bluuebunny/crossref_metadata_2025 huggingface dataset:
A finite element analysis of a low-profile femoral neck system of screws in sleeves in a vertical femoral neck fracture model
Authors: Sun Jun , Wu Le , Fang Nan , Qiao Wenze , Liu Lifeng
Published: June 2024

Background

Femoral neck system (FNS) has exhibited some drawbacks, such as non-fit of the plate with the lateral femoral cortex, postoperative pain, and the potential risk of subtrochanteric fractures. We have developed a low-profile FNS system that addresses some compatibility issues in FNS. In this study, we conducted finite element analysis on the 1-hole FNS (1 H-FNS), 2-holes FNS (2 H-FNS), and low-profile FNS (LP-FNS) and compared their biomechanical performance.

Methods

After the mesh convergence analysis, we established three groups of 1 H-FNS, 2 H-FNS, and LP-FNS. The interfragmentary gap, sliding distance, shear stress, and compressive stress and the bone-implant interface compression stress, stiffness, and displacement were determined under the neutral, flexion, or extension conditions of the hip joint, respectively. The stress and displacement of the femur after the implant removal were also investigated.

Results

(1) There were no obvious differences among the three FNS groups in terms of the IFM distance. However, the LP-FNS group showed less rotational angle compared with conventional FNS (neutral: 1 H-FNS, -61.64%; 2 H-FNS, -45.40%). Also, the maximum bone-implant interface compression stress was obviously decreased under the neutral, flexion, or extension conditions of the hip joint (1 H-FNS: -6.47%, -20.59%, or -4.49%; 2 H-FNS: -3.11%, 16.70%, or -7.03%; respectively). (2) After the implant removal, there was no notable difference in the maximum displacement between the three groups, but the maximum von Mises stress displayed a notable difference between LP-FNS and 1 H-FNS groups (-15.27%) except for the difference between LP-FNS and 2 H-FNS groups (-4.57%).

Conclusions

The LP-FNS may not only provide the same biomechanical stabilities as the 1 H-FNS and 2 H-FNS, but also have more advantages in rotational resistance especially under the neutral condition of the hip joint, in the bone-implant interface compression stress, and after the implant removal. In addition, the 1 H-FNS and 2 H-FNS have similar biomechanical stabilities except for the maximum von Mises stress after the implant removal. The femur after the LP-FNS removal not only is subjected to relatively little stress but also minimizes stress concentration areas.
The early career resilience experience of generation Z newly graduated registered nurses in standardized training in the emergency department: a qualitative study in Shanghai
Authors: Han Peng , Sun Yingying , Chen Huifeng , Liu Yue , Liu Shuyang , Wang Jing , Chi Chunwei , Dai Zhenjuan , Chen Jing , Zeng Li , Jiang Jinxia
Published: June 2024

Background

The period of standardized training is a transitional stage when Generation Z newly graduated registered nurses (Gen Z NGRNs) change their role from student to nurse. Affected by the COVID-19, they lack clinical practice and practicum experience in emergency departments in their university studies. At the beginning of career, they are under great pressure. Resilience is one of the factors that reduce their stress level and increases endurance. It is of interest to understand how this representative group of nurses gained and played the experience of resilience early in their careers.

Objective

To explore Gen Z NGRNs’ experience and process of resilience, to provide a new perspective and theoretical basis for psychological rehabilitation or intervention of medical staff who experienced transition shock.

Methods

This study employed a qualitative design based on the phenomenological approach. 18 nurses from a third-level class-A hospital in Shanghai who participated in standardized training in emergency department were enrolled using purposive sampling. Data collection was through in-depth and semi-structured interviews and continued until reaching data saturation.

Results

The investigation uncovered three themes and ten subthemes. Pressure and challenge contained high workload and high risk coexist, death’s stress response, more emergencies and high professional requirements. Coping and adaptation contained team help, psychological restructuring, peer support, transformational leadership. Reflection and planning contained enhance learning, appreciate life.

Conclusions

Our study described the embodiment and coping experience of the physical and mental stress faced by Gen Z NGRNs during their standardized training in the emergency department. It is emphasized that nurse educators should pay attention to the character and actual needs of Gen Z NGRNs, explore and formulate strategies, so as to guide NGRNs to quickly adapt and grow in the new role. The ultimate goal is to increase nurse retention and improve the quality of nursing.
Understanding the causes of missingness in primary care: a realist review
Authors: Lindsay Calum , Baruffati David , Mackenzie Mhairi , Ellis David A. , Major Michelle , O’Donnell Catherine A. , Simpson Sharon A. , Williamson Andrea E. , Wong Geoff
Published: June 2024

Background

Although missed appointments in healthcare have been an area of concern for policy, practice and research, the primary focus has been on reducing single ‘situational’ missed appointments to the benefit of services. Little attention has been paid to the causes and consequences of more ‘enduring’ multiple missed appointments in primary care and the role this has in producing health inequalities.

Methods

We conducted a realist review of the literature on multiple missed appointments to identify the causes of ‘missingness.’ We searched multiple databases, carried out iterative citation-tracking on key papers on the topic of missed appointments and identified papers through searches of grey literature. We synthesised evidence from 197 papers, drawing on the theoretical frameworks of candidacy and fundamental causation.

Results

Missingness is caused by an overlapping set of complex factors, including patients not identifying a need for an appointment or feeling it is ‘for them’; appointments as sites of poor communication, power imbalance and relational threat; patients being exposed to competing demands, priorities and urgencies; issues of travel and mobility; and an absence of choice or flexibility in when, where and with whom appointments take place.

