bluuebunny/crossref_metadata_2025 huggingface dataset:
An observational study on efficacy of atrioventricular nodal slow pathway ablation in patients with atrioventricular nodal reentrant tachycardia and its influence on atrioventricular conduction function
Authors: Wang Hongwei , Li Xiumei
Published: November 2024

The study aimed to evaluate the effectiveness of atrioventricular nodal slow pathway ablation in patients with atrioventricular nodal reentrant tachycardia (AVNRT) and examine its impact on the atrioventricular conduction function. A retrospective analysis was performed on the clinical data of 90 AVNRT patients who underwent radiofrequency ablation at our institution between August 2018 and February 2021. Based on the presence or absence of slow pathway conduction during the procedure, patients were classified into the slow pathway elimination group (SPE group) and the slow pathway improvement group (SPI group). Procedure-related parameters, His bundle electrogram, atrioventricular nodal effective refractory period (AVN-ERP), Wenckebach point of anterograde atrioventricular nodal conduction (AVN-WKB), Wenckebach point of retrograde atrioventricular nodal conduction (VAV-WKB), myocardial function were compared between the 2 groups. Additionally, the recurrence rates 1 and 2 years post-ablation were noted. Both groups reported a 100% success rate for the procedure. Post-ablation, 42 patients exhibited persisting atrioventricular nodal slow pathway, whereas 48 showed its disappearance, signifying the absence of the jump phenomenon and atrial echo. Post-ablation, the SPI group showed an increase in slow pathway AVN-ERP compared to pre-ablation values (P < .05), with no significant change in the fast pathway AVN-ERP (P > .05). The SPE group showed a reduction in both slow pathway and fast pathway AVN-ERP post-ablation (P < .05). Post-ablation, both slow pathway and fast pathway AVN-ERP in the SPI group were higher than in the SPE group (P < .05). AVN-WKB and VAV-WKB values increased in both groups after ablation (P < .05). There were no recurrences 1 or 2 years after ablation in the SPE group and 1 case of recurrence 2 years after ablation in the SPI group (2.38%). Different ablation endpoints during radiofrequency ablation had no apparent impact on atrioventricular conduction time, recurrence rate, and myocardial function in patients with AVNRT, but they advanced AVN-WKB and VAV-WKB. Slow pathway improvement led to an elongation of slow pathway AVN-ERP, while slow pathway elimination resulted in a reduction of both slow pathway and fast pathway AVN-ERP.
Research frontiers and hotspots of coronary chronic total occlusion: A bibliometric analysis
Authors: Li Shudi , Zhang Menghe , Li Wenwen , Sun Zhenhai , Zhang Yunxiao , Zuo Yaoyao , Chen Shouqiang
Published: November 2024

By analyzing the relevant literature, we can accurately grasp the current status of diagnosis and treatment of chronic total occlusion of coronary artery, and clarify the development trend, research frontiers and hotspots of this disease. A literature search with “chronic total occlusion” as the title was performed in the Web of Science database. The title, author, abstract, keywords, institution, publication, country, reference, and other endnotes of the selected literature were exported in the form of text. The author, country, institution, and keywords of the literature were analyzed through Citespace and VOSviewer. The United States has the highest proportion of articles. The institution with the largest number of publications in this field is the Minneapolis Heart Institute Foundation. Brilakis Emmanouil S is the author with the most published articles. The journal system with the largest number of articles in this field is Cardiac Cardiovascular Systems. The keywords with the highest frequency are “chronic total occlusion,” “percutaneous coronary intervention,” “recanalization,” and “revascularization.” The burst detection analysis of hot keywords shows that “algorithm,” “management,” and “mortality” are the research hotspots in this field in recent years. At present, the research on this disease mainly focuses on the opening of occluded coronary arteries through various treatment methods. In the near future and the next few years, the research hotspots may be the scoring system algorithms for the treatment of chronic total occlusion of coronary artery and the management strategies for patients.
Characteristics of patients leaving the emergency department without being seen by a doctor: The first report from Türkiye
Authors: Şengüldür Erdinç , Demir Mehmet Cihat , Selki Kudret , Erdem Emre , Güldal Hatice
Published: November 2024

The presence of patients who leave without being seen (LWBS) by a physician in the emergency department (ED) is an essential indicator of the accessibility and quality of healthcare delivery. A high LWBS rate implies low patient satisfaction. This study aims to analyze the prevalence and characteristics of LWBS patients in Türkiye and their ED readmission rate within 3 days. This retrospective, single-center, observational study was conducted in the ED of a Turkish tertiary university hospital. It looked at patients who left without being evaluated by a physician admitted to the ED between June 01, 2021, and June 01, 2023. Data on age, gender, residential area, health insurance status, ED readmission within 3 days, complaints, and hospitalization were obtained through the hospital’s electronic record system. The prevalence of LWBS patients was 0.43%. Only 0.6% (n = 5) of LWBS patients had no health insurance. About 12.8% (n = 99) of them were 65 years and older. About 10.2% (n = 79) of LWBS patients were readmitted to the ED within 72 hours. The most common reason for readmission was musculoskeletal system complaints. Statistically, ED readmission was significantly more common in older adults (P = .05). Older LWBS patients are more likely hospitalized upon return visits to the ED (P = .014). LWBS patients are both a result and a consequence of ED crowding. A zero LWBS rate is crucial for older adults’ health as they may fall victim to an invisible accident while avoiding ED traffic. Prioritizing older adults and reorganizing waiting areas can reduce ED crowding and cost burden due to delayed treatments.
Bioinformatics-based screening of hub genes for prostate cancer bone metastasis and analysis of immune infiltration
Authors: Lin Shu-Kun , Zhang Chen-Ming , Men Bo , Hua Zhong , Ma Si-Cheng , Zhang Fang
Published: November 2024

