bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of three ILM peeling techniques for myopic traction maculopathy with high risk of postoperative macular hole development
Authors: Feng Jingyang , Shao Qing , Xie Jiaming , Yu Jiayi , Li Menghan , Liu Chen , Zhou Siheng , Zhou Hao , Wang Weijun , Fan Ying
Published: October 2023

Purpose:

To compare three different internal limiting membrane (ILM) peeling techniques, including standard ILM peeling, fovea-sparing ILM peeling (FSIP) and inverted ILM flap (ILMF), in the treatment of myopic traction maculopathy (MTM) with high risk of postoperative macular hole development.

Method:

This retrospective cohort study enrolled 101 eyes suffering from lamellar macular hole (LMH) combined with MTM in 98 consecutive patients who underwent vitrectomy with either standard ILM peeling, FSIP or ILMF from July 2017 to August 2020. All patients were followed up for at least 12 months after surgery. Best-corrected visual acuity (BCVA), macular anatomic outcomes and postoperative full-thickness macular hole (FTMH) formation were evaluated.

Results:

No significant differences were found among the three surgical groups in baseline characteristics. Twelve months after surgery, the mean BCVA was significantly improved (P < 0.001) and showed no significant differences among groups (P = 0.452). None of the eyes in the ILMF group, 5 eyes (15.6%) in the standard ILM peeling group and 6 eyes (17.1%) in the FSIP group developed a postoperative FTMH (P = 0.026). Logistic regression showed that the ILM peeling technique was an independent influencing factor for FTMH formation (OR = 0.209, P = 0.014).

Conclusion:

Compared with standard ILM peeling or FSIP technique, the ILMF technique resulted in similar visual outcomes but a relatively low incidence of postoperative FTMH in the treatment of LMH combined with MTM. ILMF is an effective technique for treating MTM with high risk of postoperative FTMH development.
AN EIGHT-YEAR RETROSPECTIVE STUDY OF THE ETIOLOGIES, CLINICAL CHARACTERISTICS, AND VISUAL OUTCOMES OF PEDIATRIC LAMELLAR MACULAR HOLE
Authors: Liu Jingjing , Zhang Qi , Zhao Peiquan
Published: October 2023

Purpose:

To explore the etiologies, characteristics, and prognosis of lamellar macular hole (LMH) in pediatric patients.

Methods:

A consecutive series of 59 patients (62 eyes) aged <16 years with MHs (lamellar and full-thickness) treated from 2013 to 2021 in a tertiary center was reviewed. Data collected included demographic and clinical characteristics, management, and outcomes of patients presenting with LMH.

Results:

Twelve eyes (19.4%) of 11 children had LMH. Seven patients were male, with an average age of 6.9 years. The primary pathologies included X-linked retinoschisis in six eyes (50%); familial exudative vitreoretinopathy in two (16.7%); and ocular toxocariasis, Coats disease, persistent hyperplastic primary vitreous, and idiopathic LMH with associated lenticonus in one eye (8.3%) each. Four eyes (36.4%) showed tractional appearance and seven (63.6%) degenerative. All degenerative LMH showed ellipsoidal zone defect, significantly higher than that in the tractional group (25%, 1/4) (P = 0.024). Five eyes achieved closed LMH and limited visual gain, four underwent surgery, and one closed spontaneously.

Conclusion:

X-linked retinoschisis was the most frequent primary cause in pediatric LMH. Two types of LMH can be classified: tractional and degenerative. The latter showed a higher rate of ellipsoidal zone defect. Vision improved after LMH closed, regardless of surgery or spontaneous closure.
NATIONWIDE DEMOGRAPHIC DISPARITIES IN UNITED STATES EMERGENCY DEPARTMENT VISITS IN PATIENTS WITH RHEGMATOGENOUS RETINAL DETACHMENT
Authors: Shaheen Abdulla R. , Ashkenazy Noy , Iyer Prashanth G. , Flynn Harry W. , Sridhar Jayanth , Yannuzzi Nicolas A.
Published: October 2023

Background/Purpose:

Within the evolving landscape of healthcare in the United States (US), delineating the demographic nuances and financial implications of emergent conditions, such as rhegmatogenous retinal detachment (RRD), is paramount. This study seeks to analyze the demographic and hospital billing amount/cost of service disparities in RRD visits to emergency departments (EDs) nationwide.

Methods:

We conducted a retrospective, cross-sectional, population-based study using International Classification of Diseases, 10th revision, and Current Procedural Terminology codes in the 2016 to 2019 Nationwide Emergency Department Sample databases to identify RRD visits. The analysis included demographics, hospital billing amount, and cost of service of RRD ED management.

Results:

A total of 12,492 RRD encounters were identified with men constituting 64% and a prominent age group being 50 to 64 years (49.3%). Most patients (90%) were managed in metropolitan teaching hospitals, predominantly in the southern U.S. region (56.1%). Private insurance covered 45% of patients. Same-day RRD repair odds increased in November and December. Whites had a higher likelihood for same-day treatment. Hospital billing amount rose from $23,600 in 2016 to $30,354 in 2019, with stable mean total cost of service. Rhegmatogenous retinal detachment ED visit incidence did not show seasonal variation (P = 0.819).

