bluuebunny/crossref_metadata_2025 huggingface dataset:
Immediate Clinical Complications Occurring During Membrane Change in Patients on Veno-Venous Extracorporeal Membrane Oxygenation
Authors: Masi Paul , Gouriet Loic , Radu Costin , Folliguet Thierry , Fiore Antonio , Gallet Romain , Bagate François , Mekontso Dessap Armand , De Prost Nicolas
Published: July 2024

The clinical tolerance of extracorporeal membrane oxygenation (ECMO) membrane changes in acute respiratory distress syndrome (ARDS) patients under veno-venous ECMO (VV-ECMO) has not been reported. The aim of this study was to describe the tolerance of membrane change. Patients requiring VV-ECMO were retrospectively included between March 2020 and May 2022. In case of membrane dysfunction or an increase in hemolysis markers or an alteration in gas exchange, a membrane change was performed. The primary outcome was a composite measure defined as the occurrence of at least one of the following events within 1 hour of membrane change: severe hypoxemia, hemodynamic collapse, bradycardia, arrhythmia, cardiac arrest, and death. During the study period, 70 patients required a VV-ECMO, 29 (41%) of whom died. Thirty-two patients required a membrane change for a total of 56 changes. The primary outcome occurred for 33 (59%) changes. Arterial desaturation <80% occurred for all complicated membrane changes and cardiac arrest concerned nine changes (16%). Low tidal volume (VT), respiratory system compliance (Crs), PaO2, and high ECMO blood flow (QECMO) were associated with poor tolerance of membrane change. Threshold values of 130 ml for VT, 9.3 cm H2O for Crs, 72 mm Hg for PaO2, and 3.65 L/minute for QECMO best determined the risk of poor tolerance of membrane change.
Central Venous Catheter-associated Venous Thromboembolism in Children: A Prospective Observational Study
Authors: Narayan Aditya S. , Ramamoorthy Jaikumar Govindaswamy , Parameswaran Narayanan , RamKumar G. , Kayal Smita
Published: July 2024

Our objective was to study the proportion of children developing Catheter-related thrombosis (CRT) following central venous Catheter (CVC) insertion and the risk factors of CRT in pediatric patients with CVC. One hundred four children aged 29 days to 18 years who had a percutaneous non-tunneled CVC inserted were enrolled. Ultrasonogram (USG) with venous Doppler scan was performed within 48 hours of CVC removal to diagnose CRT. The major indications for CVC insertion were surgical care 34 (32.6%) and ICU care 28(26.9%). The median age of the patients was 3 years, and 75% were males. The median number of CVC days was 10 (IQR 5.15). CRT was seen in 45(43.3%), of which 33 (73.3%) were asymptomatic. The rate of CRT was 35.69 cases per 1000 CVC days (95% CI 26.03-47.75). The number of days a catheter was in place and USG-guided catheter insertion was a significant risk factor. The multivariate logistic regression model showed that the duration of CVC in situ was independently associated with the development of CRT (OR, 1.06; 95% CI 1.0-1.1; P=0.02). CVC duration was a major risk factor for the development of CRT. There was a higher risk of developing a symptomatic CRT with central venous catheters than hemodialysis sheaths.
Using the Electronic Health Record to Implement Expedited Partner Therapy in the Pediatric Emergency Department
Authors: Brown Angela M. , Kennebeck Stephanie S. , Kerlin Melissa J. , Widecan Michelle L. , Zhang Yin , Reed Jennifer L.
Published: July 2024

Objectives

Expedited partner therapy (EPT) is a partner treatment strategy for sexually transmitted infections (STIs) including gonorrhea and chlamydia as well as trichomoniasis in some states. The process allows healthcare providers to write prescriptions for STI treatment among partners of infected patients without a previous medical evaluation. The Centers for Disease Control (CDC) has recommended EPT as a useful option to facilitate partner treatment, particularly male partners of women with chlamydia or gonorrhea infections. Our institution implemented EPT in 2016 after Ohio legislation was passed to authorize its use. We aim to describe the implementation process and descriptive outcomes of EPT adoption in a pediatric emergency department.

Methods

This study describes use of the electronic health record for implementation of EPT in our institution. We conducted a retrospective review of EPT utilization from implementation. Electronic records from the implementation date of January 1, 2017, through December 31, 2021, were reviewed. We describe basic demographics and overall uptake of the intervention. Fisher exact tests were used for categorical variables and two-sample t-tests for continuous variables.

Results

There was a total of 3275 positive test results and 739 EPT prescriptions written. Adolescent patients who received prescriptions for EPT were more likely to be female (78.7% of all EPT prescriptions, P = 0.007) and older than other patients (average age 17.7 vs 17.4 years, P = 0.004). There was no significant difference in race, insurance, or ethnicity among adolescent patients receiving and not receiving EPT. The percentage of positive STI tests associated with an EPT prescription ranged between 11.4% and 18.2%. Metronidazole was the most prescribed EPT medication.

