bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics, pharmacodynamics, safety, and efficacy of crizanlizumab in patients with sickle cell disease: final results from the phase II SOLACE-adults study
Authors: Kanter Julie , Mennito Sarah , Nair Santosh M. , Manwani Deepa , Kutlar Abdullah , Shah Nirmish , Keefe Deborah , Madhamshetty Hariprasad , Nassin Michele , Reshetnyak Evgeniya , Mendonza Anisha E. , Liles Darla 
Published: November 2024

Background: Crizanlizumab is a novel inhibitor of P-selectin, a key player in multicellular adhesion and inflammatory signaling, that leads to vaso-occlusion in sickle cell disease (SCD). Objectives: The SOLACE-adults study evaluated the pharmacokinetics, pharmacodynamics (P-selectin inhibition), safety, and efficacy of crizanlizumab, with or without hydroxyurea/hydroxycarbamide, in patients with SCD. Design: Phase II, single-arm, multicenter study. Methods: Patients with SCD aged 16–70 years, with ⩾1 vaso-occlusive crisis (VOC) within 12 months before screening, received crizanlizumab 5.0 or 7.5 mg/kg intravenous infusion every 4 weeks; dose groups were enrolled sequentially. Results: Of 57 patients enrolled, 45 received crizanlizumab 5.0 mg/kg and 12 received 7.5 mg/kg for a median duration of 206 and 170 weeks, respectively. Crizanlizumab concentrations reached maximum levels after a 30-min infusion and remained steady for 6 h, without significant accumulation. P-selectin inhibition was nearly complete for both doses. The median (interquartile range) absolute change in the annualized rate of VOCs leading to healthcare visit from baseline was −0.79 (−3.04, 2.01) in the 5.0 mg/kg group and −0.98 (−1.11, −0.41) in the 7.5 mg/kg group. All patients experienced at least one adverse event (AE), with no apparent differences between the two doses in the frequency and severity of AEs. Grade ⩾3 AEs occurred in 60% of the 5.0 mg/kg group and 58% of the 7.5 mg/kg group. Two patients in the 5.0 mg/kg group and one in the 7.5 mg/kg group had severe crizanlizumab-related infusion-related reactions, which resolved with treatment. No patients developed antibodies against crizanlizumab. Conclusion: Crizanlizumab 5.0 and 7.5 mg/kg demonstrated a dose-proportional increase in exposure, sustained P-selectin inhibition, a tolerable safety profile, and a sustained reduction in VOCs leading to healthcare visit. This suggests that crizanlizumab is a useful treatment option for patients with SCD who have experienced VOCs. Trial Registration: NCT03264989
Multi-target gene therapy AUP1602-C to improve healing and quality of life for diabetic foot ulcer patients: a phase I, open-label, dose-finding study
Authors: Schindler Christoph , Mikosiński Jacek , Mikosiński Pawel , Kärkkäinen Hanna-Riikka , Sanio Mirka , Kurkipuro Jere , Mierau Igor , Smith Wesley , Vartiainen Aki , Décory Laurent , Weber Dirk , Wirth Thomas , Yrjänheikki Juha , Schellong Sebastian , Samaranayake Haritha 
Published: November 2024

Background: Diabetic foot ulcer (DFU) is a common and highly morbid complication of diabetes with high unmet medical needs. AUP1602-C, a topical four-in-one gene therapy medicinal product (GTMP), consisting of a Lactococcus cremoris strain that produces fibroblast growth factor-2, interleukin-4, and colony-stimulating factor-1, is a promising novel treatment for DFU. Objectives: The aim of this first-in-human study was to investigate whether AUP1602-C is safe and effective in improving wound healing and quality of life (QoL) in patients with non-healing DFU (nhDFU), and to determine the recommended phase II dose. Design: Phase I, single-arm, open-label, uncontrolled, dose escalation study. Methods: The study consisted of four cohorts of patients receiving AUP1602-C as a single dose of 2.5 × 105 colony-forming units (CFU)/cm2 ulcer size or as repeated doses between 2.5 × 106 and 2.5 × 108 CFU/cm2 administered 3 times per week for 6 weeks. Within each cohort, a 3 + 3 scheme for monitoring safety, tolerability, and efficacy was applied. Results: In total, 16 patients aged 53–80 years were included, 3 each in the safety and low dose, 4 in the medium dose, and 6 in the high-dose cohort. AUP1602-C demonstrated a favorable safety profile with almost 100% dosing compliance. The most frequently reported side effect related to treatment was skin maceration. No serious adverse reactions, systemic toxicity, deaths, or side effects suggestive of immunogenicity, hypersensitivity, allergic reaction, or dose-limiting toxicities related to treatment were reported. No biodistribution events were observed and shedding-related events were rare and did neither show accumulation nor dose dependency. The recommended phase II dose of 2.5 × 108 CFU/cm2 demonstrated complete healing in 83% of patients without recurrence of ulcers during follow-up. Conclusion: AUP1602-C was safe and well tolerated and demonstrated dose-dependent efficacy in patients with nhDFU. Data supports further clinical development of AUP1602-C. Trial registration: The study was registered in ClinicalTrials.gov (NCT04281992) and ClinicalTrialsRegister.eu (2018-003415-22).
Towards Improvement of Heatwave Warnings for Older Adults: The Case of Queensland Australia
Authors: Oberai Mehak , Baker Steven , Bach Aaron J. E. , Forbes Connor , Jackman Ella , Binnewies Sebastian , Xu Zhiwei , Cunningham Sarah , Nghiem Son , Phung Dung , Rutherford Shannon 
Published: November 2024