Conclusion:

Most patients with RRD in U.S, EDs were middle-aged men, with Whites more likely to receive same-day repair. There was no sex bias observed in same-day repair decision-making. Although hospital billing amount increased over the study period, total cost of service remained stable. The incidence of RRD ED visits showed no seasonal variation.
Promoting Type 1 Diabetes Self-care Management in the Hospital
Authors: Combs Pamela , Duffy Evelyn , Modic Mary Beth
Published: October 2023

Purpose

The specific aim of the study was to determine whether there was an increased time in target glucose range for individuals with type 1 diabetes mellitus who were permitted to self-manage their insulin plan while hospitalized.

Design

A retrospective chart review was conducted of 60 inpatients with type 1 diabetes mellitus who met the criteria to self-manage their diabetes care with the use of their continuous subcutaneous insulin infusion pump or a multiple daily injection insulin regimen. A comparison of the 2 groups was examined to assess differences in glucose outcomes and glycemic stability.

Results

Seven hundred fifty-three glucose results were examined. The total number of hypoglycemic events in both groups was 37. The number of glucose values labeled as stable was 405, and the remaining 311 glucose values were categorized as hyperglycemic. There were no statistically significant differences in glucose levels between the 2 groups.

Conclusion

No patients experienced severe hypoglycemia leading to cognitive impairment or severe hyperglycemia leading to diabetic ketoacidosis. The outcomes of this study suggest that diabetes self-management practices in select individuals hospitalized with type 1 diabetes mellitus can contribute to greater glucose stability and time in targeted glucose range.
Clinical Comparison of High-Resolution and Standard Refractions and Prescriptions
Authors: Meyer Dawn , Rickert Martin , Reed Olivia , Joret Paul , Kollbaum Pete
Published: October 2023

Significance

Recently, novel refraction and lens manufacturing technology claims to provide more efficient, higher-resolution refractions and resulting lenses. It is unclear, however, if these benefits are realized and appreciated by the patient.

Purpose

This study investigated benefits and drawbacks of high-resolution refraction technology over standard, specifically in terms of the refraction, glasses prescription, and participant’s perceptions of the technology.

Methods

Sixty progressive addition lens (PAL) wearers (aged 35-70) and 60 single-vision (SV) wearers (age 18+) were randomized to a high-resolution refraction (Vision-R 800, essilorinstrumentsusa.com) and standard refraction in a 2-week crossover dispensing design. Refractive results were converted to M, J0 and J45 and analyzed using multivariate t-tests. Bayesian estimation was used to analyze differences between refraction type and age group for subjective outcomes.

Results

Differences in refractive error between the two refractions were small and none differed statistically (P value > .05) or clinically (e.g., <0.25D) in either subgroup. Visual acuities at distance and near were better than 0.00 logMAR; none of the mean differences between the refractions reached statistical or clinical (e.g., <0.25D) significance. Participants significantly preferred the high-resolution refraction for its quickness and efficiency, improved comfort, and less stress. Bayesian analysis indicated a 76% probability that participants had higher confidence in the high-resolution refraction, 93% probability they would seek it out for their care, and 94% probability they would recommend an optometrist using this technology.

Conclusions

Refractive and acuity endpoints were similar with the high-resolution and standard refraction. Participants, however, perceived several key benefits of the high-resolution refraction and prescription for their care, the care of their friends/family, and the practice itself.
Colorectal cancer screening status and its association with health belief model variables in a rural population
Authors: Bateman Andre G. , Greeson Emily M. , Lowenstein Kathleen , Rodriguez Michael G. , Lyons James A. , Stack Matthew A. , O'Rourke Michael
Published: October 2023

Background:

Rural populations exhibit low colorectal cancer (CRC) screening rates, which may be a consequence of social determinants of health but may also result from individual health beliefs. This study aimed to explore the association between key health belief model (HBM) variables and CRC screening status in a rural Midwest population.

Methods:

One hundred thirty six people participated in this cross-sectional study. A survey instrument was developed to capture demographic information and measure the following HBM variables: perceived barriers, perceived benefits, self-efficacy beliefs associated with CRC screening, and knowledge associated with CRC.

Results:

The response rate for the study was 17.6%. The most endorsed (28.5%) barrier to CRC screening was fear of something going wrong. The most endorsed (86.5%) benefit of CRC screening was confidence that privacy and confidentiality would be protected. There were significant differences (P < .01) in means for perception of barriers, benefits, and self-efficacy according to CRC screening status. In a model which included perception of barriers, benefits, and self-efficacy, only perceived barriers made a unique, significant (P < .05) contribution (OR = 0.823 [0.706–0.958]) in predicting CRC screening status.

Conclusions:

Key HBM variables, perception of barriers, benefits, and self-efficacy seem to be important factors associated with CRC screening in rural populations and may be appropriate targets for interventions to increase CRC screening.
Low UPB1 Level Correlates With Poor Prognosis in Lung Adenocarcinoma
Authors: Zhang Libin , Liu Jun , Wang Han , Xu Zheyuan , Wang Yang , Chen Yun , Peng Hao
Published: October 2023

Objectives:

Lung adenocarcinoma (LUAD) is a critical cancer with high mortality, worse prognosis, and crucial lymphatic metastasis. Consequently, prognostic biomarkers for LUAD are truly required. β-Ureidopropionase (UPB1) is abnormally expressed in various cancers. However, the function of UPB1 in LUAD is still ambiguous. This study aimed to explore the expression profile and prognostic significance of UPB1 in LUAD.