Conclusions

The use of the electronic health record provides a platform for implementation of EPT. Our study highlights a potential strategy for increasing treatments of STIs through EPT prescribing in the emergency department setting.
Confusing Histopathological Features and HPV Testing Results in Vulvar Squamous Cell Carcinoma Arising in a Young Woman: A Case Solved Using Next-Generation Sequencing
Authors: Sisuashvili Lia , Saco Adela , Carreras-Dieguez Núria , Celada Cristina , Marimon Lorena , Montironi Carla , Ordi Jaume , Rakislova Natalia
Published: July 2024

Vulvar squamous cell carcinoma (VSCC) can be classified according to human papillomavirus (HPV) status as HPV-associated (HPV-A) and HPV-independent (HPV-I). However, a small subset of tumors may show overlapping features and become a serious diagnostic challenge for pathologists. We report an unusual case of VSCC arising in a 21-year-old patient with type 1 diabetes mellitus. The tumor had keratinizing histologic features, was associated with a premalignant lesion with features of a high-grade squamous intraepithelial lesion (HSIL), and showed consistent p53 immunohistochemical (IHC) overexpression, but variable results in the HPV testing and p16 IHC staining. Molecular analysis revealed mutation of TP53 and overexpression of cell cycle-regulating genes (including CCND1) and collagen-coding genes (such as COL6A1). These molecular findings in genes, previously reported as upregulated in HPV-I VSCC, supported an etiological origin independent of HPV for the tumor. In conclusion, molecular analysis may help to correctly classify challenging VSCC, showing puzzling clinical, morphologic, and IHC characteristics.
A Review and Economic Analysis of the Dapivirine Vaginal Ring as HIV Pre-Exposure Prophylaxis for Women, to Inform South African Public-Sector Guidelines
Authors: Leong Trudy D. , Nel Jeremy , Jamieson Lise , Osih Regina , Dawood Halima , Subedar Hasina , McCaul Michael , Johnson Leigh F. , Cohen Karen
Published: July 2024

Background:

South Africa has a high HIV incidence and oral pre-exposure prophylaxis (PrEP) is available as public-sector standard of care. Access to alternative prevention methods for women may further reduce HIV acquisition.

Setting:

South African public sector.

Methods:

We performed a systematic search for high-quality up-to-date guidelines recommending dapivirine rings as PrEP using the Grading of Recommendations Assessment, Development, and Evaluation-Adolopment process. We appraised the systematic review and randomized controlled trial (RCT) evidence underpinning the selected guideline's recommendations and conducted a cost-effectiveness analysis. The Grading of Recommendations Assessment, Development, and Evaluation evidence-to-decision framework guided the adaptation of source guideline recommendations, according to our local context.

Results:

We identified the 2021 World Health Organization PrEP Guidelines, informed by 2 placebo-controlled RCTs, which were included in a contemporaneous systematic review. There were 23 fewer HIV acquisitions per 1000 clients with dapivirine ring vs placebo (95% confidence interval: 10 to 34), with no increase in adverse events (moderate certainty evidence). We found no RCTs comparing dapivirine to oral PrEP or among adolescent/pregnant/breastfeeding clients. Dapivirine is less cost-effective than oral PrEP at $14.59/ring, at the current price.

Conclusions:

The source guideline recommendation was adapted for the local context. Dapivirine ring seems to be less efficacious than oral PrEP, although comparative studies are lacking. Data on adolescents and pregnancy are also lacking, currently limiting the use of dapivirine as an alternative for women unable to take oral PrEP. At the current price, dapivirine is not cost-effective and unaffordable for inclusion in the South African Essential Medicines List.
Myiasis in Patients after Surgery, Brachytherapy, and Exenteration of the Orbit Due to Basal Cell Carcinoma
Authors: Valaskova Jela , Furdova Alena , Beran Eduard , Furda Robert , Jalili Nasir
Published: July 2024

Massive infiltration of the orbital tissues by dipterous fly larvae (ophthalmomyiasis) occurs throughout the world but is very rare in middle Europe countries. We report a patient with periocular basal cell carcinoma treated by surgical excisions, due to relapses followed by a high dose rate of HDR Ir192 brachytherapy which led to the necessity of orbital exenteration. The patient after many surgical operations and radiotherapy for recurrent periocular basal cell carcinoma through the years. Since 2021 the patient has not attended doctors during the COVID pandemic period. Due to socioeconomic problems, the patient continued in 2023 with infiltration of the orbital cavity and paranasal sinuses with myiasis. Exenteration of the orbit can be necessary after a relapsed infiltrative type of basal cell carcinoma infiltrating also periorbital cavities. Fly maggots may have had beneficial but also destructive effects on the exenterated cavity healing process.
The role of emergency department thoracotomy in patients with cranial gunshot wounds
Authors: Hatchimonji Justin S. , Meredyth Nicole A. , Gummadi Sriharsha , Kaufman Elinore J. , Yelon Jay A. , Cannon Jeremy W. , Martin Niels D. , Seamon Mark J.
Published: July 2024

BACKGROUND

Although several society guidelines exist regarding emergency department thoracotomy (EDT), there is a lack of data upon which to base guidance for multiple gunshot wound (GSW) patients whose injuries include a cranial GSW. We hypothesized that survival in these patients would be exceedingly low.

METHODS

We used Pennsylvania Trauma Outcomes Study data, 2002 to 2021, and included EDTs for GSWs. We defined EDT by International Classification of Diseases codes for thoracotomy or procedures requiring one, with a location flagged as emergency department. We defined head injuries as any head Abbreviated Injury Scale (AIS) score of ≥1 and severe head injuries as head AIS score of ≥4. Head injuries were “isolated” if all other body regions have an AIS score of <2. Descriptive statistics were performed. Discharge functional status was measured in five domains.