Bioinformatics analysis of genes and immune cells that influence prostate cancer (PCa) bone metastases. Using the gene expression omnibus database, we analyzed a PCa bone metastasis dataset. Differentially expressed genes were identified through the utilization of GEO2R and weighted gene co-expression network analysis. Gene set enrichment analysis software was used to identify important pathways. In addition to creating a network of protein–protein interactions, functional enrichment analyses were conducted using Kyoto encyclopedia of genes databases. To screen hub genes, Cytoscape software was used with the CytoHubba plug-in and performed mRNA and survival curve validation analysis of key genes using the cBioPortal website and GEPIA2 database. Immune infiltration analysis was performed using the CIBERSORTx website, and finally, immune cell correlation analysis was performed for key genes according to the TIMER database. A total of 197 PCa bone metastasis risk genes were screened, “G2M_CHECKPOINT” was significantly enriched in PCa bone metastasis samples according to genomic enrichment analysis. Based on the protein interactions network, we have identified 10 alternative hub genes, and 3 hub genes, CCNA2, NUSAP1, and PBK, were validated by the cBioPortal website and the GEPIA2 database. T cells regulatory and macrophages M0 may influence PCa to metastasize to bones, according to CIBERSORTx immune cell infiltration analysis. TIMER database analysis found different degrees of correlation between 3 key genes and major immune cells. PCa bone metastasis has been associated with CCNA2, NUSAP1, and PBK. T cells regulatory and macrophages (M0) may also be involved.
Clinical evaluation of the efficacy of focused extracorporeal shock-wave therapy in patients with cervical spondylosis: A randomized control trial
Authors: Li Shuangyue , Liu Jie , Wang Yan , Zhu Chan , Tang Yahong , Gu Minghong
Published: November 2024

Background:

Extracorporeal shock wave therapy (ESWT) has emerged as a contemporary modality in physiotherapy, demonstrating efficacy in addressing musculoskeletal disorders. Despite its potential, the clinical efficacy of ESWT in the context of cervical spondylosis remains understudied, with a dearth of robust empirical evidence. To bridge this gap, the present study was designed to evaluate the therapeutic impact of focused ESWT (fESWT) on pain alleviation and functional improvement in individuals afflicted with cervical spondylosis.

Method:

A multicenter, randomized controlled clinical study was conducted, collecting data from 5 clinical studies on the treatment of cervical spondylosis with fESWT from June 2021 to March 2024. The inclusion criteria were patients diagnosed with cervical spondylosis, aged 20 to 70, without severe underlying diseases such as heart disease, hypertension, diabetes, etc. The exclusion criteria included pregnant women, nursing women, patients with bleeding tendencies, or those with cardiac pacemakers. The control group underwent a sham fESWT, while the experimental group received fESWT administered via the Duolith SD1 Tower device. The main observation indicators included the Visual Analogue Scale (VAS) for pain scoring, Neck Disability Index (NDI) scoring, cervical range of motion (ROM) scoring, and the Short Form-36 (SF-36) quality of life survey scoring.

Results:

A total of 320 subjects were included in the study, with 160 in the experimental group and 160 in the control group. Post-treatment, the VAS and NDI scores in the experimental group were significantly lower than those in the control group (P < .05), while the cervical range of motion (ROM) and SF-36 scores were significantly higher than in the control group (P < .05). The overall treatment efficacy rate in the experimental group exceeded 90%, markedly higher than the approximately 70% rate in the control group (P < .05). There was no significant difference in the incidence of adverse reactions between the 2 groups.

Conclusion:

The fESWT has shown promising therapeutic effects in the treatment of cervical spondylosis. It effectively reduces patient pain, improves cervical function, and enhances the quality of life, making it worthy of clinical promotion and application.
Twenty year outcomes following short-segment posterior instrumentation and fusion for thoracolumbar burst fractures: A retrospective observational study
Authors: Kultur Yigit , Sarikaya İlker , Ozsahin Mahmut Kursat , Davulcu Cumhur Deniz , Aydingoz Onder
Published: November 2024

This study reviews the long-term efficacy of short-segment posterior instrumentation and fusion (SSPIF) in treating thoracolumbar burst fractures. Authors retrospectively reviewed the radiographic results of single-level thoracolumbar burst fractures treated by SSPIF. Vertebral body height and wedge angles were measured on the preoperative, postoperative, and follow-up radiographic images. The degree of pain and work ability was measured using the Denis scale. The analysis consisted of 12 patients with a mean age of 39.7 years (range 21–60) and a mean follow-up of 225.6 ± 20.3 months. There were significant differences among the wedge angles at preoperative and other periods of time, but there was no significant difference between the early postoperative and all other time periods afterwards (P < .001, P = .567, P = .937, P = .879). SSPIF effectively restored the anterior and middle vertebral body height and wedge angle deformities, and the improvement was maintained for almost 20 years after the surgery. Therefore, SSPIF is a safe and effective modality of treatment for thoracolumbar burst fractures.
Factors impacting the efficacy of the retrograde autologous priming in isolated coronary artery bypass surgery
Authors: Erol Mehmet Emir , Özyalçin Sertan , Beyazpinar Deniz Sarp , Yiğit Görkem , Türkmen Ufuk
Published: November 2024