Materials and Methods:

The differential UPB1 levels in pan cancers and their prognostic significance were comprehensively investigated through Gene Expression Profiling Interactive Analysis, UALCAN, Tumor Immune Estimation Resource, and Kaplan-Meier plotter platform. The correlation between UPB1 and tumor infiltration immune cells was explored using Tumor Immune Estimation Resource, Gene Expression Profiling Interactive Analysis, and Tumor-Immune System Interactions and Drug Bank database databases.

Results:

The UPB1 level was abnormally expressed in pan-tumor tissue than in adjacent tissue from The Cancer Genome Atlas tool. Low UPB1 level was correlated with poor overall survival in patients with LUAD. Furthermore, a comparison of the various pathologic characteristics of LUAD between high and low UPB1 level subgroups revealed that low UPB1 expression was correlated with lymph node metastasis. Kaplan-Meier survival analysis indicated that a low UPB1 level was associated with worse progression‑free survival and overall survival in patients with LUAD. Univariate and multivariate analyses suggested that UPB1 could be a useful prognostic indicator for LUAD. Abnormal UPB1 may be correlated with aberrant LUAD immune infiltration, prompting a worse survival outcome.

Conclusions:

Results showed that low UPB1 is correlated with a worse prognosis of LUAD and may be a valuable prognostic indicator for LUAD.
Targeted RNA Sequencing Highlights a Diverse Genomic and Morphologic Landscape in Low-grade Endometrial Stromal Sarcoma, Including Novel Fusion Genes
Authors: Kolin David L. , Nucci Marisa R. , Turashvili Gulisa , Song Sharon J. , Corbett-Burns Sophie , Cesari Matthew , Chang Martin C. , Clarke Blaise , Demicco Elizabeth , Dube Valerie , Lee Cheng-Han , Rouzbahman Marjan , Shaw Patricia , Cin Paola Dal , Swanson David , Dickson Brendan C.
Published: October 2023

Low-grade endometrial stromal sarcoma (LGESS) represents a morphologically and genetically heterogenous mesenchymal neoplasm. Previous work has shown that approximately half of LGESS are characterized byJAZF1::SUZ12gene fusions, while a smaller proportion involves rearrangement of other genes. However, a subset of cases has no known genetic abnormalities. To better characterize the genomic landscape of LGESS, we interrogated a cohort with targeted RNA sequencing (RNA-Seq). Cases previously diagnosed as low-grade endometrial stromal neoplasia (n=51) were identified and re-reviewed for morphology and subjected to RNA-Seq, of which 47 were successfully sequenced. The median patient age was 49 years (range: 19 to 85). The most commonly detected fusions wereJAZF1::SUZ12(n=26, 55%) andBRD8::PHF1(n=3, 6%). In addition to the usual/typical LGESS morphology, someJAZF1::SUZ12fusion tumors showed other morphologies, including fibrous, smooth muscle, sex-cord differentiation, and myxoid change. Novel translocations were identified in 2 cases:MEAF6::PTGR2andHCFC1::PHF1. Ten tumors (21%) had no identifiable fusion, despite a similar morphology and immunophenotype to fusion-positive cases. This suggests that a subset of cases may be attributable to fusion products among genes that are not covered by the assay, or perhaps altogether different molecular mechanisms. In all, these findings confirm that RNA-Seq is a potentially useful ancillary test in the diagnosis of endometrial stromal neoplasms and highlight their diverse morphology.
Management of Biofilm with Breast Implant Surgery
Authors: Myckatyn Terence M. , Duran Ramirez Jesus M. , Walker Jennifer N. , Hanson Blake M.
Published: October 2023

Learning Objectives:

After studying this article, the participant should be able to: 1. Understand how bacteria negatively impact aesthetic and reconstructive breast implants. 2. Understand how bacteria infect breast implants. 3. Understand the evidence associated with common implant infection-prevention strategies, and their limitations. 4. Understand why implementation of bacteria-mitigation strategies such as antibiotic administration or “no-touch” techniques may not indefinitely prevent breast implant infection.

Bacterial infection of aesthetic and reconstructive breast implants is a common and expensive problem. Subacute infections or chronic capsular contractures leading to device explantation are the most commonly documented sequelae. Although bench and translational research underscores the complexities of implant-associated infection, high-quality studies with adequate power, control groups, and duration of follow-up are lacking. Common strategies to minimize infections use antibiotics—administered systemically, in the breast implant pocket, or by directly bathing the implant before insertion—to limit bacterial contamination. Limiting contact between the implant and skin or breast parenchyma represents an additional common strategy. The clinical prevention of breast implant infection is challenged by the clean-contaminated nature of breast parenchyma, and the variable behavior of not only specific bacterial species but also their strains. These factors impact bacterial virulence and antibiotic resistance.
Prosthetic device and service satisfaction, quality of life, and functional performance in lower limb prosthesis clients
Authors: DadeMatthews Oluwagbemiga O. , Roper Jaimie A. , Vazquez Adan , Shannon David M. , Sefton JoEllen M.
Published: October 2023

Objective:

The aim of this study was to characterize the relationship between prosthetic device and service satisfaction, health-related quality of life (HRQOL), and functional movement in a diverse population of lower limb prosthesis users.

Methods:

An online survey was conducted on individuals with lower limb amputation between September and October 2021. Sample validated questionnaires assessing demographic and clinical features, satisfaction, functional outcomes, and quality of life were analyzed using path analysis.

