bluuebunny/crossref_metadata_2025 huggingface dataset:
Operational Definition of the Concept of Success in Peripheral Intravenous Catheterization in Hospitalized Children
Authors: Santos Luciano Marques Dos , Kusahara Denise Miyuki , Rodrigues Elisa Conceição , Manzo Bruna Figueiredo , Pedreira Mavilde da Luz Gonçalves , Avelar Ariane Ferreira Machado
Published: July 2024

The objective of this study was to operationally define the concept of success in peripheral intravenous catheterization in children considering the Walker and Avant model. This is a methodological study, carried out through the following steps: concept selection, the definition of the analysis objective, identification of possible uses of the concept, determination of critical or essential attributes, construction of a model and opposite case, and identification of antecedents and consequences. The study was carried out based on a search in international databases from January to March 2021. The sample consisted of 47 studies conducted in 17 countries between 2008 and 2021. Five attributes, 20 antecedents, 10 consequences, and an empirical reference of the studied concept were identified. Also, 2 cases, model and opposite, were elaborated, and an operational definition of the concept was developed. The Walker and Avant method enabled the operationalization of the concept of success of peripheral intravenous catheterization in children based on attributes, antecedents and consequents, and model and opposite cases.
Using Implementation Science to Improve Short Peripheral Intravenous Catheter Outcomes
Authors: Hook Mary , Woda Aimee , Bohr Kelsey , Ford Cailin , Singh Maharaj
Published: July 2024

Short peripheral intravenous catheters (short PIVCs) are commonly used in acute care, guided by evidence-based policy with interventions to limit premature failure. Research on how nurses use evidence and change processes to optimize outcomes is needed. The study objective was to use a theory-based implementation science approach to evaluate and improve short PIVC insertion and care processes and reduce removals for adverse outcomes in acute care. This mixed-methods study was conducted with inpatient nursing units (n = 23) at a large urban quaternary medical center. Units identified and implemented one PIVC care intervention that could lower catheter removals for adverse outcomes over 3 months. Data from multiple sources were convergently analyzed to evaluate process and outcomes postintervention. Although overall frequency of PIVC removals for adverse outcomes was unchanged, several units improved their outcomes using implementation strategies. The determinant framework provides a plausible explanation for the study results. While adverse outcome rates remained below published rates, some units had limited success improving outcomes with traditional change strategies. Implementation strategies and readily accessible data can offer nursing units a new approach to effectively deploy, monitor, and maintain interventions to achieve improved outcomes.
Vegetarianism, Traditional Practices, and Belief Systems in India
Authors: Saldanha Leila , Krishnaswamy Sheela
Published: July 2024

Eighty-three percent of the Indian population belongs to religions founded in India that promote vegetarianism. Thirty-nine percent of all Indians say they are vegetarians. This percentage varied by religion (8%-92%) and region (9%-90%), reflecting the enormous cultural diversity in the country. This article explores the various religious and cultural belief systems that undergird the practice of vegetarianism in India. It provides a perspective on vegetarianism and traditional practices in India. Examples of these practices are how foods are classified in Ayurveda, the thali eating system, and fasting. These practices can be incorporated into other eating behaviors and habits to help meet individual needs and preferences.
Have We Considered Women in Current Sports Nutrition Guidelines?
Authors: Smith Ella S. , Burke Louise M.
Published: July 2024

The need to address the underrepresentation of female athletes in sports nutrition research is receiving substantial attention from practitioners and academics alike. To systematically and efficiently direct priorities for future research activities, we have developed a protocol to “audit” the current literature across various areas of sports nutrition research. This process provides detailed information regarding the quantity, quality, and nature of existing research including women. We have conducted such audits across the areas of dietary performance (auditPERF) and medical (auditMED) supplements, both acute and chronic carbohydrate (CHO) fueling strategies (auditCHOAC and auditCHOCH), as well as protocols for heat adaptation (auditHEAT). Women accounted for between 11% and 23% of the total participant count across these themes, with the exception of auditMED where female participants dominated (71%). Across all audits, few studies compared responses between the sexes or investigated sex-specific differences. Furthermore, methodological consideration of menstrual status was poor, with only 0.25% of studies implementing best practice recommendations and 79% of studies failing to classify menstrual status entirely. Females were most poorly represented in studies examining sports performance outcomes, and few studies involved elite female athletes (national/international level) within participant cohorts. Our findings demonstrate an overall lack of female-specific considerations in the literature underpinning the current guidelines in the areas of dietary performance/medical supplementation, CHO fueling, and heat adaptation. As such, current guidelines may not reflect optimal practice for female athletes. New research should therefore implement female-specific methodological considerations, with particular attention to menstrual status, before these current sports nutrition guidelines can be applied to female athletes with complete confidence.
Navigating test accuracy metrics used in diagnostic evaluation
Authors: Hamdan Ahmad , Zar Lubna A. , Doi Suhail A. , Chivese Tawanda , Khan Muhammad N. , Khaled Salma M. , Babu Giridhara R. , Farooqui Habib Hasan
Published: July 2024

Purpose of review

Accurate diagnosis stands as the cornerstone of effective medical practice, influencing treatment decisions and patient outcomes. Additionally, grasping basic statistical concepts behind diagnostic tests is crucial for clinicians to interpret results accurately and make informed clinical judgments. This article discusses the evolution and application of diagnostic indices, using a clinical example to apply fundamental concepts.

