bluuebunny/crossref_metadata_2025_split huggingface dataset:
It is not all about the alpha: elevated expression of p53β variants is associated with lower probability of survival in a retrospective melanoma cohort
Authors: Groen Kira , Steffens Reinhardt Luiza , Bourdon Jean-Christophe , Avery-Kiejda Kelly A. 
Published: October 2023

Abstract
Background
Melanoma is the deadliest type of skin cancer and despite improvements in treatment outcomes, melanoma claimed 57,043 lives in 2020. In most malignancies, p53 mutation rates are above 50% and provide prognostic indications. However, in melanoma where less than a quarter of cases harbour a p53 mutation, the significance of the tumour suppressor may be questioned. Instead, p53 isoforms, which modulate p53’s canonical function, may be of greater clinical importance.

Methods
The expression of p53 isoforms was evaluated in 123 melanoma specimens by immunohistochemistry using p53 isoform-specific antibodies (DO-1, KJC8, KJC40, and KJC133). To determine whether TP53 mutations may be driving p53 isoform expression, TP53 was sequenced in 30 FFPE melanoma samples.

Results
The C-terminally truncated p53β isoforms (KJC8) were found to be the most highly expressed p53 isoforms compared to all other isoforms. Further, elevated KJC8 staining was found to correlate with reduced probability of melanoma-specific survival, while KJC40 staining (Δ40p53) positively correlated with reduced melanoma thickness. TAp53 isoforms (p53 retaining both transactivation domains, DO-1), were the second highest p53 isoforms expressed across all samples. Elevated DO-1 staining was also associated with worse survival outcomes and more advanced stages of cancer. Given that the isoforms are likely to work in concert, composite isoform profiles were generated. Composite biomarker profiles revealed that elevated TAp53 (DO-1) and p53β (KJC8) expression, accompanied by low Δ40p53 (KJC40) and Δ133p53 (KJC133) expression was associated with the worst survival outcomes. Supporting the lack of predictive biomarker potential of TP53 in melanoma, no clinicopathological or p53 isoform expression associations could be linked to TP53 status.

Conclusions
Given the lack of prognostic biomarker potential derived from TP53 status, this study highlights how p53 isoform expression might progress this field and, pending further validation, may provide additional information to treating oncologists that might be factored into treatment decisions.
Trends in retail sales of insecticide-treated nets and untreated nets in Tanzania: cross-section surveys
Authors: Kamala Benjamin , Mwingizi Deo , Dadi David , Loll Dana , Gitanya Peter , Mwalimu Charles , Chacky Frank , Kajange Stella , Malima Sara , Khamis Mwinyi , Ibrahim Raya , Serbantez Naomi , Msangi Lulu , Koenker Hannah 
Published: October 2023

Abstract
Background
The commercial sector plays a vital role in mosquito net ownership and access in Tanzania. The National Malaria Strategic Plan (NMSP) includes long-lasting insecticidal nets (LLIN) delivery through the commercial sector as a complementary mechanism. The NMSP aims to increase LLIN sales while decreasing untreated mosquito net sales. This survey aimed to track quantities, market share of different net categories, prices, and origins of mosquito nets in retail markets and to engage stakeholders to analyse market trends.

Methods
This mixed-method mosquito net retail outlet survey was conducted in mid-2021 in six and in mid-2022 in eight regions. Field teams identified net-selling outlets in major urban and peri-urban markets and used snowball sampling to identify additional outlets. A structured questionnaire was used, and photos of available mosquito net products were taken. Key informant interviews were conducted with wholesalers and retailers. The relative market share of a product was calculated by using the mean of each sales category as frequency weights. Qualitative data analysis was undertaken by summarizing common themes and observations based on the research question.

Results
A total of 394 and 1139 outlets were surveyed in 2021 and 2022, respectively. More than 96% of distributed brands in both years were untreated nets. The market share for untreated mosquito nets was 99.2% in 2021 and 88.3% in 2022. Bed net sales were seasonal, peaking in the rainy season and at the start of the school year. Leaked LLINs from the public sector comprised 0.3% of the market share in 2021 and 8.3% in 2022. Kigoma markets had the most significant frequency of leaked LLIN products. Legitimate LLINs were rare in 2021 (n = 2) and not found in 2022, despite the presence of a local LLIN manufacturer. A small number (n = 3) of untreated nets fabricated in China claiming to be LLINs were observed in 2022.