Results:

Participants were 1736 individuals with lower limb amputation. Overall, 44% of participants reported dissatisfaction with prosthetic device, whereas 37% were dissatisfied with prosthetic service. Low functional mobility was reported by 58% of participants and 61% reported low HRQOL. Lower extremity functional status (β = 0.55), HRQOL (β = 0.08), Activities-specific Balance Scale (β = 0.22), and modified fall efficacy scale (β = −0.07) are significantly associated with prosthetic device satisfaction (P < 0.0005, R2 = 0.47). Satisfaction with provider service was significantly associated with lower extremity functional status (β = 0.44) and balance confidence (β = 0.18) (P < 0.0005, R2 = 0.34).

Conclusion and Clinical Relevance:

Civilians, veterans, and service members reported low functional mobility, low quality of life, and moderate levels of dissatisfaction with their lower extremity prosthetic device and provider service. Improvements in mobility, balance, quality of life, and fall efficacy may enhance device satisfaction. Functional mobility and balance improvements may increase ratings of provider service. This study provides feedback that may improve clinical decisions on lower limb prosthesis patient care.
ANNEXIN A2 FACILITATES NEOVASCULARIZATION TO PROTECT AGAINST MYOCARDIAL INFARCTION INJURY VIA INTERACTING WITH MACROPHAGE YAP AND ENDOTHELIAL INTEGRIN Β3
Authors: Zhang Yu , Wang Yan , Li Jiao , Li Chaofu , Liu Weiwei , Long Xianping , Wang Zhenglong , Zhao Ranzun , Ge Junbo , Shi Bei
Published: October 2023

Cardiac macrophages with different polarization phenotypes regulate ventricular remodeling and neovascularization after myocardial infarction (MI). Annexin A2 (ANXA2) promotes macrophage polarization to the repair phenotype and regulates neovascularization. However, whether ANXA2 plays any role in post-MI remodeling and its underlying mechanism remains obscure. In this study, we observed that expression levels of ANXA2 were dynamically altered in mouse hearts upon MI and peaked on the second day post-MI. Using adeno-associated virus vector–mediated overexpression or silencing of ANXA2 in the heart, we also found that elevation of ANXA2 in the infarcted myocardium significantly improved cardiac function, reduced cardiac fibrosis, and promoted peri-infarct angiogenesis, compared with controls. By contrast, reduction of cardiac ANXA2 exhibited opposite effects. Furthermore, using in vitro coculture system, we found that ANXA2-engineered macrophages promoted cardiac microvascular endothelial cell (CMEC) proliferation, migration, and neovascularization. Mechanistically, we identified that ANXA2 interacted with yes-associated protein (YAP) in macrophages and skewed them toward pro-angiogenic phenotype by inhibiting YAP activity. In addition, ANXA2 directly interacted with integrin β3 in CMECs and enhanced their growth, migration, and tubule formation. Our results indicate that increased expression of ANXA2 could confer protection against MI-induced injury by promoting neovascularization in the infarcted area, partly through the inhibition of YAP in macrophages and activation of integrin β3 in endothelial cells. Our study provides new therapeutic strategies for the treatment of MI injury.
TERLIPRESSIN COMBINED WITH NOREPINEPHRINE IN THE TREATMENT OF SEPTIC SHOCK: A SYSTEMATIC REVIEW
Authors: Mao Fengkai , Liang Dongcheng , Tang Zewen , Xu Yuxuan , Lin Leqing
Published: October 2023

Objective: The objective of this study was to provide an in-depth analysis of the advantages and potential research directions concerning the utilization of terlipressin (TP) in combination with norepinephrine (NE) for the management of septic shock. Methods: A systematic search was conducted across five major electronic databases, namely, PubMed, Cochrane, Embase, ScienceDirect, and MEDLINE, using the Boolean method. The search encompassed articles published until May 22, 2023. Randomized controlled trials investigating the efficacy of TP combined with NE in the treatment of patients with septic shock were considered for inclusion. Results: A total of seven trials met the inclusion criteria. The combination therapy of TP and NE exhibited potential benefits in the treatment of adult patients suffering from septic shock. Furthermore, the concurrent administration of TP with NE demonstrated improvements in cardiac output and central venous pressure. However, it is important to acknowledge the presence of certain risks and potential adverse events, including an elevated risk of peripheral ischemia. Conclusions: The available evidence supports the notion that early combination therapy involving NE and TP holds promise in terms of reducing the required dosage of NE, enhancing renal perfusion, and improving microcirculation in patients diagnosed with septic shock.
Association of Prophylactic Antibiotics With Early Infectious Complications in Children With Cancer Undergoing Central Venous Access Device Placement
Authors: Papastefan Steven T. , Zeineddin Suhail , Blakely Martin L. , Lovvorn Harold N. , Huang Lynn Wei , Raval Mehul V. , Lautz Timothy B.
Published: October 2023

Objective:

To evaluate the impact of prophylactic antibiotics on early infectious complications after central venous access device (VAD) placement in children with cancer.

Background:

Despite the frequency of VAD procedures in children, the effectiveness of prophylactic antibiotics for reducing infectious complications is unknown.

Methods:

This was a retrospective cohort study of children with cancer undergoing central VAD placement identified in the Pediatric Health Information System database between 2017 and 2021. The primary outcome was the rate of early infectious complications (composite surgical site infections, central line-associated bloodstream infections, and bacteremia). Multivariable logistic regression was used to evaluate factors associated with early infection, and heterogeneity of treatment effect of prophylactic antibiotics was compared across subgroups.