During retrograde autologous priming (RAP), some patients develop hypotension and hemodynamic instability, which impedes the procedure. This study aimed to demonstrate the effects of RAP on transfusion requirements and the development of hemodynamic instability. Overall, 443 patients who were operated upon for coronary artery bypass surgery (CABG) between January 2017 and December 2022 were enrolled and examined, including 162 who underwent RAP (RAP group) and 281 who did not (non-RAP group). Further, data regarding demographic characteristics, preoperative and intraoperative characteristics, and postoperative outcomes of both groups were analyzed. The demographic characteristics and intraoperative data were similar between both groups. Meanwhile, the amount of intraoperative and postoperative blood transfusion and postoperative drainage was lower in the RAP group than in the non-RAP group (P = .001 and .001, respectively). The length of intensive care unit (ICU) stay was shorter in the RAP group, whereas the length of overall hospital stay was the same in both groups. In 17% of the RAP patients, the procedure was terminated following hemodynamic instability. Further, regression analysis revealed body surface area (BSA) and baseline central venous pressure (CVP) as risk factors for the development of hemodynamic instability. In the receiver operating characteristic (ROC) curve analysis, the cutoff values for BSA and CVP were found to be 1.73 (sensitivity = 84.2%, specificity = 80.3%, the area under the ROC curve [AUC] = 0.905) and 4.5 (sensitivity = 97.7%, specificity = 99.7%, AUC = 0.994), respectively. Our finding suggest that RAP is associated with a reduction in the requirement in blood transfusion during both intra-and postoperative periods, as well as a decrease in postoperative drainage. Additionally, the risk of hemodynamic instability during RAP appears to be minimal in patients with a body surface area (BSA) >1.73 and a baseline CVP exceeding 4.5.
A retrospective study for clinical characteristics of 293 patients with dermatomyositis
Authors: Xie Xiaowen , Dai Xinyue , Liu Huaxiang , Xing Yi
Published: November 2024

This retrospective study aimed to investigate differences in clinical characteristics between different antibody phenotypes in patients with dermatomyositis (DM). Two hundred and ninety-three patients with DM were included in this study from September 2018 to September 2023. We collected basic clinical data from the patients, using statistical methods to analyze the clinical characteristics, and used survival analysis and COX regression to assess the prognosis of the patients. In the 293 patients, the antibody distribution was as follows: antibody negative (50, 20.3%), anti-melanoma differentiation-associated gene 5 (MDA5) antibody (104, 42.3%), anti-transcription intermediary factor γ (TIF-γ) antibody (41, 16.7%), anti-complex nucleosome remodeling histone deacetylase (Mi2) antibody (28, 11.4%), anti-nuclear matrix protein 2 (NXP2) antibody (19, 7.7%), anti-small ubiquitin-like modifier activating enzyme (SAE) antibody (4, 1.6%). Interstitial pneumonia (P < .001), lung infection (P < .001), respiratory symptoms (P < .001), arthralgia (P < .001), and fever (P < .001) were more likely to be seen in patients with anti-MDA5 antibody. Malignancy (P < .001) and V-sign (P = .017) were more likely to occur in anti-TIF1-γ antibody positive patients. Anti-NXP2 antibody-positive patients showed more symptoms of muscle involvement, such as myasthenia (P = .002), myalgia (P = .003) and dysphagia (P = .001). In the analysis of prognosis, age at onset (hazard ratio = 1.096, 95% CI: 1.064–1.129, P < .001), fever (hazard ratio = 2.449, 95% CI: 1.183–5.066, P = .016), γ-glutamyl transferase level (hazard ratio = 1.005, 95% CI: 1.002–1.008, P < .001), eosinophil level (hazard ratio = 0.000, 95% CI: 0.000–0.324, P = .024), and complement 3 (C3) level (hazard ratio = 0.115, 95% CI: 0.023–0.575, P = .008) had a statistically significant effect on survival time. The clinical features of DM are associated with myositis-specific antibodies. At the same time, advanced age, fever, elevated γ-glutamyl transferase levels, and reduced C3 and eosinophil levels may be associated with poor prognosis in patients with DM. These data may provide useful information for clinical management of patients with DM.
Timing of Palliative Care Consultation and End-of-Life Care Intensity in Pediatric Patients With Advanced Heart Disease: Single-Center, Retrospective Cohort Study, 2014–2022
Authors: Songer Kathryn L. , Wawrzynski Sarah E. , Olson Lenora M. , Harousseau Mark E. , Meeks Huong D. , Moresco Benjamin L. , Delgado-Corcoran Claudia
Published: November 2024

OBJECTIVES:

Pediatric patients with advanced heart disease (AHD) often receive high intensity medical care at the end of life (EOL). In this study, we aimed to determine whether receipt and timing of pediatric palliative care (PPC) consultation was associated with EOL care intensity of pediatric patients with AHD.

DESIGN:

Retrospective cohort study.

SETTING:

Single-center, 16-bed cardiac ICU (CICU) in a children’s hospital in the Mountain West.

PATIENTS:

Pediatric patients (0–21 yr) with AHD treated in the CICU and subsequently died from January 2014 to December 2022.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

We compared demographics, EOL characteristics, and care, including medical interventions and mortality characteristics for patients by receipt and timing of PPC (i.e., ≥ 30 d from [early] or < 30 d of death [late]) using chi-square and Wilcoxon rank-sum tests. Of 218 patients, 78 (36%) did not receive PPC, 76 received early PPC (35%), and 64 received late PPC (29%). Compared with patients who did not receive PPC, patients receiving PPC had lower EOL care intensity (77% vs. 96%; p = 0.004) and fewer invasive interventions within 14 days of death (74% vs. 92%; p = 0.004). Receipt of PPC, vs. not, was associated with lower rate of death during cardiopulmonary resuscitation (12% vs. 32%; p = 0.004) and more use of comfort care (23% vs. 3%; p = 0.004). Among patients receiving PPC, early PPC was associated with fewer invasive interventions within 14 days of death (65% vs. 85%; p = 0.033). Care intensity was high for patients with early and late PPC.

