bluuebunny/crossref_metadata_2025_split huggingface dataset:
Three-Year Efficacy and Safety of Mirikizumab Following 152 Weeks of Continuous Treatment for Ulcerative Colitis: Results From the LUCENT-3 Open-Label Extension Study
Authors: Sands Bruce E , D’Haens Geert , Clemow David B , Irving Peter M , Johns Jordan T , Gibble Theresa Hunter , Abreu Maria T , Lee Scott D , Hisamatsu Tadakazu , Kobayashi Taku , Dubinsky Marla C , Vermeire Severine , Siegel Corey A , Peyrin-Biroulet Laurent , Moses Richard E , Milata Joe , Panaccione Remo , Dignass Axel 
Published: October 2024

Abstract

Background
Mirikizumab, a p19-directed interleukin-23 monoclonal antibody, has demonstrated induction of clinical remission at week 12 with maintenance through week 104 in patients with moderately-to-severely active ulcerative colitis (UC). Results are presented from the LUCENT-3 open-label extension study through week 152.

Methods
Of 868 LUCENT clinical trial program mirikizumab-treated induction patients, 544 were responders of whom 365 were rerandomized to mirikizumab maintenance. Of these, 324 completed week 52 and 316 entered extension treatment (286 week 52 responders; 179 week 52 remitters). Efficacy and safety outcomes are reported for mirikizumab-treated LUCENT-3 participants, including biologic-failed patients, with data for week 52 maintenance responders/remitters. Discontinuations or missing data were handled by nonresponder imputation, modified nonresponder imputation (mNRI), and observed cases.

Results
Using mNRI, 81.6% of week 52 responders demonstrated clinical response at week 152. Week 152 remission rates for week 52 responders included clinical (56.1%), corticosteroid-free (CSF; 54.5%), endoscopic (61.0%), histologic-endoscopic mucosal remission (HEMR; 52.6%), symptomatic (74.9%), and bowel urgency (BU; 58.6%). At week 152, 53.3% of week 52 responders achieved histologic-endoscopic mucosal improvement (HEMI) and 74.3% achieved BU clinically meaningful improvement (CMI). Among week 52 remitters, 85.4% showed a clinical response at week 152, with clinical (70.1%), CSF (68.9%), endoscopic (72.0%), HEMR (63.4%), symptomatic (81.4%), and BU (60.8%) remission. At week 152, among week 52 remitters, 64.0% of patients achieved HEMI and 75.6% achieved BU CMI. Stool frequency, rectal bleeding, BU, and abdominal pain score reductions from induction baseline to maintenance week 52 were sustained through week 152 for week 52 completers. Overall, in the safety population, 7.4% of patients reported severe adverse events (AEs); 5.3% discontinued treatment due to AEs. AEs of special interest included opportunistic infection (1.8%), hepatic disorders (3.2%), cerebrocardiovascular events (1.5%), and malignancy (0.3%). Patients with antidrug antibodies reduced over time from 23.6% in year 1 to 3.2% in year 3.

Conclusions
Symptomatic, clinical, endoscopic, histologic, and quality-of-life outcomes support long-term sustained benefit of mirikizumab treatment up to 152 weeks in patients with UC, including biologic-failed patients, with no new safety concerns.

Clinical Trial Registry
ClinicalTrials.gov: NCT03518086; NCT03524092; NCT03519945.
Troglitazone Reduction of Intracellular Mycobacterium tuberculosis Survival Via Macrophage Autophagy Through LKB1-AMPKα Signaling
Authors: Bi Jing , Guo Qinglong , Gong Yaqi , Chen Xi , Wu Haojia , Song Li , Xu Yating , Ou Min , Wang Zhaoqin , Chen Jiean , Jiang Chenran , Liu Aimei , Li Guobao , Zhang Guoliang 
Published: October 2024