Results:

A total of 9216 patients were included (6058 ports and 3158 tunneled lines). Prophylactic antibiotics were associated with lower early infectious complications overall [1.3% vs 2.4%; odds ratio (OR): 0.55 (95% CI: 0.39–0.79), P < 0.001], an effect demonstrated for tunneled lines (OR: 0.59, 95% CI: 0.41–0.84) but not ports (OR: 3.01, 95% CI: 0.66–13.78). On multivariate analysis, prophylactic antibiotics (OR: 0.67, 95% CI: 0.45–0.97) and solid tumors (OR: 0.38, 95% CI: 0.22–0.64) were associated with reduced odds of early infections, whereas tunneled lines (OR: 20.78, 95% CI: 9.83–43.93) and acute myelogenous leukemia (OR: 2.37, 95% CI: 1.58–3.57) had increased odds.

Conclusions:

Prophylactic antibiotics are associated with reduced early infectious complications after central VAD placement overall. Despite recommendations from multiple national organizations against prophylactic antibiotics, these findings suggest a benefit in children with malignancy undergoing tunneled line placement.
Progression of Site-specific Recurrence of Pancreatic Cancer and Implications for Treatment
Authors: Rompen Ingmar F. , Levine Jonah , Habib Joseph R. , Sereni Elisabetta , Mughal Nabiha , Hewitt Daniel Brock , Sacks Greg D. , Welling Theodore H. , Simeone Diane M. , Kaplan Brian , Berman Russell S. , Cohen Steven M. , Wolfgang Christopher L. , Javed Ammar A.
Published: October 2023

Objective:

To analyze postrecurrence progression in the context of recurrence sites and assess implications for postrecurrence treatment.

Background:

Most patients with resected pancreatic ductal adenocarcinoma (PDAC) recur within 2 years. Different survival outcomes for location-specific patterns of recurrence are reported, highlighting their prognostic value. However, a lack of understanding of postrecurrence progression and survival remains.

Methods:

This retrospective analysis included surgically treated patients with PDAC at NYU Langone Health (2010–2021). Sites of recurrence were identified at the time of diagnosis and further follow-up. Kaplan-Meier curves, log-rank test, and Cox regression analyses were applied to assess survival outcomes.

Results:

Recurrence occurred in 57.3% (196/342) patients with a median time to recurrence of 11.3 months (95% CI: 12.6–16.5). The first site of recurrence was local in 43.9% of patients, liver in 23.5%, peritoneal in 8.7%, lung in 3.6%, whereas 20.4% had multiple sites of recurrence. Progression to secondary sites was observed in 11.7%. Only lung involvement was associated with significantly longer survival after recurrence compared with other sites (16.9 vs 8.49 months, P = 0.003). In local recurrence, 21 (33.3%) patients were alive after 1 year without progression to secondary sites. This was associated with a CA19-9 of <100 U/mL at the time of primary diagnosis (P = 0.039), nodal negative disease (P = 0.023), and well-moderate differentiation (P = 0.042) compared with patients with progression.

Conclusion:

Except for lung recurrence, postrecurrence survival after PDAC resection is associated with poor survival. A subset of patients with local-only recurrence do not quickly succumb to systemic spread. This is associated with markers for favorable tumor biology, making them candidates for potential curative re-resections when feasible.
Duration of Dialysis in Acute Kidney Injury Donors and Transplant Outcomes
Authors: Punukollu Rachana , Ohara Stephanie , Budhiraja Pooja , Smith Maxwell L , Kumm Kayla , Ruch Brianna , Misra Suman , Reddy Kunam S , Heilman Raymond , Jadlowiec Caroline C
Published: October 2023

Background:

Acute kidney injury (AKI) kidneys, including those from donors on dialysis, are often underutilized, although there is increasing data available demonstrating good transplant outcomes. To date, data on the duration of donor dialysis and transplant outcomes are limited.

Study design:

This was a single-center study of deceased donor kidney transplants (DDKT) from 2010 to 2022. The study cohort consisted of recipients of DDKT from donors with AKI and on dialysis. Three groups were identified based on the predetermined interquartile range of donor dialysis duration: a) 1-2 dialysis days, b) 3-4 dialysis days, and c) ≥5 dialysis days.

Results:

During this period, 765 AKI DDKT were performed, of which 230 were from donors on dialysis. The median dialysis duration was two days with a maximum of 13 days. Across the three groups, there were no differences in recipient age (p=0.23) or dialysis vintage (p=0.70). Donor age (p=0.86) and KDPI (p=0.57) were comparable between the groups. DDKT from donors on dialysis ≥5 days had lower terminal creatinine levels (p=0.003) and longer cold ischemia times (p=0.04). Post-transplant, the median length of hospital stay was 3 days for all groups (p=0.75). There were no differences in delayed graft function occurrence (94.4% vs. 86.8% vs. 92.1%, p=0.19), duration of DGF (p=0.56) or readmissions (p=0.99). At one-year, the estimated glomerular filtration rate (p=0.76), patient survival (p=0.82), or death-censored graft survival (p=0.28) were comparable.