Conclusions

Interventions to address missingness at policy and practice levels should be theoretically informed, tailored to patients experiencing missingness and their identified needs and barriers; be cognisant of causal domains at multiple levels and address as many as practical; and be designed to increase safety for those seeking care.
Nocturnal hypoxemic burden and micro- and macrovascular disease in patients with type 2 diabetes
Authors: Driendl Sarah , Stadler Stefan , Arzt Michael , Zeman Florian , Heid Iris M. , Baumert Mathias
Published: June 2024

Background

Micro- and macrovascular diseases are common in patients with type 2 diabetes mellitus (T2D) and may be partly caused by nocturnal hypoxemia. The study aimed to characterize the composition of nocturnal hypoxemic burden and to assess its association with micro- and macrovascular disease in patients with T2D.

Methods

This cross-sectional analysis includes overnight oximetry from 1247 patients with T2D enrolled in the DIACORE (DIAbetes COhoRtE) study. Night-time spent below a peripheral oxygen saturation of 90% (T90) as well as T90 associated with non-specific drifts in oxygen saturation (T90non − specific), T90 associated with acute oxygen desaturation (T90desaturation) and desaturation depths were assessed. Binary logistic regression analyses adjusted for known risk factors (age, sex, smoking status, waist-hip ratio, duration of T2D, HbA1c, pulse pressure, low-density lipoprotein, use of statins, and use of renin-angiotensin-aldosterone system inhibitors) were used to assess the associations of such parameters of hypoxemic burden with chronic kidney disease (CKD) as a manifestation of microvascular disease and a composite of cardiovascular diseases (CVD) reflecting macrovascular disease.

Results

Patients with long T90 were significantly more often affected by CKD and CVD than patients with a lower hypoxemic burden (CKD 38% vs. 28%, p < 0.001; CVD 30% vs. 21%, p < 0.001). Continuous T90desaturation and desaturation depth were associated with CKD (adjusted OR 1.01 per unit, 95% CI [1.00; 1.01], p = 0.008 and OR 1.30, 95% CI [1.06; 1.61], p = 0.013, respectively) independently of other known risk factors for CKD. For CVD there was a thresholdeffect, and only severly and very severly increased T90non−specific was associated with CVD ([Q3;Q4] versus [Q1;Q2], adjusted OR 1.51, 95% CI [1.12; 2.05], p = 0.008) independently of other known risk factors for CVD.

Conclusion

While hypoxemic burden due to oxygen desaturations and the magnitude of desaturation depth were significantly associated with CKD, only severe hypoxemic burden due to non-specific drifts was associated with CVD. Specific types of hypoxemic burden may be related to micro- and macrovascular disease.
The prevalence of contraceptive use among postpartum women and its associated factors during the early phase of COVID-19 outbreak: a time series study
Authors: Sathitloetsakun Sarochinee , Phutrakool Phanupong , Maitreechit Duangporn , Santibenchakul Somsook , Jaisamrarn Unnop , Puangsricharoen Pimpitcha
Published: June 2024

Background

Unintended pregnancies can adversely affect maternal health, preventable through timely postpartum contraception. During the COVID-19 pandemic, family planning services were constrained by policies that curtailed outpatient visits. We investigated the prevalence of postpartum contraceptive initiation at King Chulalongkorn Memorial Hospital (KCMH) during January to June 2020, comparing with the same period in 2019, and identified factors associated with such initiation.

Methods

We reviewed the medical records of 4506 postpartum women who delivered at KCMH during the study period. Logistic regression was conducted to test the association between early COVID-19 phase deliveries and post-partum long acting reversible contraception (LARC) initiation including copper intrauterine devices, levonorgestrel intrauterine systems, contraceptive implants, and progestogen-only injectable contraceptives.

Results

A total of 3765 women (83.6%), of whom 1821 delivered during the pandemic and 1944 during the historical cohort period, were included in this study. The proportion of women who initiated non-permanent modern contraceptives at six weeks postpartum was comparable between the COVID-19 (73.4%) and historical cohort (75.3%) (p = 0.27) periods. The proportion of women who initiated LARC at six weeks postpartumwas comparable between the historical cohort period (22.5%) and the COVID-19 (19.7%) (p = 0.05) period. Accessing a six-week postpartum check-up was independently associated with LARC initiation, of which the adjusted odds ratio (OR) (95% confidence interval) was 3.01 (2.26 to 4.02).

Conclusions

Our findings demonstrated that accessing postpartum care significantly associate with the use of LARC. The data suggest the strong influence of postpartum check-ups in facilitating the adoption of effective contraception, emphasizing the need for accessible postpartum care to sustain maternal health during health crises.
Management for persistent HPV infection and cervical lesions among women infected with HIV: a retrospective observational cohort study
Authors: Bi Dewu , Wei Shuzhen , Luo Xiaolu , Luo Xiaocheng , Tang Xike
Published: June 2024

Background

Early diagnosis and treatment of HPV persistent infection and cervical intraepithelial neoplasia, which have yet to be thoroughly characterized in Guangxi, Southwestern China, are the key preventative measures for the development of cervical cancer in women, particularly in HIV-infected women.