Recent findings

Advances in our understanding of statistical methods are giving rise to new interpretations of diagnostic indices, altering how we relate them to test performance. These new metrics reveal previously unnoticed details within existing diagnostic measures. Consequently, these developments have been discussed and will help to increase understanding of their interpretation and utility in clinical settings.

This article provides a concise overview of the latest updates on diagnostic indices and stresses the importance of an updated understanding of their inter-connectedness and interpretation for optimal application to evidence-based care.
Fully Automatic Quantitative Measurement of Equilibrium Radionuclide Angiocardiography Using a Convolutional Neural Network
Authors: Ha Sejin , Seo Seung Yeon , Park Byung Soo , Han Sangwon , Oh Jungsu S. , Chae Sun Young , Kim Jae Seung , Moon Dae Hyuk
Published: July 2024

Purpose

The aim of this study was to generate deep learning–based regions of interest (ROIs) from equilibrium radionuclide angiography datasets for left ventricular ejection fraction (LVEF) measurement.

Patients and Methods

Manually drawn ROIs (mROIs) on end-systolic and end-diastolic images were extracted from reports in a Picture Archiving and Communications System. To reduce observer variability, preprocessed ROIs (pROIs) were delineated using a 41% threshold of the maximal pixel counts of the extracted mROIs and were labeled as ground-truth. Background ROIs were automatically created using an algorithm to identify areas with minimum counts within specified probability areas around the end-systolic ROI. A 2-dimensional U-Net convolutional neural network architecture was trained to generate deep learning–based ROIs (dlROIs) from pROIs. The model’s performance was evaluated using Lin’s concordance correlation coefficient (CCC). Bland-Altman plots were used to assess bias and 95% limits of agreement.

Results

A total of 41,462 scans (19,309 patients) were included. Strong concordance was found between LVEF measurements from dlROIs and pROIs (CCC = 85.6%; 95% confidence interval, 85.4%–85.9%), and between LVEF measurements from dlROIs and mROIs (CCC = 86.1%; 95% confidence interval, 85.8%–86.3%). In the Bland-Altman analysis, the mean differences and 95% limits of agreement of the LVEF measurements were −0.6% and −6.6% to 5.3%, respectively, for dlROIs and pROIs, and −0.4% and −6.3% to 5.4% for dlROIs and mROIs, respectively. In 37,537 scans (91%), the absolute LVEF difference between dlROIs and mROIs was <5%.

Conclusions

Our 2-dimensional U-Net convolutional neural network architecture showed excellent performance in generating LV ROIs from equilibrium radionuclide angiography scans. It may enhance the convenience and reproducibility of LVEF measurements.
Atypical Presentation of Gall Bladder Adenocarcinoma as Paraneoplastic Myeloneuropathy
Authors: Majeed Althaf K. , Datta Deepanksha , Aggarwal Divya , Panda Bijayalaxmi , Kumar Rajesh
Published: July 2024

Paraneoplastic neurologic syndromes are a rare, heterogeneous group of complications associated with malignancy, unrelated to direct tumor invasion or metastasis. They are the remote effects of a malignancy owing to immune-mediated reaction toward the antigens that are common to both the malignant and normal cells. Few paraneoplastic syndromes are reported with gall bladder cancer. However, neurological symptoms are infrequent. Here we share an interesting case of adenocarcinoma of gall bladder with initial presentation as a paraneoplastic noncompressing myeloneuropathy.
Prostate-Specific Membrane Antigen Use in Glioma Management
Authors: McBriar Joshua D. , Shafiian Neeva , Scharf Stephen , Boockvar John A. , Wernicke A. Gabriella
Published: July 2024

Background

Prostate-specific membrane antigen (PSMA) is a membrane-bound metallopeptidase highly expressed in the neovasculature of many solid tumors including gliomas. It is a particularly enticing therapeutic target due to its ability to internalize, thereby delivering radioligands or pharmaceuticals to the intracellular compartment. Targeting the neovasculature of gliomas using PSMA for diagnosis and management has been a recent area of increased study and promise. The purpose of this review is to synthesize the current state and future directions of PSMA use in the histopathologic study, imaging, and treatment of gliomas.

Methods

PubMed and Scopus databases were used to conduct a literature review on PSMA use in gliomas in June 2023. Terms searched included “PSMA,” “Prostate-Specific Membrane Antigen” OR “PSMA” OR “PSMA PET” AND “glioma” OR “high grade glioma” OR “glioblastoma” OR “GBM.”

Results

Ninety-four publications were screened for relevance with 61 studies, case reports, and reviews being read to provide comprehensive context for the historical, contemporary, and prospective use of PSMA in glioma management.

Conclusions

PSMA PET imaging is currently a promising and accurate radiographic tool for the diagnosis and management of gliomas. PSMA histopathology likely represents a viable tool for helping predict glioma behavior. More studies are needed to investigate the role of PSMA-targeted therapeutics in glioma management, but preliminary reports have indicated its potential usefulness in treatment.
Increased Uptake of 18F-THK5351 in Isocitrate Dehydrogenase-Wildtype Glioblastoma But Not in Meningioma
Authors: Mitamura Katsuya , Norikane Takashi , Yamamoto Yuka , Miyake Keisuke , Nishiyama Yoshihiro
Published: July 2024