Background: Heatwave warnings provide crucial information about the nature of the event and the steps that can be taken to mitigate its impact. It is well known that heat events disproportionately impact the health of older adults. Therefore, it’s critical that heatwave warnings reach this population. However, our current understanding of the effectiveness of heatwave warning messages among older Queenslanders is limited. Methods: A Queensland wide survey was conducted in 2022 among 547 older adults (≥65 years), aiming to collect information on their perception of heat-related health risk, their knowledge of the existing heatwave warnings, and if they had ever heard of a heatwave warning. Chi-square analysis followed by multinomial or binomial logistic regression was utilized to understand various socio-economic and personal factors that impact the heatwave warning reach to older Queenslanders. Results: Only 43% of the respondents had heard a heatwave warning and only 49% of those who heard a warning(s) changed their behavior as a result. The results showed 20% of respondents perceived themselves to be at heat-related health risk, and these individuals were 1.98 times more likely to have heard heatwave warnings. Further, individuals who perceived themselves to be at heat-related health risk were 3.62 times more likely to adopt adaptive measures in response to heatwave warnings. Implications: This study suggests that in older adults, higher knowledge and perception of heat-related health risk are associated with higher likelihoods of attention to heatwave warnings and adoption of cooling measures.
Prolotherapy in the Treatment of Sports-Related Tendinopathies: A Systematic Review of Randomized Controlled Trials
Authors: Capotosto Salvatore , Nazemi Alireza K. , Komatsu David E. , Penna James 
Published: November 2024

Background: As sports have increased in popularity, the incidence of tendinopathy has also grown dramatically. Nonoperative techniques and treatments used to address these pathologies continue to evolve and improve. One such treatment, prolotherapy (PrT), has become increasingly popular and may provide patients with an alternative nonoperative treatment option. Purpose: To review high-quality randomized controlled trials (RCTs) that analyzed PrT treatments for the most common tendinopathies. Specifically, this review aims to provide meaningful data regarding methods and outcomes for each condition treated and guide professionals who are considering PrT as a treatment option. Study Design: Systematic review; Level of evidence, 2. Methods: All RCTs published in English between January 1, 1980, and July 30, 2021, and reported in Embase, Medline, and Web of Science databases were reviewed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. After the initial search, a total of 3264 articles were identified. Studies analyzing sports medicine injuries and musculoskeletal pathologies using an RCT design were included, while case-reports, case-studies, reviews, and observational studies were excluded. Two independent researchers reviewed the search results, and conflicts were resolved by discussion of inclusion and exclusion criteria among all authors. The articles’ quality was evaluated using the Cochrane tool for assessing the risk of bias. Statistical analysis and graphical representations were performed using SPSS Version 28.00. Results: A total of 20 articles, including 1136 patients, met the inclusion criteria and were included in the study. Overall, in 85% of the studies, PrT was found to be effective in the treatment of tendinopathy. Specifically, PrT was superior to or as effective as the control in 83% (10/12) of the studies analyzing lateral epicondylitis (LE) and rotator cuff (RC) tendinopathies and in 88% (7/8) of the studies on plantar fasciitis (PF), Osgood-Schlatter disease (OSD), and Achilles tendinosis (AT). LE, RC, and PF tendinopathies were the most studied conditions (17/20 studies), while AT and OSD were the least studied (3/20 studies). Of the studies, 95% (19/20) used dextrose solutions, with only 1 using solutions of 2.5% phenol, 25% glycerin, and 25% dextrose in sterile water. Conclusion: Our systematic review suggests that PrT appears to be a promising alternative treatment for common tendinopathies. Most studies used a hypertonic dextrose solution. Even though further, larger randomized controlled trials comparing PrT with other orthobiologics would be beneficial, based on this review, sports medicine physiciansmay safely pursue PrT as an additional component of conservative treatment.
Stigma About Mental Health in Slovenian First-Year Medical Students
Authors: Vučinić Nina , Holnthaner Rok , Plakolm Erlač Sara , Skokauskas Norbert , Gregorič Kumperščak Hojka 
Published: November 2024