Conclusions
Despite NMCP’s strategic approach to increasing retail market share for legitimate LLINs, significant challenges remain. Efforts are needed to change the current situation given the context of large-scale public sector distributions of LLINs, the higher consumer cost of LLINs, the lack of bed net varieties. Improvement of registration process is recommended.
Associations between plant-based dietary patterns and risks of type 2 diabetes, cardiovascular disease, cancer, and mortality – a systematic review and meta-analysis
Authors: Wang Yeli , Liu Binkai , Han Han , Hu Yang , Zhu Lu , Rimm Eric B. , Hu Frank B. , Sun Qi 
Published: October 2023

Abstract
Background
Plant-based dietary patterns are gaining more attention due to their potential in reducing the risk of developing major chronic diseases, including type 2 diabetes (T2D), cardiovascular disease (CVD), cancer, and mortality, while an up-to-date comprehensive quantitative review is lacking. This study aimed to summarize the existing prospective observational evidence on associations between adherence to plant-based dietary patterns and chronic disease outcomes.

Methods
We conducted a systematic review and meta-analysis of evidence across prospective observational studies. The data sources used were PubMed and MEDLINE, Embase, Web of Science, and screening of references. We included all prospective observational studies that evaluated the association between adherence to plant-based dietary patterns and incidence of T2D, CVD, cancer, and mortality among adults (≥ 18 years).

Results
A total of 76 publications were identified, including 2,230,443 participants with 60,718 cases of incident T2D, 157,335 CVD cases, 57,759 cancer cases, and 174,435 deaths. An inverse association was observed between higher adherence to a plant-based dietary pattern and risks of T2D (RR, 0.82 [95% CI: 0.77–0.86]), CVD (0.90 [0.85–0.94]), cancer (0.88 [0.84–0.92]), and all-cause mortality (0.84 [0.78–0.92]) with moderate to high heterogeneity across studies (I2 ranged: 30.2–95.4%). The inverse associations with T2D, CVD and cancer were strengthened when healthy plant-based foods, such as vegetables, fruits, whole grains, and legumes, were emphasized in the definition of plant-based dietary patterns (T2D: 0.79 [0.72–0.87]; CVD: 0.85 [0.80–0.92]; cancer: 0.86 [0.80–0.92]; I2 ranged: 53.1–84.1%). Association for mortality was largely similar when the analyses were restricted to healthy plant-based diets (0.86 [0.80–0.92], I2 = 91.9%). In contrast, unhealthy plant-based diets were positively associated with these disease outcomes. Among four studies that examined changes in dietary patterns, increased adherence to plant-based dietary patterns was associated with a significantly reduced risk of T2D (0.83 [0.71–0.96]; I2 = 71.5%) and a marginally lower risk of mortality (0.95 [0.91–1.00]; I2 = 0%).

Conclusions
Better adherence to plant-based dietary patterns, especially those emphasizing healthy plant-based foods, is beneficial for lowering the risks of major chronic conditions, including T2D, CVD, cancer, as well as premature deaths.

Registration of review protocol
This review was registered at the PROSPERO International Prospective Register of Systematic Reviews (https://www.crd.york.ac.uk/PROSPERO/) with the registration number CRD42022290202.
Non-HDL cholesterol and long-term follow-up outcomes in patients with metabolic syndrome
Authors: Vazirian Fatemeh , Darroudi Susan , Rahimi Hamid Reza , Latifi MohamadReza , Shakeri Behrouz , Abolbashari Samaneh , Mohammadpour Amir Hooshang , Esmaily Habibollah , Mouhebati Mohsen , Samadi Sara , Mobarhan Majid Ghayour 
Published: October 2023

Abstract
Background
Non-high-density lipoprotein-cholesterol (non-HDL-C) has been identified as a potential biomarker for metabolic syndrome (MetS). However, its predictive capability for MetS varies among different ethnic groups, necessitating further investigation. This study aimed to assess the role of non-HDL-C in the early diagnosis of MetS in the Iranian population through a longitudinal study with a 10-year follow-up period.

Methods
Our study enrolled 4684 individuals from the MASHAD (Mashhad Stroke and Heart Atherosclerotic Disorder) cohort who were followed for 10 years to examine the association between non-HDL-C and the incidence of MetS. Additionally, the contribution of individual MetS components to the overall burden was evaluated.

Results
A total of 1599 subjects developed MetS, while 3085 did not. Non-HDL-C levels ≥ 130 were associated with a 42% higher risk of developing MetS (relative risk (RR), 1.42; 95% confidence interval (CI), 1.25–1.62). Regarding MetS components, elevated waist circumference (WC) showed the strongest association with MetS incidence (RR, 2.32; 95% CI, 1.45–2.9), whereas triglyceride (TG) levels ≥ 150 mg/dL demonstrated the weakest association (RR, 1.23; 95% CI, 1.04–1.46). Additionally, higher HDL-C levels were reported to be 20% protective against the risk of MetS (RR, 0.8; 95% CI, 0.73–0.86). Moreover, fasting blood glucose (FBG) levels ≥ 100 mg/dL were not significantly linked to MetS burden, while systolic blood pressure (BP) levels ≥ 130 mmHg or diastolic BP levels ≥ 85 mmHg increased the risk of MetS incidence (RR, 1.25; 95% CI: 1.11–1.41).

