bluuebunny/crossref_metadata_2025 huggingface dataset:
Serial fractional flow reserve, coronary flow reserve and index of microcirculatory resistance after percutaneous coronary intervention in patients treated for stable angina pectoris assessed with PET
Authors: Bendix Kristoffer , Thomassen Anders , Junker Anders , Veien Karsten Tange , Jensen Lisette Okkels
Published: November 2023

Background

Cardiac 15O-water PET is a noninvasive method to evaluate epicardial and microvascular dysfunction and further quantitate absolute myocardial blood flow (MBF).

Aim:

The aim of this study was to assess the impact of revascularization on MBF and myocardial flow reserve (MFR) assessed with 15O-water PET and invasive flow and pressure measurements.

Methods

In 21 patients with single-vessel disease referred for percutaneous coronary intervention (PCI), serial PET perfusion imaging and fractional flow reserve (FFR), coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) were performed during PCI and after 3 months.

Results

In the affected myocardium, stress MBF and MFR increased significantly from before revascularization to 3 months after revascularization: stress MBF 2.4 ± 0.8 vs. 3.2 ± 0.8; P < 0.001 and MFR 2.5 ± 0.8 vs. 3.4 ± 1.1; P = 0.004. FFR and CFR increased significantly from baseline to after revascularization and remained stable from after revascularization to 3-month follow-up: FFR 0.64 ± 0.20 vs. 0.91 ± 0.06 vs. 0.91 ± 0.07; P < 0.001; CFR 2.4 ± 1.2 vs. 3.6 ± 1.9 vs. 3.6 ± 1.9; P < 0.001, whereas IMR did not change significantly: 30.3 ± 22.9 vs. 30.1 ± 25.3 vs. 31.9 ± 25.2; P = ns. After revascularization, an increase in stress MBF was associated with an increase in FFR (r = 0.732; P < 0.001) and an increase in MFR (r = 0.499; P = 0.021). IMR measured before PCI was inversely associated with improvement in stress MBF, (r = −0.616; P = 0.004).

Conclusion

Recovery of myocardial perfusion after PCI was associated with an increase in FFR 3 months after revascularization. Microcirculatory dysfunction was associated with less improvement in myocardial perfusion.
Fibrous dysplasia in children and its management
Authors: Gun Zubeyir Hasan , Arif Aleena , Boyce Alison M.
Published: November 2023

Purpose of review

The purpose of this review is to provide a comprehensive overview into the diagnosis and management of fibrous dysplasia (FD) in children.

Recent Findings

FD is a mosaic disorder arising from somatic Gαs variants, leading to impaired osteogenic cell differentiation. Fibro-osseous lesions expand during childhood and reach final disease burden in early adulthood. The mainstay of treatment focuses on surgical correction of skeletal deformities, physiatric care, and medical management of associated hyperfunctioning endocrinopathies. Bisphosphonates may be helpful to treat bone pain, but do not alter lesion quality or progression. Emerging evidence suggests that the RANKL inhibitor denosumab may be effective in improving lesion activity and mineralization, however further studies are needed to determine the potential utility of this and other novel therapies, particularly in children with FD.

Management of children with FD has unique challenges related to skeletal growth and age-related lesion progression. Inclusion of children in clinical research is critical to develop effective treatment strategies to treat FD lesions and prevent their development.
Longitudinally extensive transverse myelitis, a disabling disorder with a good prognosis: a case series from Nepal
Authors: Dhakal Bishal , Bogati Kanchan , Baniya Sunil , Muhammad Qurat U. A. , Pathak Bishnu D. , Pokharel Rojina , Adhikari Sandip , Upadhaya Regmi Binit , Subedi Ram C. , Pant Prashant , Paudel Raju
Published: November 2023

Introduction:

Longitudinally extensive transverse myelitis (LETM) is a rare spinal cord disorder with variable etiologies and presentations. It can present solely or as an association with other neurological disorders.

Methodology:

It was a series of cases of LETM in a tertiary care hospital.

Clinical presentation and outcomes:

The initial three cases presented with bilateral lower extremity weakness and were diagnosed as transverse myelitis while, the fourth case, already diagnosed as LETM presented with seizure followed by loss of consciousness. All four cases had a good prognosis to date with continued physiotherapy.

Conclusion:

The early diagnosis of the disease helps to guide the optimal management and decide the potential need for physiotherapy.
Effectiveness of Dyadic Psychoeducational Intervention on Cancer Patients and Their Caregivers
Authors: Chen Daoming , Liu Qing , Zhang Linlin , Qian Hongying
Published: November 2023

Background

Dyadic psychoeducational intervention targets the dyads of cancer patients and caregivers as active participants in partnership, which can potentially address the needs and challenges faced by patients with cancer and their caregivers. However, there is insufficient evidence on the effectiveness of the intervention on psychological health and illness-related outcomes among the dyads.

Objective

To systematically examine the dyadic psychoeducational intervention of cancer patients and their caregivers on psychological health and illness-related outcomes.

Methods

Cochrane Library, EMBASE, CINAHL, PsycINFO, PubMed, Web of Science, and 4 Chinese databases were searched from inception to May 29, 2022. Two investigators independently extracted data and evaluated methodological quality. RevMan 5.4 was used for meta-analysis; heterogeneity was evaluated using Higgins’ I
2 (%). Standardized mean difference (SMD) with a 95% confidence interval (CI) was used to assess the effects.