Abstract
Tuberculosis caused by Mycobacterium tuberculosis (Mtb), results in significant disease and death worldwide. Host-directed therapy, including conventional drugs, is a promising antituberculosis strategy that shows synergistic antibacterial effects when combined with antituberculosis drugs. Here, the mycobactericidal effect of 3 antidiabetic drugs was examined. Of these, only troglitazone (Trog) enhanced the antimycobacterial effect in vitro and in vivo. This was due to Trog-mediated autophagy activation. Moreover, a knock-down experiment revealed that Trog activated autophagy and exhibited antimycobacterial activity through the serine/threonine-protein kinase STK11 (LKB1)-5'-AMP-activated protein kinase (AMPK) signaling pathway. Molecular docking and coimmunoprecipitation experiments demonstrated that Trog promoted LKB1 phosphorylation and activation by targeting STE20-related kinase adapter protein alpha (STRADA). Finally, we found that Trog inhibited the intracellular survival of clinical isoniazid-resistant Mtb, and the combination of Trog and isoniazid showed additive antibacterial effects against Mtb H37Rv. Taken together, antidiabetic Trog may be repurposed as a candidate for host-directed therapy and combined with first-line antituberculosis drugs.
Soil nutrient amendment increases the potential for inter-kingdom resource competition among foliar endophytes
Authors: Hansen Zoe A , Fulcher Michael R , Wornson Nicholas , Spawn-Lee Seth A , Johnson Mitch , Song Zewei , Michalska-Smith Matthew , May Georgiana , Seabloom Eric W , Borer Elizabeth T , Kinkel Linda L 
Published: October 2024

Abstract
Foliar endophytes play crucial roles in large-scale ecosystem functions such as plant productivity, decomposition, and nutrient cycling. While the possible effects of environmental nutrient supply on the growth and carbon use of endophytic microbes have critical implications for these processes, these impacts are not fully understood. Here, we examined the effects of long-term elevated nitrogen, phosphorus, potassium, and micronutrient (NPKμ) supply on culturable bacterial and fungal foliar endophytes inhabiting the prairie grass Andropogon gerardii. We hypothesized that elevated soil nutrients alter the taxonomic composition and carbon use phenotypes of foliar endophytes and significantly shift the potential for resource competition among microbes within leaves. We observed changes in taxonomic composition and carbon use patterns of fungal, but not bacterial, endophytes of A. gerardii growing in NPKμ-amended versus ambient conditions. Fungal endophytes from NPKμ-amended plants had distinct carbon use profiles and demonstrated greater specialization across carbon sources compared to control plots. Resource niche overlap between bacterial and fungal endophytes also increased with plot nutrient supply, suggesting enhanced potential for inter-kingdom competition. Collectively, this work suggests that soil nutrient enrichment alters how fungal endophyte communities exist in the foliar environment, with potentially significant implications for broad-scale ecosystem function.
Antibiotic use and adherence to the WHO AWaRe guidelines across 16 hospitals in Zambia: a point prevalence survey
Authors: Chizimu Joseph Yamweka , Mudenda Steward , Yamba Kaunda , Lukwesa Chileshe , Chanda Raphael , Nakazwe Ruth , Shawa Misheck , Chambaro Herman , Kamboyi Harvey K , Kalungia Aubrey Chichonyi , Chanda Duncan , Fwoloshi Sombo , Jere Elimas , Mufune Tiza , Munkombwe Derick , Lisulo Peter , Mateele Tebuho , Thapa Jeewan , Kapolowe Kenneth , Sinyange Nyambe , Sialubanje Cephas , Kapata Nathan , Mpundu Mirfin , Masaninga Freddie , Azam Khalid , Nakajima Chie , Siyanga Makomani , Bakyaita Nathan Nsubuga , Wesangula Evelyn , Matu Martin , Suzuki Yasuhiko , Chilengi Roma 
Published: October 2024

Abstract

Background
The inappropriate use of antibiotics in hospitals contributes to the development and spread of antimicrobial resistance (AMR). This study evaluated the prevalence of antibiotic use and adherence to the World Health Organization (WHO) Access, Watch and Reserve (AWaRe) classification of antibiotics across 16 hospitals in Zambia.

Methods
A descriptive, cross-sectional study employing the WHO Point Prevalence Survey (PPS) methodology and WHO AWaRe classification of antibiotics was conducted among inpatients across 16 hospitals in December 2023, Zambia. Data analysis was performed using STATA version 17.0.

Results
Of the 1296 inpatients surveyed in the 16 hospitals, 56% were female, and 54% were aged between 16 and 50 years. The overall prevalence of antibiotic use was 70%. Additionally, 52% of the inpatients received Watch group antibiotics, with ceftriaxone being the most prescribed antibiotic. Slightly below half (48%) of the inpatients received Access group antibiotics. Compliance with the local treatment guidelines was 53%.

