bluuebunny/crossref_metadata_2025 huggingface dataset:
Emerging tropane alkaloids: Global development and potential health threats
Authors: Wang Zile , Chen Shiqi , Zheng Pimiao , Ren Zhenhui , Zhang Huixia , Zhang Jing , Shao Bing , Wu Congming , Jiang Haiyang
Published: October 2023

Tropane alkaloids (TAs) are a kind of plant secondary metabolite that mainly originate from Solanaceae. They have potent anticholinergic activity, and are well-known anticholinergic drugs, but have also been reported as plant toxins. Many studies have been conducted on TAs, but no scientometric research has been performed. This study aimed to expound the knowledge network and development of the field of TAs and predict the emerging development topics based on bibliometrics. In particular, this research combined VOSviewer and CiteSpace for visualization and covered 1,298 related scientific publications (1953–2022). The research on TAs is rapidly developing, with the participation of 86 countries, 1,129 research institutions, and 4,087 researchers. China, the University of Geneva, and P. Christen are the most productive country, institution, and researcher, respectively. Currently, the main research topics on TAs include biosynthesis, in vitro synthesis, chemical synthesis, and determination methods. Since 2018, the monitoring of TAs in food related to human health has shown citation burst characteristics, which is considered an emerging development trend in the future. The findings of this study will enable researchers to quickly tap into the knowledge background/structure of TAs from massive data to provide a reference for further research.
Effects of thidiazuron on the quality and storage properties of mango fruit during postharvest
Authors: Jiang Tangxin , Luo Cong , Wan Wen , Liang Rongzhen , Lu Tingting , Li Yuze , Xie Fangfang , Chen Canbin , Li Xi , Xie Xiaona , He Xinhua
Published: October 2023

Thidiazuron (TDZ) is used for the expansion of fruits, but excessive levels of TDZ lead to a decline in fruit quality. The appropriate concentration of TDZ for mango expansion without a decline in quality is not clear. In the present study, four different concentrations (5, 10, 15, and 20 mg/L) of TDZ were applied via spraying on mango plants, and several physiological and biochemical indicators were measured. The results showed that TDZ treatment significantly increased mango fruit size and single-fruit weight. In mango fruit, TDZ treatment decreased the disease index, delayed the increase in the malondialdehyde and H2O2 content, and maintained firmness and antioxidant capacities at a relatively high level during postharvest storage. At the same time, TDZ treatment delayed the decrease in the giberellin, indoleacetic acid and jasmonic acid content in mango, and reduced the accumulation of abscisic acid and ethylene. These trends are consistent with TDZ treatment leading to extension of the shelf life of mango. Furthermore, ethylene biosynthesis, signal transduction, and cell wall dismantling-related genes were investigated. The results indicated that the expression of the MiACS, MiETR2, MiERF113, MiERF010, MiERF054, MiEXP, MiPG14, MiPG21, MiCEL, and MiPEL genes in mango was inhibited under TDZ treatment compared with the control. In summary, TDZ treatment can significantly increase the size and weight of mango fruit and can extend its shelf life. The most suitable concentration is 10–15 mg/L TDZ, which will not affect the quality of mango fruit.
Dynamic mRNA expression during chicken ovarian follicle development
Authors: Kui Hua , Li Penghao , Wang Tao , Luo Yingyu , Ning Chunyou , Li Mengmeng , Liu Siying , Zhu Qing , Li Jing , Li Diyan
Published: October 2023

Ovarian follicle development is a complex and well-orchestrated biological process of great economic significance for poultry production. Specifically, understanding the molecular mechanisms underlying follicular development is essential for high-efficiency follicular development can benefit the entire industry. In addition, domestic egg-laying hens often spontaneously develop ovarian cancer, providing an opportunity to study the genetic, biochemical, and environmental risk factors associated with the development of this cancer. Here, we provide high-quality RNA sequencing data for chicken follicular granulosa cells across 10 developmental stages, which resulted in a total of 204.57 Gb of clean sequencing data (6.82 Gb on average per sample). We also performed gene expression, time-series, and functional enrichment analyses across the 10 developmental stages. Our study revealed that SWF (small while follicle), F1 (F1 hierarchical follicles), and POFs (postovulatory follicles) best represent the transcriptional changes associated with the prehierarchical, preovulatory, and postovulatory stages, respectively. We found that the preovulatory stage F1 showed the greatest divergence in gene expression from the POF stage. Our research lays a foundation for further elucidation of egg-laying performance of chicken and human ovarian disease.
Comparison of clinical efficacy between LAPS and ALPPS in the treatment of hepatitis B virus-related hepatocellular carcinoma
Authors: Chen Zebin , Shen Shunli , Xie Wenxuan , Liao Junbin , Feng Shiting , Li Shaoqiang , Tan Jiehui , Kuang Ming
Published: October 2023

Background

Insufficient post-operative future liver remnant (FLR) limits the feasibility of hepatectomy for patients. Staged hepatectomy is an effective surgical approach that can improve the resection rate of hepatocellular carcinoma (HCC). This study aimed to compare the safety and efficacy of laparoscopic microwave ablation and portal vein ligation for staged hepatectomy (LAPS) and classical associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) in the treatment of hepatitis B virus (HBV)-related HCC.

Methods

Clinical data of patients with HBV-related HCC who underwent LAPS or ALPPS in our institute between January 2017 and May 2022 were retrospectively analysed.