Conclusions:

Excellent outcomes have been observed in AKI DDKT, including those coming from donors on dialysis. In this small cohort, the duration of donor dialysis did not adversely affect outcomes. Cautious expansion of the donor pool, including donors on dialysis, should be considered given the ongoing organ shortage.
Detection of EGFR and its Activity State in Plasma CD63-EVs from Glioblastoma Patients: Rapid Profiling using an Anion Exchange Membrane Sensor
Authors: Maniya Nalin H. , Kumar Sonu , Franklin Jeffrey L. , Higginbotham James N. , Scott Andrew M , Gan Hui K , Coffey Robert J. , Senapati Satyajyoti , Chang Hsueh-Chia
Published: October 2023

We present a novel quantitative immunoassay for CD63 EVs (extracellular vesicles) and a constituent surface cargo, EGFR and its activity state, that provides a sensitive, selective, fluorophore-free and rapid alternative to current EV-based diagnostic methods. Our sensing design utilizes a charge-gating strategy, with a hydrophilic anion exchange membrane and a charged silica nanoparticle reporter. With sensitivity and robustness enhancement by the ion-depletion action of the membrane, this hydrophilic design with charged reporters minimizes interference from dispersed proteins and fluorophore degradation, thus enabling direct plasma analysis. With a limit of detection of 30 EVs/μL and a high relative sensitivity of 0.01% for targeted proteomic subfractions, our assay enables accurate quantification of the EV marker, CD63, with colocalized EGFR by an operator/sample insensitive universal normalized calibration. Glioblastoma necessitates improved non-invasive diagnostic approaches for early detection and monitoring. Notably, we target both total and “active” EGFR on EVs; with a monoclonal antibody mAb806 that recognizes a normally hidden epitope on overexpressed or mutant variant III EGFR. This approach offers direct glioblastoma detection from untreated human patient samples. Analysis of glioblastoma clinical samples yielded an area-under-the-curve (AUC) value of 0.99 and low p-value of 0.000033, significantly surpassing the performance of existing assays and markers.
Threat of mining to African great apes
Authors: Junker Jessica , Quoss Luise , Valdez Jose , Arandjelovic Mimi , Barrie Abdulai , Campbell Genevieve , Heinicke Stefanie , Humle Tatyana , Kouakou Célestin Yao , Kühl Hjalmar S. , Ordaz-Nemeth Isabel , Pereira Henrique M. , Rainer Helga , Refisch Johannes , Sonter Laura , Sop Tenekwetche
Published: October 2023

The rapid growth of clean energy technologies is driving a rising demand for critical minerals. In 2022 at the UN Biodiversity Conference (COP 15), seven major economies formed an alliance to enhance the sustainability of mining these essential decarbonization minerals. However, there is a scarcity of studies assessing the threat of mining to global biodiversity. By integrating a global mining dataset with ape density distribution estimates, we explored the potential negative impact of industrial mining on African great apes. Our findings reveal that up to one-third of Africa’s great ape population faces mining-related risks. This is especially pronounced in West Africa, where numerous mining areas overlap with fragmented ape habitats, often occurring in high-density ape regions. For 97% of mining areas, no ape survey data are available, underscoring the importance of increased accessibility to environmental data within the mining sector to facilitate research into the complex interactions between mining, climate, biodiversity and sustainability.

Teaser

Mining for clean energy minerals could put one-third of Africa’s ape population at risk.
A gene selection analysis of TAS1R1 and TAS1R3 to examine human carnivory
Authors: Cross Mackenzie , Kitchen Andrew
Published: October 2023

Humans are considered to have a unique reliance on meat compared to other primates, as much of humans unique evolutionary trajectory, such as human brain expansion, is linked to the increased consumption of meat for calories and nutrients. However, other primates such as chimpanzees (Pan troglodytes) and bonobos (Pan paniscus) are also known to consume meat. While humans meat consumption is considered to be unique in humans’ increased incorporation of tools to process the prey carcass and consumption of a broader range of prey, these distinctions are less obvious when contextualized within the broader behavioral repertoire ofPanspecies carnivory. This research seeks to identify if the taste perception of meat is different between humans and other ape clades through gene selection analyses. Specifically, this work examines the umami taste receptor genes, TAS1R1 and TAS1R3, which enable the savory flavor perceived when eating meat. Using PAML, we test for positive selection in these genes across several ape clades. We infer positive selection in TAS1R1 for the homininae clade and positive selection in TAS1R3 for theHomo/Panclade. No selection was detected in only the human lineage, which complicates claims that human carnivory is unique compared to other primates while simultaneously suggesting the role of meat may be unappreciated in chimpanzees and bonobos as well as the role of insectivory in gorillas.
dismo: building and analysing discrete spatial ODE models
Authors: van Aalst Marvin , Ebenhöh Oliver
Published: October 2023

dismois a Python package for building and analysing discrete spatial models based on ordinary differential equations. Its primary purpose is to allow arbitrarily complex internal and transport processes to easily be mapped over multiple different regular grids. For this it features one, two and threedimensional layouts, with standard and non-standard (e.g. hexagonal or triangular) grids.