Methods

A retrospective study of 181 patients with HPV infection or cervical intraepithelial neoplasia who received surgical excision of lesions and were prospectively enrolled at the Fourth People’s Hospital of Nanning between January 2018 and February 2023 was performed. HPV-infected patients were divided into two subgroups: HIV-infected and HIV/HPV-coinfected patients and compare differences between these groups.

Results

HPV16, 18, 52, and 58 were the most prevalent HPV genotypes. High-risk HPV was significantly co-infected with multiple genotypes (P = 0.0332). HIV-infected women were predisposed to HPV infection (P < 0.0001), and the development of cervical cancer at a young age (P = 0.0336) compared to HIV-uninfected women and the loop electrosurgical excision procedure (P = 0.0480) is preferred for the treatment.

Conclusions

HIV infection may increase HPV prevalence and lead to cervical cancer development at a young age. The loop electrosurgical excision procedure is an efficient evaluation and treatment strategy for HIV-infected women suffering from cervical intraepithelial neoplasia.
Exploring the ethnobiological practices of fire in three natural regions of Ecuador, through the integration of traditional knowledge and scientific approaches
Authors: Carrión-Paladines Vinicio , Correa-Quezada Liliana , Valdiviezo Malo Huayra , Zurita Ruáles Jonathan , Pereddo Tumbaco Allison , Zambrano Pisco Marcos , Lucio Panchi Nataly , Jiménez Álvarez Leticia , Benítez Ángel , Loján-Córdova Julia
Published: June 2024

This study examines the convergence between traditional and scientific knowledge regarding the use of fire and its potential to trigger wildfires, with possible impacts on ecosystems and human well-being. The research encompasses three distinct natural regions of Ecuador: the coast, the highlands, and the Amazon. Data on traditional fire use were collected through semi-structured interviews with 791 members from five local communities. These data were compared with climatic variables (rainfall (mm), relative humidity (%), wind speed (km/h), and wind direction) to understand the climatic conditions conducive to wildfires and their relationship with human perceptions. Furthermore, the severity of fires over the past 4 years (2019–2022) was assessed using remote sensing methods, employing the Normalized Burn Ratio (NBR) and the difference between pre-fire and post-fire conditions (NBR Pre-fire–NBR Post-fire). The results revealed a significant alignment between traditional knowledge, climatic data, and many fires, which were of low severity, suggesting potential benefits for ecosystems. These findings not only enable the identification of optimal techniques and timing for traditional burns but also contribute to human well-being by maintaining a harmonious balance between communities and their environment. Additionally, they provide valuable insights for the development of more inclusive and effective integrated fire management strategies in these natural areas of Ecuador.
Joint effects of CD8A and ICOS in Long QT Syndrome (LQTS) and Beckwith-Wiedemann Syndrome (BWS)
Authors: Meng Ling-bing , Li Yongchao , Lv Tingting , Lv Changhua , Liu Lianfeng , Zhang Ping
Published: June 2024

Background

Long QT Syndrome (LQTS) and Beckwith-Wiedemann Syndrome (BWS) are complex disorders with unclear origins, underscoring the need for in-depth molecular investigations into their mechanisms. The main aim of this study is to identify the shared key genes between LQTS and BWS, shedding light on potential common molecular pathways underlying these syndromes.

Methods

The LQTS and BWS datasets are available for download from the GEO database. Differential expression genes (DEGs) were identified. Weighted gene co-expression network analysis (WGCNA) was used to detect significant modules and central genes. Gene enrichment analysis was performed. CIBERSORT was used for immune cell infiltration analysis. The predictive protein interaction (PPI) network of core genes was constructed using STRING, and miRNAs regulating central genes were screened using TargetScan.

Results

Five hundred DEGs associated with Long QT Syndrome and Beckwith-Wiedemann Syndrome were identified. GSEA analysis revealed enrichment in pathways such as T cell receptor signaling, MAPK signaling, and adrenergic signaling in cardiac myocytes. Immune cell infiltration indicated higher levels of memory B cells and naive CD4 T cells. Four core genes (CD8A, ICOS, CTLA4, LCK) were identified, with CD8A and ICOS showing low expression in the syndromes and high expression in normal samples, suggesting potential inverse regulatory roles.

Conclusion

The expression of CD8A and ICOS is low in long QT syndrome and Beckwith-Wiedemann syndrome, indicating their potential as key genes in the pathogenesis of these syndromes. The identification of shared key genes between LQTS and BWS provides insights into common molecular mechanisms underlying these disorders, potentially facilitating the development of targeted therapeutic strategies.
Nonconforming gender expression and adolescent anabolic-androgenic steroids misuse
Authors: Li Ruili , Liu Yuexi , Lian Qiguo
Published: June 2024

Background

Gender nonconformity (GNC) is an under-researched area of adolescent health that is of increasing interest to researchers and general public. However, little is known about whether it is associated with anabolic-androgenic steroids (AAS) misuse. We aimed to investigate the association among high school students using a cross-sectional design.

Methods

We pooled the 6 school districts data from the Youth Risk Behavior Survey in 2017 and 2019. We compared the prevalence of AAS misuse among gender nonconforming and conforming students. AAS misuse was determined on the reported experience of lifetime non-prescription steroid use. GNC was derived from perceived gender expression and sex. We estimated the sex-stratified adjusted odds ratios (AORs) for the association of GNC with AAS misuse after adjusting for race/ethnicity, grade, and sexual orientation.