Results

Eight randomized controlled trials that involved 1234 dyads were collected. Meta-analysis showed that the intervention was effective in reducing the dyadic depression (patients’ SMD, −0.41 [95% CI, −0.78 to −0.04; P = .03]; caregivers’ SMD, −0.70 [95% CI, −1.31 to −0.09; P = .03]). It also improved caregivers’ quality of life (SMD, −0.29 [95% CI, −0.56 to −0.03; P = .03]), whereas no significant effect was found on patients’ quality of life. Dyadic results including anxiety, self-efficacy, disease communication, and appraisals of illness/caregiving were observed.

Conclusion

Dyadic psychoeducational intervention reduced the dyadic depression. It also improved caregivers’ quality of life.

Implications for Practice

Nurses can apply dyadic psychoeducational intervention in clinical practice. More studies are needed to draw higher-quality conclusions and investigate the effects on psychological health and illness-related outcomes in cancer patients and caregivers.
Contemporary Issues in Urothelial Carcinoma of Upper Urinary Tract
Authors: Zhao Jianping , Guo Charles C. , Rao Priya
Published: November 2023

Upper urinary tract urothelial carcinoma (UTUC) is an uncommon malignancy involving the renal pelvis and ureter. Careful pathologic analysis plays a critical role in the diagnosis and clinical management of UTUC. In combination with clinical and radiologic evaluation, pathologic features can be used to stratify patients into low-risk and high-risk groups. This risk stratification can help clinicians select the optimal treatment for patients with UTUC, such as kidney-sparing (conservative) treatment, radical nephroureterectomy or ureterectomy, and perioperative systemic therapy. However, due to the technical difficulty of obtaining sufficient tissue from the upper urinary tract, it is often challenging for pathologists to accurately grade the tumor and assess tumor invasion in small biopsy specimens. Although the majority of UTUCs are pure urothelial carcinoma, a considerable subset of UTUCs show histologic subtypes or divergent differentiation. Recent studies have identified genetically distinct molecular subtypes of UTUC by examining DNA, RNA, and protein expression profiles. The prognosis of pT3 UTUC, particularly renal pelvic UC, remains controversial, and several studies have proposed subclassification of pT3 UTUC. Lynch syndrome is a significant risk factor for UTUC, and screening tests may be considered in young patients and those with familial histories of the disease. Despite significant progress in recent years, several issues remain to be addressed in the pathologic diagnosis, molecular classification, and treatment of UTUC.
DNA Damage Response and Mismatch Repair Gene Defects in Advanced and Metastatic Prostate Cancer
Authors: Akhoundova Dilara , Francica Paola , Rottenberg Sven , Rubin Mark A.
Published: November 2023

Alterations in DNA damage response (DDR) and related genes are present in up to 25% of advanced prostate cancers (PCa). Most frequently altered genes are involved in the homologous recombination repair, the Fanconi anemia, and the mismatch repair pathways, and their deficiencies lead to a highly heterogeneous spectrum of DDR-deficient phenotypes. More than half of these alterations concern non-BRCA DDR genes. From a therapeutic perspective, poly-ADP-ribose polymerase inhibitors have demonstrated robust clinical efficacy in tumors with BRCA2 and BRCA1 alterations. Mismatch repair–deficient PCa, and a subset of CDK12-deficient PCa, are vulnerable to immune checkpoint inhibitors. Emerging data point to the efficacy of ATR inhibitors in PCa with ATM deficiencies. Still, therapeutic implications are insufficiently clarified for most of the non-BRCA DDR alterations, and no successful targeted treatment options have been established.
Correlations Among Clinical Phenotypes, Radiological Examination Indexes, and Hearing Status in Congenital Microtia
Authors: Wang Yuchen , Jiang Haiyue , Pan Bo , Ma Lunkun , Zhou Jiayu , Song Yupeng , Yu Xiaobo , Lin Lin
Published: November 2023

Microtia is a congenital malformation of the external ear that often presents with other anatomical abnormalities and ipsilateral hearing loss (HL). The aim of this study was to present the correlation among important phenotypic abnormalities in microtia and their relationship with HL in a clinical population in China. In this study, a retrospective analysis was conducted on 307 patients diagnosed with microtia who visited the Department of Auricular Reconstruction of the Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, for surgical auricle reconstruction from April 2021 to April 2022. Standardized classification of ear malformations, craniofacial CT scans, and pure tone audiometric data were collected, and statistical analyses were performed using the rank sum test, Kruskal-Wallis test, and Spearman’s rank correlation coefficient. The results showed that group differences between ear malformation and variations in the development of mandible, external auditory canal (EAC), and mastoid pneumatization were statistically significant and each had a positive correlation. Among them, the correlation between development of ear and EAC was the most significant (Ρ=0.72). Besides, the severity of HL (97% were conductive) was positively correlated with ear and EAC dysplasia with or without mandibular hypoplasia. Based on the statistical analysis of the correlation between ear malformation and HL, the authors strongly recommend that facial phenotype reconstruction and hearing improvement of microtia should be considered comprehensively, regardless of whether children with microtia show HL or not, early diagnosis of audiology evaluation and appropriate intervention measures should be implemented.
Dental Protraction Versus Surgery for Cleft Lip and Palate: A Budget Impact Analysis
Authors: Gong Cynthia L. , Choi Dylan G. , Dominguez Annaliza , Deng Ronald , Lo Richard , Pappa Sean , Johns Alexis L. , Urata Mark M. , Hammoudeh Jeffrey A. , Yen Stephen L-K.
Published: November 2023