CONCLUSIONS:

Early PPC was associated with fewer invasive interventions within 14 days of death, yet the care intensity at EOL remained high. With early PPC, families likely receive timely psychosocial and advance care planning support without significantly altering goals of care.
Protocol for the Catheter-Related Early Thromboprophylaxis With Enoxaparin (CRETE) Studies
Authors: Faustino E. Vincent S. , Kandil Sarah B. , Leroue Matthew K. , Sochet Anthony A. , Kong Michele , Cholette Jill M. , Nellis Marianne E. , Pinto Matthew G. , Chegondi Madhuradhar , Ramirez Michelle , Schreiber Hilary , Kerris Elizabeth W. J. , Glau Christie L. , Kolmar Amanda , Muisyo Teddy M. , Sharathkumar Anjali , Polikoff Lee , Silva Cicero T. , Ehrlich Lauren , Navarro Oscar M. , Spinella Philip C. , Raffini Leslie , Taylor Sarah N. , McPartland Tara , Shabanova Veronika ,   for the Catheter-Related Early Thromboprophylaxis with Enoxaparin (CRETE) Studies Investigators and the Pediatric Critical Care Blood Research Network (BloodNet) of the Pediatric Acute Lung Injury and Sepsis Investigators Network (PALISI)
Published: November 2024

OBJECTIVES:

In post hoc analyses of our previous phase 2b Bayesian randomized clinical trial (RCT), prophylaxis with enoxaparin reduced central venous catheter (CVC)-associated deep venous thrombosis (CADVT) in critically ill older children but not in infants. The goal of the Catheter-Related Early Thromboprophylaxis with Enoxaparin (CRETE) Studies is to investigate this newly identified age-dependent heterogeneity in the efficacy of prophylaxis with enoxaparin against CADVT in critically ill children.

DESIGN:

Two parallel, multicenter Bayesian superiority explanatory RCTs, that is, phase 3 for older children and phase 2b for infants, and an exploratory mechanistic nested case-control study (Trial Registration ClinicalTrials.gov NCT04924322, June 7, 2021).

SETTING:

At least 15 PICUs across the United States.

PATIENTS:

Older children 1–17 years old (n = 90) and infants older than 36 weeks corrected gestational age younger than 1 year old (n = 168) admitted to the PICU with an untunneled CVC inserted in the prior 24 hours. Subjects with or at high risk of clinically relevant bleeding will be excluded.

INTERVENTIONS:

Prophylactic dose of enoxaparin starting at 0.5 mg/kg then adjusted to anti-Xa range of 0.2–0.5 international units (IU)/mL for older children and therapeutic dose of enoxaparin starting at 1.5 mg/kg then adjusted to anti-Xa range of greater than 0.5–1.0 IU/mL or 0.2–0.5 IU/mL for infants while CVC is in situ.

MEASUREMENTS AND MAIN RESULTS:

Randomization is 2:1 to enoxaparin or usual care (no enoxaparin) for older children and 1:1:1 to either of 2 anti-Xa ranges of enoxaparin or usual care for infants. Ultrasonography will be performed after removal of CVC to assess for CADVT. Subjects will be monitored for bleeding. Platelet poor plasma will be analyzed for markers of thrombin generation. Samples from subjects with CADVT will be counter-matched 1:1 to subjects without CADVT from the opposite trial arm. Institutional Review Board approved the “CRETE Studies” on July 1, 2021. Enrollment is ongoing with planned completion in July 2025 for older children and July 2026 for infants.
Development of a Scoring Model to Predict Severe Dengue in Children at Admission to Emergency Care
Authors: Srinivasan Ranjini , Govardhan Chaitra , Krishna Sushma , Selvam Sumithra
Published: November 2024

Objective

Dengue has emerged as the most widely spread mosquito-borne disease, hyperendemic in India. Although severe dengue occurs only in a small proportion of cases, delays in the recognition and management can result in significant morbidity and mortality. Risk stratification of children in the emergency care and identifying those at risk for worsening during hospital stay facilitates optimum utilization of health care resources. The objective of our study was to develop and validate a scoring model to predict the development of severe dengue in hospitalized children by identifying risk factors present in them at the time of admission to the emergency department.

Methods

A retrospective study of consecutive children aged 1 month to 18 years admitted with serologically confirmed dengue from January 2019 through December 2021 was conducted. Analysis of clinical and laboratory parameters of children resulted in the development of a comprehensive predictive scoring model. This model was internally validated prospectively on 107 children presenting with nonsevere dengue to emergency care.

Results

A total of 743 children with confirmed dengue were studied out of which 216 (29.1%) had severe dengue. Presence of third spacing (odds ratio [OR] 3.74, 95% confidence interval [CI] 1.088–7.42, P < 0.001), tender hepatomegaly (OR 1.62, 95% CI 1.04–2.52, P < 0.032), respiratory distress (OR 3.50, 95% CI 1.89–6.51, P < 0.001), and moderate (OR 3.51, 95% CI 1.82–6.74, P < 0.001) to severe (OR 4.76, 95% CI 2.59–8.76, P < 0.001) elevation of aspartate aminotransferase were independent risk factors found to be associated with development of severe dengue. A score ≥7 had a specificity of 87%, negative predictive value of 86%, and overall diagnostic accuracy of 78.5% for predicting severe dengue.