18F-THK5351 demonstrates a strong binding affinity and selectivity for tau. However, off-target binding with monoamine oxidase-B enzyme, highly expressed in the outer mitochondrial membranes of astrocytes, is possible. In a case with isocitrate dehydrogenase–wildtype glioblastoma, 11C-MET PET and 18F-THK5351 PET exhibited increased uptake in the tumor. Conversely, in another case with intracranial meningioma, MET PET revealed increased uptake in the tumor, whereas 18F-THK5351 PET showed no abnormal uptake in the tumor. However, it is challenging to distinguish meningiomas from glioblastomas on MRI. 18F-THK5351 PET might help differentiate between isocitrate dehydrogenase–wildtype glioblastoma and meningioma.
18F-FDG PET/CT of Benign Tracheal Schwannoma
Authors: Lu Kai-yu , Cheng You , Jiang Zhen-Peng , Shao Dan , Wang Si-yun
Published: July 2024

Schwannoma is a benign tumor originating from Schwann cells. It commonly occurs in the head, neck, and extremities, but rarely occurs in the trachea. Tracheal schwannoma is usually asymptomatic. We reported the 18F-FDG PET/CT findings of a 61-year-old man with bronchoscopically biopsy-proven schwannoma, which presented challenges in differentiation from certain benign tumors and low-grade malignancies in the trachea.
Feasibility of Using a Novel Drop-In Gamma Probe for 99mTc-PSMA-I&S–Guided Lymph Node Detection During Robot-Assisted Radical Prostatectomy for Primary Prostate Cancer
Authors: Harke Nina N. , Fuhrmann Christian , Czerner Christoph , Rudolf Frank , Ross Tobias Ludwig , Katzendorn Olga , Bengel Frank , Kuczyk Markus A. , Weiberg Desiree , Derlin Thorsten
Published: July 2024

Purpose

Prostate-specific membrane antigen (PSMA)–targeted radioguided surgery (RGS) has gained increased interest in prostate cancer (PCa). This analysis aims to evaluate the feasibility, safety, and limitations of RGS with a novel drop-in gamma probe in primary PCa.

Patients and Methods

The data of 13 patients with primary PCa undergoing RGS were analyzed retrospectively. After preoperative administration of 99mTc-PSMA-I&S, a SPECT/CT was conducted and a robotic radical prostatectomy was performed the following day including intraoperative assessment of the lymph node stations using a novel robotic drop-in gamma probe. This was followed by an extended pelvic lymph node dissection (ePLND) with ex vivo control measurement using the drop-in and a conventional rigid gamma probe.

Results

Eleven patients (median PSA value of 11 ng/mL) had high-risk and 2 patients had intermediate-risk PCa. Overall, a median of 22 ePLND lymph nodes were dissected. In 1 patient, preoperative SPECT/CT imaging showed suspicious lymph nodes, which could be confirmed intraoperatively with the robotic drop-in probe and subsequently in the final histopathological analysis. RGS failed to identify 2 patients with micrometastases (<3 mm) preoperatively and intraoperatively. No postoperative complications related to 99mTc-PSMA-I&S RGS or ePLND occurred.

Conclusions

RGS with the novel drop-in gamma probe and 99mTc-PSMA-I&S allows for a reliable intraoperative screening for lymph node metastases in robot-assisted radical prostatectomy for primary PCa with an acceptable safety profile. However, limitations in the detection of micrometastases need to be overcome before omitting extended ePLND in patients at risk for lymphatic spread.
The genetics of amyotrophic lateral sclerosis
Authors: Nijs Melissa , Van Damme Philip
Published: July 2024

Purpose of review

Amyotrophic lateral sclerosis (ALS) has a strong genetic basis, but the genetic landscape of ALS appears to be complex. The purpose of this article is to review recent developments in the genetics of ALS.

Recent findings

Large-scale genetic studies have uncovered more than 40 genes contributing to ALS susceptibility. Both rare variants with variable effect size and more common variants with small effect size have been identified. The most common ALS genes are C9orf72, SOD1, TARDBP and FUS. Some of the causative genes of ALS are shared with frontotemporal dementia, confirming the molecular link between both diseases. Access to diagnostic gene testing for ALS has to improve, as effective gene silencing therapies for some genetic subtypes of ALS are emerging, but there is no consensus about which genes to test for.

Our knowledge about the genetic basis of ALS has improved and the first effective gene silencing therapies for specific genetic subtypes of ALS are underway. These therapeutic advances underline the need for better access to gene testing for people with ALS. Further research is needed to further map the genetic heterogeneity of ALS and to establish the best strategy for gene testing in a clinical setting.
Bacterial profile of wound site infections and evaluation of risk factors for sepsis among road traffic accident (RTA) patients from Apex trauma centre, Northern India
Authors: Singh Aparna , Singh Patel Sangram , Sahu Chinmoy , Singh Amit Kumar , Tejan Nidhi , Varghese Gerlin , Jamwal Ashima , Singh Pooja , Ghar Malay
Published: July 2024