Class III malocclusion for individuals with cleft lip and palate has historically been managed with surgery. Orthodontic protraction is a noninvasive alternative that may be associated with lower costs. This analysis investigated the budget impact of protraction versus surgery from an institutional perspective. Using a decision tree, analysis was conducted using costs derived from Medicaid reimbursement codes and using actual institutional reimbursement. Probabilities of success, failure, and complications were based on a clinical trial comparing the 2 treatment modalities. One-way and probabilistic sensitivity analyses tested the robustness of results to model parameters. Based on Medicaid fee schedules and failure rates requiring additional surgery, the total cost of protraction was $79,506 versus $172,807 for surgery, resulting in $93,302 cost-savings per patient. The cost and probability of surgery success, as well as the cost of surgery failure and repeat surgery, had the largest impact on these cost-savings. Probabilistic sensitivity analysis showed cost-savings of nearly $92,000 or higher in >50% of simulations. This study showed that protraction is associated with lower costs than surgery and may present a cost-effective alternative to surgery in eligible, appropriate patients.
Knockdown of circ_0114428 alleviates LPS-induced HK2 cell apoptosis and inflammation injury via targeting miR-215-5p/TRAF6/NF-κB axis in Septic acute kidney injury
Authors: Li Yan , Zhang Chunmei , Zhao Zhongyan
Published: November 2023

Background

Sepsis is a systemic inflammatory disease that can cause multiple organ damage. Circular RNAs (circRNAs) have been reported to play a regulatory role in sepsis-induced acute kidney injury (AKI), however, the role of circ_0114428 has not been studied.

Methods

In this study, HK2 cells were treated with different concentrations of lipopolysaccharide (LPS) to induce cell damage, and then the expressions of circ_0114428, microRNA-215-5p (miR-215-5p), tumor necrosis factor receptor-associated factor 6 (TRAF6) were detected by quantitative real-time polymerase chain reaction (qRT-PCR), and western blot examined the Bax and Cleaved-caspase-3 proteins. Cell proliferation was detected by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and thymidine analog 5-ethynyl-2’-deoxyuridine (EdU) assay. And cell apoptosis was detected by flow cytometry, and the levels of inflammatory factors were detected by ELISA.

Results

After LPS treatment with different concentrations, we found that LPS at 10 μg/mL had the best effect on HK2 cells. Circ_0114428 was highly expressed in sepsis-AKI patients and LPS-treated HK2 cells. Knockdown of circ_0114428 restored the effects of LPS treatment on proliferation, apoptosis and inflammatory response of HK2 cells. MiR-215-5p was a target of circ_0114428, and TRAF6 was a downstream target of miR-215-5p. Circ_0114428 regulated TRAF6 expression by sponging miR-215-5p in LPS-treated HK2 cells. Circ_0114428 regulated LPS-induced NF-κB signaling in HK2 cells by targeting miR-215-5p/TRAF6 axis.

Conclusion

Circ_0114428 knockdown abolished the cell proliferation, apoptosis and inflammatory damage in LPS-induced HK2 cells by targeting miR-215-5p/TRAF6/NF-κB.
PROLONGED MECHANICAL VENTILATION IN ACUTE RESPIRATORY DISTRESS SYNDROME
Authors: Andrianopoulos Ioannis , Giannakoulis Vassilis G. , Papoutsi Eleni , Papathanakos Georgios , Koulouras Vasilios , Thompson B. Taylor , Siempos Ilias I.
Published: November 2023

Purpose: Trajectory of acute respiratory distress syndrome (ARDS) spans from rapidly improving cases to cases receiving prolonged mechanical ventilation (PMV). We attempted to estimate temporal trends of prevalence and mortality of PMV and to identify risk factors associated with mortality of patients with ARDS receiving PMV. Methods: We performed a secondary analysis of individual patient data from six randomized controlled clinical trials conducted by the ARDS Network. Prolonged mechanical ventilation was defined as the need for mechanical ventilation for >21 consecutive days. Results: Of 4,216 patients with ARDS, 646 (15.3%) received PMV. Prevalence of PMV gradually declined from 18.4% in the ARDS Network: Low-Tidal-Volume Trial (published in 2000) trial to 10.9% in the SAILS (2014) trial (R
2 = 0.728, P = 0.031). Ninety-day mortality of patients receiving PMV did not change over time (R
2 = 0.271, P = 0.290) and remained as high as 36.8%. Ιn the three most recent trials, risk factors associated with mortality among the 250 patients with ARDS receiving PMV included age, malignancy, pneumonia as the cause of ARDS, coagulation dysfunction, and hepatic dysfunction during the first 21 days after trial enrollment. Conclusion: Although prevalence of PMV among patients enrolled in ARDS Network trials gradually declined, mortality did not change. Risk factors associated with mortality were mostly nonmodifiable.
New predictive biomarkers for screening COVID-19 patients with rhabdomyolysis in combination with cystatin C
Authors: Yu Mengyang , Zhang Chengying , Wan Sitong , Lu Yang , Wang Yufei , Liu Ting , Wang Huimin , Chen Wei , Liu Yahua
Published: November 2023

Purpose

Cystatin C (CysC) has been linked to the prognosis of Corona Virus Disease 2019 (COVID-19). The study aims to investigate a predictor correlated with CysC screening for poor prognosis in COVID-19 patients combined with skeletal muscle (SKM) impairment and rhabdomyolysis (RM).

Methods

A single-center retrospective cohort analysis was carried out. Demographic information, clinical data, laboratory test results, and clinical outcome data were gathered and analyzed.