RESULTS

Over 20 years in Pennsylvania, 3,546 EDTs were performed; 2,771 (78.1%) were for penetrating injuries. Most penetrating EDTs (2,003 [72.3%]) had suffered GSWs. Survival among patients with isolated head wounds (n = 25) was 0%. Survival was 5.3% for the non–head injured (n = 94 of 1,787). In patients with combined head and other injuries, survival was driven by the severity of the head wound—0% (0 of 81) with a severe head injury (p = 0.035 vs. no severe head injury) and 4.5% (5 of 110) with a nonsevere head injury. Of the five head-injured survivors, two were fully dependent for transfer mobility, and three were partially or fully dependent for locomotion. Of 211 patients with a cranial injury who expired, 2 (0.9%) went on to organ donation.

CONCLUSION

Although there is clearly no role for EDT in patients with isolated head GSWs, EDT may be considered in patients with combined injuries, as most of these patients have minor head injuries and survival is not different from the non–head injured. However, if a severe head injury is clinically apparent, even in the presence of other body cavity injuries, EDT should not be pursued.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level IV.
Cysteine as an Innovative Biomarker for Kidney Injury
Authors: Woo Hye Young , An Jong Min , Park Min Young , Han Ahram , Kim Youngwoong , Kang Jisoo , Ahn Sanghyun , Min Seung-Kee , Ha Jongwon , Kim Dokyoung , Min Sangil
Published: July 2024

Background.

Kidney transplantation is a widely used treatment for end-stage kidney disease. Nevertheless, the incidence of acute kidney injury (AKI) in deceased donors poses a potential hazard because it significantly increases the risk of delayed graft function and potentially exerts an influence on the kidney allograft outcome. It is crucial to develop a diagnostic model capable of assessing the existence and severity of AKI in renal grafts. However, no suitable kidney injury markers have been developed thus far.

Methods.

We evaluated the efficacy of the molecular probe NPO-B, which selectively responds to cysteine, as a new diagnostic tool for kidney injury. We used an in vitro model using ischemia/reperfusion injury human kidney-2 cells and an in vivo ischemia/reperfusion injury mouse model. Additionally, cysteine was investigated using urine samples from deceased donors and living donors to assess the applicability of detection techniques to humans.

Results.

This study confirmed that the NPO-B probe effectively identified and visualized the severity of kidney injury by detecting cysteine in both in vitro and in vivo models. We observed that the fluorescence intensity of urine samples measured using NPO-B from the deceased donors who are at a high risk of renal injury was significantly stronger than that of the living donors.

Conclusions.

If implemented in clinical practice, this new diagnostic tool using NPO-B can potentially enhance the success rate of kidney transplantation by accurately determining the extent of AKI in renal grafts.
Normothermic Regional Perfusion in Controlled Donation After the Circulatory Determination of Death: Understanding Where the Benefit Lies
Authors: Royo-Villanova Mario , Miñambres Eduardo , Coll Elisabeth , Domínguez-Gil Beatriz
Published: July 2024

Controlled donation after the circulatory determination of death (cDCDD) has emerged as a strategy to increase the availability of organs for clinical use. Traditionally, organs from cDCDD donors have been subject to standard rapid recovery (SRR) with poor posttransplant outcomes of abdominal organs, particularly the liver, and limited organ utilization. Normothermic regional perfusion (NRP), based on the use of extracorporeal membrane oxygenation devices, consists of the in situ perfusion of organs that will be subject to transplantation with oxygenated blood under normothermic conditions after the declaration of death and before organ recovery. NRP is a potential solution to address the limitations of traditional recovery methods. It has become normal practice in several European countries and has been recently introduced in the United States. The increased use of NRP in cDCDD has occurred as a result of a growing body of evidence on its association with improved posttransplant outcomes and organ utilization compared with SRR. However, the expansion of NRP is precluded by obstacles of an organizational, legal, and ethical nature. This article details the technique of both abdominal and thoracoabdominal NRP. Based on the available evidence, it describes its benefits in terms of posttransplant outcomes of abdominal and thoracic organs and organ utilization. It addresses cost-effectiveness aspects of NRP, as well as logistical and ethical obstacles that limit the implementation of this innovative preservation strategy.
Ex Vivo Surgical Removal Versus Conservative Management of Small Asymptomatic Kidney Stones in Living Donors and Long-term Kidney Transplant Outcomes
Authors: Yin Saifu , Tang Yangming , Zhu Mengli , Zeng Jun , Li Xingxing , Wu Lijuan , Wang Xianding , Song Turun , Lin Tao
Published: July 2024

Background.

Donors with small asymptomatic kidney stones have been increasingly accepted because of organ shortages and advances in endoscopic urology. This study aims to evaluate and compare long-term living-donor kidney transplant outcomes following ex vivo surgical removal versus conservative management of donors’ gifted asymptomatic stones.

Methods.

Between January 2007 and December 2021, 119 kidney transplant recipients received stone-bearing kidneys, divided into the removal group (N = 63) and observation group (N = 56). We evaluated posttransplant stone events, urinary infections, kidney function, delayed graft function, length of hospital stay, and survival outcomes.

Results.

After a median follow-up of 75.5 mo, the removal group had a 10.9% lower absolute incidence of stone events (7/56 [12.5%] versus 1/63 [1.6%]; hazard ratio, 0.08; 95% confidence interval, 0.01-0.77) and a 14.3% lower absolute incidence of urinary infections (16/56 [28.6%] versus 9/63 [14.3%]; hazard ratio, 0.42; 95% confidence interval, 0.19-0.95) than the observation group. The removal group also showed superior kidney graft function. The 2 groups had comparable length of hospital stay (11.0 versus 12.0 d; P = 0.297) and exhibited similar delayed graft function incidence (1/56 [1.8%] versus 2/63 [3.2%]; P = 1.000) and urinary stricture incidence (1/56 [1.8%] versus 3/63 [4.8%]; P = 0.621). Graft survival (P = 0.350) and patient survival (P = 0.260) were comparable between 2 groups. Subgroup analyses in recipients who received kidneys with stones <4 mm also reported similar results.