Background: Among the most significant yet often ignored health issues worldwide are trauma and accidents. India accounts for 11% of global deaths in road accidents, highest in the world according to the World Bank report. There is limited data about the bacterial contamination of road traffic accident (RTA) wounds and their antibiotic susceptibility pattern.
Materials and Methods: This prospective study was conducted in a tertiary care centre in northern India from January 2023 to January 2024. Wound deep swabs or aspirates were collected from RTA patients with traumatic injuries at different time interval.  Gram stain and culture was performed and positive aerobic culture was subjected to antibiotic susceptibility testing. Organism identification was done using MALDI-TOF MS and routine biochemical test. Blood samples were also collected to rule out blood stream infections during follow up if patient became febrile or shown symptoms of systemic infection. Sepsis was defined in those patients who had two or more score in SIRS criteria with positive microbiological culture. Risk factors were evaluated for sepsis on the basis of patient’s vitals, injury characteristics, procalcitonin, glasgow coma scale score, need for mechanical ventilation and complete blood count which was obtained from the patient’s admission file.
Results: A total of 189 wound samples were collected in which 99 (52.38%) samples showed the growth of microorganisms. The aerobic isolates included 69 (69.69%) gram-negative bacilli in which majority were Klebsiella pneumoniae, 28 (28.28%) gram-positive cocci in which majority were Staphylococcus aureus and 02 (2.02%) anaerobic isolates. Among the gram-negative isolates, none of the isolates were resistant to colistin. All Staphylococcus aureus isolates were susceptible to vancomycin, teicoplanin and levonadifloxacin. Sepsis developed in 50 (26.45%) patients. Risk factors evaluated as significant for sepsis were raised procalcitonin level, low glasgow coma scale score (GCS), higher injury severity score (ISS), need for mechanical ventilation, raised qSOFA (quick sequential organ failure assessment) score.
Conclusion: It is essential to ascertain the profile of microorganism isolated from RTA wounds in order to reduce antibiotic resistance and to deliver efficient treatment.
Promethearchaeum syntrophicum gen. nov., sp. nov., an anaerobic, obligately syntrophic archaeon, the first isolate of the lineage ‘Asgard’ archaea, and proposal of the new archaeal phylum Promethearchaeota phyl. nov. and kingdom Promethearchaeati regn. nov.
Authors: Imachi Hiroyuki , Nobu Masaru K. , Kato Shingo , Takaki Yoshihiro , Miyazaki Masayuki , Miyata Makoto , Ogawara Miyuki , Saito Yumi , Sakai Sanae , Tahara Yuhei O. , Takano Yoshinori , Tasumi Eiji , Uematsu Katsuyuki , Yoshimura Toshihiro , Itoh Takashi , Ohkuma Moriya , Takai Ken
Published: July 2024

An anaerobic, mesophilic, syntrophic, archaeon strain MK-D1T, was isolated as a pure co-culture with Methanogenium sp. strain MK-MG from deep-sea methane seep sediment. This organism is, to our knowledge, the first cultured representative of ‘Asgard’ archaea, an archaeal group closely related to eukaryotes. Here, we describe the detailed physiology and phylogeny of MK-D1T and propose Promethearchaeum syntrophicum gen. nov., sp. nov. to accommodate this strain. Cells were non-motile, small cocci, approximately 300–750 nm in diameter and produced membrane vesicles, chains of blebs and membrane-based protrusions. MK-D1T grew at 4–30 °C with optimum growth at 20 °C. The strain grew chemoorganotrophically with amino acids, peptides and yeast extract with obligate dependence on syntrophy with H2-/formate-utilizing organisms. MK-D1T showed the fastest growth and highest maximum cell yield when grown with yeast extract as the substrate: approximately 3 months to full growth, reaching up to 6.7×106 16S rRNA gene copies ml−1. MK-D1T had a circular 4.32 Mb chromosome with a DNA G+C content of 31.1 mol%. The results of phylogenetic analyses of the 16S rRNA gene and conserved marker proteins indicated that the strain is affiliated with ‘Asgard’ archaea and more specifically DHVC1/DSAG/MBG-B and ‘Lokiarchaeota’/‘Lokiarchaeia’. On the basis of the results of 16S rRNA gene sequence analysis, the most closely related isolated relatives were Infirmifilum lucidum 3507LTT (76.09 %) and Methanothermobacter tenebrarum RMAST (77.45 %) and the closest relative in enrichment culture was Candidatus ‘Lokiarchaeum ossiferum’ (95.39 %). The type strain of the type species is MK-D1T (JCM 39240T and JAMSTEC no. 115508). We propose the associated family, order, class, phylum, and kingdom as Promethearchaeaceae fam. nov., Promethearchaeales ord. nov., Promethearchaeia class. nov., Promethearchaeota phyl. nov., and Promethearchaeati regn. nov., respectively. These are in accordance with ICNP Rules 8 and 22 for nomenclature, Rule 30(3)(b) for validation and maintenance of the type strain, and Rule 31a for description as a member of an unambiguous syntrophic association.
Tumor Regression Following Engineered Polyomavirus-Specific T Cell Therapy in Immune Checkpoint Inhibitor-Refractory Merkel Cell Carcinoma
Authors: Asano Yuta , Veatch Joshua , McAfee Megan , Bakhtiari Jakob , Lee Bo , Martin Lauren , Zhang Shihong , Mazziotta Francesco , Paulson Kelly G. , Schmitt Thomas M. , Munkbhat Ariunnaa , Young Cecilia , Seaton Brandon , Hunter Daniel , Horst Nick , Lindberg Marcus , Miller Natalie , Stone Matt , Bielas Jason , Koelle David , Voillet Valentin , Gottardo Raphael , Gooley Ted , Oda Shannon , Greenberg Philip D. , Nghiem Paul , Chapuis Aude G.
Published: July 2024