Results

A total of 18 patients with HBV-related HCC were retrospectively analysed and divided into the LAPS group (n = 9) and ALPPS group (n = 9). Eight patients in the LAPS group and eight patients in the ALPPS group proceeded to a similar resection rate (88.9% vs 88.9%, P = 1.000). The patients undergoing LAPS had a lower total comprehensive complication index than those undergoing ALPPS but there was not a significant different between the two groups (8.66 vs 35.87, P = 0.054). The hypertrophy rate of FLR induced by ALPPS tended to be more rapid than that induced by LAPS (24.29 vs 13.17 mL/d, P = 0.095). The 2-year recurrence-free survival (RFS) was 0% for ALPPS and 35.7% for LAPS (P = 0.009), whereas the 2-year overall survival for ALPPS and LAPS was 33.3% and 100.0% (P = 0.052), respectively.

Conclusions

LAPS tended to induce lower morbidity and FLR hypertrophy more slowly than ALPPS, with a comparable resection rate and better long-term RFS in HBV-related HCC patients.
Genome-wide association analysis identified molecular markers and candidate genes for flower traits in Chinese orchid (Cymbidium sinense)
Authors: Yang Fengxi , Guo Yudi , Li Jie , Lu Chuqiao , Wei Yonglu , Gao Jie , Xie Qi , Jin Jianpeng , Zhu Genfa
Published: October 2023

The orchid, the champagne of flowers, brings luxury, elegance, and novelty to nature. Cymbidium sinense is a symbol of gigantic floral variability on account of wavering shapes and sizes of floral organs, although marker–trait association (MTA) has not been studied for its floral traits. We evaluated markers associated with 14 floral traits of C. sinense through a genome-wide association study (GWAS) of 195 accessions. A total of 65 318 522 single-nucleotide polymorphisms (SNPs) and 3 906 176 insertion/deletion (InDel) events were identified through genotyping-by-sequencing. Among these, 4694 potential SNPs and 477 InDels were identified as MTAs at −log10 P > 5. The genes related to these SNPs and InDels were largely associated with floral regulators, hormonal pathways, cell division, and metabolism, playing essential roles in tailoring floral morphology. Moreover, 20 candidate SNPs/InDels linked to 11 genes were verified, 8 of which were situated on exons, one was located in the 5′-UTR and two were positioned in introns. Here, the multitepal trait-related gene RABBIT EARS (RBE) was found to be the most crucial gene. We analyzed the role of CsRBE in the regulation of flower-related genes via efficient transient overexpression in C. sinense protoplasts, and found that the floral homeotic genes CsAP3 and CsPI, as well as organ boundary regulators, including CsCUC and CsTCP genes, were regulated by CsRBE. Thus, we obtained key gene loci for important ornamental traits of orchids using genome-wide association analysis of populations with natural variation. The findings of this study can do a great deal to expedite orchid breeding programs for shape variability.
Final report of the phase II NEXT/CNS-GCT-4 trial: GemPOx followed by marrow-ablative chemotherapy for recurrent intracranial germ cell tumors
Authors: Shatara Margaret , Blue Megan , Stanek Joseph , Liu Yin A , Prevedello Daniel M , Giglio Pierre , Puduvalli Vinay K , Gardner Sharon L , Allen Jeffrey C , Wong Kenneth K , Nelson Marvin D , Gilles Floyd H , Adams Roberta H , Pauly Jasmine , O’Halloran Katrina , Margol Ashley S , Dhall Girish , Finlay Jonathan L
Published: October 2023

Background

Patients with relapsed intracranial germinoma can achieve durable remission with standard chemotherapy regimens and/or reirradiation; however, innovative therapies are required for patients with relapsed and/or refractory intracranial nongerminomatous germ cell tumors (NGGCTs) due to their poor prognosis. Improved outcomes have been reported using reinduction chemotherapy to achieve minimal residual disease, followed by marrow-ablative chemotherapy (HDCx) with autologous hematopoietic progenitor cell rescue (AuHPCR). We conducted a phase II trial evaluating the response and toxicity of a 3-drug combination developed for recurrent intracranial germ cell tumors consisting of gemcitabine, paclitaxel, and oxaliplatin (GemPOx).

Methods

A total of 9 patients with confirmed relapsed or refractory intracranial GCT were enrolled after signing informed consent, and received at least 2 cycles of GemPOx, of which all but 1 had relapsed or refractory NGGCTs. One patient with progressive disease was found to have pathologically confirmed malignant transformation to pure embryonal rhabdomyosarcoma (without GCT elements), hence was ineligible and not included in the analysis. Patients who experienced sufficient responses proceeded to receive HDCx with AuHPCR. Treatment response was determined based on radiographic tumor assessments and tumor markers.

Results

A total of 7 patients achieved sufficient response and proceeded with HDCx and AuHPCR, and 5 subsequently received additional radiotherapy. A total of 2 patients developed progressive disease while receiving GemPOx. Myelosuppression and transaminitis were the most common treatment-related adverse events. With a mean follow-up of 44 months, 4 patients (3 NGGCTs, 1 germinoma) are alive without evidence of disease.