Conclusions.

Ex vivo surgical removal might outperform conservative management for donors’ gifted asymptomatic kidney stones, improving long-term transplant outcomes and reducing stone events without increasing perioperative complications, even for stones <4 mm.
A genus-specific nsp12 region impacts polymerase assembly in Alpha- and Gammacoronaviruses
Authors: Hoferle Peter J. , Anderson Thomas K. , Kirchdoerfer Robert N.
Published: July 2024

Coronavirus relevancy for human health has surged over the past 20 years as they have a propensity for spillover into humans from animal reservoirs resulting in pandemics such as COVID-19. The diversity within theCoronavirinaesubfamily and high infection frequency in animal species worldwide creates a looming threat that calls for research across all genera within theCoronavirinaesubfamily. We sought to contribute to the limited structural knowledge within theGammacoronavirusgenera and determined the structure of the viral core replication-transcription complex (RTC) from Infectious Bronchitis Virus (IBV) using single-particle cryo-EM. Comparison between our IBV structure with published RTC structures from otherCoronavirinaegenera reveals structural differences across genera. Usingin vitrobiochemical assays, we characterized these differences and revealed their differing involvement in core RTC formation across different genera. Our findings highlight the value of cross-generaCoronavirinaestudies, as they show genera specific features in coronavirus genome replication. A broader knowledge of coronavirus replication will better prepare us for future coronavirus spillovers.
Detection and decontamination of chronic wasting disease prions during venison processing
Authors: Milstein Marissa , Gresch Sarah C. , Schwabenlander Marc D. , Li Manci , Bartz Jason C. , Bryant Damani N. , Christenson Peter R. , Lindsey Laramie L. , Lurndahl Nicole , Oh Sang-Hyun , Rowden Gage R. , Shoemaker Rachel L. , Wolf Tiffany M. , Larsen Peter A. , Lichtenberg Stuart S.
Published: July 2024

Prion diseases, including chronic wasting disease (CWD), are caused by prions, which are misfolded aggregates of normal cellular prion protein. Prions possess many characteristics that distinguish them from conventional pathogens, in particular, an extraordinary recalcitrance to inactivation and a propensity to avidly bind to surfaces. In mid to late stages of CWD, prions begin accumulating in cervid muscle tissues. These features collectively create scenarios where occupational hazards arise for workers processing venison and pose risks to consumers through direct prion exposure via ingestion and cross-contamination of food products. In this work, we show that steel and plastic surfaces used in venison processing can be directly contaminated with CWD prions and that cross-contamination of CWD-negative venison can occur from equipment that had previously been used with CWD-positive venison. We also show that several decontaminant solutions (commercial bleach and potassium peroxymonosulfate) are efficacious for prion inactivation on these same surfaces.
Sex-specific perching: Monitoring of artificial plants reveals dynamic female-biased perching behavior in the black soldier fly,Hermetia illucens(Diptera: Stratiomyidae)
Authors: Lemke Noah B , Rollinson Lisa N , Tomberlin Jeffery K
Published: July 2024

Artificial perches are implemented by many companies that mass-rear the black soldier fly,Hermetia illucens,to create a more natural breeding environment or provide additional surface area for flies to rest. However, basic information related to perching behavior is lacking. This experiment tested the effect of adding perches to breeding cages on fitness and behavior. Perches were constructed from artificial leaves affixed to wooden dowels inserted into foam blocks, placed in the center of cage floors. The four treatment-levels had an added surface area of 0.00-, 0.04-, 0.26-, and 0.34-m2. Each 0.93-m3cage was supplied with 90 male and 90 female flies, and female thoraxes marked with acrylic paint. Beyond the tested range, a linear model suggests that 1.00-m2additional surface area can accommodate a 1.46-fold increase in flies without negative fitness impacts. Time-series analysis revealed; (a) females utilized perches 1.42-times more often than males across two trials; (b) especially in the morning where the difference could be as high as 2.56-times more than males; (c) this decreased to 0.20-1.57 times more females than males by 1600 h, and (d) this cyclical pattern repeated each day throughout the week with decreasing female-bias, starting from 2.41-times more females on Day 1 to 0.88-1.98-times more females than males on Day 6. These dynamics are likely due to the presence of male flies engaging in aerial contests near lamps providing light needed for mating, especially during early hours and early adulthood, aligning with prior knowledge of black soldier fly mating behavior.

LAY SUMMARY

Female black soldier flies perch on artificial plants much more often than males, especially early in the day and early in their reproductive lives, times when males are competing with one another in aerial swarms.
We Are on the Verge of Breakthrough Cures for Type 1 Diabetes, but Who Are the 2 Million Americans Who Have It?
Authors: Smith Rebecca , Eisenberg Samara , Turner-Pfifer Aaron , Le Grand Jacqueline , Pincus Sarah , Omer Yousra , Wang Fei , Pyenson Bruce
Published: July 2024