OBJECTIVE Stigma surrounding mental health persists as a significant impediment to adequate support and help-seeking behaviors in Slovenia, despite advancements in psychiatric care and education. This study investigates stigma among first-year medical students at the University of Maribor, Slovenia and how the stigma changes after completing a course in mental health literacy. PARTICIPANTS Participants were first-year medical students at the University of Maribor in the academic year 2023/2024. A total of 116 students participated in the baseline study, with 66 students participating in the follow-up study. STUDY METHOD The intervention involved implementing the “Transitions” program, aimed at enhancing mental health literacy and reducing stigma. We conducted a baseline study and a follow-up study, then used Wilcoxon signed rank test for repeated measures to compare the differences in ranks before and after implementation of the program. FINDINGS There was a significant reduction in stigma after intervention (Wilcoxon Z = −3.06, P < .01), suggesting a positive impact of the educational program. This reduction aligns with findings from similar programs globally, suggesting the efficacy of educational interventions in mitigating mental health stigma. CONCLUSIONS The study emphasizes the importance of integrating mental health education into medical curricula to foster stigma reduction and enhance mental health literacy among future medical doctors.
Is there a difference in pelvic and femoral morphology in early periprosthetic femoral fracture in cementless short stem total hip arthroplasty via an anterolateral approach?
Authors: Luger Matthias , Feldler Sandra , Schopper Clemens , Gotterbarm Tobias , Stadler Christian 
Published: November 2024

Abstract
Background
The pelvic and femoral morphology are associated with the occurrence of early periprosthetic femoral fractures (PFFs) in cementless total hip arthroplasty (THA). Differences exist depending on the performed approach and implanted stem design. Therefore, this study was conducted to analyze the pelvic and femoral morphology in cementless short stem THA via a minimally-invasive (MIS) anterolateral approach.

Methods
A retrospective, single-center, multi-surgeon, comparative propensity-score matched study of a cohort of 1826 short stem THAs was conducted. A total of 39 PFFs within the first 90 days after surgery was matched on a 2:1 ratio to non-fracture patients. The morphology of the proximal femur was analyzed with canal flare index (CFI), canal-calcar ratio (CCR), canal-bone ratio (CBR), morphological cortical index (MCI), and femoral cortical index (CI). The pelvic morphology was analyzed with ilium–ischial ratio (IR), distance anterior superior iliac spine to the tip of the greater trochanter (AGT). Both groups were analyzed regarding several parameters for femoral and pelvic morphology in non-parametric testing and univariate regression analysis.

Results
A significantly higher AGT was detected in the fracture group (104.5 mm ± 18 versus 97.4 mm ± 9.8; p = 0.016). All other femoral and pelvic parameters did not differ between both groups, also when compared depending on the Vancouver type of the PFF.

Conclusions
The morphology of the proximal femur and the pelvis do not differ in several radiological parameters in patients sustaining a PFF in cementless short stem THA via an anterolateral approach compared with matched non-fracture group. The findings are controversial to other studies with different stem types and approaches. Future studies should focus on analyzing the influence of the pelvic geometry and the shape of the proximal femur in the occurrence of PFFs in different approaches with the same stem type and vice versa.
Level of Evidence Level III case-controlled study
Mortality from external causes in late adolescence and early adulthood by gestational age and sex: a population-based cohort study in four Nordic countries
Authors: Bilsteen Josephine Funck , Opdahl Signe , Pulakka Anna , Finseth Per Ivar , Yin Weiyao , Pape Kristine , Schei Jorun , Metsälä Johanna , Andersen Anne-Marie Nybo , Sandin Sven , Kajantie Eero , Risnes Kari 
Published: November 2024

Abstract
Background
External causes of death, such as accidents, substance use, and suicide, contribute substantially to mortality during adolescence and early adulthood and show marked sex differences. Individuals born preterm are at increased risk of mental disorders, and impaired cognitive and executive functions, potentially increasing their vulnerability to death from external causes. We investigated sex-specific associations between gestational age at birth and mortality from external causes during late adolescence and early adulthood.