Conclusions

The dengue severity scoring model was found to have reasonable diagnostic accuracy in predicting severe disease prior to hospitalization. However, more studies are required to validate the score in different emergency care settings with varied pediatric populations.
Oral Ketamine and Midazolam for Procedural Sedation in the Pediatric Emergency Department
Authors: Del Pizzo Jeannine , Fein Joel A.
Published: November 2024

Introduction

Needle-free procedural sedation (PS) is an attractive option for children presenting to the emergency department (ED) who require a painful procedure, as it avoids inflicting additional pain either with intravenous line placement or intramuscular injection. While use of oral (PO) ketamine has been reported in the literature, limited information is available to guide ED-based use in children.

Methods

This is a descriptive study of the patient experience receiving PS with the following regimen: PO ketamine 6 mg/kg (max of 200 mg) with or without PO midazolam 0.5 mg/kg (max 15 mg) approximately 30 minutes before a procedure. We performed a retrospective chart review of children younger than 18 years receiving this PS regimen at a tertiary care children's hospital ED and an affiliated community hospital ED from January 1 through September 30, 2023.

Results

Fifty-eight children were sedated with PO ketamine during the study period. The most common procedure performed was laceration repair (46.5%), followed by incision and drainage (17.3%). All but 2 children received PO midazolam along with PO ketamine. Eight patients received additional medications due to inadequate sedation. Sedation depth was clinician-reported as moderate in 74.1% (43), mild in 15.5% (9), and deep in 10.3% (6). Procedures were completed in 98.3% (57) cases. 93.1% (54) of patients had no adverse event (AE) of any kind and no patient had a significant adverse event (SAE).

Discussion

PO ketamine with or without midazolam resulted in procedure completion of a variety of procedures in the pediatric ED with minimal AE, no SAE, and without need for additional sedative medications in 86.2% (50). This regimen is an option for needle-free moderate PS in this setting. Further study is needed to clarify the benefit of the addition of midazolam to PO ketamine, rates of AE and SAE, sedation duration, and recovery times.
Evaluating the Effectiveness of a Mobile Health Intervention on Enhancing HIV Knowledge in Sexual and Gender Minority Men
Authors: Dos Santos Fabiana Cristina , Garofalo Robert , Kuhns Lisa M. , Scherr Thomas , Schnall Rebecca
Published: November 2024

Background:

In the United States, young men who have sex with men (YMSM) and young transgender women (YTGW) are disproportionately affected by HIV infection. Adequate HIV knowledge is critical for protecting adolescents and young adults at risk for HIV. This study aimed to evaluate the effectiveness of the mLab App intervention in enhancing HIV knowledge among YMSM and YTGW.

Methods:

This study was a secondary analysis of data collected from a randomized controlled trial (RCT) evaluating the effect of the mLab App on HIV knowledge. We calculated interactions between groups (mLab App intervention, standard of care, at-home testing) over time (6 and 12 months) following the baseline observation, indicating a difference in the outcome scores from baseline to each time across groups.

Results:

Although the mLab App group initially had lower HIV knowledge than those in other groups, access to the App demonstrated a progressive impact on HIV knowledge over time. Despite the absence of a statistically significant effect at the 6-month follow-up, the long-term evaluation suggests improvements in HIV knowledge during the 12-month intervention follow-up.

Conclusions:

Our study suggests the potential of the mLab App as a valuable tool for long-term HIV education and awareness for YMSM and YTGW. Further research is needed to understand the factors influencing the short-term effect on HIV knowledge. The mLab App may be a useful intervention for improving HIV knowledge.
Recognition of an appropriate mating partner using cuticular hydrocarbons in a species with an extreme intra-sexual dimorphism
Authors: Moris Victoria , Wirtgen Aline , Niehuis Oliver , Schmitt Thomas
Published: November 2024

Attracting a mate at the right time is critical for many species that reproduce sexually. In insects, short-range communication between potential mates is often mediated by cuticular hydrocarbons (CHCs), which cover most of the insect cuticle. Although the CHC profiles of many insects have been studied, we know little about what aspects of a CHC profile cause changes in mate attractiveness over the lifetime of an individual. We addressed this question by studying the mason waspOdynerus spinipes, whose females exhibit age-related quantitative changes in their CHC profile composition. First, we created an ethogram of the male mating behavior. We knew from preliminary investigations that males do not attempt to mate with recently eclosed adult females. By coating wasp dummies with different CHC extracts, we were able to show that the CHC profiles of 3-day-old females are indeed more attractive to males than those of 0-day-old females. The increased attractiveness of 3-day-old females compared to younger females was negatively correlated with the relative abundance of methyl-branched alkanes in the CHC profile of the females. These results, and the fact that the CHC profile of males is characterized by a high relative abundance of methyl-branched alkanes throughout the adult wasp lifetime, suggest that inO. spinipes, methyl-branched alkanes may act as anti-aphrodisiacs that reduce the harassment of females by males before the females are ready to mate.
Prey attracting but not repelled by predators suggests an asymmetric investment in the encounter-avoid-escape sequence
Authors: Ferry Nicolas , Fiderer Christian , Peters Anne , Ballmann Axel , Heurich Marco
Published: November 2024