Although immune check-point inhibitors (CPIs) revolutionized treatment of Merkel cell carcinoma (MCC), patients with CPI-refractory MCC lack effective therapy. More than 80% of MCC express T-antigens encoded by Merkel cell polyomavirus, which is an ideal target for T-cell receptor (TCR)-based immunotherapy. However, MCC often repress HLA expression, requiring additional strategies to reverse the downregulation for allowing T cells to recognize their targets. We identified TCRMCC1that recognizes a T-antigen epitope restricted to human leukocyte antigen (HLA)-A*02:01. Seven CPI-refractory metastatic MCC patients received CD4 and CD8 T cells transduced with TCRMCC1(TTCR-MCC1) preceded either by lymphodepleting chemotherapy or an HLA-upregulating regimen (single-fraction radiation therapy (SFRT) or systemic interferon gamma (IFNγ)) with concurrent avelumab. Two patients who received preceding SFRT and IFNγ respectively experienced tumor regression. One experienced regression of 13/14 subcutaneous lesions with 1 ‘escape’ lesion and the other had delayed tumor regression in all lesions after initial progression. Although TTCR-MCC1cells with an activated phenotype infiltrated tumors including the ‘escape’ lesion, all progressing lesions transcriptionally lacked HLA expression. While SFRT/IFNγ did not immediately upregulate tumor HLA expression, a secondary endogenous antigen-specific T cell infiltrate was detected in one of the regressing tumors and associated with HLA upregulation, indicating in situ immune responses have the potential to reverse HLA downregulation. Indeed, supplying a strong co-stimulatory signal via a CD200R-CD28 switch receptor allows TTCR-MCC1cells to control HLA-downregulated MCC cells in a xenograft mouse model, upregulating HLA expression. Our results demonstrate the potential of TCR gene therapy for metastatic MCC and propose a next strategy for overcoming epigenetic downregulation of HLA in MCC.
Chitosan reduces naturally occurring plant pathogenic fungi and increases nematophagous fungusPurpureocilliumunder field soil conditions
Authors: Lopez-Nuñez Raquel , Prieto-Rubio Jorge , Bautista-Carrascosa Inmaculada , Lidón-Cerezuela Antonio L. , Valverde-Urrea Miguel , Lopez-Moya Federico , Lopez-Llorca Luis V.
Published: July 2024

Chitosan reduced soil pH, conductivity (CE) and cation exchange capacity (CEC) in pots when applied at field capacity. However, chitosan did not affect these soil physicochemical properties, when applied monthly to agricultural fields. Chitosan did not affect field respiration. Increases in field soil respiration found in chitosan plots, especially in spring-midsummer, were not significant. Although, no differences in soil mineral nitrogen were found, chitosan influenced field soil microbiota. Metabarcoding showed chitosan significantly modifies fungal genera composition of ecologically managed field soil. On the contrary, chitosan caused no significant differences in bacterial taxa composition of field soil. Chitosan coacervates increase naturally occurring nematophagous fungusPurpureocilliumin soil respect to chitosan solution treated soil and untreated controls. Besides chitosan reduces inoculum of plant pathogenic fungiAlternariaandFusariumin field soil. Soil microbial co-occurrence network analysis clustering coefficient (CC) for ITS+V1-V2 regions show that the nematophagous fungusPochoniapromoted network clustering into modules. In addition, CC in ITS+V3-V4 regions show that the nematode trapping-fungusOrbiliaand bacteria belonging toAcidimicrobialesandCytophagalesalso significantly contributed to microbial network clustering in field soil. Our results show that chitosan coacervates increase soil nematophagous microbiota and that both nematode egg-parasites and trapping-fungi help to structure soil microbiota.
Co-creating aChoosing WiselyLeaflet Supporting the Reduction of Imaging Usage in Low Back Pain Management - A Multi-Method Study
Authors: Djurtoft Chris , O’Hagan Edel , Laursen Monika D. , Lejbølle Lars , Bisgaard Mia , Johansen Simon K. , Lyng Kristian D. , Hoegh Morten , Pourbordbari Negar , Bruun Malene K. , Eiger Bettina , Larsen Jesper B. , Rathleff Michael S.
Published: July 2024

Introduction

Low back pain is a global health challenge with negative consequences for both individuals and healthcare systems. TheChoosing Wiselyinitiative aims to improve communication between patients and clinicians to promote informed healthcare decisions while avoiding unnecessary tests and treatments. The objective of this project is to co-create an information resource in the form of a leaflet, to be distributed in clinical settings, websites or social media targeting people with low back pain.

Methods

This multi-method study was conducted in four stages: literature search, input from practice consultants, program theory development, and think-aloud interviews with people experiencing low back pain. Each stage was followed by a consensus meeting in which the steering group refined the leaflet based on the emerging knowledge.

Results

The literature search highlighted patients’ need for understandable information about diagnosis, treatment options, and self-management strategies. Practice consultants emphasized concise, relatable content. The program theory identified potential mechanisms and design targets for content creation, development, and implementation of the leaflet, such as addressing patient concerns, reducing diagnostic uncertainty, offering insights into management options, and validation. Think-aloud interviews with 18 people living with low back pain informed the iteration of the leaflet, enhancing language clarification and content comprehension.