Conclusions
Elevated non-HDL-C and increased WC serve as significant predictors of MetS in Iranians. Strategies targeting non-HDL-C levels and weight loss should be emphasized to mitigate the risk of MetS development.
Respiratory health effects of e-cigarette substitution for tobacco cigarettes: a systematic review
Authors: Qureshi Maria Ahmed , Vernooij Robin W. M. , La Rosa Giusy Rita Maria , Polosa Riccardo , O’Leary Renee 
Published: October 2023

Abstract
Background
E-cigarettes (electronic nicotine delivery system, ENDS) have been presented as a harm reduction strategy for people who smoke tobacco cigarettes but who cannot achieve abstinence, or for those who wish to continue to enjoy nicotine and the habit of smoking. What are the health effects of the substitution of ENDS for tobacco cigarettes? This systematic review evaluates the evidence of human clinical tests on the respiratory effects of ENDS use in participants who smoke tobacco cigarettes.

Methods
A registered and published protocol was developed conforming to PRISMA 2020 and AMSTAR2 standards. The literature search was conducted in PubMed, Scopus, and the CENTRAL Cochrane Library and updated to May 2022. Three supplementary searches and a grey literature search were performed. Studies were evaluated with the JBI quality tools and the Oxford Catalogue of Bias. Due to the heterogeneity (diversity) of the studies, a narrative data synthesis was performed on the test findings plus three sub-group analyses.

Results
The review consists of sixteen studies and twenty publications. Spirometry tests comprised the majority of the data. In total, 66 respiratory test measurements were reported, out of which 43 (65%) were not significant. Statistically significant findings were mixed, with 9 tests showing improvements and 14 measuring declines, none of which was clinically relevant. Ten studies were rated at a high risk of bias, and six had some concerns primarily due to inadequate research designs and the conduct of the studies. Reporting bias was documented in thirteen studies.

Conclusions
Most of the studies showed no difference in respiratory parameters. This indicates that ENDS substitution for smoking likely does not result in additional harm to respiratory health. Due to the low quality of the studies, confidence in the conclusions is rated as low. Robust studies with a longer duration and sufficient power are required to validate any potential benefits or possible harms of ENDS substitution.
Registration PROSPERO #CRD42021239094, International Registered Report Identifier (IRRID): DERR1-10.2196/29084.
Metabolic/endocrine disorders in survivors of childhood-onset and cranial radiotherapy- treated ALL/NHL: a meta-analysis
Authors: Zhang Dan , Gu Min 
Published: October 2023

Abstract
Background
Cranial radiotherapy (CRT) is recommended to high-risk pediatric patients with acute lymphoblastic leukemia or aggressive non-Hodgkin’s lymphoma (ALL/NHL). However, effects of CRT treatment on the development of metabolic/endocrine disorders remain unclear. This meta-analysis aimed to identify metabolic and endocrine disturbances in survivors of childhood-onset and CRT-treated ALL/NHL.

Methods
Different online databases were searched using restricted search fields. Follow-up data and outcome measurements, including the prevalence of growth hormone (GH) deficiency, hypothyroidism, vitamin D deficiency, overweight/obesity, and hypogonadism were recorded. The height data was indicated by height-standard deviation score (height-SDS). Statistical estimates such as odds ratio (OR) and weighted standard mean difference (SMD) were compared between additional CRT treatment group and non-CRT treatment group. Study-to-study heterogeneity was calculated by calculating I-squared statistic, and fixed/random effect was applied to synthesize and analyze extracted data.

Results
Fifteen studies were included (4269 patients in total). Adult height SDS was lower in CRT-treated patients (pooled SMD = -0.581, 95% CI: -0.649–-0.512), and CRT-treated patients were likely to develop short stature (pooled OR = 2.289, 95% CI:1.674–3.130). Regardless of the study year, which potentially reflects the state-of-the-art CRT technique, the prevalence of short stature and GH deficiency was time-independent. Additionally, previous CRT can increase the risk of precocious puberty (pooled OR = 2.937, 95% CI: 1.281–6.736), hypothyroidism (pooled OR = 2.057, 95% CI:1.510–2.801), and hypogonadism (pooled OR = 3.098, 95% CI:2.521–3.807). However, the risk of being overweight/obese was similar between the patients with and without CRT (pooled OR = 1.278, 95% CI: 0.675–2.421).