Two million Americans have Type 1 Diabetes. Innovative treatments have standardized insulin delivery and improved outcomes for patients, but patients’ access to such technologies depends on social determinants of health, including insurance coverage, proper diagnosis, and appropriate patient supports. Prior estimates of US prevalence, incidence, and patient characteristics have relied on data from select regions and younger ages and miss important determinants. By contrast, our research leveraged nationally representative administrative claims datasets to build a nuanced picture of the population with T1DM. Our work also supports future policy and research efforts with 2024, 2029, and 2033 projections of demographic and insurance coverage for people with T1DM.
Evaluation of SARS-CoV-2 antibody response between paired fingerprick (hemaPEN®) and venepuncture collected samples in children and adults
Authors: Mazarakis Nadia , Toh Zheng Quan , Nguyen Jill , Higgins Rachel A. , Rudge James , Whittle Belinda , Woudberg Nicholas J. , Devine Justin , Gooley Andrew , Lapierre Florian , Crawford Nigel W. , Tosif Shidan , Licciardi Paul V
Published: July 2024

Serological surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies is important to monitor population COVID-19 immunity. Dried blood spots (DBS) are a valuable method for serosurveys, particularly in remote settings and in children. We compared the measurement of SARS-CoV-2 spike-specific IgG in paired blood samples collected by standard venepuncture (serum) and the hemaPEN® microsampling DBS device from children and adults using an established in-house ELISA. A total of 83 participants (10 months – 65 years of age) with paired serum and hemapen samples were included in the analysis; N=41 adults (36 COVID-positive and 5 COVID-negative) and N=42 children (37 COVID positive and 5 COVID-negative). Moderate-to strong-correlations between paired hemaPEN DBS eluates and serum SARS-CoV-2 IgG antibodies for RBD (r=0.9472, P<.0001) and S1 proteins (r=0.6892, P<.0001) were found. Similar results were observed in both adult and paediatric populations. SARS-CoV-2 spike-specific IgG in hemaPEN DBS samples remained stable for at least 35 weeks at room temperature. HemaPEN samples showed high specificity and sensitivity (100% and 89.89%, respectively) compared with serum. The use of the microsampling hemaPEN device for DBS sample collection is a feasible approach for assessing SARS-CoV-2 antibodies for serosurveillance studies, particularly in remote settings and in children.
Framework for Implementation of Poisson MaxSPRT Technique with Variations for Vaccine Safety
Authors: Samiullah Md , Buttery Jim , Clothier Hazel J. , Yin Jiying , Mallard John , Munakabayo Jeremiah , Kattan Gonzalo Sepulveda , Dimaguila Gerardo Luis
Published: July 2024

For direct, continuous, and sequential drug and vaccine safety surveillance, the Maximized Sequential Probability Ratio Test (MaxSPRT) was developed by the Centers for Disease Control and Prevention (CDC) (Kulldorff et al, 2011). Its predictive value and power to detect signals and the ability to monitor adverse events continuously have made it an emerging technique for vaccine adverse event surveillance. Moreover, being able to use a statistical method e.g. MaxSPRT in the absence of dose distributed denominator is a practical advantage for spontaneous reporting systems to function as stand-alone signal detection systems. In this paper, we present a comprehensive framework for implementing MaxSPRT for vaccine safety surveillance and Poisson data. We analysed the literature regarding MaxSPRT and sequential analysis. Our analysis revealed numerous variations of MaxSPRT, adapted to the specific requirements and objectives of the users. Variations are due to differing types of data and purpose of use, including whether used for epidemiological surveillance or for regulatory monitoring. This paper provides a comprehensive guide for organisations contemplating the implementation of MaxSPRT. It synthesises existing literature on MaxSPRT, identifies variations based on specific requirements, and describes an implementation framework. We offer a detailed explanation of the steps and challenges associated with the implementation of MaxSPRT on the adverse event following immunisation (AEFI) reporting database of Surveillance of Adverse Events Following Vaccination in the Community, Victoria, Australia (SAEFVIC), the largest jurisdictional reporting service by volume in Australia. It also proposes some techniques and measures to deal with the challenges associated with the implementation process.

Key Points

MaxSPRT is a powerful method for ongoing vaccine surveillance, offering flexibility to adapt to various situations and data limitations. However, this flexibility can lead to challenges in implementation. Our paper simplifies the MaxSPRT method with clear explanations and step-by-step guidance, addressing potential issues and proposing solutions to improve its use in monitoring vaccine and drug safety.
Discovery and evaluation of novel biomarkers reveal dasatinib as a potential treatment for a specific subtype of Triple-Negative Breast Cancer
Authors: Ortega-Álvarez D , Tébar-García D , Casado-Pelaez M , Castillo-Agea E , Balibrea-Rull J , Olivares-Osuna D , Pérez-Parra D , Guardia C , Musulén E , Vinuesa-Pitarch E , Sánchez-López E , Postigo-Corrales F , Ballana E , Martínez-Cardús A , Margelí M , Esteller M , Fernández-Ruiz PL , Luengo-Gil G , Mereu E , Galán-Moya EM , Rodilla V
Published: July 2024