Results

According to the inclusion and exclusion criteria, 382 patients were included in this study. The subjects were divided into three groups based on CysC tertiles. Multivariate analysis revealed that SaO2 (HR 0.946, 95%CI: 0.906-0.987, P = 0.011), CysC (HR 2.124, 95%CI: 1.223-3.689, P = 0.008), AST (HR 1.009, 95%CI. 1.000-1.018, P = 0.041), and hypersensitive CRP (HR 1.005, 95%CI: 1.000-1.010, P = 0.045) were significantly associated with survivals. The area under curve (AUC) in the model characterized by RM incidence was 0.819 (0.698-0.941), as shown by CysC ROC curves. LDH*CysC and AST*CysC had better predictive values than CysC, and the best prediction for RM, with an AUC of 0.880 (0.796,0.964) for LDH*CysC (P<0.05, vs CysC) and 0.925 (0.878,0.972) for AST*CysC (P<0.05, vs CysC).

Conclusion

CysC is an essential evaluation indicator for COVID-19 patients’ prognosis. AST*CysC and LDH*CysC have superior predictive value to CysC for SKM, RM, and death, and optimal classification for RM.
Machine Learning for Predicting Hemodynamic Deterioration of Patients with Intermediate-risk Pulmonary Embolism in Intensive Care Unit
Authors: Xu Jiatang , Hu Zhensheng , Miao Jianhang , Cao Lin , Tian Zhenluan , Yao Chen , Huang Kai
Published: November 2023

Background

Intermediate-risk pulmonary embolism (PE) patients in the Intensive Care Unit (ICU) are at a higher risk of hemodynamic deterioration than those in the general ward. This study aims to construct a machine learning (ML) model to accurately identify the tendency for hemodynamic deterioration in ICU’s patients with intermediate-risk PE.

Method

A total of 704 intermediate-risk PE patients from the MIMIC-IV database were retrospectively collected. The primary outcome was defined as hemodynamic deterioration occurring within 30 days after admission to ICU. Four ML algorithms were used to construct models on the basis of all variables from MIMIC IV database with missing values less than 20%. The XGBoost model was further simplified for clinical application. The performance of the ML models was evaluated by using the receiver operating characteristic curve (ROC), calibration plots and decision curve analysis (DCA). Predictive performance of simplified XGBoost was compared with sPESI score. SHAP was performed on simplified XGBoost model to calculate the contribution and impact of each feature on the predicted outcome and presents it visually.

Results

Among the 704 intermediate-risk PE patients included in this study, 120 patients experienced hemodynamic deterioration within 30 days after admission to the ICU. Simplified XGBoost model demonstrated the best predictive performance with an AUC of 0.866 (95% CI: 0.800-0.925), and after recalibrated by isotonic regression, the AUC improved to 0.885 (95% CI: 0.822-0.935). Based on simplified XGBoost model, a Web APP was developed to identify the tendency for hemodynamic deterioration in ICU’s intermediate-risk PE patients.

Conclusion

Simplified XGBoost model can accurately predict the occurrence of hemodynamic deterioration for intermediate-risk PE patients in ICU, assisting clinical workers in providing more personalized management for PE patients in the ICU.
METFORMIN MITIGATES SEPSIS-ASSOCIATED PULMONARY FIBROSIS BY PROMOTING AMPK ACTIVATION AND INHIBITING HIF-1α–INDUCED AEROBIC GLYCOLYSIS
Authors: Zhong Han , Tang Ri , Feng Jin-Hua , Peng Ya-Wen , Xu Qiao-Yi , Zhou Yang , He Zheng-Yu , Mei Shu-Ya , Xing Shun-Peng
Published: November 2023

Recent research has revealed that aerobic glycolysis has a strong correlation with sepsis-associated pulmonary fibrosis (PF). However, at present, the mechanism and pathogenesis remain unclear. We aimed to test the hypothesis that the adenosine monophosphate-activated protein kinase (AMPK) activation and suppression of hypoxia-inducible factor 1α (HIF-1α)–induced aerobic glycolysis play a central role in septic pulmonary fibrogenesis. Cellular experiments demonstrated that lipopolysaccharide increased fibroblast activation through AMPK inactivation, HIF-1α induction, alongside an augmentation of aerobic glycolysis. By contrast, the effects were reversed by AMPK activation or HIF-1α inhibition. In addition, pretreatment with metformin, which is an AMPK activator, suppresses HIF-1α expression and alleviates PF associated with sepsis, which is caused by aerobic glycolysis, in mice. Hypoxia-inducible factor 1α knockdown demonstrated similar protective effectsin vivo. Our research implies that targeting AMPK activation and HIF-1α–induced aerobic glycolysis with metformin might be a practical and useful therapeutic alternative for sepsis-associated PF.
PROTECTIVE ROLE OF MELATONIN FOR ACUTE KIDNEY INJURY: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Yue Jing , Bao Xin , Meng Ling-Fei
Published: November 2023

Introduction: Acute kidney injury (AKI) is an important clinical issue that arouses global concerns, which puzzles clinicians and lacks effective drug treatment for AKI until the present. Melatonin has been well recognized to modulate the sleep-wake cycle and had the renal protective effect. However, there are still few clinical trials investigating the relationship between melatonin and AKI. The conclusions drawn in existing clinical studies are still inconsistent. The study systematically reviewed and assessed the efficacy of melatonin in preventing AKI.Methods: A systematic literature search was conducted in the PubMed, Embase, and Cochranelibrary on May 19, 2023. Eligible records were screened according to the inclusion and exclusion criteria. The risk ratio and the corresponding 95% confidence intervals were selected to evaluate the effects of melatonin on AKI. We pooled extracted data using a fixed- or random effects model based on a heterogeneity test.Results: Six randomized controlled trials regarding the use of melatonin in preventing kidney injury met our inclusion criteria. The pooled results showed that melatonin increased the estimated glomerular filtration rate, and effectively inhibited the occurrence of AKI. Melatonin tended to reduce the serum creatinine and urea nitrogen levels, but there was no statistical significance.Conclusions: Melatonin can increase the estimated glomerular filtration rate and effectively inhibit the occurrence of AKI. More well-designed randomized controlled trials are needed to verify the protective effect of melatonin in the future.
COMPARISON BETWEEN ACTIVE ABDOMINAL COMPRESSION-DECOMPRESSION CARDIOPULMONARY RESUSCITATION AND STANDARD CARDIOPULMONARY RESUSCITATION IN ASPHYCTIC CARDIAC ARREST RATS WITH MULTIPLE RIB FRACTURES
Authors: Dai Zhichu , Zhang Sisen , Wang Hongyu , He Liwei , Liao Jiankun , Wu Xuanyu
Published: November 2023