Conclusions

GemPOx demonstrates efficacy in facilitating stem cell mobilization, thus facilitating the feasibility of both HDCx and radiotherapy.
Citronellol biosynthesis in pelargonium is a multistep pathway involving progesterone 5β-reductase and/or iridoid synthase-like enzymes
Authors: Martinelli Laure , Bihanic Camille , Bony Aurélie , Gros Florence , Conart Corentin , Fiorucci Sébastien , Casabianca Hervé , Schiets Frédéric , Chietera Giorgiana , Boachon Benoît , Blerot Bernard , Baudino Sylvie , Jullien Frédéric , Saint-Marcoux Denis
Published: October 2023

Citronellol is a pleasant-smelling compound produced in rose (Rosa spp.) flowers and in the leaves of many aromatic plants, including pelargoniums (Pelargonium spp.). Although geraniol production has been well studied in several plants, citronellol biosynthesis has been documented only in crab-lipped spider orchid (Caladenia plicata) and its mechanism remains open to question in other species. We therefore profiled 10 pelargonium accessions using RNA sequencing and gas chromatography-MS analysis. Three enzymes from the progesterone 5β-reductase and/or iridoid synthase-like enzymes (PRISE) family were characterized in vitroand subsequently identified as citral reductases (named PhCIRs). Transgenic RNAi lines supported a role for PhCIRs in the biosynthesis of citronellol as well as in the production of mint-scented terpenes. Despite their high amino acid sequence identity, the 3 enzymes showed contrasting stereoselectivity, either producing mainly (S)-citronellal or a racemate of both (R)- and (S)-citronellal. Using site-directed mutagenesis, we identified a single amino acid substitution as being primarily responsible for the enzyme's enantioselectivity. Phylogenetic analysis of pelargonium PRISEs revealed 3 clades and 7 groups of orthologs. PRISEs from different groups exhibited differential affinities toward substrates (citral and progesterone) and cofactors (NADH/NADPH), but most were able to reduce both substrates, prompting hypotheses regarding the evolutionary history of PhCIRs. Our results demonstrate that pelargoniums evolved citronellol biosynthesis independently through a 3-step pathway involving PRISE homologs and both citral and citronellal as intermediates. In addition, these enzymes control the enantiomeric ratio of citronellol thanks to small alterations of the catalytic site.
Deep learning unmasks the ECG signature of Brugada syndrome
Authors: Melo Luke , Ciconte Giuseppe , Christy Ashton , Vicedomini Gabriele , Anastasia Luigi , Pappone Carlo , Grant Edward
Published: October 2023

One in 10 cases of sudden cardiac death strikes without warning as the result of an inherited arrhythmic cardiomyopathy, such as Brugada Syndrome (BrS). Normal physiological variations often obscure visible signs of this and related life-threatening channelopathies in conventional electrocardiograms (ECGs). Sodium channel blockers can reveal previously hidden diagnostic ECG features, however, their use carries the risk of life-threatening proarrhythmic side effects. The absence of a nonintrusive test places a grossly underestimated fraction of the population at risk of SCD. Here, we present a machine-learning algorithm that extracts, aligns, and classifies ECG waveforms for the presence of BrS. This protocol, which succeeds without the use of a sodium channel blocker (88.4% accuracy, 0.934 AUC in validation), can aid clinicians in identifying the presence of this potentially life-threatening heart disease.
Improved Double-Stranded RNA Extraction and Hyphal Tip-Touch Techniques for the Detection of Mycoviruses
Authors: Mokhtari Samira , Ali Akhtar
Published: October 2023

Mycoviruses infect a wide range of fungal species, and many of them have double-stranded RNA (dsRNA) genomes. Using a dsRNA technique makes it easier to detect unknown mycoviruses in fungi. Previously, a few studies reported dsRNA extraction methods from fungal tissues, but the procedures required a significant amount of starting material and time, particularly in growing fungal cultures. In this study, we report an efficient and quick dsRNA extraction method that is reproducible to extract quality dsRNA of mycoviruses from a small amount of fungal culture in a short time. Extracted dsRNA was subsequently used in Illumina sequencing and reverse transcription-polymerase chain reaction assays, followed by Sanger sequencing, to confirm the identity of the mycovirus. Additionally, a rapid and efficient technique named hyphal tip-touch (HTT) was developed to identify known mycoviruses without the need for dsRNA extraction. The HTT technique uses the edge of mycelia as a template for preparing complementary DNA in the reverse transcription reaction, which was used in the polymerase chain reaction assay followed by sequencing.

[Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Risk factors for incident venous thromboembolism in patients with renal tumor and inferior vena cava tumor thrombus: A retrospective case-control study
Authors: Wang Hanfeng , Chen Xinran , Wang Kailong , Cao Wenzhe , Huang Qingbo , Peng Cheng , Jia Tongyu , Liang Qiyang , Wang Baojun , Gu Liangyou , Zhang Xu , Ma Xin
Published: October 2023

Background:

Venous thromboembolism (VTE) is a principal cause of mortality and adverse oncologic outcomes in patients with renal tumor and inferior vena cava tumor thrombus (RT-IVCTT). However, the preoperative thrombotic risk factors in these patients remain not fully characterized.

Objectives:

To identify preoperative thrombotic risk factors in patients with RT-IVCTT.

Patients/Methods:

257 consecutive postsurgical patients with RT-IVCTT aged 18–86 years were enrolled between January 2008 and September 2022. Clinicopathological variables were retrospectively reviewed. A multivariate logistic regression model was performed. Preoperative hemoglobin, neutrophils, and serum albumin levels were analyzed as both continuous and categorical variables.