Conclusion

We co-created a newChoosing Wiselyleaflet, created with end-users in mind, specifically focused on reducing unnecessary imaging for low back pain. Valuable feedback from end-users prompted significant revisions, underscoring the importance of involving multiple end-user viewpoints into the creation process.
Improved estimates of COVID-19 correlates of protection, antibody decay and vaccine efficacy waning: a joint modelling approach
Authors: Phillips Daniel J. , Christodoulou Maria D. , Feng Shuo , Pollard Andrew J. , Voysey Merryn , Steinsaltz David
Published: July 2024

Reliable estimation of the relationship between COVID-19 antibody levels at the time of exposure and the risk of infection is crucial to inform policy decisions on vaccination regimes. We fit a joint model of anti-spike IgG antibody decay and risk of COVID-19 infection to data from a randomized efficacy trial of the ChAdOx1 nCoV-19 vaccine. Our model improves upon previous analyses by accounting for measurement error, decay in antibody levels and variation between different individuals. We estimated correlates of protection, antibody decay, and vaccine efficacy waning. Increased anti-spike IgG antibody levels at the time of exposure correlate with increased vaccine-induced protection. We estimated vaccine efficacy against symptomatic COVID-19 infection of 88.1% (95% CrI: 77.2, 93.6) at day 35, waning to 60.4% (44.6, 71.0) at day 189 since the second dose. We report that longer intervals between the first and second vaccine dose give lasting increased protection, and observe lower efficacy in individuals aged ≥70 years from around 3 months after second dose. Our methods can be used in future vaccine trials to help inform the timings and priority of vaccine administration against novel diseases.
Intratumoral T-cell composition predicts epcoritamab-based treatment efficacy in B-cell non-Hodgkin lymphomas
Authors: Falchi Lorenzo , Rahman Jahan , Melendez Lauren , Douglas Monifa , Amador Walter Ramos , Hamlin Paul , Kumar Anita , Hoehn Daniela , Lin Ya-Hui , Gao Qi , Roshal Mikhail , Ewalt Mark D. , Dogan Ahmet , Greenbaum Benjamin , Salles Gilles A. , Vardhana Santosha A.
Published: July 2024

Leveraging endogenous tumor-resident T-cells for immunotherapy using bispecific antibodies (BsAb) targeting CD20 and CD3 has emerged as a promising therapeutic strategy for patients with B-cell non-Hodgkin lymphomas. However, features associated with treatment response or resistance are unknown. To this end, we analyzed data from patients treated with epcoritamab-containing regimens in the EPCORE NHL-2 trial (NCT04663347). We observed downregulation of CD20 expression on B-cells following treatment initiation both in progressing patients and in patients achieving durable complete responses (CR), suggesting that CD20 downregulation does not universally predict resistance to BsAb-based therapy. Single-cell immune profiling of tumor biopsies obtained following one cycle of therapy revealed substantial clonal expansion of cytotoxic CD4+ and CD8+ T-cells in patients achieving CR, and an expansion of follicular helper and regulatory CD4+ T-cells in patients whose disease progressed. These results identify distinct tumor-resident T-cell profiles associated with response or resistance to BsAb therapy.
Short-Term Relative Effectiveness of Homologous NVX-CoV2373 and BNT162b2 COVID-19 Vaccinations in South Korea
Authors: Gwak Eunseon , Choe Seung-Ah , Bolormaa Erdenetuya , Choe Young June , Wang Chengbin , Fix Jonathan , Vadivale Muruga , Rousculp Matthew D.
Published: July 2024

To estimate the relative, short-term effectiveness of NVX-CoV2373 versus BNT162b2 (Pfizer– BioNTech) in preventing SARS-CoV-2 infection and severe COVID-19 disease during the Omicron variant dominance in South Korea. Retrospective cohort-study among ≥12-year-olds using the K-COV-N database, which links COVID-19 vaccine registry data with health insurance claims data. The Cox proportional-hazards model and inverse probability of treatment weighting were employed to calculate adjusted hazard ratios (aHRs). Among homologous primary-series NVX-CoV2373 versus BNT162b2 recipients, the aHR was 0.86 (95% CI: 0.82–0.91) for all laboratory-confirmed and 0.80 (95% CI: 0.48–1.33) for severe infections. Among homologous 1st-booster recipients, it was 0.74 (95% CI: 0.61–0.90) for all laboratory-confirmed and 0.48 (95% CI: 0.12–1.92) for severe infections. At 30-days post-immunization, we observed homologous, NVX-CoV2373 primary-series and 1st-booster offered added protection against SARS-CoV-2 infection versus BNT162b2; while there was numerically lower risk of severe disease among NVX-CoV2373-vaccinated, no statistically significant differences were observed.
Perceived risk for hypertension and associated factors among adult persons living with HIV in Kamuli district, Uganda
Authors: Buyinza Thomas , Ssengooba Freddie , Mayega Roy William , Nankya Mutyoba Joan , Warugaba Birungi Shamim , Mutole Geofrey , Ndejjo Rawlance
Published: July 2024

Background

Persons living with Human Immunodeficiency Virus (PLHIV) are at a higher risk of developing hypertension. Preventive measures can be taken to lower this risk, but it is important for PLHIV to be aware of this risk. However, it is unclear whether PLHIV perceive themselves to be at risk for hypertension, and if they do, it is unknown to what extent they perceive this risk. This information is crucial in designing and implementing appropriate preventive measures for hypertension targeting this high-risk population. Our study aimed to provide evidence on the level of risk perception for hypertension and associated factors among PLHIV in Kamuli District.

Methodology

This was a cross-sectional study conducted among 392 adult PLHIV in Kamuli District. The participants were selected using consecutive sampling and pretested structured questionnaires were used to collect data which later analysed in STATA version 15.0. Descriptive analysis was carried out and data was summarized using frequencies and means. Modified Poisson regression was used to determine factors independently associated with low-risk perception for hypertension.