Results

The study population consisted of 17,754 US high school students including 9143 (49.67%) female students. Among female students, GNC was significantly associated with moderate (AOR, 3.69; 95% CI 1.28–10.62; P = 0.016) and severe (AOR, 5.00; 95% CI 1.05–23.76; P = 0.043) AAS misuse, but not with any AAS misuse (AOR, 0.85; 95% CI 0.34–2.14; P = 0.734). Among male students, GNC was significantly associated with any (AOR, 4.75; 95% CI 2.93–7.69; P < 0.001), moderate (AOR, 4.86; 95% CI 2.66–8.89; P < 0.001) and severe (AOR, 4.13; 95% CI 1.43–11.95; P = 0.009) AAS misuse. We did not observe a dose-response relationship between GNC and any AAS misuse in female and male students.

Conclusions

This study suggests that AAS misuse is associated with GNC among female and male adolescents.
A Phase 1, randomized, double-blind, placebo-controlled, single- and multiple-dose escalation study to evaluate the safety and pharmacokinetics/pharmacodynamics of PF-06835375, a C-X-C chemokine receptor type 5 directed antibody, in patients with systemic lupus erythematosus or rheumatoid arthritis
Authors: Cohen Stanley , Beebe Jean S. , Chindalore Vishala , Guan Shunjie , Hassan-Zahraee Mina , Saxena Madhurima , Xi Li , Hyde Craig , Koride Sarita , Levin Robert , Lubaczewski Shannon , Salganik Mikhail , Sloan Abigail , Stevens Erin , Peeva Elena , Vincent Michael S. , Martin David A. , Chu Myron
Published: June 2024

Background

The objective of this study was to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of PF‑06835375, a potent selective afucosyl immunoglobulin G1 antibody targeting C-X-C chemokine receptor type 5 (CXCR5) that potentially depletes B cells, follicular T helper (Tfh) cells, and circulating Tfh-like (cTfh) cells, in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).

Methods

This first-in-human, multicenter, double-blind, sponsor-open, placebo-controlled Phase 1 study recruited patients aged 18–70 years with SLE or RA. In Part A, patients received single doses of intravenous PF-06835375 (dose range: 0.03–6 mg) or placebo in six sequential single ascending dose (SAD) cohorts. In Part B, patients received repeat doses of subcutaneous PF-06835375 (dose range: 0.3–10 mg) or placebo on Days 1 and 29 in five multiple ascending dose (MAD) cohorts. Tetanus/Diphtheria (Td) and Meningococcal B (MenB/Trumenba™) vaccines were administered at Day 4 (Td and MenB) and Week 8 (MenB only) to assess PF-06835375 functional effects. Endpoints included treatment-emergent adverse events (TEAEs), pharmacokinetic parameters, pharmacodynamic effects on B and cTfh cells, and biomarker counts, vaccine response, and exploratory differential gene expression analysis. Safety, pharmacokinetic, and pharmacodynamic endpoints are summarized descriptively. The change from baseline of B and Tfh cell-specific genes over time was calculated using a prespecified mixed-effects model, with a false discovery rate < 0.05 considered statistically significant.

Results

In total, 73 patients were treated (SAD cohorts: SLE, n = 17; RA, n = 14; MAD cohorts: SLE, n = 22; RA, n = 20). Mean age was 53.3 years. Sixty-two (84.9%) patients experienced TEAEs (placebo n = 17; PF-06835375 n = 45); most were mild or moderate. Three (9.7%) patients experienced serious adverse events. Mean t1/2 ranged from 3.4–121.4 h (SAD cohorts) and 162.0–234.0 h (MAD cohorts, Day 29). B and cTfh cell counts generally showed dose-dependent reductions across cohorts (range of mean maximum depletion: 67.3–99.3%/62.4–98.7% [SAD] and 91.1–99.6%/89.5–98.1% [MAD], respectively). B cell-related genes and pathways were significantly downregulated in patients treated with PF-06835375.

Conclusions

These data support further development of PF-06835375 to assess the clinical potential for B and Tfh cell depletion as a treatment for autoimmune diseases.

Trial registration

ClinicalTrials.gov identifier: NCT03334851.
Public support and willingness to pay for a carbon tax in Hungary: can revenue recycling make a difference?
Authors: Muth Daniel , Weiner Csaba , Lakócai Csaba
Published: June 2024

Background

To curb human-made carbon-dioxide emissions, the European Union will introduce carbon pricing for buildings and transport in 2027. Central and East European (CEE) countries are pressured to embark on ambitious decarbonization pathways leading to carbon-neutral economies by 2050. This paper is the first to investigate the public acceptance of and the willingness to pay (WTP) for a carbon tax in a CEE country, Hungary. It analyzes the support-increasing effects of five revenue-recycling mechanisms (tax cuts, green spending, support for poor households, funding for health care and education, and debt reduction), a wider range than covered in previous studies. A national face-to-face survey of 3013 adults on public attitudes to climate change, conducted in summer 2022, is the main method of data collection. This is combined with secondary analysis of related statistics and documentary analysis of relevant materials.

Results

The results show low public acceptance, with only a modest increase from 20.3% to 27.3% due to revenue recycling. This is accompanied by low WTP values and WTP increases. All these are lower than those found in Western surveys. A novel empirical result is the relative popularity of public health care and education in revenue recycling, though differences in revenue-recycling preferences are apparent between those who accept a carbon tax even without a redistribution mechanism and those who are willing to pay only if redistribution is included. Green spending also performed relatively well, while supporting the poor fared less well, albeit with relatively high WTP values. Reducing taxes and public debt were the least likely to instigate carbon-tax acceptance.