Understanding predator-prey interactions, particularly how species use space and time to influence encounter rates, is crucial in ecology. Camera traps, while not being able to directly measure encounters of large free-roaming species, can help estimating how species tolerate or avoid proximity with eachother. We used data from a one-year study in four German protected areas used 283 camera traps and applied recurrent event analysis to explore interactions among three prey species (red deer, roe deer, wild boar) and two predators (grey wolf, Eurasian lynx). Prey visitation rates were unaffected by predators, but wolves showed a strong attraction to prey, with visitation rates approximatively seven times higher right after prey occurrence. Insufficient data hindered robust pattern estimation regarding the Eurasian lynx. This suggests an asymmetry where predators need to succeed at every stage of the encounter sequence, while prey can disrupt the process at any stage to avoid being caught.
Fibroblast-derived Osteoglycin Promotes Epithelial Cell Repair
Authors: van der Koog Luke , Woest Manon E. , Gorter Iris C. , Verschut Vicky , Elferink Robin A.B. , Zuidhof Annet B. , Nugraha Dyan F. , Koloko Ngassie Maunick L. , Bos Sophie I.T. , Dhakad Deepesh , Wolters Justina C. , Horvatovich Peter L. , Prakash Y.S. , Timens Wim , Yildirim Önder A. , Brandsma Corry-Anke , Frijlink Henderik W. , Nagelkerke Anika , Gosens Reinoud
Published: November 2024

There is an urgent need for innovative pharmacological treatments targeting defective epithelial repair in chronic diseases, such as chronic obstructive pulmonary disease. The mesenchymal niche is a critical regulator in epithelial stem cell activation during repair. We hypothesized that secreted factors in this interaction are potent drug targets. Utilizing a cutting-edge proteomics-guided drug discovery strategy, we explored the lung fibroblast secretome to uncover impactful drug targets. Our lung organoid assays identified several regenerative ligands, with the secreted matrix protein osteoglycin (OGN) surprisingly showing the most profound effects. Transcriptomic analyses revealed that OGN enhances alveolar progenitor cell differentiation, boosts reactive oxygen species detoxification, reduces cellular senescence, and strengthens fibroblast-epithelial crosstalk. Critically, OGN expression was diminished in COPD patients and smoke-exposed mice. An active fragment of OGN, encompassing leucine-rich repeat regions 4-7, demonstrated regenerative potential akin to full-length OGN. This fragment significantly ameliorated elastase-induced lung injury precision-cut lung slices and improved lung functionin vivo. These findings highlight lung fibroblast-derived OGN as a pivotal secreted protein for alveolar epithelial growth, positioning its active fragment as a promising therapeutic for epithelial repair in individuals with accelerated lung tissue damage.
Multi-layered ecological interactions determine growth of clinical antibiotic-resistant strains within human microbiomes
Authors: Leon-Sampedro Ricardo , Boumasmoud Mathilde , Reichlin Markus , Pfrunder-Cardozo Katia R. , Noll Nicholas , Egli Adrian , Hall Alex R.
Published: November 2024

Understanding the spread of antibiotic-resistant bacteria in human-associated microbial communities, particularly in the gut microbiome, is critical for combating the global resistance crisis. However, the role of various ecological factors, such as intraspecies or interspecies interactions, in modulating this process is poorly understood. We hypothesized that different strains within the same species would exhibit distinct interactions with the resident microbiota, leading to variable invasion outcomes. To test this, we examined the population growth of multiple clinically relevant antibiotic-resistantE. colistrains carrying ESBL and carbapenemase resistance plasmids. We introduced these strains into human gut microbiome samples from healthy individuals, using replicated anaerobic microcosms treated or untreated with antibiotics. We found that while antibiotic exposure significantly influenced the growth of these incoming strains, some were successful even in the absence of antibiotics. The variation in ecological success across strain-microbiome sample combinations was positively associated with the intrinsic growth capacities of the strains in local abiotic conditions and their competitive interactions with residentE. coli. Furthermore, the incoming resistant strains had strain- specific effects on the taxonomic composition of the resident microbiota; different strains not only varied in their growth performance in human microbiomes, in some cases they pushed taxonomic composition of the resident community in different directions. In contrast with phenotypes measured in gut microcosms, metabolic profiles measured across various single-carbon-source environments were not reliable predictors of population growth in human microbiomes. Overall, this controlled design reveals the multi-layered ecological dynamics and strain-specific mechanisms that govern the spread of antibiotic-resistant bacteria in individual human-associated microbiomes.
Tumor Spheroid Uptake of Fluorescent Nanodiamonds is limited by Mass Density: a 4D Light-Sheet Assay
Authors: Niora Maria , Dufva Martin , Jauffred Liselotte , Berg-Sørensen Kirstine
Published: November 2024

Fluorescent nanodiamonds (FNDs) with nitrogen-vacancy centers are promising candidates for long-term biolabeling and biosensing applications due to their biocompatibility and unique optomagnetic properties. The employment of nanomaterials in cancer therapy and diagnostics, requires a deep understanding of how nanoparticles (NPs) interact with the three-dimensional (3D) tumor environment. We developed a novel approach, the “Tumor-in-a-Tube” platform, using 4D light-sheet microscopy to explore the spatio-temporal dynamics of FNDs with 3D tumor spheroids. By monitoring the real-time NP sedimentation, spheroid penetration, and cellular uptake of FNDs and polystyrene nanoparticles (PNPs), we marked the impact of NP mass density on their spheroid interaction. Unlike PNPs, higher-density FNDs underwent rapid sedimentation, which minimized their effective concentration and hindered the FND – spheroid interactions. This results in constrained intratumoral accumulation, and size-independent uptake and penetration. Longer FND effective-exposure-time promotes size-dependent cell uptake, verified by FND treatment on 2D monolayers. Nonetheless, FNDs exhibited good biocompatibility and long-term spheroid labeling, allowing for cell isolation from different spheroid layers. Our results suggest the need for NP effective-exposure-time calibration in comparative NP assays, in 3D static models. Overall, our platform provides a valuable tool for bridging the gap between 2D and 3D static models in NP assessment, drug delivery, toxicology profiling and translational research.
Development and use of integrated wetland condition index for lacustrine fringe wetlands of Lake Tana, Ethiopia
Authors: Wondim Yirga Kebede , Melese Ayalew Wondie
Published: November 2024