Result

More than half, 68.1% (267/392) perceived themselves to be at low-risk for hypertension. Factors associated with low-risk perception were: residing in peri-urban area (APR=1.23; 95%CI: 1.04 −1.46) and urban areas (APR=0.73; 95%CI:0.54-0.99); having low knowledge of hypertension (APR=1.98; 95%CI: 1.55-2.53); low trust for health workers (APR=1.13; 95%CI: 1.01-1.25); having no other NCD (APR=1.38; 95%CI: 1.00-1.89); having no family history of hypertension (APR=1.42; 95%CI: 1.20-1.68); and consumption of sufficient fruits/vegetables (APR=1.13; 95%CI: 1.01-1.27).

Recommendation

There is need to implement appropriate health education programs specifically tailored to increasing knowledge and risk perception for hypertension among PLHIV. Health workers can integrate routine risk assessments into HIV care to identify PLHIV who are at very high-risk of developing hypertension and provide them with personalized care. This can influence adoption of hypertension preventive measures.
Relationship between midwifery density and midwifery regulatory environments in International Confederation of Midwives member countries
Authors: Clark Emma Virginia , LaNoue Marianna , Clouse Kate , Zuber Alexandra , Neal Jeremy
Published: July 2024

Background

Midwives are a cost-effective solution for reducing preventable maternal death, but barriers to their recruitment, training, deployment, and retention exist. Improved midwifery regulation is proposed to address these challenges through activities related to education and qualification, licensure, registration/re-licensure, and scope and conduct of practice. However, no quantitative analysis of the associations between midwifery regulation and workforce density in low- and middle-income countries has been conducted, limiting actionable insights for policymakers. The objective of this study was to evaluate the relationship between midwifery regulatory environments and midwifery workforce densities (midwives per 10,000 population) in International Confederation of Midwives member countries.

Methods

The study used secondary data from the 2019 Global Midwives’ Associations Map Survey to perform a cross-sectional analysis of 103 International Confederation of Midwives member countries. To operationalize the strength of a country’s midwifery regulatory environment, we used a previously developed Midwifery Regulatory Environment Index. We conducted multivariable linear regression analysis to evaluate the relationship between this index and country-level midwifery density, available from the National Health Workforce Accounts.

Results

Midwifery regulatory environments are significantly associated with midwifery workforce densities across countries. For every 1-point increase in the Midwifery Regulatory Environment Index (indicating activities in at least one additional regulatory domain), midwifery density increased by 0.66 midwives per 10,000 population (p = 0.011). This effect decreased to 0.41 midwives per 10,000 population yet remained significant even after controlling for country level income, per capita health spending, income inequality, and human development index (p = 0.04).

Conclusion

Stronger regulatory environments are associated with higher densities of midwives, even when controlling for potential confounding factors such as country-level income and health spending. This relationship suggests that policymakers should invest in midwifery regulation to improve maternal health outcomes.
MAJIQ V3 offers improvements in accuracy, performance, and usability for splicing analysis from RNA sequencing
Authors: Aicher Joseph K , Slaff Barry , Jewell San , Barash Yoseph
Published: July 2024

RNA splicing plays important roles in cell-type-specific expression of gene isoforms and is causally linked to numerous diseases. Previously, our group developed MAJIQ V1 and V2 for RNA splicing detection, quantification, and visualization from RNA sequencing. Here we report an update, MAJIQ V3, that offers several improvements in time, memory, accuracy, and usability. We demonstrate the benefits of MAJIQ V3 using GTEx data for different analysis scenarios involving different dataset sizes.
Prevalence of GIT nematodes and associated risk factors of exotic chickens in selected farm of poultry in and around Ambo, Ethiopia
Authors: Temesgen Abraham Belete , Wassie Zerihun Getie , Abebe Saleamlak
Published: July 2024

Poultry are raised worldwide in backyards and commercial systems with fewer social and religious taboos than other livestock. However, the chicken industry faces significant challenges from nematode parasites. A cross-sectional study with a random sampling technique was conducted from April to June 2019 to estimate gastrointestinal (GI) nematode parasites in chickens in selected farms in and around Ambo, Ethiopia. The fecal analysis results revealed that out of 70 samples collected, 60% were positive for gastrointestinal (GI) nematode eggs. Prevalence varied significantly by body condition, with the highest rates in chickens in poor condition (78.57%), followed by medium (54.54%) and good condition (40%). Location also played a significant role, with Ambo University Poultry Farm having the highest prevalence (83.87%), followed by Abebe Private Farm (55%) and Guder Campus Poultry Farm (26.31%). The main nematode species identified wereAscaridia galli(57.1%) andHeterakis gallinarum(2.9%). Infestation rates differed significantly by sex, age, location, and body condition, with males having higher rates ofAscaridia galli(61.53%) than females (56.14%), andHeterakis gallinarumexclusively affecting females (3.51%). Adults showed significantly higher rates ofAscaridia galli(85.71%) than young chickens (38.09%), with some infestation ofHeterakis gallinarum(7.14%) observed in adults but absent in young chickens. This prevalence rate suggests limited awareness among chicken producers and insufficient control strategies in the study area. Hence, implementing targeted control strategies is advisable.
YAP1 Contributes to The Development of Contractile Force and Sarcomere Maturation in Human Pluripotent Stem Cell-Derived Cardiomyocytes
Authors: Vinarsky Vladimir , Pagliari Stefania , Martino Fabiana , Mazzotti Cristina , Jirakova Katerina , Garlikova Zuzana , Iuri Enrico Di , Kytyr Daniel , Benzoni Patrizia , Arici Martina , Metallo Alessia , Zeevaert Kira , Barbuti Andrea , Wagner Wolfgang , Rocchetti Marcella , Forte Giancarlo
Published: July 2024

Background

Perspective regenerative therapies for injured myocardium focus on reactivating developmental processes to regenerate damaged contractile tissue. In animal models, the Hippo pathway was shown to improve heart regeneration after myocardial infarction, possibly by expanding the pool of cardiomyocytes. We hypothesized that activating the Hippo pathway’s downstream effector, Yes Associated Protein (YAP1), may have effects beyond promoting proliferation in human cardiomyocytes. We have therefore investigated how YAP1 influences human cardiomyocyte maturation, sarcomere structure, electrophysiological properties, their response to mechanical stimuli, intracellular Ca2+″ dynamics and force development using models of cardiomyocytes derived from pluripotent stem cells.