Results:

VTE was identified in 63 patients (24.5%). On both continuously and categorically coded variables, advanced IVC thrombus (OR 3.2, 95% CI 1.4–7.0; OR 2.7, 95% CI 1.2–6.1), renal sinus fat invasion (OR 3.4, 95% CI 1.6–7.0; OR 3.7, 95% CI 1.8–7.7), IVC wall invasion (OR 3.6, 95% CI 1.6–7.9; OR 4.3, 95% CI 1.9–10.0), IVC blockage status of >75% (OR 5.2, 95% CI 1.7–15.8; OR 6.1, 95% CI 1.9–19.7), and higher neutrophils (OR 1.3, 95% CI 1.0–1.7; OR 2.4, 95% CI 1.1–5.4) were significantly associated with increased VTE risk in patients with RT-IVCTT. Except hemoglobin, categorically coded serum albumin (OR 0.36, 95% CI 0.17–0.75) was validated as an independent risk factor for VTE.

Conclusions:

This study provided an insight of risk factors contributing to preoperative VTE in patients with RT-IVCTT, which may be beneficial for optimizing strategies to manage VTE in clinical practice.
Consolidating a program theory on how social media supports healthcare providers’ knowledge use in clinical practice: a realist-informed qualitative study
Authors: Zhao Junqiang , Harvey Gillian , Vandyk Amanda , Huang Mandy , Gifford Wendy
Published: October 2023

Objective:

This study aimed to consolidate a program theory, developed from a previous realist review, to further understand how and under what circumstances social media supports healthcare providers’ knowledge use.

Methods:

A realist-informed qualitative study was conducted. We carried out in-depth interviews with 11 participants, including content developers and healthcare providers from China, Australia, and Canada. The data analysis was informed by categorizing and connecting strategies.

Results:

Ten context-mechanism-outcome configurations (CMOs) were developed to consolidate the program theory. Among these, four CMOs confirmed the original CMOs from the realist review, four refined the original ones, and two were new propositions. These 10 CMOs were situated within four interconnected levels of outcomes: social media product, access, engagement, and knowledge use. They considered 1) content developers’ capabilities and capacities, 2) healthcare providers’ increased attention, 3) fulfillment of information needs, 4) access to social influence and support, 5) perception of message value and implementability, 6) behaviour capabilities, self-efficacy, intention, and awareness; and 7) ability to exercise professional autonomy as the key mechanisms. We developed the consolidated program theory based on the 10 CMOs.

Conclusions:

Social media can promote knowledge use by healthcare providers. Future empirical studies drawing on the program theory need to be conducted to further optimize the theoretical understanding.
The Importance of Remodeling the Physiological Mandibular Angle: Mandibular V-Line versus Long Curved Ostectomy
Authors: Ge Han , Zhao Qing , Al-Watary Mohammed Qasem Hezam , Hsu Yuchun , Wei Yiyuan , Wang Yu , Li Jihua
Published: October 2023

Background:

Numerous surgical options for correcting prominent mandibular angles in East Asian patients have been reported. The objective of this study was to investigate the importance of remodeling physiological mandibular angle by comparing the surgical effects and complications of mandibular V-line ostectomy and long curved ostectomy.

Methods:

A retrospective study was conducted on patients who underwent either mandibular V-line ostectomy (group 1) or long curved ostectomy (group 2). The outcomes were evaluated using computed tomography images in combination with medical records and photographs. Data were collected preoperatively and at 6- to 12-month intervals postoperatively. Mandibular angle, posterior mandibular ramus height, radian of the ostectomy line, and mandibular symmetry, as well as complications, were investigated. FACE-Q reports of facial appearance and psychosocial measures were also compared between the 2 groups.

Results:

All 106 patients showed improved lower facial contours. Although the postoperative mandibular angle (116.67 ± 7.14 versus 118.31 ± 6.80 degrees; P = 0.233) and mandibular symmetry (2.36 ± 1.21 mm versus 2.56 ± 1.19 mm; P = 0.395) were similar in the 2 groups, larger postoperative posterior mandibular height and lower radian of the ostectomy line were observed in group 1 (P < 0.001). Physiological mandibular angle was also remodeled in group 1. The gonial deficiency, more soft-tissue sagging, and significantly lower FACE-Q scores for facial appearance were observed in group 2 (P < 0.001).

Conclusions:

V-line ostectomy is better suited for achieving a more physiological mandibular angle with fewer complications compared with mandibular long curved ostectomy. V-line ostectomy may be the preferred option for mandibular contouring.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Lymphedema-Associated Fibroblasts Are Related to Fibrosis and Stage Progression in Patients and a Murine Microsurgical Model
Authors: Will Patrick A. , Kilian Katja , Bieback Karen , Fricke Fabia , Berner Juan Enrique , Kneser Ulrich , Hirche Christoph
Published: October 2023

Background:

The driver of secondary lymphedema (SL) progression is chronic inflammation, which promotes fibrosis. Despite advances in preclinical research, a specific effector cell subpopulation as a biomarker for therapy response or stage progression is still missing for SL.

Methods:

Whole skin samples of 35 murine subjects of a microsurgically induced SL model and 12 patients with SL were collected and their fibroblasts were isolated. These lymphedema-associated fibroblasts (LAFs) were cultured in a collagen I-poly-D-lysine 3-dimensional hydrogel to mimic skin conditions. Fibroblasts from nonlymphedema skin were used as negative control and transforming growth factor β (TGF-β)–stimulated fibroblasts were used to recreate profibrotic myofibroblasts. Quantitative immunocytofluorescence confocal microscopy analysis and invasion functional assays were performed in all subpopulations and statistically compared.