Background:Active abdominal compression-decompression cardiopulmonary resuscitation (AACD-CPR) is potentially more effective for cardiac arrest (CA) with multiple rib fractures. However, its effect on survival rates and neurological outcomes remains unknown. This study aimed to assess if AACD-CPR improves survival rates and neurological outcomes in a rat model of asphyctic CA with multiple rib fractures.Methods:Adult male Sprague-Dawley rats were randomized into three groups—AACD group (n = 15), standard cardiopulmonary resuscitation (STD-CPR) group (n = 15), and sham group (n = 10)—after bilateral rib fractures were surgically created and endotracheal intubation was performed. AACD-CPR and STD-CPR groups underwent 8 min of asphyxia followed by different CPR techniques. The sham group had venous catheterization only. Physiological variables and arterial blood gases were recorded at baseline and during a 4-h monitoring period. Neurological deficit scores (NDSs) and cumulative survival rates were assessed at 24, 48, and 72 h. NDS, serum biomarkers, and hippocampal neuron analysis were used to evaluate neurological outcomes.Results:No statistical differences were observed in the return of spontaneous circulation (ROSC), 24-, 48-, and 72-h survival rates between the AACD-CPR and STD-CPR groups. AACD-CPR rats had lower serum levels of neuron-specific enolase and S100B at 72 h post-ROSC, and higher NDS at 72 h post-ROSC compared with STD-CPR animals. Cellular morphology analysis, hematoxylin and eosin staining, and TUNEL/DAPI assays showed more viable neurons and fewer apoptotic neurons in the AACD-CPR group than in the STD-CPR group.Conclusions:AACD-CPR can achieve similar survival rates and better neurological outcome after asphyxial CA in rats with multiple rib fractures when compared with STD-CPR.
Strongyloides ratti
infection in mice: immune response and immune modulation
Authors: Breloer Minka , Linnemann Lara
Published: November 2023

Strongyloides ratti
is a natural parasite of wild rats and most laboratory mouse strains are also fully permissive. The infection can be divided into three distinct phases: the tissue migration of the infective third stage larvae during the first two days, the early intestinal establishment of
S. ratti
parasites molting to adults on days three to six and the later intestinal parasitic phase until the end of infection. Immunocompetent mice terminate the
S. ratti
infection after one month and are semi-resistant to a second infection. Employing the powerful tools of mouse immunology has facilitated a detailed analysis of the initiation, execution and regulation of the immune response to
S. ratti
. Here we review the information collected to date on the protective immune response to migrating
S. ratti
larvae in tissues and to adult parasites in the intestine. We show that depending on the phase of infection, a site-specific portfolio of immune effector mechanisms is required for infection control. In addition, we summarize the strategies employed by
S. ratti
to evade the immune system and survive long enough in its host to replicate despite an effective immune response. Selected murine studies using the closely related
Strongyloides venezuelensis
will be discussed.

This article is part of the Theo Murphy meeting issue ‘
Strongyloides
: omics to worm-free populations’.
The transmission dynamics of
Strongyloides stercoralis
and the impact of mass drug administration
Authors: Collyer Benjamin S. , Anderson Roy
Published: November 2023

The epidemiology of
Strongyloides stercoralis
is briefly reviewed with an emphasis on cross section and longitudinal studies of infection prevalence stratified by age, performance of different diagnostic tools, mass drug administration (MDA) impact and estimates of key population parameters within the complex life cycle of the parasite that determine transmission intensity and response to control measures. The paucity of studies is highlighted, and gaps in current knowledge identified about the population biology of this very prevalent infection in tropical and sub-tropical regions around the world. A stochastic individual based stochastic model is described in part to highlight gaps in knowledge. The impact of repeated MDA is simulated to illustrate some aspects of transmission dynamics of this helminth infection. Specifically, the impact and bounce back times in either the intervals between treatment rounds, or post the cessation of treatment, depend critically on the magnitude of two distinct components of the basic reproductive number
R
0
. The absence of data on these key components is highlighted, as is the value of studies of longitudinal cohorts of people in regions of endemic infection post rounds of MDA to record how infection levels bounce back post treatment at individual and population levels of study.

This article is part of the Theo Murphy meeting issue ‘
Strongyloides
: omics to worm-free populations’.
A standard workflow for community-driven manual curation ofStrongyloidesgenome annotations
Authors: Bryant Astra S. , Akimori Damia , Stoltzfus Jonathan D. C. , Hallem Elissa A.
Published: November 2023

Advances in the functional genomics and bioinformatics toolkits forStrongyloidesspecies have positioned these species as genetically tractable model systems for gastrointestinal parasitic nematodes. As community interest in mechanistic studies ofStrongyloidesspecies continues to grow, publicly accessible reference genomes and associated genome annotations are critical resources for researchers. Genome annotations for multipleStrongyloidesspecies are broadly available via the WormBase and WormBase ParaSite online repositories. However, a recent phylogenetic analysis of the receptor-type guanylate cyclase (rGC) gene family in twoStrongyloidesspecies highlights the potential for errors in a large percentage of currentStrongyloidesgene models. Here, we present three examples of gene annotation updates within theStrongyloidesrGC gene family; each example illustrates a type of error that may occur frequently within the annotation data forStrongyloidesgenomes. We also extend our analysis to 405 previously curatedStrongyloidesgenes to confirm that gene model errors are found at high rates across gene families. Finally, we introduce a standard manual curation workflow for assessing gene annotation quality and generating corrections, and we discuss how it may be used to facilitate community-driven curation of parasitic nematode biodata.