Methods

We employed genetic models of YAP1 deficient human embryonic and induced pluripotent stem cells, cardiomyocyte differentiation, compliant cultivation substrates, mechanical actuation, ECM deposition, super resolution microscopy, electrophysiological measurements and engineered heart tissues (EHTs) to characterize the effects of YAP1 deficiency on cardiomyocytes during maturation. We also used full length YAP1 re- expression to rescue the effects of YAP1 deficiency in contracting cardiomyocytes.

Results

YAP1 contributes to cardiomyocyte maturation, participates in the formation and alignment of myofibrils, as well as in the maturation of electrophysiological properties. The net effect of YAP1 deficiency in cardiomyocytes is the inability to respond to physiological stimuli by compensatory growth resulting in reduced force development. Additionally, YAP1 reactivation in contracting cardiomyocytes leads to rescue of myofibril maturation.

Conclusions

This research demonstrates that YAP1 activity is essential to promote cardiomyocyte maturation, contractility, and response to regeneration inducing stimuli.
Self-Organization of Sinusoidal Vessels in Pluripotent Stem Cell-derived Human Liver Bud Organoids
Authors: Saiki Norikazu , Nio Yasunori , Yoneyama Yosuke , Kawamura Shuntaro , Iwasawa Kentaro , Kawakami Eri , Araki Kohei , Fukumura Junko , Sakairi Tsuyoshi , Kono Tamaki , Ohmura Rio , Koido Masaru , Funata Masaaki , Thompson Wendy L. , Cruz-Encarnacion Pamela , Chen Ya-Wen , Takebe Takanori
Published: July 2024

The induction of tissue-specific vessels inin vitroliving tissue systems remains challenging. Here, we directly differentiated human pluripotent stem cells into CD32b+putative liver sinusoidal progenitors (iLSEP) by dictating developmental pathways. By devising an inverted multilayered air-liquid interface (IMALI) culture, hepatic endoderm, septum mesenchyme, arterial and sinusoidal quadruple progenitors self-organized to generate and sustain hepatocyte-like cells neighbored by divergent endothelial subsets composed of CD32blowCD31high, LYVE1+STAB1+CD32bhighCD31lowTHBD-vWF-, and LYVE1-THBD+vWF+cells. Wnt2 mediated sinusoidal-to-hepatic intercellular crosstalk potentiates hepatocyte differentiation and branched endothelial network formation. Intravital imaging revealed iLSEP developed fully patent human vessels with functional sinusoid-like features. Organoid-derived hepatocyte- and sinusoid-derived coagulation factors enabled correction ofin vitroclotting time with Factor V, VIII, IX, and XI deficient patients’ plasma and rescued the severe bleeding phenotype in hemophilia A mice upon transplantation. Advanced organoid vascularization technology allows for interrogating key insights governing organ-specific vessel development, paving the way for coagulation disorder therapeutics.
Sensitive detection of synthetic response to cancer immunotherapy driven by gene paralog pairs
Authors: Dong Chuanpeng , Zhang Feifei , He Emily , Ren Ping , Verma Nipun , Zhu Xinxin , Feng Di , Zhao Hongyu , Chen Sidi
Published: July 2024

Emerging immunotherapies such as immune checkpoint blockade (ICB) and chimeric antigen receptor T-cell (CAR-T) therapy have revolutionized cancer treatment and have improved the survival of patients with multiple cancer types. Despite this success many patients are unresponsive to these treatments or relapse following treatment. CRISPR activation and knockout (KO) screens have been used to identify novel single gene targets that can enhance effector T cell function and promote immune cell targeting and eradication of tumors. However, cancer cells often employ multiple genes to promote an immunosuppressive pathway and thus modulating individual genes often has a limited effect. Paralogs are genes that originate from common ancestors and retain similar functions. They often have complex effects on a particular phenotype depending on factors like gene family similarity, each individual gene’s expression and the physiological or pathological context. Some paralogs exhibit synthetic lethal interactions in cancer cell survival; however, a thorough investigation of paralog pairs that could enhance the efficacy of cancer immunotherapy is lacking. Here we introduce a sensitive computational approach that uses sgRNA sets enrichment analysis to identify cancer-intrinsic paralog pairs which have the potential to synergistically enhance T cell-mediated tumor destruction. We have further developed an ensemble learning model that uses an XGBoost classifier and incorporates features such as gene characteristics, sequence and structural similarities, protein-protein interaction (PPI) networks, and gene coevolution data to predict paralog pairs that are likely to enhance immunotherapy efficacy. We experimentally validated the functional significance of these predicted paralog pairs using double knockout (DKO) of identified paralog gene pairs as compared to single gene knockouts (SKOs). These data and analyses collectively provide a sensitive approach to identify previously undetected paralog pairs that can enhance cancer immunotherapy even when individual genes within the pair has a limited effect.