Results:

In contrast to normal skin fibroblasts, LAFs exhibit α–smooth muscle actin–positive stress fibers and a reduced number of tight junctions in 3-dimensional hydrogel conditions. The switch from normal E-cadherinhigh phenotype to an N-cadherinhigh-E-cadherinlow morphology suggests epithelial-to-mesenchymal transition for expansion and proliferation. This pathologic behavior of LAF was confirmed by live cell imaging analysis of invasion assays. The significant activation of markers of the TGF-β receptor 2–Smad pathway and collagen synthesis (HSP-47 [heat shock protein 47]) in LAFs supports epithelial-to-mesenchymal transition phenotypic changes and previous findings relating to TGF-β1 and fibrosis with lymphedema.

Conclusions:

A characteristic SL myofibroblast subpopulation was identified and translationally related to fibrosis and TGF-β1–associated stage progression. This SL-related subpopulation was termed LAFs. A comprehensive stage-related characterization is required to validate LAFs as a reliable biomarker for SL disease progression.

Clinical Relevance Statement:

The authors identify a cellular effector for fibrosis and stage progression of secondary lymphedema as a possible biomarker for surgical indication and therapy response.
Analyzing the Costs and Impact of the TakeMeHome Program, a Public–Private Partnership to Deliver HIV Self-Test Kits in the United States
Authors: Shrestha Ram K. , Hecht Jennifer , Chesson Harrell W.
Published: October 2023

Background:

HIV testing is an entry point to access HIV care and prevention services. Building Healthy Online Communities developed a website (TakeMeHome.org) where participants can order HIV home test kits. The purpose of this study was to analyze the costs and impact of the TakeMeHome program.

Methods:

We estimated the costs of TakeMeHome across all participating jurisdictions for the first year of the program. We estimated program costs using purchase orders and invoices, contracts, and allocation of staff time, and the costs included website design, participant recruitment, administration and overhead, HIV self-test kits, and shipping and handling. Primary outcomes of the analysis were total program cost, cost per HIV test, and cost per new HIV diagnosis.

Results:

The TakeMeHome program distributed 5323 HIV self-tests to 4859 participants over a 12-month period. The total program cost over this period was $314,870. The cost per HIV test delivered was estimated at $59, and the cost per person tested was $65. The program identified 18 confirmed new HIV diagnoses (0.6% positivity) verified with surveillance data in 7 health jurisdictions at $169,890. The cost per confirmed new HIV diagnosis was estimated at $9440.

Conclusions:

The TakeMeHome program delivered HIV self-testing at a reasonable cost, and the program may be a cost-effective use of HIV prevention resources. The public–private partnership can be an effective mechanism to validate HIV diagnoses identified with self-testing and provide HIV prevention and linkage to care services.
Imaging Update for Hereditary Abdominopelvic Neuroendocrine Neoplasms
Authors: Ferreira Dalla Pria Hanna R. , Sharbidre Kedar G. , Virarkar Mayur , Javadi Sanaz , Bhosale Hrishabh , Maxwell Jessica , Lall Chandana , Morani Ajaykumar C.
Published: October 2023

Neuroendocrine neoplasms have shown a linear increase in incidence and prevalence in recent decades, primarily due to improved cross-sectional imaging, expanded use of endoscopic procedures, and advanced genetic analysis. However, diagnosis of hereditary neuroendocrine tumors is still challenging because of heterogeneity in their presentation, the variety of tumor locations, and multiple associated syndromes. Radiologists should be familiar with the spectrum of these tumors and associated hereditary syndromes. Furthermore, as the assessment of multiple tumor elements such as morphology, biochemical markers, and presence of metastatic disease are essential for the treatment plan, conventional anatomic and functional imaging methods are fundamental in managing and surveilling these cases. Our article illustrates the role of different cross-sectional imaging modalities in diagnosing and managing various hereditary abdominopelvic neuroendocrine tumors.
The Association Between Pediatric Readiness and Mortality for Injured Children Treated at US Trauma Centers
Authors: Melhado Caroline , Remick Katherine , Miskovic Amy , Patel Bhavin , Hewes Hilary A. , Newgard Craig D. , Nathens Avery B. , Macias Charles , Gray Lisa , Yorkgitis Brian K. , Dingeldein Michael W. , Jensen Aaron R.
Published: October 2023

Objective:

To use updated 2021 weighted Pediatric Readiness Score (wPRS) data to identify a threshold level of trauma center emergency department (ED) pediatric readiness.

Background:

Most children in the United States receive initial trauma care at nonpediatric centers. The aim of the National Pediatric Readiness Project (NPRP) was to ensure that all EDs are prepared to provide quality care for children. Trauma centers reporting the highest quartile of wPRS on the 2013 national assessment have been shown to have lower mortality. Significant efforts have been invested to improve pediatric readiness in the past decade.

Study Design:

A retrospective cohort of trauma centers that completed the NPRP 2021 national assessment and contributed to the National Trauma Data Bank (NTDB) from 2019 to 2021 was analyzed. Center-specific observed-to-expected mortality estimates for children (0–15 y) were calculated using Pediatric Trauma Quality Improvement Program models. Deterministic linkage was used for transferred patients to account for wPRS at the initial receiving center. Center-specific mortality odds ratios were then compared across quartiles of wPRS.