Conclusions
This study found a high prevalence of prescribing and use of antibiotics in hospitalized patients across the surveyed hospitals in Zambia. The high use of Watch group antibiotics was above the recommended threshold indicating non-adherence to the WHO AWaRe guidelines for antibiotic use. Hence, there is a need to establish and strengthen antimicrobial stewardship programmes that promote the rational use of antibiotics in hospitals in Zambia.
Postmortem diphenhydramine blood concentrations in children
Authors: Wallage H. Rachelle , Elliot Marie 
Published: October 2024

Abstract
Diphenhydramine has been available for decades in non-prescription formulations for the treatment of allergic reactions, insomnia, and symptomology associated with colds. In addition, dimenhydrinate, a precursor to diphenhydramine, is available in preparations for the treatment of nausea and vomiting. Diphenhydramine and other first-generation antihistamines are being replaced by second- and third-generation antihistamines, which are associated with fewer side effects, notably the lack of drowsiness; however, there are still a variety of therapeutic uses that have persisted in both adults and children. In this study, postmortem blood concentrations of diphenhydramine were determined, by liquid chromatography–tandem mass spectrometry, in seven children with concentrations ranging from 0.051 to 2.6 mg/l. The cause of death in two cases was attributed, at least in part, to diphenhydramine toxicity, while diphenhydramine detection in five cases was considered incidental to the cause of death.
Engaging Burn Survivors, Their Families, and the Burn Community in Patient-Centered Outcomes Research: A Burn Survivor- and Burn Community Stakeholder-Generated and Prioritized Research Agenda
Authors: Thompson Callie M , Acton Amy , Alexander William , Beyene Robel , Brownson Elisha G , Carrougher Gretchen J , Christensen Brennan , Hoarle Kimberly , Irven Jessica , Johnson Laura S , Kirkham Monica P , Lewis Giavonni M , Lucio J Xavier , Matagi Samoana , Morris Laura , Prazak Ann Marie B , Price-Smith Erin , Stuchly Bridget , Webb Crystal , Quinn Kristen ,   Burn Survivor-Centered Outcomes Research (BSCOR) Collaborative, Bergfeld Megan , Haley Mark , Johnson Erin , Matagi Fatu , Steffensen Dan 
Published: October 2024

Abstract
Burn survivors are involved in burn research, but typically in the role of research subject. We believe that the outcomes and impact of burn research can be improved by engaging survivors as collaborators in the planning, implementation, and dissemination of burn research. The goal of this work was to produce the first burn research agenda generated and prioritized by burn survivors and other stakeholders from the burn community. A series of structured focus groups covering 5 topics (Patient and Family Education, Aftercare, Navigating the Healthcare System, Recovery: Physical and Psychosocial, and Barriers to Research) were held with burn survivors and their family members. Specific research questions/topics were identified from the transcripts and prioritized via an anonymous survey of burn survivors, their caregivers, and other stakeholders from the burn community. From these sessions, 37 specific research questions/topics were identified and ranked. In addition, 19 research barriers were identified and ranked. This work presents an innovative approach to burn research through co-production with survivors and other stakeholders. Burn survivors and their caregivers are experts in their lived experiences. By involving them in burn research as collaborators and contributors from the very first steps of research and throughout the continuum of the research planning, conducting projects, and distributing findings, we believe that the research will be both more successful and more impactful. We have taken the first steps in burn research co-production with this novel stakeholder-generated research agenda for the burn community.
CD56 does not contribute to the antitumor, tissue homing, and glycolytic capacity of human NK cells
Authors: Portillo Ana L , Rojas Eduardo A , Mehboob Misaal , Moinuddin Adnan , Balint Elizabeth , Feng Emily , Silvestri Christopher , Vahedi Fatemeh , Ritchie Tyrah M , Mansour Alexa J , Bramson Jonathan L , Ashkar Ali A 
Published: October 2024

Abstract
Natural killer (NK) cells are critical innate immune cells involved in the clearance of virally infected and malignant cells. Human NK cells are distinguished by their surface expression of CD56 and a lack of CD3. While CD56 expression and cell surface density has long been used as the prototypic marker to characterize primary human NK cell functional subsets, the exact functional role of CD56 in primary human NK cells is still not fully understood. Here, we eliminated the expression of CD56 in human ex vivo expanded NK cells (CD56bright) using CRISPR/Cas9 in order to assess the function of CD56 in this highly activated and cytotoxic NK cell population. We show that the expression of CD56 has no effect on NK cell proliferative capacity or expression of various activation and inhibitory markers. Further, CD56 does not contribute to NK cell–mediated cytotoxicity, inflammatory cytokine production, or the ability of NK cells to control tumor engraftment in vivo. We also found that while deletion of CD56 did not impact NK cell glycolytic metabolism, it did increase NK cell reliance on oxidative phosphorylation. Last, CD56 does not alter expanded NK cell in vivo tissue trafficking. Our results indicate that while CD56 expression could be used to indicate a hyperfunctional state of NK cells, it does not directly influence the antitumor functions of expanded NK cells.
Barriers to healthy behaviors: perspectives from teens with comorbid Type 1 diabetes and overweight/obesity, caregivers, and pediatric endocrinologists
Authors: Warnick Jennifer L , Darling Katherine E , Swartz Topor Lisa , Jelalian Elissa 
Published: October 2024

