomic selection, but non-model species lack efficient genotyping solutions. The aim of this study was to optimize a genotyping-by-sequencing (GBS) double-digest RAD-sequencing (ddRAD) pipeline. Bovine data was used to automate the bioinformatic analysis. The application of the optimization was demonstrated on non-model European whitefish data.

Results

DdRAD data generation was designed for a reliable estimation of relatedness and is scalable to up to 384 samples. The GBS sequencing yielded approximately one million reads for each of the around 100 assessed samples. Optimizing various strategies to create a de-novo reference genome for variant calling (mock reference) showed that using three samples outperformed other building strategies with single or very large number of samples. Adjustments to most pipeline tuning parameters had limited impact on high-quality data, except for the identity criterion for merging mock reference genome clusters. For each species, over 15k GBS variants based on the mock reference were obtained and showed comparable results with the ones called using an existing reference genome. Repeatability analysis showed high concordance over replicates, particularly in bovine while in European whitefish data repeatability did not exceed earlier observations.

Conclusions

The proposed cost-effective ddRAD strategy, coupled with an efficient bioinformatics workflow, enables broad adoption of ddRAD GBS across diverse farmed species. While beneficial, a reference genome is not obligatory. The integration of Snakemake streamlines the pipeline usage on computer clusters and supports customization. This user-friendly solution facilitates genotyping for both model and non-model species.
Criticality and partial synchronization analysis in Wilson-Cowan and Jansen-Rit neural mass models
Authors: Kazemi Sheida , Farokhniaee AmirAli , Jamali Yousef
Published: October 2023

Synchronization is a phenomenon observed in neuronal networks involved in diverse brain activities. Neural mass models such as Wilson-Cowan (WC) and Jansen-Rit (JR) manifest synchronized states. Although they have been studied for decades, their ability to demonstrate second-order phase transition (SOPT) and criticality has not received enough attention, which serves as candidates for the development of healthy brain networks. In this study, two networks of coupled WC and JR nodes with small-world topologies were constructed and Kuramoto order parameter (KOP) was used to quantify the amount of synchronization. In addition, we investigated the presence of SOPT using the synchronization coefficient of variation. Both networks reached high synchrony by changing the coupling weight between their nodes. Moreover, they exhibited abrupt changes in the synchronization at certain values of the control parameter not necessarily related to a phase transition. While SOPT was observed only in JR model, neither WC nor JR model showed power-law behavior. Our study further investigated the global synchronization phenomenon that is known to exist in pathological brain states, such as seizure. JR model showed global synchronization, while WC model seemed to be more suitable in producing partially synchronized patterns.

Corresponding author summary

Yousef Jamali received his M.Sc. degree in physics from Sharif University, Tehran, Iran, in 2004, and his Ph.D. degree in physics from Sharif University, Tehran, Iran, in 2009. After finishing his Ph.D. thesis, in 2009, he got two years postdoctoral research associate position at the University of California at Berkeley, Department of Bioengineering. He is currently an Associate Professor in the Applied Mathematics Department (Biomathematics division), at Tarbiat Modares University, Tehran, Iran. His current research interests include the interdisciplinary area of the complex system especially on the modeling of brain. In fact, his interests are how the brain works at the critical state and how this complex system synchronized under different conditions.
eNODAL: an experimentally guided nutriomics data clustering method to unravel complex drug-diet interactions
Authors: Xu Xiangnan , Senior Alistair M. , Le Couteur David G. , Cogger Victoria C. , Raubenheimer David , James David E. , Parker Benjamin , Simpson Stephen J. , Muller Samuel , Yang Jean Y.H.
Published: October 2023

Unraveling the complex interplay between nutrients and drugs via their effects on ‘omics’ features could revolutionize our fundamental understanding of nutritional physiology, personalized nutrition and ultimately human health-span. Experimental studies in nutrition are starting to use large-scale ‘omics’ experiments to pick apart the effects of such interacting factors. However, the high dimensionality of the omics features, coupled with complex fully-factorial experimental designs together pose a challenge to the analysis. Current strategies for analyzing such types of data are based on between-feature correlations. However, these techniques risk overlooking important signals that arise from the experimental design and produce clusters that are hard to interpret. We present a novel approach for analyzing high-dimensional outcomes in nutriomics experiments, termedexperiment-guidedNutriOmicsDatAcLustering (eNODAL). This three-step hybrid framework takes advantage of both ANOVA-type analyses and unsupervised learning methods to extract maximum information from experimental nutriomics studies. First, eNODAL categorizes the omics features into interpretable groups based on the significance of response to the different experimental variables using an ANOVA-like test. Such groups may include the main effects of a nutritional intervention, and drug exposure, or their interaction. Second, consensus clustering is performed within each interpretable group to further identify subclusters of features with similar response profiles to these experimental factors. Third, eNODAL annotates these subclusters based on their experimental responses and biological pathways enriched within the subcluster. We validate eNODAL using data from a mouse experiment to test for the interaction effects of macronutrient intake and drugs that target aging mechanisms in mice.
EMDB - the Electron Microscopy Data Bank
Authors: Turner Jack ,   The wwPDB Consortium
Published: October 2023

The Electron Microscopy Data Bank (EMDB) is the archive of three-dimensional electron microscopy (3DEM) maps of biological specimens. As of 2021, EMDB has been managed by the Worldwide Protein Data Bank (wwPDB) as a wwPDB Core Archive. Today, the EMDB houses over 29,000 entries with maps containing cells, organelles, viruses, complexes and macromolecules. Herein, we provide an overview of the rapidly growing EMDB archive, including its current holdings, recent updates, and future plans.
Eliminating steam pops and improving lesion safety in atrial ablation with conductive hydrogels
Authors: Post Allison , Jaworski Lukas , Bernard Drew , Gao Shang , Nkansah Abbey , Zhang Haichong , Cosgriff-Hernandez Elizabeth , Razavi Mehdi
Published: October 2023

Background

Atrial fibrillation (AF) is a significant burden worldwide, and the existing treatments leave much to be desired. There are, however, opportunities to improve the safety and efficacy of the most popular treatment, radiofrequency (RF) cardiac ablation, using conductive hydrogels as an ablation mediator.

Methods

Lesions were created in ex vivo ventricular tissues using bare metal traditional RF catheters and three different hydrogels with varying conductivities to assess the effect of conductivity on lesion formation. Similar procedures were performed in atrial/esophageal tissue stacks to mimic physiological AF ablation and demonstrate the initial safety profile of conductive hydrogel-mediated ablation.

Results

The hydrogel mediated lesions were overall shallower and narrower than bare metal, and also exhibited less char and improved lesion homogeneity. The hydrogel also eliminated steam pops. Finally, the hydrogel appeared to be more thermally protective of the esophagus in the atrial/esophageal tissue stack, greatly reducing the lesion formation on the esophagus while still achieving transmural lesions in the atrial tissue.

Conclusions

Hydrogel-mediated RF ablation holds promise as a novel method to improve ablation outcomes for AF patients. Future work will confirm this in vivo and establish the chemistry required to create a conductive hydrogel coating for RF ablation catheters.