This article is part of the Theo Murphy meeting issue ‘Strongyloides: omics to worm-free populations’.
Syntenic relationship of chromosomes in
Strongyloides
species and
Rhabditophanes diutinus
based on the chromosome-level genome assemblies
Authors: Kounosu Asuka , Sun Simo , Maeda Yasunobu , Dayi Mehmet , Yoshida Akemi , Maruyama Haruhiko , Hunt Vicky , Sugimoto Asako , Kikuchi Taisei
Published: November 2023

The
Strongyloides
clade, to which the parasitic nematode genus
Strongyloides
belongs, contains taxa with diverse lifestyles, ranging from free-living to obligate vertebrate parasites. Reproductive strategies are also diverse in this group of nematodes, employing not only sexual reproduction but also parthenogenesis, making it an attractive group to study genome adaptation to specific conditions. An in-depth understanding of genome evolution, however, has been hampered by fragmented genome assemblies. In this study, we generated chromosome-level genome assemblies for two
Strongyloides
species and the outgroup species
Rhabditophanes diutinus
using long-read sequencing and high‐throughput chromosome conformation capture (Hi-C). Our synteny analyses revealed a clearer picture of chromosome evolution in this group, suggesting that a functional sex chromosome has been maintained throughout the group. We further investigated sex chromosome dynamics in the lifecycle of
Strongyloides ratti
and found that bivalent formation in oocytes appears to be important for male production in the mitotic parthenogenesis.

This article is part of the Theo Murphy meeting issue ‘
Strongyloides
: omics to worm-free populations’.
Progresses and challenges in
Strongyloides
spp. proteomics
Authors: Tiberti Natalia , Manfredi Marcello , Piubelli Chiara , Buonfrate Dora
Published: November 2023

The availability of high-quality data of helminth genomes provided over the past two decades has supported and accelerated large-scale ‘omics studies and, consequently, the achievement of a more in-depth molecular characterization of a number of pathogens. This has also involved
Strongyloides
spp. and since their genome was made available transcriptomics has been rather frequently applied to investigate gene expression regulation across their life cycle.
Strongyloides
proteomics characterization has instead been somehow neglected, with only a few reports performing high-throughput or targeted analyses associated with protein identification by tandem mass spectrometry. Such investigations are however necessary in order to discern important aspects associated with human strongyloidiasis, including understanding parasite biology and the mechanisms of host–parasite interaction, but also to identify novel diagnostic and therapeutic targets. In this review article, we will give an overview of the published proteomics studies investigating strongyloidiasis at different levels, spanning from the characterization of the somatic proteome and excretory/secretory products of different parasite stages to the investigation of potentially immunogenic proteins. Moreover, in the effort to try to start filling the current gap in host-proteomics, we will also present the first serum proteomics analysis in patients suffering from human strongyloidiasis.

This article is part of the Theo Murphy meeting issue ‘
Strongyloides
: omics to worm-free populations’.
Strongyloides
: omics to worm-free populations
Authors: Buonfrate Dora , Hunt Vicky L. , Odermatt Peter , Streit Adrian
Published: November 2023

This article is part of the Theo Murphy meeting issue ‘
Strongyloides
: omics to worm-free populations’.
The influence of a soil amendment upon the abundance and interaction of arbuscular mycorrhizal fungi with arable soils and host winter wheat
Authors: Wilkes Thomas I
Published: November 2023

Arbuscular mycorrhizal (AM) fungi form close symbiotic relationships with an estimated 70% of terrestrial plant species and aid in the acquisition of soil nutrients. Due to their symbiotic relationship, AM fungi are able to provide a host with acquired soil bound nutrients in exchange for host produced photosynthetic carbohydrates. AM fungal-host relationships are affected by land and soil management practices employed in arable farming. Tillage, for example, can be one of the most detrimental physical disturbances to AM fungal populations. The present study aims to utilise compost and a commercially available AM fungal inoculant to amend arable soils supporting Zulu winter wheat, under controlled conditions, to determine changes in the degree of AM fungal-host symbiosis, crop growth and development, as well as comment on the potential integration of these soil amendments into arable soil management practices. Soils were sampled from 3 field from each of the 3 participating farms practicing either conventional, reduced, or zero tillage. Soil textures were assessed for each sampled soil. Via the employment of AM fungal symbiosis quantification methods, and proxy parameters for fungal biomass, AM fungi were able to be compared between soil amendments and their effects on crop growth and development. The current study was able to show soils amended with multipurpose compost produced a greater degree of AM fungal-host associations for all soil types across all tillage practices. Compost amended soils were also able to show increases in crop tiller numbers and their respective crop height. Reduced wheat root length was also seen from compost amended soils, however, this was correlated to an increase in AM fungal root arbuscules. Commercial AM fungal inocula, on the other hand, was seen to reduce AM fungal associations with their host as well as have little to no influence on crop root length and crop height. Number of tillers per plant were, however, seen to marginally increase with the addition of a commercial AM fungal inocula. From results presented in the current study, conclusions can be drawn towards the advantageous addition of multipurpose compost to arable soils for the tillage and soil types studied. Furthermore, the addition of compost is a more cost effective change to soil management.
The intra-host evolutionary landscape and pathoadaptation of persistent Staphylococcus aureus in chronic rhinosinusitis
Authors: Houtak Ghais , Bouras George , Nepal Roshan , Shaghayegh Gohar , Cooksley Clare , Psaltis Alkis James , Wormald Peter-John , Vreugde Sarah
Published: November 2023