Results:

A total of 66,588 children from 630 centers with a median (interquartile range) wPRS of 79 (66–93) were analyzed. The average observed-to-expected odds of mortality [1.02 (0.97–1.06)] for centers in the highest quartile (wPRS≥93) was lower than any of the lowest 3 wPRS quartiles [1.19 (1.14–1.23) (Q1), 1.29 (1.24–1.33) (Q2), and 1.28 (1.19–1.36) (Q3), all P<0.05). The presence of a pediatric-specific quality improvement plan was the domain with the strongest independent association with mortality [standardized beta −0.095 (−0.146 to −0.044)].

Conclusion:

Trauma centers should address gaps in pediatric readiness to include a pediatric-specific quality improvement plan and aim to achieve wPRS ≥93.
Peste des petits ruminants virus non-structural V and C proteins interact with the NF-κB p65 subunit and modulate pro-inflammatory cytokine gene induction
Authors: Jain Juhi , Chaudhary Yash , Gaur Sharad Kumar , Tembhurne Prabhakar , Sekar Shanmugam Chandra , Dhanavelu Muthuchelvan , Sehrawat Sharvan , Kaul Rajeev
Published: October 2023

Peste des petits ruminants virus (PPRV) is known to induce transient immunosuppression in infected small ruminants by modulating several cellular pathways involved in the antiviral immune response. Our study shows that the PPRV-coded non-structural proteins C and V can interact with the cellular NF-κB p65 subunit. The PPRV-C protein interacts with the transactivation domain (TAD) while PPRV-V interacts with the Rel homology domain (RHD) of the NF-κB p65 subunit. Both viral proteins can suppress the NF-κB transcriptional activity and NF-κB-mediated transcription of cellular genes. PPRV-V protein expression can significantly inhibit the nuclear translocation of NF-κB p65 upon TNF-α stimulation, whereas PPRV-C does not affect it. The NF-κB-mediated pro-inflammatory cytokine gene expression is significantly downregulated in cells expressing PPRV-C or PPRV-V protein. Our study provides evidence suggesting a role of PPRV non-structural proteins V and C in the modulation of NF-κB signalling through interaction with the NF-κB p65 subunit.
Modular multiwell viscoelastic hydrogel platform for two- and three-dimensional cell culture applications
Authors: Skelton Mackenzie L. , Gentry James L. , Astrab Leilani R. , Goedert Joshua A. , Earl E. Brynn , Pham Emily L. , Bhat Tanvi , Caliari Steven R.
Published: October 2023

Hydrogels have gained significant popularity as model platforms to study the reciprocal interactions between cells and their microenvironment. While hydrogel tools to probe many characteristics of the extracellular space have been developed, fabrication approaches remain challenging and time-consuming, limiting multiplexing or widespread adoption. Thus, we have developed a modular fabrication approach to generate distinct hydrogel microenvironments within 96-well plates for increased throughput of fabrication as well as integration with existing high-throughput assay technologies. This approach enablesin situhydrogel mechanical characterization and was used to generate both elastic and viscoelastic hydrogels across a range of stiffnesses. Additionally, this fabrication method enabled a 3-fold reduction in polymer and up to an 8-fold reduction in fabrication time required per hydrogel replicate. The feasibility of this platform for cell culture applications was demonstrated by measuring both population-level and single cell-level metrics via microplate reader and high-content imaging. Finally, the 96-well hydrogel array was utilized for 3D cell culture, demonstrating the ability to support high cell viability. Together, this work demonstrates a versatile and easily adoptable fabrication approach that can support the ever-expanding tool kit of hydrogel technologies for cell culture applications.
Physiological stress response of koala joeys to visitors
Authors: Pahuja Harsh K. , Bee Izzy , Bee Ali , Narayan Edward J.
Published: October 2023

Koala (Phascolarctos cinereus) joey rescues are increasing over the years, and rehabilitation of a joey requires extensive care, close proximity and handling by humans. These novel environments are likely to present a suite of biotic and abiotic stressors during rehabilitation. In this study, we longitudinally monitored the faecal cortisol metabolites (FCMs) of three koala joeys within the context of potential stressors at the Magnetic Island Koala Hospital, Queensland, Australia. A total of 92 faecal samples were analysed for FCMs using a polyclonal R4866 cortisol enzyme-immunoassay which has been previously validated in koalas. The iterative baseline method was used to establish FCM profiles of all individuals, and to identify significant peaks in FCM concentrations. Visitor events were identified and confirmed as an acute stressor based on the FCM profiles of the koala joeys. All three koala joeys elicited a significant rise in FCM concentrations after each visitor encounter. To our knowledge, this is the first study to report on the acute stress response of koala joeys to visitors. We recommend that visitor encounters be kept to a minimum, and perhaps avoided altogether especially for joeys that are being rehabilitated to be released back into the wild.
Tricyclic and tetracyclic antidepressants upregulate VMAT2 activity and rescue disease-causing VMAT2 variants
Authors: Wang Xunan , Marmouzi Ilias , Finnie Peter SB , Støve Svein I , Bucher Meghan L , Lipina Tatiana V , Ramsey Amy J , Miller Gary W , Salahpour Ali
Published: October 2023