Triple-negative breast cancer (TNBC) represents the most heterogeneous and aggressive subtype of breast carcinomas, characterized by the absence of clinical biomarkers (ERα, PR, and HER2) and the lack of targeted therapies. In this regard, several clinical trials have consistently failed to effectively stratify patients and identify specific treatments that elicit substantial responses. This study aims to pinpoint biomarkers expressed exclusively in the basal mammary epithelial compartment, facilitating a refined subclassification of this breast cancer subtype. Using computational analyses of single-cell RNA sequencing data, we have identified a list of genes associated with basal identity (BC-markers). Histological validation in 137 human samples has enabled us to categorize TNBC patients into BC-positive and BC-negative TNBC subtypes. Significantly, the presence of these markers correlates with a poorer prognosis in TNBC patients. Functional analyses have revealed a pivotal role forTAGLNin cell migration, likely influencing tumor aggressiveness. Further, we discovered that BC-marker expression is associated with the mesenchymal phenotype and increased sensitivity to the tyrosine kinase inhibitor dasatinib, particularly in BC-positive TNBC, suggesting novel therapeutic avenues. In our study,TAGLNemerged as a potential predictive biomarker for dasatinib responsiveness, offering new directions for personalized therapy for TNBC patients.
A Viral-Encoded Homologue of IPS-1 Modulates Innate Immune Signaling During KSHV Lytic Replication
Authors: Miranda Daniel , He Buyuan , Sanchez Julio C. , Sennatti Ashkon , Bontemps Johnny R. , Tran James T. , Tang Wilson S. , Sanchez David Jesse
Published: July 2024

Modulation of innate immunity is critical for virus persistence in a host. In particular, viral-encoded disruption of type I interferon, a major antiviral cytokine induced to fight viral infection, is a key component in the repertoire of viral pathogenicity genes. We have identified a previously undescribed open reading frame within the Kaposi’s sarcoma-associated herpesvirus (KSHV) genome that encodes a homologue of the human IPS-1 (also referred to as MAVS) protein that we have termed viral-IPS-1 (v-IPS-1). This protein is expressed during the lytic replication program of KSHV, and expression of v-IPS-1 blocks induction of type I interferon upstream of the TRAF3 signaling node including signaling initiated via both the RLR and TLR3/4 signaling axes. This disruption of signaling coincides with destabilization of the cellular innate signaling adaptors IPS-1 and TRIF along with a concatenate stabilization of the TRAF3 protein. Additionally, expression of v-IPS-1 leads to decreased antiviral responses indicating a blot to type I interferon induction during viral infection. Taken together, v-IPS-1 is the first described viral homologue of IPS-1 and this viral protein leads to reprogramming of innate immunity through modulation of type I interferon signaling during KSHV lytic replication.
Unlocking data inKlebsiellalysogens to predict capsular type-specificity of phage depolymerases
Authors: Concha-Eloko Robby , Beamud Beatriz , Domingo-Calap Pilar , Sanjuán Rafael
Published: July 2024

Viral entry is a critical step in the infection process.Klebsiellaspp. and other clinically relevant bacteria often express a complex polysaccharide capsule that acts as a barrier to phage entry. In turn, mostKlebsiellaphages encode depolymerases for capsule removal. This virus-host arms race has led to extensive genetic diversity in both capsules and depolymerases, complicating our ability to understand their interaction. This study exploits the information encoded inKlebsiellaprophages to model the interplay between the bacteria, the prophages, and their depolymerases, using a graph neural network and a sequence clustering-based method. Both approaches showed significant predictive ability for prophages capsular tropism and, importantly, were transferrable to lytic phages. In addition to creating a comprehensive database linking depolymerase sequences to their specific targets, this study demonstrates the predictability of phage-host interactions at the subspecies level, providing new insights for improving the therapeutic and industrial applicability of phages.
Laboratory experiments suggests limited impact of increased nitrogen deposition on snow algae blooms
Authors: Almela Pablo , Elser James J. , Giersch J. Joseph , Hotaling Scott , Rebbeck Victoria , Hamilton Trinity L.
Published: July 2024

Snow algal blooms decrease snow albedo and increase local melt rates. However, the causes behind the size and frequency of these blooms are still not well understood. One factor that is likely contributing is nutrient availability, specifically nitrogen (N) and phosphorus (P). However, the nutrient requirements of the taxa responsible for these blooms is not known. Here, we assessed the growth of three commercial strains of snow algae under 24 different nutrient treatments that varied in both absolute and relative concentrations of N and P. After 38 days of incubation, we measured total biomass and cell size and estimated their effective albedo reduction surface (EARS). Snow algal strains tended to respond similarly and achieved bloom-like cell densities over a wide range of NP conditions. However, the molar ratio of N:P at which maximum biomass was achieved was between 4 and 7. Our data indicate a high requirement for P for snow algae and suggest that additional N inputs into the ecosystem may not significantly impact the productivity and abundance of snow algae blooms. This highlights P availability as a critical factor influencing the frequency and extent of snow algae blooms and their potential contribution to snow melt through altered albedo.
First-Year Dynamics of the Anaerobic Microbiome and Archaeome in Infants Oral and Gastrointestinal Systems
Authors: Neumann Charlotte Julia , Mohammadzadeh Rokhsareh , Woh Pei Yee , Kobal Tanja , Pausan Manuela-Raluca , Shinde Tejus , Haid Victoria , Mertelj Polona , Mahnert Alexander , Kumpitsch Christina , Jantscher-Krenn Evelyn , Moissl-Eichinger Christine
Published: July 2024