Chronic rhinosinusitis (CRS) is a common chronic sinonasal mucosal inflammation associated with

Staphylococcus aureus

biofilm and relapsing infections. This study aimed to determine rates of

S. aureus

persistence and pathoadaptation in CRS patients by investigating the genomic relatedness and antibiotic resistance/tolerance in longitudinally collected

S. aureus

clinical isolates. A total of 68

S

.

aureus

paired isolates (34 pairs) were sourced from 34 CRS patients at least 6 months apart. Isolates were grown into 48 h biofilms and tested for tolerance to antibiotics. A hybrid sequencing strategy was used to obtain high-quality reference-grade assemblies of all isolates. Single nucleotide variants (SNV) divergence in the core genome and sequence type clustering were used to analyse the relatedness of the isolate pairs. Single nucleotide and structural genome variations, plasmid similarity, and plasmid copy numbers between pairs were examined. Our analysis revealed that 41 % (14/34 pairs) of

S. aureus

isolates were persistent, while 59 % (20/34 pairs) were non-persistent. Persistent isolates showed episode-specific mutational changes over time with a bias towards events in genes involved in adhesion to the host and mobile genetic elements such as plasmids, prophages, and insertion sequences. Furthermore, a significant increase in the copy number of conserved plasmids of persistent strains was observed. This was accompanied by a significant increase in biofilm tolerance against all tested antibiotics, which was linked to a significant increase in biofilm biomass over time, indicating a potential biofilm pathoadaptive process in persistent isolates. In conclusion, our study provides important insights into the mutational changes during

S. aureus

persistence in CRS patients highlighting potential pathoadaptive mechanisms in

S. aureus

persistent isolates culminating in increased biofilm biomass.
GPT-4 Multimodal Analysis on Ophthalmology Clinical Cases Including Text and Images
Authors: Sorin Vera , Kapelushnik Noa , Hecht Idan , Zloto Ofira , Glicksberg Benjamin S. , Bufman Hila , Barash Yiftach , Nadkarni Girish N. , Klang Eyal
Published: November 2023

Objective

Recent advancements in GPT-4 have enabled analysis of text with visual data. Diagnosis in ophthalmology is often based on ocular examinations and imaging, alongside the clinical context. The aim of this study was to evaluate the performance of multimodal GPT-4 (GPT-4V) in an integrated analysis of ocular images and clinical text.

Methods

This retrospective study included 40 patients seen in our institution with ocular pathologies. Cases were selected by a board certified ophthalmologist, to represent various pathologies and match the level for ophthalmology residents. We provided the model with each image, without and then with the clinical context. We also asked two non-ophthalmology physicians to write diagnoses for each image, without and then with the clinical context. Answers for both GPT-4V and the non-ophthalmologists were evaluated by two board-certified ophthalmologists. Performance accuracies were calculated and compared.

Results

GPT-4V provided the correct diagnosis in 19/40 (47.5%) cases based on images without clinical context, and in 27/40 (67.5%) cases when clinical context was provided. Non-ophthalmologists physicians provided the correct diagnoses in 24/40 (60.0%), and 23/40 (57.5%) of cases without clinical context, and in 29/40 (72.5%) and 27/40 (67.5%) with clinical context.

Conclusion

GPT-4V at its current stage is not yet suitable for clinical application in ophthalmology. Nonetheless, its ability to simultaneously analyze and integrate visual and textual data, and arrive at accurate clinical diagnoses in the majority of cases, is impressive. Multimodal large language models like GPT-4V have significant potential to advance both patient care and research in ophthalmology.
Efficacy ofWolbachia-mediated sterility to suppress adultAedes aegyptipopulations
Authors: Bansal Somya , Chong Chee-Seng , Dickens Borame , Lim Jue Tao , Ng Youming , Deng Lu , Lee Caleb , Tan Li Yun , Kakani Evidoxia , Yu David Du , Chain Grace , Ma Pei , Sim Shuzhen , Ng Lee Ching , Tan Cheong Huat
Published: November 2023

Incompatible insect technique coupled with sterile insect technique (IIT-SIT) via releases of sterile maleWolbachia-infected mosquitoes is a promising tool for dengue control. In a six-year trial from 2016 to 2022, comprising 10.35 km2of high-rise housing estates and 607,872 residents, we designed a synthetic control study methodology to assess the efficacy of IIT-SIT in reducing adult femaleAedes aegyptipopulations, using data from a large, routinely collected, nationwide surveillance system of 57,990 unique mosquito traps in public housing estates.

We demonstrated thatWolbachia-based IIT-SIT dramatically reduces wildtypeAedes aegyptipopulations by an average of 60.64% (95% CI: 59.59%–61.44%) and 79.37% (95% CI: 78.85%–79.87%) in 3, 6 months of releases and eventually 90.17% (95% CI: 89.92%–90.42%) in 12 and more months of releases. We further found a smaller but non-negligible suppression effect which gradually increased over time (47.91%, 95% CI: 47.29%–48.52%) in adjacent, non-intervention sites. Our results demonstrate the potential of IIT-SIT for strengthening dengue control in tropical cities, where dengue burden is the greatest.
The use of intravascular ultrasound (IVUS) during percutaneous coronary intervention does not reduce all cause in-hospital mortality but doubles the cost with higher utilization in privately insured patients
Authors: Movahed Mohammad Reza , Nathan Allistair , Hashemzadeh Mehrtash
Published: November 2023

Background

The effect of using intravascular ultrasound (IVUS) during percutaneous coronary intervention (PCI) on short-term mortality is not well established. The goal of this study was to evaluate any association between the use of IVUS during PCI on mortality vs no ICUC in a large inpatient database.