The primary objective of this research was to develop an integrated wetland condition index (IWCI) for lacustrine fringe wetlands (LFWs) in Lake Tana, Ethiopia, which has been highly impacted by recessionary agriculture, water hyacinth infestation, and both short- and long-term water level fluctuations (WLFs), as well as a heavy sediment load. The index of lacustrine wetland condition was developed based on four wetland characteristics that define wetlands: hydrology, water quality, sediment quality, and wetland biota. The value obtained from field and laboratory measurements of each wetland hydrology, water chemistry, and sediment characteristics indicator was normalized by allocating scores based on literature information and the results of this research project from three different disturbance-level lacustrine wetlands in Lake Tana. Macrophyte, diatom, and zooplankton indicator species tests (IndVal% and p (raw)) were calculated using PAST (PAleontological STatistics). Scores were allocated on a scale from 1 to 10, in such a way that the highest scores reflected the best conditions and the lowest scores the most disturbed and unhealthy conditions. Within four sub-indexes, there is more than one measure, with each measure given equal weighting, whereas the four wetland components (hydrology, water chemistry, sediment, and biota) are weighted as per their contribution to the overall wetland condition. Weights were assigned using the Decision Support System Software of DEFINITE. Finally, the total IWCI was classified into five wetland condition categories, namely: very poor or very far from the reference (0–3), poor (3–5), moderate (5–7), good (7-9), and excellent wetland condition or reference condition (9–10). According to the IWCI of the low water level period, eight wetland sampling sites were found within a moderately impacted condition (44.44%); similarly, eight wetland sampling sites were found within a good or mildly impacted condition; and only two wetland sampling sites (11.11%) were found in an excellent or reference condition. Thus, this IWCI developed and tested in this study could be a powerful tool to inform decision-makers on lacustrine wetland conservation and restoration priorities throughout the Lake Tana Ecosystem.
Thermal Plasticity of Stage Specific Development Time inDrosophila melanogasterunder Shifting Temperatures
Authors: Chattopadhyay Aradhya , Roy Rishav , Biswas Payel , Ghosh Shampa M.
Published: November 2024

Thermal shifts and fluctuations are inherent aspects of the natural environment. How different developmental stages of the fly respond to thermal fluctuations and shifts are not properly understood. In view of this, we studied how durations of different developmental stages are affected by current and previous stage developmental temperatures when they experience upshifts and downshifts of temperature during developmental transitions. The study revealed a complex interaction of current and prior stage temperatures in shaping development time. The egg-stage temperature is found to exert its effect on both larval and pupal stage. However, the impacts of larva-pupa thermal shifts on pupal and overall development time are greater than that of egg-larva thermal shifts. As one would predict, a prior cold temperature extends subsequent pupal duration, while prior warm condition reduces it. Surprisingly, for larval duration, both prior warm and cold condition had the same effect-both led to significant reductions in subsequent larval stage duration. The warm egg temperature had an accelerating effect on larval development as expected. The other shift from cold egg to warm larval condition that also made development faster than constant warm rearing, was possibly caused by a shift from prior sub-optimal to optimal thermal condition used in the experiment. We also found warm larval stage followed by cold pupal stage makes development time shorter than cold larval followed by warm pupal rearing, suggesting a dominating role of the early-stage temperature in determining overall course of development. And lastly, we also observed two subsequent thermal shifts leave a decelerating effect on pupal development, possibly revealing a difficulty in developmental adjustments in the face of frequent thermal changes.
Engineered paediatric tumours retain maintains tumour genotype and phenotype for precision medicine
Authors: Jung MoonSun , Poltavets Valentina , Skhinas Joanna N. , Tax Gabor , Kamili Alvin , Xie Angela (Jinhan) , Ghamrawi Sarah , Graber Philipp , Mao Jie , Wong-Erasmus Marie , Cui Louise , Kimpton Kathleen , Venkat Pooja , Mayoh Chelsea , Fleuren Emmy D. G. , Fordham Ashleigh M. , Barger Zara , Grady John , Thomas David M. , Du Eric Yiwei , Cowley Mark J. , Gifford Andrew J. , Fletcher Jamie I. , Lau Loretta M. S. , Dolman M. Emmy M. , Gooding J. Justin , Kavallaris Maria
Published: November 2024

Precision medicine for paediatric and adult cancers that includes drug sensitivity profiling, can identify effective therapies for individual patients. However, obtaining adequate biopsy samples for high-throughput (HTP) screening remains challenging, with tumours needing to be expanded in culture or patient-derived xenografts – this is time-consuming and often unsuccessful. Herein, we have developed paediatric patient-derived tumour models using an engineered extracellular matrix (ECM) tissue mimic hydrogel system and HTP 3D bioprinting. Gene expression analysis from neuroblastoma and sarcoma patients identified key components of the ECM in these tumour types. Engineered hydrogels with ECM-mimic peptides were used to create patient-specific tumour organoids, modelling tumour growth conditions. Expanded tumour organoids recapitulated the genetic and phenotypic characteristics of the original tumours and retained tumourgenicity. Screening of these models identified individualised drug sensitivities. Our approach offers a timely and clinically relevant technology platform for precision medicine in paediatric cancers, potentially transforming preclinical testing across cancer types.
Generative Approaches for Nucleotide Sequences to Enhance Non-coding RNA Classification
Authors: Chiquitto Alisson Gaspar , Oliveira Liliane Santana , Bugatti Pedro Henrique , Saito Priscila Tiemi Maeda , Basham Mark , Raittz Roberto Tadeu , Paschoal Alexandre Rossi
Published: November 2024