Availability and implementation

https://gitlab.com/qtb-hhu/dismo

Contact

oliver.ebenhoeh@hhu.de
Biological Function of Exosome-like Particles Isolated from Rose (Rosa Damascena) Stem Cell Culture Supernatant
Authors: Won Yu Jin , Lee Esther , Min Seon Young , Cho Byong Seung
Published: October 2023

Rose stem cell (RSC) extracts have been claimed to have multiple beneficial effects in skin. Many cells release extracellular vesicles, also called exosomes, that involved in cell-to-cell communication. There is however no information on whether exosomes are released in RSC cultures, and what the biological function of these may be. We hypothesized that RSC in culture can release exosome-like particles (RSCEs) and that the RSCEs may have biological function in cells relevant to skin. RSC culture supernatant was purchased and standard exosome-isolation was performed, using tangential flow filtration. The characterization of RSCEs was measured with TEM and NTA, that revealed round structures and reports the presence of particles approximate 90-200nm size. Proteins and miRNAs were isolated from the exosomes, and 206 peptides containing likely cytosolic and membrane proteins and miRNA containing Let-7 families were identified. The RSCEs were found to be non-toxic on human dermal papilla cells, whereas a high concentration of the crude supernatant induced widespread cell death. Further, the RSCEs enhanced growth of human dermal fibroblasts and increased the closure of scratch assay, whereas the crude supernatant lacked this effect. Further, the RSCEs reduce the amount of melanin in cultured melanocytes and IL-6 released by Raw264.7 cells stimulated by LPS in a dose-dependent manner. These data collectively show that RSC in culture released RSCEs that contain miRNA and proteins have multiple biological functions in skin-related assays such as fibroblast growth and melanin content in melanocytes. Combined with the anti-inflammatory function of the RSCEs, we suggest that they have appropriate features to be useful in aesthetic medicine for improving skin quality.
Single-cell Transcriptional Analysis of the Cellular Immune Response in the Oral Mucosa of Mice
Authors: Cantalupo P , Diacou A , Park S , Soman V , Chen J , Glenn D , Chandran U , Clark D
Published: October 2023

Periodontal health is dependent on a symbiotic relationship of the host immune response with the oral microbiota. Pathologic shifts of the microbial plaque elicit an immune response that eventually leads to the recruitment and activation of osteoclasts and matrix metalloproteinases and the eventual tissue destruction that is evident in periodontal disease. Once the microbial stimulus is removed, an active process of inflammatory resolution begins. The goal of this work was to use scRNAseq to demonstrate the unique cellular immune response across three distinct conditions of periodontal health, disease, and resolution using mouse models. Periodontal disease was induced using a ligature model. Resolution was modeled by removing the ligature and allowing the mouse to recover. Immune cells (Cd45+) were isolated from the periodontium and analyzed via scRNAseq. Gene signature shifts across the three conditions were characterized and shown to be largely driven by macrophage and neutrophils during the periodontal disease and resolution conditions. Resolution of periodontal disease was characterized by the differential regulation of unique gene subsets. Clustering analysis characterized multiple cellular subpopulations within B Cells, macrophages, and neutrophils that demonstrated differential expansion and contraction across conditions of periodontal health, disease, and resolution. Interestingly, we identified a transcriptionally distinct macrophage subpopulation that expanded during the resolution condition and demonstrated an immunoregulatory gene signature. We identified a cell surface marker for this resolution-associated macrophage subgroup (Cd74) and validated the expansion of this subgroup during resolution via flow cytometry. This work presents a robust immune cell atlas for study of the immunological changes in the oral mucosa during three distinct conditions of periodontal health, disease, and resolution and it improves our understanding of the cellular and molecular markers that characterize health from disease for the development of future diagnostics and therapies.
Cerebral hypoperfusion exacerbates traumatic brain injury in male but not female mice
Authors: Whitehead Bailey J. , Corbin Deborah , Alexander Megan L. , Bumgarner Jacob , Zhang Ning , Karelina A. Kate , Weil Zachary M.
Published: October 2023

Mild-moderate traumatic brain injuries are common and while many individuals recover fully there is mounting clinical and epidemiological evidence that for a substantial subset, even when the acute TBI symptoms resolve, long term health can still be impacted. Individuals with a history of TBI are disproportionately vulnerable to many disease conditions including age-related neurodegeneration. These relationships are difficult to predict but these outcomes very likely interact with other disease risk factors such as cardiovascular disease. Here we tested the hypothesis that a mild pre-injury reduction in cerebral blood flow (bilateral carotid artery stenosis; BCAS) would impair recovery from TBI. Male and female mice underwent BCAS using steel microcoils around the carotid arteries, a mild-moderate closed-head TBI, or a combination of BCAS followed by TBI 30 days post-implantation. Cerebral blood flow, spatial learning and memory, axonal damage, and gene expression profiles were assessed. BCAS led to a ∼10% reduction in CBF, while TBI caused a similar decrease. However, mice exposed to both BCAS and TBI exhibited more pronounced reductions in CBF, associated with marked spatial learning and memory deficits, particularly in males. Axonal damage in male mice was also exacerbated by the combination of BCAS and TBI compared to either injury alone. Females exhibited spatial memory deficits associated with BCAS, but this was not exacerbated by TBI. We performed single nuclei RNA sequencing on male brain tissue to investigate the mechanisms underlying poorer long term functional outcomes in in TBI-BCAS animals. TBI and BCAS independently altered gene expression profiles in neurons and glia but in most cases BCAS and TBI together produced markedly different transcriptional patterns than either challenge alone. Overall, our findings reveal that the presence of mild reductions in cerebrovascular blood flow as a proxy for preexisting cardiovascular disease significantly exacerbated TBI outcomes in male but not female mice, indicating that even relatively mild comorbidities could significantly alter TBI outcomes and increase the probability of secondary disease processes.
Hybrid Cellular Automata Modelling Reveals the Effects of Glucose Gradients on Tumour Spheroid Growth
Authors: Messina Luca , Ferraro Rosalia , Peláez Maria J. , Wang Zhihui , Cristini Vittorio , Dogra Prashant , Caserta Sergio
Published: October 2023

Purpose

In recent years, mathematical models have become instrumental in cancer research, offering insights into tumor growth dynamics, and guiding the development of pharmacological strategies. These models, encompassing diverse biological and physical processes, are increasingly used in clinical settings, showing remarkable predictive precision for individual patient outcomes and therapeutic responses.