Vesicular monoamine transporter 2 (VMAT2) is an essential transporter that regulates brain monoamine transmission and is important for mood, cognition, motor activity, and stress regulation. However, VMAT2 remains underexplored as a pharmacological target. In this study, we report that tricyclic and tetracyclic antidepressants acutely inhibit, but persistently upregulate VMAT2 activity by promoting VMAT2 protein maturation. Importantly, the VMAT2 upregulation effect was greater in BE(2)-M17 cells that endogenously express VMAT2 as compared to a heterologous expression system (HEK293). The net sustained effect of tricyclics and tetracyclics is an upregulation of VMAT2 activity, despite their acute inhibitory effect. Furthermore, imipramine and mianserin, two representative compounds, also demonstrated rescue of nine VMAT2 variants that cause Brain Vesicular Monoamine Transport Disease (BVMTD). VMAT2 upregulation could be beneficial for disorders associated with reduced monoamine transmission, including mood disorders and BVMTD, a rare but often fatal condition caused by a lack of functional VMAT2. Our findings provide the first evidence that small molecules can upregulate VMAT2 and have potential therapeutic benefit for various neuropsychiatric conditions.
scDILT: a model-based and constrained deep learning framework for single-cell Data Integration, Label Transferring, and clustering
Authors: Lin Xiang , Ren Jianlan , Gao Le , Wei Zhi , Wang Junwen
Published: October 2023

The scRNA-seq technology enables high-resolution profiling and analysis of individual cells. The increasing availability of datasets and advancements in technology have prompted researchers to integrate existing annotated datasets with newly sequenced datasets for a more comprehensive analysis. It is important to ensure that the integration of new datasets does not alter the cell clusters defined in the old/reference datasets. Although several methods have been developed for scRNA-seq data integration, there is currently a lack of tools that can simultaneously achieve the aforementioned objectives. Therefore, in this study, we have introduced a novel tool called scDILT, which leverages a conditional autoencoder and deep embedding clustering to effectively remove batch effects among different datasets. Moreover, scDILT utilizes homogeneous constraints to preserve the cell-type/clustering patterns observed in the reference datasets, while employing heterogeneous constraints to map cells in the new datasets to the annotated cell clusters in the reference datasets. We have conducted extensive experiments to demonstrate that scDILT outperforms other methods in terms of data integration, as confirmed by evaluations on simulated and real datasets. Furthermore, we have shown that scDILT can be successfully applied to integrate multi-omics single-cell datasets. Based on these findings, we conclude that scDILT holds great promise as a tool for integrating single-cell datasets derived from different batches, experiments, times, or interventions.
Sarbecovirus disease susceptibility is conserved across viral and host models
Authors: Leist Sarah R. , Schäfer Alexandra , Risemberg Ellen L , Bell Timothy A. , Hock Pablo , Zweigart Mark R. , Linnertz Colton L. , Miller Darla R. , Shaw Ginger D. , Manuel de Villena Fernando Pardo , Ferris Martin T. , Valdar William , Baric Ralph S.
Published: October 2023

Coronaviruses have caused three severe epidemics since the start of the 21stcentury: SARS, MERS and COVID-19. The severity of the ongoing COVID-19 pandemic and increasing likelihood of future coronavirus outbreaks motivates greater understanding of factors leading to severe coronavirus disease. We screened ten strains from the Collaborative Cross mouse genetic reference panel and identified strains CC006/TauUnc (CC006) and CC044/Unc (CC044) as coronavirus-susceptible and resistant, respectively, as indicated by variable weight loss and lung congestion scores four days post-infection. We generated a genetic mapping population of 755 CC006xCC044 F2 mice and exposed the mice to one of three genetically distinct mouse-adapted coronaviruses: clade 1a SARS-CoV MA15 (n=391), clade 1b SARS-CoV-2 MA10 (n=274), and clade 2 HKU3-CoV MA (n=90). Quantitative trait loci (QTL) mapping in SARS-CoV- and SARS-CoV-2-infected F2 mice identified genetic loci associated with disease severity. Specifically, we identified seven loci associated with variation in outcome following infection with either virus, including one,HrS45, that is present in both groups. Three of these QTL, includingHrS45, were also associated with HKU3-CoV MA outcome.HrS45overlaps with a QTL previously reported by our lab that is associated with SARS-CoV outcome in CC011xCC074 F2 mice and is also syntenic with a human chromosomal region associated with severe COVID-19 outcomes in humans GWAS. The results reported here provide: (a) additional support for the involvement of this locus in SARS-CoV MA15 infection, (b) the first conclusive evidence that this locus is associated with susceptibility across theSarbecovirussubgenus, and (c) demonstration of the relevance of mouse models in the study of coronavirus disease susceptibility in humans.
Genetically predicted smoking behaviors on Graves’ disease: A two-sample mendelian randomization
Authors: Akbarzadeh Mahdi , Pourganji Maryam , Tabashiri Arefeh , Fateh Sahand Tehrani , Salarabedi Mahdi , Habibi Danial , Moeinafshar Aysan , Saeidian Amir Hossein , Ghanooni Amir Hossein , Riahi Parisa , Zarkesh Maryam , Hakonarson Hakon , Valizadeh Majid , Azizi Fereidoun , Hedayati Mehdi , Daneshpour Maryam Sadat
Published: October 2023

Background/Aim

The potential link between smoking and the susceptibility to Graves’ disease (GD) has been scrutinized in observational studies, yielding inconsistent results. We conducted a Mendelian randomization (MR) analysis to ascertain the causal relationship between smoking behaviors and the risk of GD.

Method

The data on smoking behaviors, including smoking initiation and lifetime smoking, were obtained from the published GWAS of individuals of European descent who participated in the GSCAN consortium. The genetic variants associated with Graves’ disease were identified using a GWAS of 458,620 participants of European descent from the UK Biobank.