Abstract

Objectives
This study aimed to understand barriers to engagement in healthy lifestyle behaviors among adolescents with comorbid Type 1 diabetes (T1D) and overweight/obesity (n = 12), their caregivers (n = 12), and pediatric endocrinologists (n = 9).

Methods
Participants (n = 33) completed individual, semi-structured interviews. Interviews were transcribed verbatim, and applied thematic analysis was used to analyze the interview data.

Results
Results from adolescents, caregivers, and pediatric endocrinologists revealed three thematic barriers to healthy lifestyle behaviors for adolescents with T1D and overweight/obesity: (1) discomfort with aspects of T1D that draw attention to the self; (2) T1D as a barrier to engagement in healthy lifestyle behaviors; and (3) physiological dysregulation due to T1D impacting health behaviors.

Conclusions
Results identify perceived limitations to engaging in recommended healthy lifestyle behaviors and diabetes management concurrently. Results may assist research and clinical care in identifying supports and guidance needed to support adolescents in meeting behavioral recommendations for their health.
Primary Adjunctive Corticosteroids in the Acute Management of High-Risk Kawasaki Disease in a North American Cohort
Authors: Wang Alan P , Khan Huthaifah , Dong Siyuan , Kim Kwang-Youn A , Jone Pei-Ni , Lee Simon , Shulman Stanford , Innocentini Nancy , Zielinski Tresa , Rowley Anne H 
Published: October 2024

Abstract

Background
Primary adjunctive therapy with corticosteroids has been shown to reduce coronary artery (CA) abnormalities in high-risk Kawasaki disease (KD) patients in Japan (the randomized control trial to assess immunoglobulin plus steroid efficacy [RAISE] study). We evaluated their effect on outcomes in North American patients with high-risk KD.

Methods
We performed a single-center retrospective review of high-risk KD patients between 2010 and 2023. From 2017 to 2023, adjunctive corticosteroids in a modified RAISE regimen (mRAISE) were given to high-risk patients as primary adjunctive therapy with intravenous gammaglobulin (IVIG) and aspirin. We compared CA outcomes in these patients and those presenting from 2010 to 2016, when mRAISE therapy was not administered.

Results
A total of 221 high-risk KD patients were treated at our institution between 2010 and 2023. Among these, 83 received the mRAISE regimen and 138 did not (no corticosteroid, n = 82, corticosteroid in a non-mRAISE regimen, n = 56). There were no significant differences in CA outcomes in the mRAISE and non-mRAISE groups. Patients receiving the mRAISE regimen were significantly less likely to receive more than one dose of IVIG when compared to those who did not receive this regimen (11% vs 33%, p &lt; .001).

Conclusions
Use of adjunctive primary therapy with corticosteroids in a mRAISE regimen in high-risk KD patients resulted in significantly decreased IVIG retreatment.
Global burden, trends and inequalities for typhoid and paratyphoid fever among children younger than 15 years over the past 30 years
Authors: Wang Haitao , Zhang Ping , Zhao Qi , Ma Wei 
Published: October 2024

Abstract

Background
Typhoid and paratyphoid fever, collectively known as enteric fever, are systemic infections caused by Salmonella enterica and are highly prevalent in children. We aimed to describe the global burden, trends and inequalities of enteric fever among children under 15 years from 1990 to 2019 based on data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019).

Methods
In this secondary analysis of GBD 2019, we extracted data for incident cases, deaths and disability-adjusted life-years (DALYs) as measures of enteric fever burden. We estimated the average annual percentage changes (AAPCs) in enteric fever incidence, mortality and DALYs rate to quantify trends over time. Cross-country inequalities in enteric fever incidence were measured using the slope index of inequality and concentration index.