Conclusions

The results highlight the importance of carefully assessing the distributional impact of implementing carbon pricing mechanisms and thoroughly integrating social considerations into climate policy. Based on this, as well as the analysis of the social conditions and political economy of climate policy development in Hungary, policies—such as a gradually increasing carbon tax, social cushioning, legal earmarking of carbon-tax revenues, and policy bundling—are proposed to make carbon pricing socially tolerable and politically acceptable. The findings and conclusions might also be relevant for other parts of the CEE region.
Inactivation of KDM6A promotes the progression of colorectal cancer by enhancing the glycolysis
Authors: Zhang Dexiang , Zhao Xiaohong , Gao Yu , Wang Meixing , Xiao Mi , Zhu Kaihua , Niu Wei , Dai Yuedi
Published: June 2024

KDM6A (lysine demethylase 6A) has been reported to undergo inactivating mutations in colorectal cancer, but its function in the progression of colorectal cancer has not been evaluated using animal models of colorectal cancer. In this study, we found that knocking out KDM6A expression in mouse intestinal epithelium increased the length of villus and crypt, promoting the development of AOM (azoxymethane)/DSS (dextran sulfate sodium salt)-induced colorectal cancer. On the other hand, knocking down KDM6A expression promoted the growth of colorectal cancer cells. In molecular mechanism studies, we found that KDM6A interacts with HIF-1α; knocking down KDM6A promotes the binding of HIF-1α to the LDHA promoter, thereby promoting LDHA expression and lactate production, enhancing glycolysis. Knocking down LDHA reversed the malignant phenotype caused by KDM6A expression loss. In summary, this study using animal models revealed that KDM6A loss promotes the progression of colorectal cancer through reprogramming the metabolism of the colorectal cancer cells, suggesting that restoring the function of KDM6A is likely to be one of the strategies for colorectal cancer treatment.
Novel therapeutic activities of dragon blood from palm tree Daemonorops draco for the treatment of chronic diabetic wounds
Authors: Chen Hong-Chi , You Ren-In , Lin Fang-Mei , Lin Guan-Ling , Ho Tsung-Jung , Chen Hao-Ping
Published: June 2024

Background

The clinical efficacy of Jinchuang Ointment, a traditional Chinese medicine (TCM), in treating chronic non-healing diabetic wounds has been demonstrated over the past decades. Both in vitro and in vivo angiogenic activities have been reported for its herbal ingredients, including dragon blood from the palm tree Daemonorops draco and catechu from Uncaria gambir Roxb. Additionally, crude extracts of dragon blood have exhibited hypoglycemic effects not only in animal studies but also in cell-based in vitro assays.

Results

Our findings indicate that crude dragon blood extract promotes the differentiation of myoblasts into myotubes. Partially purified fractions of dragon blood crude extract significantly enhance the expression of muscle cell differentiation-related genes such as myoG, myoD, and myoHC. Our results also demonstrate that crude extracts of dragon blood can inhibit platelet-derived growth factor-induced PAI-1 expression in primary rat vascular smooth muscle cells, thereby favoring changes in hemostasis towards fibrinolysis. Consistent with previous reports, reduced expression of plasminogen activator inhibitor 1 (PAI-1) accelerates wound healing. However, further separation resulted in a significant loss of both activities, indicating the involvement of more than one compound in these processes. Stem cells play a crucial role in muscle injury repair. Neither dragon blood nor catechu alone stimulated the proliferation of human telomerase reverse transcriptase (hTERT)-immortalized and umbilical cord mesenchymal stem cells. Interestingly, the proliferation of both types of stem cells was observed when crude extracts of dragon blood and catechu were present together in the stem cell growth medium.

Conclusions

Dragon blood from D. draco offers multifaceted therapeutic benefits for treating chronic nonhealing diabetic wounds from various perspectives. Most drugs in Western medicine consist of small molecules with defined ingredients. However, this is not the case in TCM, as the activities of dragon blood reported in this study. Surprisingly, the activities documented here align with descriptions in ancient Chinese medical texts dating back to A.D. 1625.
Does consensus contour improve robustness and accuracy in 18F-FDG PET radiomic features?
Authors: Zhuang Mingzan , Li Xianru , Qiu Zhifen , Guan Jitian
Published: June 2024

Purpose

The purpose of our study is to validate the robustness and accuracy of consensus contour in 2-deoxy-2-[$$^{18}$$

18

F]fluoro-D-glucose ($$^{18}$$

18

F-FDG) PET radiomic features.

Methods

225 nasopharyngeal carcinoma (NPC) and 13 extended cardio-torso (XCAT) simulated data were enrolled. All segmentation were performed with four segmentation methods under two different initial masks, respectively. Consensus contour (ConSeg) was then developed using the majority vote rule. 107 radiomic features were extracted by Pyradiomics based on segmentation and the intraclass correlation coefficient (ICC) was calculated for each feature between masks or among segmentation, respectively. In XCAT ICC between segmentation and simulated ground truth were also calculated to access the accuracy.

Results

ICC varied with the dataset, segmentation method, initial mask and feature type. ConSeg presented higher ICC for radiomic features in robustness tests and similar ICC in accuracy tests, compared with the average of four segmentation results. Higher ICC were also generally observed in irregular initial masks compared with rectangular masks in both robustness and accuracy tests. Furthermore, 19 features (17.76%) had ICC ≥ 0.75 in both robustness and accuracy tests for any of the segmentation methods or initial masks. The dataset was observed to have a large impact on the correlation relationships between radiomic features, but not the segmentation method or initial mask.