Classifying non-coding RNA (ncRNA) sequences, particularly mirtrons, is essential for elucidating gene regulation mechanisms. However, the prevalent class imbalance in ncRNA datasets presents significant challenges, often resulting in overfitting and diminished generalization in machine learning models. In this study,GENerative Approaches forNUcleotideSequences (GENNUS) is proposed, introducing novel data augmentation strategies using Generative Adversarial Networks (GANs) and Synthetic Minority Over-sampling Technique (SMOTE) to enhance ncRNA classification performance. Our GAN-based methods effectively generate high-quality synthetic data that capture the intricate patterns and diversity of real mirtron sequences, eliminating the need for extensive feature engineering. Through four experiments, it is demonstrated that models trained on a combination of real and GAN-generated data improve classification accuracy compared to traditional SMOTE techniques or only with real data. Our findings reveal that GANs enhance model performance and provide a richer representation of minority classes, thus improving generalization capabilities across various machine learning frameworks. This work highlights the transformative potential of synthetic data generation in addressing data limitations in genomics, offering a pathway for more effective and scalable ncRNA classification methodologies.
Pharming: Joint Clonal Tree Reconstruction of SNV and CNA Evolution from Single-cell DNA Sequencing of Tumors
Authors: Weber Leah L. , Hart Anna , Ochoa Idoia , El-Kebir Mohammed
Published: November 2024

Cancer arises through an evolutionary process in which somatic mutations, including single nucleotide variants (SNVs) and copy number aberrations (CNAs), drive the development of a malignant, heterogeneous tumor. Reconstructing this evolutionary history from sequencing data is critical for understanding the order in which mutations are acquired and the dynamic interplay between different types of alterations. Advances in modern whole genome single-cell sequencing now enable the accurate inference of copy number profiles in individual cells. However, the low sequencing coverage of these low pass sequencing technologies poses a challenge for reliably inferring the presence or absence of SNVs within tumor cells, limiting the ability to simultaneously study the evolutionary relationships between SNVs and CNAs.

In this work, we introduce a novel tumor phylogeny inference method, Pharming, that jointly infers the evolutionary histories of SNVs and CNAs. Our key insight is to leverage the high accuracy of copy number inference methods and the fact that SNVs co-occur in regions with CNAs in order to enable more precise tumor phylogeny reconstruction for both alteration types. We demonstrate via simulations that Pharmingoutperforms state-of-the-art single-modality tumor phylogeny inference methods. Additionally, we apply Pharmingto a triple-negative breast cancer case, achieving high-resolution, joint reconstruction of CNA and SNV evolution, including thede novodetection of a clonal whole-genome duplication event. Thus, Pharmingoffers the potential for more comprehensive and detailed tumor phylogeny inference for high-throughput, low-coverage single-cell DNA sequencing technologies compared to existing approaches.

Availability

https://github.com/elkebir-group/Pharming
Lipid droplet protein Perilipin 2 is critical for the regulation of insulin secretion through beta cell lipophagy and glucagon expression in pancreatic islets
Authors: Liu Siming , Wipf Israel , Joglekar Aditya , Freshly Aidan , Bovee Corinne E , Kim Lucy , Richtsmeier Syreine L , Peachee Spencer , Kopriva Shayla , Vikram Anamika , Ladiki Dalal El , Ilerisoy Fatma , Ilerisoy Beyza , Sagona Gianna , Jun Claudia , Giedt Michelle , Tootle Tina L , Ankrum James , Imai Yumi
Published: November 2024

Knockdown (KD) of lipid droplet (LD) protein perilipin 2 (PLIN2) in beta cells impairs glucose-stimulated insulin secretion (GSIS) and mitochondrial function. Here, we addressed a pathway responsible for compromised mitochondrial integrity in PLIN2 KD beta cells. In PLIN2 KD human islets, mitochondria were fragmented in beta cells but not in alpha cells. Glucagon but not insulin level was elevated. While the formation of early LDs followed by fluorescent fatty acids (FA) analog Bodipy C12 (C12) was preserved, C12 accumulated in mitochondria over time in PLIN2 KD INS-1 cells. A lysosomal acid lipase inhibitor Lali2 prevented C12 transfer to mitochondria, mitochondrial fragmentation, and the impairment of GSIS. Direct interactions between LD-lysosome and lysosome-mitochondria were increased in PLIN2 KD INS-1 cells. Thus, FA released from LDs by microlipophagy cause mitochondrial changes and impair GSIS in PLIN2 KD beta cells. Interestingly, glucolipotoxic condition (GLT) caused C12 accumulation and mitochondrial fragmentation similar to PLIN2 KD in beta cells. Moreover, Lali2 reversed mitochondrial fragmentation and improved GSIS in human islets under GLT. In summary, PLIN2 regulates microlipophagy to prevent excess FA flux to mitochondria in beta cells. This pathway also contributes to GSIS impairment when LD pool expands under nutrient load in beta cells.