Methods
Individual level data from national health registries in Denmark (1978–2001), Finland (1987–2003), Norway (1967–2002), and Sweden (1974–2001) were linked to form nationwide cohorts. In total, 6,924,697 participants were followed from age 15 years to a maximum of 50 years in 2016–2018. Gestational age was categorized as “very/moderately preterm” (23–33 weeks), “late preterm” (34–36 weeks), “early term” (37–38 weeks), “full term” (39–41 weeks), and “post term” (42–44 weeks). Outcomes were mortality from external causes overall and from the largest subgroups transport accidents, suicide, and drugs or alcohol. We estimated sex-specific hazard ratios (HRs), with full term as the reference, and pooled each country’s estimates in meta-analyses.

Results
Across gestational ages mortality was higher for males than females. Individuals born very/moderately preterm had higher mortality from external causes, with HRs 1.11 (95% confidence interval [CI] 0.99–1.24) for males and 1.55 (95% CI 1.28–1.88) for females. Corresponding estimates for late preterm born were 1.11 (95% CI 1.04–1.18) and 1.15 (95% CI 1.02–1.29), respectively. Those born very/moderately preterm had higher mortality from transport accidents, but precision was low. For females, suicide mortality was higher following very/moderately preterm birth (HR 1.76, 95% CI 1.34–2.32), but not for males. Mortality from drugs or alcohol was higher in very/moderately and late preterm born males (HRs 1.23 [95% CI 0.99–1.53] and 1.29 [95% CI 1.16–1.45], respectively) and females (HRs 1.53 [95% CI 0.97–2.41] and 1.35 [95% CI 1.07–1.71], respectively, with some heterogeneity across countries).

Conclusions
Mortality from external causes overall was higher in preterm than full term born among both males and females. A clear sex difference was seen for suicide, where preterm birth was a risk factor in females, but not in males.
Efficacy and safety of Shengjiang Xiexin decoction on irinotecan-induced diarrhea in small cell lung cancer patients: a multicenter, randomized, double-blind, placebo-controlled trial
Authors: Deng Chao , Liu Qing , Yang Meng , Cui Hui-juan , Ge Yang , Li Qin , Zhu Shi-jie , Yang Guo-wang , Zhang Zhi-guo , Gao Yu , Lou Yan-ni , Jia Li-qun 
Published: November 2024

Abstract
Background
Irinotecan is a standard chemotherapeutic agent in small cell lung cancer (SCLC), however, as a common adverse reaction, diarrhea limits the use of irinotecan. Shengjiang Xiexin decoction (SXD) has been used in various gastrointestinal diseases in China two thousand years ago. We designed this clinical trial to supply more evidences on the use of SXD as prophylaxis for irinotecan-induced diarrhea, especially for high-risk population predicted by gene testing of uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1).

Methods
In this clinical trial, 120 patients with SCLC were recruited from six hospitals in China. They received two cycles of chemotherapy, meanwhile they were randomized to receive SXD or placebo for 14 days of oral administration in each cycle of chemotherapy. The primary outcome is the incidence of diarrhea. And secondary outcomes include the the degree of diarrhea and neutropenia, the number of chemotherapy cycles with diarrhea, first occurrence time and duration of diarrhea. To evaluate the effect of SXD on the intestine, a rat model with delayed-onset diarrhea induced by irinotecan was established, and the expression of inflammatory factors including IL-1β, IL-6 and TNF-α, anti-inflammatory factors including IL-10, TGF- β in jejunal tissue was detected by ELISA.

Results
101 patients (53 in SXD group, 48 in placebo group) completed the trial. The incidence of diarrhea in SXD group and placebo group were 26.42% (14/53) and 52.08% (25/48), respectively (P < 0.05), and the degree of diarrhea also had significant differences (P < 0.05). In UGT1A1 high-risk population, the incidence of diarrhea in two groups were 9.09% and 66.67% (P < 0.05), but there was no significant differences in UGT1A1 low-risk population. The incidence of neutropenia with degree 1–3 between two groups was 20.75% vs 20.83%, 13.21% vs 18.57%, 9.43% vs 20.83% (P < 0.05). No severe adverse events were reported in any group. And animal studies had shown SXD reduced content of IL-1β, IL-6, TNF-α, increased content of IL-10, TGF-β in jejunum tissue.