Conclusions

The consensus contour combined with irregular initial mask could improve the robustness and accuracy in radiomic analysis to some extent. The correlation relationships between radiomic features and feature clusters largely depended on the dataset, but not segmentation method or initial mask.
Knowledge mobilization between the food industry and public health nutrition scientists: findings from a case study
Authors: Le Bouthillier Marie , Veilleux Sophie , Loignon Jeanne , Turcotte Mylène , Trudel Laurélie , Provencher Véronique
Published: June 2024

Background

Improving the nutritional quality of the food supply increases access to nutritious foods, which improves dietary habits and population health. Yet, knowledge mobilization initiatives between public health nutrition researchers and food industries are often not adequately considered and understood. This study explored what elements related to this specific context need to be recognized so that researchers can better mobilize nutrition science knowledge with the food industry to promote the nutritional improvement of food products.

Method

A case study qualitative approach was selected to answer the research question, using semi-structured interviews as the data collection technique. Québec baking industry actors were shown a mock-up of an online mobilization platform sharing the results of the Food Quality Observatory that describes the nutritional quality of breads offered in Québec, Canada. They were asked to think aloud as they explored the web platform and were interviewed. Two coders analyzed the data using an inductive approach and thematic content analysis, starting with individual open coding, and then put forward their analyses and drafted the final themes.

Results

The final data consisted of 10 semi-structured interviews conducted between October 2019 and August 2020. Four main themes were identified: the industry’s context, the knowledge mobilization initiative, the product-related matters stemming from the information shared and the motivation within the industry. Within each theme, sub-themes were highlighted and related to the industries’ motivation to improve their products’ nutritional quality. This study also specified key considerations for changes to the sodium and fiber content in bread.

Conclusion

Other steps beyond using simple language and a website format could be taken to better mobilize scientific knowledge with food industries, such as providing more consumer information, using an integrated knowledge mobilization approach that includes a consideration of ethics, working with communication professionals, collaborating with food science experts, and providing resources to act on shared information. Legislation such as the front-of-pack regulations could accelerate the pace of collaboration between researchers and industry. Overall, establishing a prior relationship with industries could help gain a better understanding of the themes highlighted in this study. Future research could build on this case study to provide more insights and solidify these findings.

Classification codes

Public Health, Public Private, Policy Making, Research Institutions, Use of Knowledge.
Retraction Note: Acute coronary syndrome due to left main coronary trunk compression 2 months after left atrial auricle clipping: a case report
Authors: Uchida Satoshi , Takekawa Daiki , Kato Koudai , Hirota Kazuyoshi
Published: June 2024

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s40981-023-00634-8.
Remitting seronegative symmetrical synovitis with pitting edema syndrome: case report of an atypical presentation of a rare syndrome and literature review
Authors: Schulz Nils , Müller-Ladner Ulf , Lange Uwe , Klemm Philipp
Published: June 2024

Background

Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) is a rare syndrome. The following case shows an atypical course of the disease with successful treatment. In addition, the accompanied review highlights current findings in the pathogenesis and treatment. Clinicians should be aware of the differential diagnosis of RS3PE syndrome.

Case presentation

A 67-year-old female patient with recurrent, asymmetric, and painful swelling of both hands with pitting edema, predominantly affecting the dorsal right hand, presented at our in-patient clinic. Over the years of her disease, first diagnosed as rheumatoid arthritis and then psoriatic arthritis, prednisolone treatment had the most favorable effects over various disease-modifying antirheumatic drugs.

Subsequent diagnostic evaluation confirmed RS3PE syndrome, a rare inflammatory disorder primarily affecting the elderly population. Manifesting as symmetrical joint inflammation of small joints with pitting edema, RS3PE syndrome typically onsets suddenly and may be accompanied by systemic symptoms like fever, fatigue, and weight loss. Although the precise etiology remains enigmatic, both the innate and the adaptive immune system seem to play a pathogenic role. Treatment is conventionally based on prednisolone, which effectively mitigates symptoms.

Ultimately, RS3PE was diagnosed in the context of psoriatic arthritis without dermatological or nail involvement. Given the unusual presentation marked by female gender, asymmetry, and prolonged and extensive disease with various prior treatments and in the context of psoriatic arthritis, a tumor necrosis factor alpha inhibitor was initiated in addition to low-dose prednisolone resulting in clinical remission for the first time.

Conclusions

In conclusion, the aforementioned atypical manifestation highlights the significance of including RS3PE syndrome as a potential differential diagnosis, particularly in instances where specific diagnostic criteria for rheumatoid arthritis, polymyalgia rheumatica, or psoriatic arthritis are absent. RS3PE responds well to the administration of prednisolone. In refractory cases, a therapeutic trial with tumor necrosis factor alpha inhibitors can be conducted.
Implementation of Universal Pan-Cancer Germline Genetic Testing in an Arab Population: The Jordanian Exploratory Cancer Genetics Study
Authors: Abdel-Razeq Hikmat , Sharaf Baha' , Bani Hani Hira , Abu Hijlih Ramiz , Alkyam Mais , Al-Azzam Khansa , Elemian Shatha , Tbakhi Abdelghani , Al-Atary Areej , Ellsworth Rachel E. , Russell Emily M. , Esplin Edward D. , Horani Malek , Zeidan Zeidan , Alzibdeh Abdulla , Heald Brandie , Nielsen Sarah M. , Nussbaum Robert L.
Published: June 2024

PURPOSE

Germline genetic testing (GGT) significantly affects cancer care. While universal testing has been studied in Western societies, less is known about adoption elsewhere.