Results

Our results show that smoking initiation was associated with GD [OR= 1.50, 95% CI (1.03,2.18), SE□=□0.199, Pbeta□=□0.031; Cochran’s Q=36.62, p=0.999, I2=0.0%; MR–Eggerintercept= 0.003, p= 0.879], and lifetime smoking [OR□=□3.42, 95% CI (1.56, 7.50), SE□=□0.39, Pbeta<0.01; Cochran’s Q=62.68, p=0.99, I2=0.0%; Eggerintercept=0.012, p=0.49]. All other MR methods, as well as sensitivity analysis results, were consistent in terms of betas and significance levels.

Conclusion

Our findings lend support to a causal relationship between smoking behaviors and the risk of Graves’ disease. These observations raise important questions about the role of smoking in the progression of GD. So, further investigation is clinically necessary to clarify the links between smoking and GD, which could inform health policy decisions aimed at reducing the risk of GD.
Evaluating equitable care in the ICU: Creating a causal inference framework to assess the impact of life-sustaining interventions across racial and ethnic groups
Authors: Struja Tristan , Matos João , Lam Barbara , Cao Yiren , Liu Xiaoli , Jia Yugang , Sauer Christopher M. , D’Couto Helen , Dankwa-Mullan Irene , Celi Leo Anthony , Waschka Andre Kurepa
Published: October 2023

Background

Variability in the provision of intensive care unit (ICU)-interventions may lead to disparities between socially defined racial-ethnic groups.

Research Question

We used causal inference to examine the use of invasive mechanical ventilation (IMV), renal replacement therapy (RRT), and vasopressor agents (VP) to identify disparities in outcomes across race-ethnicity in patients with sepsis.

Study Design and Methods

Single-center, academic referral hospital in Boston, Massachusetts, USA. Retrospective analysis of treatment effect with a targeted trial design categorized by treatment assignment within the first 24 hours in the MIMIC-IV dataset (2008- 2019) using targeted maximum likelihood estimation. Of 76,943 ICU stays in MIMIC-IV, 32,971 adult stays fulfilling sepsis-3 criteria were included. The primary outcome was in-hospital mortality. Secondary outcomes were hospital-free days, and occurrence of nosocomial infection stratified by predicted mortality probability ranges and self-reported race-ethnicity. Average treatment effects by treatment type and race-ethnicity, Racial-ethnic group (REG) or White group (WG), were estimated.

Results

Of 19,419 admissions that met inclusion criteria, median age was 68 years, 57.4% were women, 82% were White, and mortality was 18.2%. There was no difference in mortality benefit associated with the administration of IMV, RRT, or VP between the REG and the WG. There was also no difference in hospital-free days or nosocomial infections. These findings are unchanged with different eligibility periods.

Interpretation

There were no differences in the treatment outcomes from three life-sustaining interventions in the ICU according to race-ethnicity. While there was no discernable harm from the treatments across mortality risk, there was also no measurable benefit. These findings highlight the need for research to understand better the risk-benefit of life-sustaining interventions in the ICU.
Micronutrient deficiency among pregnant adolescents in South Asia: A Systematic Review
Authors: Akombi-Inyang Blessing , Dhami Mansi , Byaruhanga Judith , Lassi Zohra S. , Agho Kingsley
Published: October 2023

Objectives

Micronutrient deficiency is an important global health concern with great impact on growth and development outcomes, which may lead to substantial losses in overall productivity and potential. The burden of micronutrient deficiency negatively impacts the health of vulnerable groups, including pregnant adolescents. Hence, this study will systematically review the available evidence on micronutrient deficiency among pregnant adolescents in South Asia.

Methods

This systematic review adhered to the 2015 Preferred Re-porting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines. A combination of selected keywords was used to search 8 computerized biblio-graphic databases: Scopus, Ovid MEDLINE, PUBMED, EMBASE, PsycINFO, CINAHL, ProQuest, and Web of Science. Potential studies were imported into an Endnote library and screened for eligibility using pre-determined criteria. The quality of the included studies was assessed using the National Institutes of Health (NIH) checklist.

Result

There is a dearth of studies on micronutrient deficiency among pregnant adolescents in South Asia. Of a total of 616 studies, five studies met the inclusion criteria. The factors associated with micronutrient deficiency among pregnant adolescents in South Asia were food (in)security, intake of dairy products, low maternal knowledge, and inadequate food intake.

Conclusion

Our review suggested that lack of awareness and knowledge of adequate micronutrient intake and household food insecurity were associated with micronutrient deficiency among pregnant adolescents. Hence, interventions targeting pregnant adolescents are needed in South Asia and such interventions could include cash transfers integrated with nutrition and health interventions.
Assessment of Model Estimated and Directly Observed Weather Data for Etiological Prediction of Diarrhea
Authors: Brintz Ben J. , Colston Josh M. , Ahmed Sharia M. , Chao Dennis L. , Zaitschik Ben , Leung Daniel T.
Published: October 2023

Recent advances in clinical prediction for diarrheal etiology in low- and middle-income countries have revealed that addition of weather data improves predictive performance. However, the optimal source of weather data remains unclear. We aim to compare model estimated satellite- and ground-based observational data with weather station directly-observed data for diarrheal prediction. We used clinical and etiological data from a large multi-center study of children with diarrhea to compare these methods. We show that the two sources of weather conditions perform similarly in most locations. We conclude that while model estimated data is a viable, scalable tool for public health interventions and disease prediction, directly observed weather station data approximates the modeled data, and given its ease of access, is likely adequate for prediction of diarrheal etiology in children in low- and middle-income countries.