Results
In 2019, the global cases of typhoid and paratyphoid were 4 833 282 and 1 793 172, respectively, both lower than those in 1990. On secondary analysis, paratyphoid incidence decreased at a faster rate than typhoid from 1990 to 2009, whereas the incidence of paratyphoid (AAPC = −3.78, 95% CI: −4.07, −3.49) declined slower than that of typhoid (AAPC = −4.32, 95% CI: −4.50, −4.13) from 2010 to 2019 (P &lt; 0.05) at the global level. The incidence burden of enteric fever increased in Australasia (AAPC = 1.28, 95% CI: 0.77, 1.78) and Western Europe (AAPC = 0.77, 95% CI: 0.44, 1.11). Death and DALYs burden in low socio-demographic index (SDI) region showed a stable trend. A significant reduction in SDI-related inequality occurred, with the concentration index falling from −0.31 in 1990 to −0.22 in 2019.

Conclusions
The global disease burden of enteric fever and the magnitude of inequalities across countries have declined since 1990, but low SDI countries remain a region of concern. Travellers from Oceania and Western Europe to endemic regions should be particularly aware of the risk of enteric fever.
Travel to malaria-endemic areas: using digital geo-location to assess potential exposure risks and health behaviours
Authors: Farnham Andrea , Hatz Christoph , Fehr Jan , Baroutsou Vasiliki , Puhan Milo A , Veit Olivia , Bühler Silja 
Published: October 2024

Abstract

Background
Travellers frequently visit popular destinations like Brazil, India, Peru, Thailand and Tanzania, each presenting varying malaria risks. The extent to which travellers enter high-risk malaria-endemic areas in destinations with heterogeneous malaria risk remains unclear. We used geo-location via a smartphone application to (i) describe where travellers go within countries with heterogeneous malaria risk (Brazil, India, Peru, Thailand) and (ii) compare mosquito bite prevention behaviours between these destinations and Tanzania, considered entirely high risk for malaria.

Methods
This analysis is a sub-study of the Tracking of Urgent Risks in Swiss Travellers (TOURIST2) cohort, which prospectively recruited 1000 travellers (≥18 years, travelling ≤4 weeks) from Swiss travel clinics (Zurich and Basel) between September 2017 and April 2019. We included 734 travellers to Brazil, India, Peru, Thailand and Tanzania who provided geo-location data. Daily health and geo-location data were collected using a smartphone application. Malaria risk was categorized using 2022 malaria maps from the Swiss Expert Committee for Travel Medicine.

Results
Of the 734 travellers, 525 travelled to Brazil, India, Peru and Thailand and 225 to Tanzania. In Brazil, India, Peru and Thailand, only 2% (n = 13) visited high-risk malaria areas. In Peru, 4% (n = 4) visited a high-risk area; in Brazil, 3% (n = 6); in Thailand, 2% when crossing the border into Myanmar (n = 3); and in India, 0%. Travellers to high-risk areas were more often male (62%), slightly older (median age 42.0) and planned longer trips (median 23.0 days) than other travellers. No participants were diagnosed with malaria. Travellers to Brazil, India, Peru and Thailand used mosquito bite prevention measures less frequently than travellers to Tanzania. Those in Tanzania had higher, but still suboptimal, use of insect spray (65% of travel days).

Conclusions
Travellers to Brazil, India, Peru and Thailand rarely visited high-risk malaria areas, and their adherence to mosquito bite prevention measures was generally low. In Tanzania, adherence was higher but still suboptimal.
Introduction
Authors: Bridge Michael , Gullifer Louise , Lomnicka Eva 
Published: October 2024

Abstract
This chapter provides a general account of the structure of proprietary security, whether it is security granted by a debtor or quasi-security, amounting to a reservation of property rights by a party providing financial accommodation. Security granted by a debtor includes mortgages and charges, of which in practice charges are the more important, as well as possessory security in the form of pledge and liens arising by operation of law. The reservation of property rights includes devices such as retention of title clauses and structures such as hire purchase and finance leases. The chapter lays emphasis on the contribution of equity to the law of security and deals with the background to the law, involving issues of insolvency, form and substance, and recharacterization risk.
Types of Interest
Authors: Bridge Michael , Gullifer Louise , Lomnicka Eva 
Published: October 2024

Abstract
This chapter considers the conceptual and practical differences between security interests and absolute interests which perform the same economic function as security interests. Practical examples of different situations in which absolute interests perform this function are analysed, including both by retention and transfer of title. The chapter examines the approach of the courts to characterization of interests labelled in a contractual structure as absolute (or, more rarely, security) interests in cases where that label is challenged. The general approach of the courts is discussed and compared to the approach to characterization in the context of fixed and floating charges. The approach in relation to particular financing structures is also examined.