MATERIALS AND METHODS

In this study, 3,319 unselected, pan-cancer Jordanian patients diagnosed between April 2021 and September 2022 received GGT. Pathogenic germline variant (PGV) frequency among patients who were in-criteria (IC) or out-of-criteria (OOC; 2020 National Comprehensive Cancer Network criteria) and changes in clinical management in response to GGT results were evaluated. Statistical analysis was performed using two-tailed Fisher's exact test with significance level P < .05.

RESULTS

The cohort was predominantly female (69.9%), with a mean age of 53.7 years at testing, and 53.1% were IC. While patients who were IC were more likely than patients who were OOC to have a PGV (15.8% v 9.6%; P < .0001), 149 (34.8%) patients with PGVs were OOC. Clinical management recommendations in response to GGT, including changes to treatment and/or follow-up, were made for 57.3% (161 of 281) of patients with high- or moderate-risk PGVs, including 26.1% (42 of 161) of patients who were OOC.

CONCLUSION

Universal GGT of patients with newly diagnosed cancer was successfully implemented in Jordan and led to identification of actionable PGVs that would have been missed with guidelines-based testing.
Trastuzumab deruxtecan in patients with breast cancer with brain metastases: The DE-REAL study.
Authors: Botticelli Andrea , Fabi Alessandra , Rossi Alessandro , Caputo Roberta , Pisegna Simona , Pantano Francesco , D'Auria Giuliana , Carbognin Luisa , Fedele Palma , Fabbri Agnese , Vernieri Claudio , Palleschi Michela , Ferretti Gianluigi , Paris Ida , Di Monte Elena , Pavese Francesco , Garrone Ornella , Giannarelli Diana , De Laurentiis Michelino , Scambia Giovanni
Published: June 2024

1032

Background: Almost 30-50% of patients with human epidermal growth factor (HER2)-positive breast cancer (BC) will develop brain metastases (BMs) in their treatment journey. Despite impressive results achieved for extracranial disease, the central nervous system (CNS) compartment remains highly challenging, and local approaches must now be associated with a prompt and adequate systemic intervention. Trastuzumab deruxtecan (T-Dxd) obtained impressive results both in heavily pretreated patients previously received TDM-1 and in the comparative DESTINY BREAST03 phase III trial. However, patients with active CNS involvement were traditionally excluded from clinical trials and BM-related outcomes are not often included among study endpoints. Moreover, a real-world evidence focused on intracranial activity for patients with BMs treated with T-Dxd is still lacking. In an effort to add further information on the clinical activity and safety of T-Dxd in both naïve and previously treated patients with BMs, we performed a sub-analysis of an Italian large retrospective database, the DE-REAL study. Methods: We reviewed a database of 143 patients with HER2-positive BC from 11 Italian Oncological Units, and obtained a total of 39 patients with CNS involvement treated in various lines setting with T-Dxd between April 2021 and October 2022. Results: Overall intracranial response rate (icRR) was 59% (43.5-74.4), with an imPFS of 14.1 months (9.3-18.9). Intracranial disease control rate (icDCR) was 94.9% (87.9-100.0), duration of response (icDoR) was 11.9 months (10.1-13.7), and clinical benefit rate (icCBr) at 6 and 12 months were 69.2% and 59%, respectively. IntracranialOS was not reached, with an overall rate of 76.6% of patients alive at 12 months. When comparing intracranial responders (CR/PR/SD) to non-responders (PD), median PFS was 15.5 months (13.7-17.3) vs 7.9 months (6.4-9.5), p<0.001. Toxicities were in line with what previously reported in larger registered clinical trials. Conclusions: Our real-world analysis indicated a clinically meaningful intracranial activity of T-Dxd in patients with HER2-positive BC and BMs, and supports its use for both patients with treated/stable and untreated/active lesions.
Multiple alternative splicing of HER2 transcripts and exon skipping with potential consequences on function and antibody-based therapy.
Authors: Albitar Maher , Zhang Hong , Charifa Ahmad , Ip Andrew , Agersborg Sally , Mohtashamian Arash , Graham Deena Mary Atieh , McNamara Donna M. , Waintraub Stanley E. , Gutierrez Martin , Pecora Andrew L , Goy Andre
Published: June 2024