Recent research provides new insights into the early establishment of the infant gut microbiome, emphasizing the influence of breastfeeding on the development of gastrointestinal (GIT) microbiomes. In our study, we longitudinally examined the taxonomic and functional dynamics of the oral and GIT microbiomes of healthy infants (n=30) in their first year, focusing on the often over-looked aspects, the development of archaeal and anaerobic microbiomes. Breastfed (BF) infants exhibit a more defined transitional phase in their oral microbiome compared to non-breastfed (NBF) infants, marked by a decrease in Streptococcus and the emergence of anaerobic genera such as Granulicatella. This phase, characterized by increased alpha diversity and significant changes in beta diversity, occurs earlier in NBF infants (months 1-3) than in BF infants (months 4-6), suggesting that breastfeeding supports later, more defined microbiome maturation. We demonstrated the presence of archaea in the infant oral cavity and GIT microbiome from early infancy, with Methanobrevibacter being the predominant genus. Still, transient patterns show that no stable archaeome is formed. The GIT microbiome exhibited gradual development, with BF infants showing increased diversity and complexity between months 3 and 8, marked by anaerobic microbial networks. NBF infants displayed complex microbial cooccurrence patterns from the start. Those strong differences between BF and NBF infants GIT microbiomes are less pronounced on functional levels than on taxonomic level. Overall, the infant microbiome differentiates and stabilizes over the first year, with breastfeeding playing a crucial role in shaping anaerobic microbial networks and overall microbiome maturation.
Population responses to environmental stochasticity are primarily driven by survival-reproduction trade-offs and mediated by aridity
Authors: Santos Gabriel Silva , Yang Xianyu , L Gascoigne Samuel J , Compagnoni Aldo , Dias André T.C. , Tuljapurkar Shripad , Kajin Maja , Salguero-Gómez Roberto
Published: July 2024

Forecasting responses of natural populations to increasingly stochastic environments is a major challenge in Ecology and Conservation Biology. We now know that populations can modulate how their vital rates (e.g., survival, reproduction) change through time to minimise the negative impacts of environmental stochasticity. However, despite the important analytical and theoretical advances that have led to this knowledge, we still do not know (1) how much this ability of natural populations to buffer against environmental stochasticity can vary in nature, nor (2) the drivers of these strategies, with likely candidates including the environmental regimes themselves, as well as the life history traits and phylogenetic ancestry of the species of interest. To address these questions, we parameterised a Bayesian generalised linear mixed model with high-resolution vital rate data from 134 natural populations across 89 species of plants and animals. We show that population responses to environmental stochasticity vary three orders of magnitude along a ‘demographic buffering continuum’. Furthermore, the position of a given population along said continuum is predicted by a survival-reproduction trade-off and by the degree of aridity the population experiences. Our findings open a promising avenue of research to improve ecological forecasts and management of natural populations in the Anthropocene.
Multiscale mechanics drive functional maturation of the vertebrate heart
Authors: Andrews Toby G R , Cornwall-Scoones Jake , Ramel Marie-Christine , Gupta Kirti , Briscoe James , Priya Rashmi
Published: July 2024

How simple tissue primordia sculpt complex functional organs, robustly and reproducibly, remains elusive. As the zebrafish embryo grows into a larva, to improve its heart function, the embryonic myocardial wall transforms into an intricate 3D architecture, composed of an outer compact layer enveloping an inner layer of multicellular trabecular ridges. How these tissue layers acquire their characteristic form suited for their function remains an open question. Here, we find that multiscale mechanochemical coupling and an emergent tissue-scale morphological transition steer functional maturation of the developing zebrafish heart. Single-celled trabecular seeds recruit outer compact layer cells to mature into clonally heterogenous multicellular ridges, thereby amplifying cardiac contractile forces. In response, remaining compact layer cells are stretched, which impedes their further recruitment, thereby constraining trabecular ridge density. Concomitantly, Notch-dependent actomyosin dampening triggers a sharp transition in myocardial tissue area, activating rapid organ growth that expands blood filling capacity. Thus, multiscale self-organizing interactions optimize heart size and contractile efficiency to support embryonic life.
Structures of the multi-domain oxygen sensor DosP: remote control of a c-di-GMP phosphodiesterase by a regulatory PAS domain
Authors: Wu Wenbi , Kumar Pankaj , Brautigam Chad A. , Tso Shih-Chia , Baniasadi Hamid R. , Kober Daniel L. , Gilles-Gonzalez Marie-Alda
Published: July 2024

The heme-based direct oxygen sensor DosP degrades c-di-GMP, a second messenger nearly unique to bacteria. In stationary phaseEscherichia coli, DosP is the most abundant c-di-GMP phosphodiesterase. Ligation of O2to a heme-binding PAS domain (hPAS) of the protein enhances the phosphodiesterase through an allosteric mechanism that has remained elusive. We determined six structures of full-length DosP in its aerobic or anaerobic conformations, with or without c-di-GMP. DosP is an elongated dimer with the regulatory heme and phosphodiesterase separated by nearly 180 Å. In the absence of substrate, regardless of the heme status, DosP presents an equilibrium of two distinct conformations. Binding of substrate induces DosP to adopt a single, ON-state or OFF-state conformation depending on its heme status. Structural and biochemical studies of this multi-domain sensor and its mutants provide insights into signal regulation of second-messenger levels.
Supervised Automation of Cell Counting in Confocal Microscopic Cochlear Imaging Datasets Using Macro in Imaris
Authors: Rahman Muhammad Taifur , Khan Nashwaan Ali , Mokbul Mobin Ibne , Razu Ibrahim , Fatima Shakila Mahmuda , Lira Samia Sultana , Garcia Cristina , Eckard Peter , Hansen Marlan R
Published: July 2024

Analyzing confocal microscopic data of biological samples using the Imaris software poses challenges due to its time-consuming nature involving tedious multiple steps and possibility of human errors. Here, we developed a supervised automation protocol to minimize manual input in cell and spot counting on confocal images obtained from mouse cochlear sections. The protocol increases efficiency by incorporating image recognition and object-oriented macros. Moreover, the protocol being adaptable allows scientists in diverse other fields to customize it for their specific needs.