Method

We used the National Inpatient Sample (NIS) database for available ICD-10 codes from 2016-2020 for IVUS and PCIs.

Results

A total of 10,059,56 PCIs were performed. 206,910 underwent IVUS-guided PCI vs 9,852,359 without IVUS use. Mortality did not differ between the two groups with 2.52% mortality in the IVUS arm vs 2.59% in no IVUS cohort, p=0.4. The mean age of patients with ICUS use was 65.5 vs 70.1 years without IVUS. Total in-hospital cost in the IVUS group was double that without IVUS (141,920$ vs 71,568$). Furthermore, IVUS utilization was significantly higher in patients with private HMO patients (28.3% vs 17.2%).

Conclusion

In-patient all-cause mortality using IVUS during PCI was similar to those patients without IVUS utilization but doubled the cost with higher utilization in privately insured patients
HandMol: Coupling WebXR, AI and HCI technologies for Immersive, Natural, Collaborative and Inclusive Molecular Modeling
Authors: Cortes Rodriguez Fabio J. , Krapp Lucien F. , Dal Peraro Matteo , Abriata Luciano A.
Published: November 2023

Except for isolated developments and specific software extensions, molecular graphics and modeling have historically been stuck at flat screens for visualization, mouse operations for molecular manipulation, menus and command line interfaces for controls, and single-user interfaces that only allow collaboration by streaming video hence limited to just sharing the view of the user operating the software. We demonstrate here how various technologies are ripe enough to enable much more fluent, immersive and natural human-computer interactions that in turn facilitate collaboration between human users, using affordable hardware through the internet and without even installing any specialized programs. For this, we introduce HandMol, a web app that exploits (i) WebXR for molecular visualization and manipulation in virtual reality, (ii) speech recognition coupled to a large language model to pass commands orally, (iii) speech synthesis for auditory feedback, (iv) WebRTC to communicate multiple instances of the tool without even requiring a server, and (v) external APIs to flexibly account for molecular mechanics, exemplified here with an endpoint running an AMBER forcefield for protein and nucleic acids and another running a DFT-trained neural network, ANI-2x, to allow exploration of conformation and some simple reactivity at high speed and accuracy. We show example applications to situations from daily work and education in chemistry and structural biology where HandMol can provide an advantage over traditional software: exploring and explaining molecular conformations and reactivity, docking and undocking small molecules into/out of protein pockets, threading molecules through nanopores, preparing systems for molecular simulations and for protein design, etc. We also present a brief study showing how users, even with limited or even no experience in VR, can significantly benefit from these kinds of technologies. As a draft prototype for the moment, HandMol is made available free of charge and without registration athttps://go.epfl.ch/handmol, in (optional but greatly appreciated) exchange for feedback on usability and on features expected for this kind of tools.
New-onset prostate cancer in type 2 diabetes mellitus exposed to the SGLT2I, DPP4I and GLP1a: A population-based cohort study
Authors: Chou Oscar Hou In , Lu Lei , Chung Cheuk To , Chan Jeffrey Shi Kai , Chan Raymond Ngai Chiu , Hiu Athena Lee Yan , Dee Edward Christopher , Ng Kenrick , Pui Hugo Hok Him , Lee Sharen , Cheung Bernard Man Yung , Tse Gary , Zhou Jiandong
Published: November 2023

Background

Sodium-glucose cotransporter 2 inhibitors (SGLT2I) have been suggested to reduce new-onset cancer amongst type-2 diabetes mellitus (T2DM) patients.

Objective

This real-world study aims to compare the risks of prostate cancer between SGLT2I and dipeptidyl peptidase-4 inhibitors (DPP4I) amongst T2DM patients.

Design, setting and participants

This was a retrospective population-based cohort study of prospectively recorded data on type-2 diabetes mellitus (T2DM) male patients prescribed either SGLT2I or DPP4I between January 1st2015 and December 31st2020 from Hong Kong.

Methods

The primary outcome was new-onset prostate cancer. The secondary outcomes included cancer-related mortality and all-cause mortality. Propensity score matching (1:1 ratio) using the nearest neighbour search was performed and multivariable Cox regression was applied to compare the risk. A three-arm sensitivity analysis including the glucagon-like peptide-1 receptor agonist (GLP1a) cohort was conducted.

Results

This study included 42129 male T2DM patients (median age: 61.0 years old [SD: 12.2]; SGLT2I: n=17120; DPP4I: n=25009). After matching, the number of prostate cancers was significantly lower in SGLT2I users (n = 60) than in DPP4I (n = 102). SGLT2I use was associated with lower prostate cancer risks (HR: 0.45; 95% CI: 0.30-0.70) after adjustments than DPP4I. The results remained consistent in the sensitivity analysis. SGLT2I reduced the risks of prostate cancer prominently amongst patients who were older (age >65), patients with 2ndand 3rdquartile of HbA1c, concurrent metformin uses, and concurrent sulphonylurea uses. SGLT2I was associated with higher risks of prostate cancer amongst sulphonylurea non-users.

Conclusion

The real-world study demonstrated SGLT2I was associated with lower risks of new-onset prostate cancer after matching and adjustments compared to DPP4I. This result warrants further prospective studies.

Graphical abstract