1033

Background: Multiple studies have demonstrated that ERBB2 (HER2) exon 16 skipping is associated with resistance to antibody-based therapy. However, ERBB2 gene contains 30 exons with potential for alternative splicing involving all exons. With the increasing utilization of antibody-drug conjugates (ADC) in treating patients, it is important to evaluate the various ERBB2 isoforms that are expressed in various tumors. Toward this goal we evaluated the various splicing forms and exons skipping in domains II and III that are involved in dimerization and binding to pertuzumab, and in domain IV, which is a juxtamembrane domain and involved in trastuzumab binding. Methods: RNA was extracted from 3170 FFPE tissue from various types of tumors including breast, ovary, endometrium, lung, colon, stomach, esophagus, and others. RNA was sequenced using a hybrid capture-targeted panel. Data analysis is focused on ERBB2 gene. Results: Of the 3170 tested solid tumor samples, 824 (26%) showed high expression meeting the criteria for gene amplification and “low-HER2”. Of these cases, 199 (24%) samples showed exon skipping in domains II and III ranging from exons 6 to 14. Skipping in domain IV was detected in 236 cases (29%) involving exons from 13 to 29. However, 107 samples of the 824 (13%) showed skipping of exons in both domains II/III and domain IV. The most common exon skipping were in exons 6 to 7 and in exon 16. Most of the cases with exon 16 skipping (1.5% of total) also showed skipping in exons 6 and 7. Conclusions: Alternative splicing and exon skipping in HER2 transcripts is common and involves critical functional domains of the protein. The percentage of skipped transcripts is low. However, since these isoforms have deficiency in critical domains for membrane anchoring and for dimerization, the biological effects might be more significant than that expected from percentage of abnormal protein. Further studies are needed to correlate exon skipping with efficacy and outcome of antibody-based therapy. [Table: see text]
EMBARK post hoc analysis of impact of treatment suspension (TxS) on health-related quality of life (HRQoL).
Authors: Freedland Stephen J. , Gleave Martin , De Giorgi Ugo , Rannikko Antti , Saad Fred , Ramirez-Backhaus Miguel , Nasr Anchen F. , Ivanova Jasmina I. , Ganguli Arijit , Kral Pavol , Reisman Arlene , Shore Neal D.
Published: June 2024

5005

Background: EMBARK (NCT02319837) showed enzalutamide (ENZ) + leuprolide (L) and ENZ mono delayed metastasis-free survival vs placebo (P) + L while maintaining high global HRQoL in high-risk biochemically recurrent nonmetastatic hormone-sensitive prostate cancer. Treatment was suspended (TxS) at week 37 if PSA <0.2 ng/mL; reinstated if PSA rose to ≥2.0 ng/mL with radical prostatectomy (RP) or ≥5.0 ng/mL without RP. This analysis examined HRQoL after TxS. Methods: Longitudinal change in HRQoL from new baseline, week 37 (time of TxS), to subsequent assessments until week 205 were assessed via mixed model repeated measures using separate models for each instrument. Intention to treat analysis was used. Results: Treatment was suspended in 90.9% (321/353), 85.9% (304/354), and 67.8% (240/354) of patients treated with ENZ + L, ENZ mono, and P + L, respectively. A numerical trend inHRQoL improvement after week 37 TxS was seen in all 3 arms, which often reached clinically meaningful threshold at week 205 (Table). Post TxS, all arms reached clinically meaningful improvement in hormonal treatment side effects at the subsequent assessments of week 49 to week 97; however, patients slowly deteriorated, with clinically meaningful deterioration at week 205 relative to week 37 with ENZ + L and P + L. No statistically significant differences were observed between arms in change from week 37 to week 205. Conclusions: This post hoc analysis confirmed that TxS, as expected, leads to clinically meaningful improvements in HRQoL. Clinical trial information: NCT02319837 . [Table: see text]
Health-related quality of life (HRQOL) results from PRESTO (AFT-19), a phase 3 randomized trial of intensification of androgen blockade in patients with high-risk biochemically relapsed castration sensitive prostate cancer.
Authors: Chen Ronald C. , Mazza Gina L. , Fruth Briant , Xiao Han , Picus Joel , Taplin Mary Ellen , Dorff Tanya B. , Appleman Leonard Joseph , Weckstein Douglas Jay , Patnaik Akash , Bryce Alan Haruo , Shevrin Daniel , Mohler James L. , Anderson Daniel M. , Rao Arpit , Tan Alan , Ryan Charles J. , Eggener Scott , Morris Michael J. , Aggarwal Rahul Raj
Published: June 2024

5006

Background: The PRESTO trial (NCT03009981) showed that in patients with biochemically relapsed prostate cancer following radical prostatectomy with a PSA doubling time of ≤ 9 months and without evidence of metastatic disease by conventional imaging, intensified androgen receptor blockade for 52 weeks (androgen deprivation therapy [ADT] plus apalutamide [Apa], or ADT plus Apa and abiraterone acetate [Abi] plus prednisone) prolonged PSA progression-free survival compared to ADT alone (Aggarwal et al, JCO 2024). Here we report the HRQOL results. Methods: HRQOL measures included the Hot Flash Related Daily Interference Scale (HFRDIS), Expanded Prostate Cancer Index Composite (EPIC)-26 Sexual domain, PROMIS Fatigue Short Form and EQ-5D-5L, which assesses overall HRQOL in the 504 randomized patients. Published minimally important difference thresholds for these HRQOL measures are: HFRDIS 1.66 points, EPIC Sexual 10-12, PROMIS Fatigue 3-5, and EQ-5D-5L 0.06. General linear mixed modeling was used to estimate between-arm mean differences in HRQOL according to an intent-to-treat approach. Results: Mean changes from baseline to end of treatment (EOT) for each arm and for each HRQOL measure are summarized in Table. No statistically significant mean difference was reported between intensified androgen receptor blockade (Arm B, Arm C) vs ADT alone (Arm A) in any HRQOL measure. Further, numerical differences across arms for all HRQOL measures are below published minimally clinically important difference thresholds. Conclusions: Intensified androgen receptor blockade with Apa or Apa/Abi added to 52 weeks of ADT improves PSA progression-free survival without negatively affecting HRQOL. These HRQOL results add further support to intensification of androgen blockade in patients with high-risk biochemically recurrent prostate cancer. Clinical trial information: NCT03009981 . [Table: see text]