bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.

Summary
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.
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

AbstractAlthough 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

AbstractChitosan 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

AbstractIntroductionLow 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.MethodsThis 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.ResultsThe 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.ConclusionWe 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

AbstractReliable 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

SummaryLeveraging 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

AbstractTo 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

AbstractBackgroundPersons 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.MethodologyThis 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.ResultMore 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).RecommendationThere 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

AbstractBackgroundMidwives 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.MethodsThe 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.ResultsMidwifery 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).ConclusionStronger 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

AbstractSummaryRNA 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.