Graphical Abstract
Complete mitochondrial genomes of Eastern Massasauga (Sistrurus catenatus) and North American Racer (Coluber constrictor)
Authors: Chen Ying , Chabot Amy A. , Swanson Bradley J. , Lougheed Stephen C.
Published: July 2024

We report the complete mitochondrial genomes of two snake species of conservation concern, Eastern Massasauga (Sistrurus catenatus) and North American Racer (Coluber constrictor). The mitogenome length is 17,245bp forS. catenatusand 17,142bp forC. constrictor. Both mitogenomes include 13 protein-coding genes, 22 transfer RNA genes, two ribosomal RNA genes and two control regions. Gene arrangements are similar between two species, except that tRNA-Pro is located between tRNA-Ile and Control Region 2 inS. catenatus, but between tRNA-Thr and Control Region 1 inC. constrictor. Such gene arrangements are typical of their respective families, Viperidae and Colubridae. A phylogenetic tree with 21 additional snake species using concatenated 12 protein-coding genes (without ND6) supported current taxonomy of two reported species. We also found that North American racers in Ohio, Michigan (USA) and Pelee Island (Canada) were more closely allied to Pennsylvania individuals from the Eastern United States.
SimMS: A GPU-Accelerated Cosine Similarity implementation for Tandem Mass Spectrometry
Authors: Onoprishvili Tornike , Yuan Jui-Hung , Petrov Kamen , Ingalalli Vijay , Khederlarian Lila , Leuchtenmuller Niklas , Chandra Sona , Duarte Aurelien , Bender Andreas , Gloaguen Yoann
Published: July 2024

Untargeted metabolomics involves a large-scale comparison of the fragmentation pattern of a mass spectrum against a database containing known spectra. Given the number of comparisons involved, this step can be time-consuming. In this work, we present a GPU-accelerated cosine similarity implementation for Tandem Mass Spectrometry (MS) with approximately 1000-fold speedup compared to the MatchMS reference at a rate of 0.005% incorrect matches and a rate of 0.002% incorrect scores. We describe the underlying reasons for these errors and provide means to avoid them.
Intracellular lipopolysaccharide regulates ER remodeling upon bacterial infection
Authors: Cheng Yi-Lin , Mello-Vieira João , Covarrubias-Pinto Adriana , Gonzalez Alexis , Kuncha Santosh Kumar , Kew Chun , Zhang Kaiyi , Afzal Muhammad Awais , Diab Nour , Borchert Sophia , Chen Wenbo , Huang Timothy Chun , Hornef Mathias Walter , Hübner Christian A. , Hensel Michael , Dikic Ivan
Published: July 2024

The remodeling of endoplasmic reticulum (ER) is finely regulated by selective autophagy, known as ER-phagy. However, whether Gram-negative bacteria, which are known to manipulate the host membranous system, regulate ER-phagy remains elusive. We find that bacterial lipopolysaccharide (LPS) released upon infection withSalmonellaTyphimurium colocalizes with FAM134B, a reticulon-like protein that operates as an ER-phagy receptor. Pulldown assays reveal that LPS binds directly to FAM134B. The interaction occurs via lipid A of LPS and positively charged amino acid residues on the amphipathic helices and C-terminal region of FAM134B. Upon binding, O-Antigen of LPS promotes FAM134B oligomerization and ER fragmentation inin vitroliposome membrane remodeling assays. Delivery of LPS into the cytoplasm via transfection significantly increases the number of FAM134B–LC3B-decorated ER fragments, which are recruited toSalmonella-containing vacuoles. Both intracellular and extracellular bacteria use outer membrane vesicles (OMVs) to deliver LPS into the cytosol for FAM134B activation and ER fragmentation. Taken together, our results show that Gram-negative bacteria subvert the host ER remodeling system to create bacteria-containing vacuoles that provide a niche for bacterial survival.

Graphical Abstract

In Brief

Cytosolic LPS binds to the ER-phagy receptor FAM134B, triggering ER fragmentation, and subsequently, the formation of FAM134B-positive vacuoles for bacterial survival.

Highlights

Intracellular LPS induces FAM134B-mediated ER fragmentation.

Lipid A of LPS binds to FAM134B.

O-antigen of LPS triggers oligomerization of FAM134B and membrane fragmentation.

FAM134B-positiveSalmonella-containing vacuoles are not acidified, providing a niche forSalmonellasurvival.

Outer membrane vesicles are required for cytosolic LPS delivery to activate FAM134B-mediated ER fragmentation.
Biomechanics of venom delivery in South America’s first spitting scorpion
Authors: Laborieux Léo
Published: July 2024

Venom is a metabolically expensive secretion used sparingly in a variety of ecological contexts, most notably predation and defense. Accordingly, few animals use their toxins in ranged attacks, and venom-squirting behaviour is only known from select taxa. In scorpions, species belonging to two genera are known to spray venom when threatened, and previous work inParabuthus transvaalicusshows that venom delivery depends on perceived levels of threat. Here, I describeTityus(Tityus)XXXsp. nov., a new species of Buthid scorpion from Cundinamarca, Colombia. Remarkably, this species is capable of venom spraying, a first for both the genus and the South American continent. Using frame-by-frame video analysis and ballistic equations, I show thatT. XXXsp. nov. employs not one, but two types of airborne attacks with dramatic differences in range and venom expenditure. Further, the new species uses an unusually large reserve of prevenom-like secretion for spraying, as opposed to the costly venom used by other spitting scorpions. In light of these key specializations, I propose that venom spraying convergently evolved in response to different selection pressures, laying the groundwork for future investigation.