Methods

Motivated by these advancements, our study introduces an innovativein silicomodel for simulating tumor growth and invasiveness. The Automated Hybrid Cell emulates critical tumor cell characteristics, including rapid proliferation, heightened motility, reduced cell adhesion, and increased responsiveness to chemotactic signals. This model explores the potential evolution of 3D tumor spheroids by manipulating biological parameters and microenvironment factors, focusing on nutrient availability.

Results

Our comprehensive Global and Local Sensitivity Analyses reveal that tumor growth primarily depends on cell duplication speed and cell-to-cell adhesion, rather than external chemical gradients. Conversely, tumor invasiveness is predominantly driven by chemotaxis. These insights illuminate tumor development mechanisms, providing vital guidance for effective strategies against tumor progression. Our proposed model is a valuable tool for advancing cancer biology research and exploring potential therapeutic interventions.

Simple Summary

In recent years, mathematical models have revolutionized cancer research, illuminating the complex dynamics of tumor growth and aiding drug development. These models, reflecting biological and physical processes, are increasingly used in clinical practice, offering precise patient-specific predictions. Our work introduces an innovative in silico model to simulate tumor growth and invasiveness. The Automated Hybrid Cell, replicating key tumor cell features, enables exploration of 3D tumor spheroid evolution. Sensitivity analyses reveal that tumor growth is primarily influenced by cell replication speed and adhesion, while invasiveness relies on chemotaxis. These insights shed light on tumor development mechanisms, guiding effective strategies against tumor progression. Our model serves as a valuable tool for advancing cancer biology research and potential therapeutic interventions.
LKB1 suppresses growth and promotes the internalization of EGFR through the PIKFYVE lipid kinase
Authors: Ferrarone John R. , Thomas Jerin , Unni Arun M. , Zheng Yuxiang , Nagiec Michal J. , Gardner Eric E. , Mashadova Oksana , Li Kate , Koundouros Nikos , Montalbano Antonino , Mustafa Meer , Cantley Lewis C. , Blenis John , Sanjana Neville E. , Varmus Harold
Published: October 2023

The tumor suppressor LKB1 is a serine/threonine protein kinase that is frequently mutated in human lung adenocarcinoma (LUAD). LKB1 regulates a complex signaling network that is known to control cell polarity and metabolism; however, the pathways that mediate the tumor suppressive activity of LKB1 are incompletely defined. To identify mechanisms of LKB1- mediated growth suppression we developed a spheroid-based cell culture assay to study LKB1- dependent growth. Using this assay, along with genome-wide CRISPR screens and validation with orthogonal methods, we discovered that LKB1 suppresses growth, in part, by activating the PIKFYVE lipid kinase, which promotes the internalization of wild-type EGFR. Our findings reveal a new mechanism of regulation of EGFR, which may have implications for the treatment ofLKB1-mutant LUAD.
Study of Motor Unit Action Potential Conduction Velocity and Firing Rate in Low Force Contractions using Empirical Mode Decomposition
Authors: Dogadov Anton , Hogrel Jean-Yves
Published: October 2023

Arrays of surface electrodes may be used to record individual motor unit action potential (MUAP) trains from the skin surface. Processing of the later gives access to direct estimation of instantaneous conduction velocity and firing rate of individual MUAPs, which are informative physiological features. However, the estimation of conduction velocity and firing rate may be sensitive to additive noise, which is always present in surface EMG recordings. In this paper, we propose to use the Ensemble Empirical Mode Decomposition (EEMD) to represent individual MU instantaneous conduction velocity and firing rate time-series as a sum of components (intrinsic mode functions) and to omit the components with energy lower than the expected noise level. This approach enables to denoise the conduction velocity and firing rate time-sequencies, extracted from the surface EMG recordings, and to unmask a physiological relationship between them.
Metabolic changes that allowPlasmodium falciparumartemisinin-resistant parasites to tolerate the oxidative stress
Authors: Bonive-Boscan Alejandro David , Acosta Héctor , Rojas Ascanio
Published: October 2023

1.

1.1

Background

Artemisinin-based treatments (ACTs) are the first therapy currently used to treat malaria produced byPlasmodium falciparum. However, in recent years increasing evidence shows that some strains ofP. falciparumare less susceptible to ACT in the Southeast Asian region.

1.2

Materials & Methods

A data reanalysis of several omics approaches currently available about parasites ofP. falciparumthat have some degree of resistance to ACT was carried out. The data used was from transcriptomics and metabolomics studies. One mitochondrial carrier of the parasite possibly involved in the mechanisms of tolerance to oxidative stress was modelled and subjected to molecular dockings with citrate and oxoglutarate.

1.3

Results

An increase in glutathione production was detected, changing the direction of the flux of metabolites in the tricarboxylic acid cycle, and boosting glucose consumed. The models of the mitochondrial carrier, called PfCOCP, show that it may be important in transporting citrate and oxoglutarate from the mitochondrial matrix to cytosol. If so, it may allow the parasite to tolerate the oxidative stress produced by artemisinin.

1.4

Conclusions

Thisin-silicoanalysis shows thatP. falciparummay tolerate the artemisinin’s oxidative stress through metabolic changes not reported before, showing the need for further research on the many metabolic aspects linked to this phenotype.