Conclusions
SXD had a prophylactic effect in the diarrhea induced by irinotecan, especially for UGT1A1 high-risk population, and this effect from SXD appeared to be maintained the completion of chemotherapy schedule. The mechanism of action of SXD was related to the regulation of inflammatory factors.
Trial registration Chinese Clinical Trial Register: ChiCTR1800018490. Registered on 20 September 2018. https://www.chictr.org.cn/showproj.html?proj=25250. The preliminary protocol of this clinical study has been published in the journal “Trials” in the form of protocol before this paper (Deng et al. in Trials 21:370, 2020).
Photo editing and the risk of anorexia nervosa among children and adolescents
Authors: Bozzola Elena , Scarpato Elena , Caruso Cinthia , Russo Rocco , Aversa Tommaso , Agostiniani Rino 
Published: November 2024

AbstractFilters and photoediting are widely used to transform or alter photos, mainly selfies, before sharing with friends or on social networks. In adult population there is a strong evidence of the potential risks of this behaviuor. Aim of the present work is to revise international literature exploring the correlation between photo manipulation and anorexia nervosa among children and adolescents. International literature focusing on photo manipulation and anorexia nervosa has been examined, according to the PRISMA Extension guidelines for Scoping Reviews using the following strategies: “Photomanipulation” Filters: English, Child: 6–12 years, Adolescent: 13–18 years, from 2000–2024 Pubmed Search: ((“Photography“[Mesh]) AND “Anorexia Nervosa“[Mesh]) AND “Anorexia Nervosa“[Majr] Filters: Adolescent: 13–18 years, Child: 6–12 years, from 2000–2024. According to the literature review strategy, only few and limited evidences are available for the pediatric population. As well as in adults, there is an increased risk for eating disorders in adolescents regularly sharing selfies and practicing photo manipulation. New social media and online chat may be associated with lower personal weight satisfaction, higher drive for thinness, and eating disorder symptoms. The Italian Pediatric Society Communication Group suggests to increase the awareness on the potential risks of photo manipulation among children and adolescents, suggesting the plan of more studies target to this population to gain evidence specifically, social campaigns and school education. Finally, the use of technology should be included as part of routine pediatric control visit, especially in the pre-adolescence period.
Menopausal hormone therapy and incidence, mortality, and survival of breast cancer subtypes: a prospective cohort study
Authors: Busund Marit , Ursin Giske , Lund Eiliv , Chen Sairah Lai Fa , Rylander Charlotta 
Published: November 2024

Abstract
Background
Menopausal hormone therapy (MHT) is associated with an increased risk of postmenopausal breast cancer, predominantly the luminal A-like subtype. The impact of MHT on deaths from breast cancer subtypes is less understood. This study aimed to explore associations between MHT use and the incidence, mortality, and survival of intrinsic-like breast cancer subtypes.

Methods
Data from 160,881 participants with self-reported MHT use from the prospective Norwegian Women and Cancer Study were analyzed. Among them, 7,844 incident breast cancer cases, and 721 breast cancer-specific deaths occurred. Cox proportional hazard regression was performed to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for the association between MHT use and the incidence, mortality, and survival of breast cancer subtypes.

Results
MHT use was associated with increased risk of overall, luminal A-like, and luminal B-like breast cancer, with respective HRs of 1.44 (95% CI 1.36–1.52), 1.41 (95% CI 1.31–1.52), and 1.23 (95% CI 1.09–1.40) among current estrogen-progestin therapy (EPT) users compared with never users. The risk increased by 4%, 4%, and 2% per year of EPT use for overall, luminal A-like, and luminal B-like breast cancers, respectively. MHT use was also associated with increased risk of overall and luminal A-like breast cancer mortality, with HRs 1.61% (95% CI 1.36–1.91) and 2.15% (95% CI 1.51–3.05) increased risk among current EPT users compared with non-users. Among patients with breast cancer, pre-diagnostic MHT use was not associated with worse survival from overall breast cancer but was inversely associated with survival from triple-negative breast cancer (TNBC; HR death 0.41; 95% CI 0.24–0.73 among current users). Results varied significantly according to tumor subtype (pheterogeneity = 0.02).

Conclusions
Our study suggests that MHT use increases the risk of incident and fatal overall and luminal A-like, and incident luminal B-like breast cancer but does not decrease overall survival among patients with breast cancer. Further research is needed to elucidate the mechanisms underlying MHT use and breast cancer lethality, and to explore whether MHT use among patients with TNBC is indeed free from harm.