Conclusion
Childhood-onset and CRT-treated ALL/NHL survivors are likely to have shorter height, precocious puberty, hypothyroidism, and hypogonadism.
Expression and significance of cathepsin C and cathepsin D during pregnancy and Preeclampsia
Authors: Song Jingzhe , Zhu Nan , Pan Xinchen , Guo Lu , Kong Xiang 
Published: October 2023

Abstract
Background
Cathepsin C (Cat C) is involved in the inflammatory-immune system and can be degraded by cathepsin D (Cat D). Preeclampsia (PE) and the inflammation-immunity relationship is currently a hot research topic, but there are still few studies. The aim was to investigate the expression and significance of Cat C and D in the serum of nonpregnant women, patients in various stages of pregnancy and patients with PE, and in the placenta of patients with normal pregnancy and PE.

Methods
Sixty young healthy nonpregnant women were selected: 180 normal pregnant women, including 60 each in the first, second, and third trimesters, and 100 women with PE, including 39 women with severe preeclampsia. The levels of Cat C and D in serum were detected by enzyme-linked immunosorbent assay (ELISA), and the expression levels of Cat C and D in placentas were detected by immunohistochemistry (IHC).

Results
The serum of Cat C in the first trimester was significantly lower than that in the nonpregnant group (P < 0.001), whereas Cat D was significantly higher than that in the nonpregnant group (P < 0.01). The levels of Cat C and D in the second trimester and third trimester were significantly higher than those in the first trimester (P < 0.05), but there was no significant difference in Cat C and D between the second trimester and third trimester. The levels of Cat C in the serum and placentas of patients with PE were significantly higher than those in the third trimester (P < 0.001) and positively correlated with the severity of PE (P < 0.001), whereas the levels of Cat D in the serum and placentas of patients with PE were significantly lower than those in the third trimester (P < 0.001) and negatively correlated with the severity of PE (P < 0.001). Age, primigravida proportion, and body mass index were significantly higher in the PE group than in the control group (P < 0.05), which were high-risk factors for PE.

Conclusions
Cat C and D are associated with the maintenance of normal pregnancy. In patients with preeclampsia, a significant increase in Cat C and a significant decrease in Cat D levels may lead to the occurrence and development of preeclampsia.
Development and validation of a new risk assessment model for immunomodulatory drug-associated venous thrombosis among Chinese patients with multiple myeloma
Authors: Li Xiaozhe , Sun Xiuli , Fang Baijun , Leng Yun , Sun Fangfang , Wang Yaomei , Wang Qing , Jin Jie , Yang Min , Xu Bing , Fang Zhihong , Chen Lijuan , Chen Zhi , Yang Qimei , Zhang Kejie , Ye Yinhai , Geng Hui , Sun Zhiqiang , Hao Dan , Huang Hongming , Wang Xiaotao , Jing Hongmei , Ma Lan , Pan Xueyi , Chen Wenming , Li Juan 
Published: October 2023

Abstract
Background
Individuals with multiple myeloma (MM) receiving immunomodulatory drugs (IMiDs) are at risk of developing venous thromboembolism (VTE), a serious complication. There is no established clinical model for predicting VTE in the Chinese population. We develop a new risk assessment model (RAM) for IMiD-associated VTE in Chinese MM patients.

Methods
We retrospectively selected 1334 consecutive MM patients receiving IMiDs from 16 medical centers in China and classified them randomly into the derivation and validation cohorts. A multivariate Cox regression model was used for analysis.

Results
The overall incidence of IMiD-related VTE in Chinese MM patients was 6.1%. Independent predictive factors of VTE (diabetes, ECOG performance status, erythropoietin-stimulating agent use, dexamethasone use, and VTE history or family history of thrombosis) were identified and merged to develop the RAM. The model identified approximately 30% of the patients in each cohort at high risk for VTE. The hazard ratios (HRs) were 6.08 (P < 0.001) and 6.23 (P < 0.001) for the high-risk subcohort and the low-risk subcohort, respectively, within both the derivation and validation cohorts. The RAM achieved satisfactory discrimination with a C statistic of 0.64. The stratification approach of the IMWG guidelines yielded respective HRs of 1.77 (P = 0.053) and 1.81 (P = 0.063). The stratification approach of the SAVED score resulted in HRs of 3.23 (P = 0.248) and 1.65 (P = 0.622), respectively. The IMWG guideline and the SAVED score-based method yielded C statistics of 0.58 and 0.51, respectively.

Conclusions
The new RAM outperformed the IMWG guidelines and the SAVED score and could potentially guide the VTE prophylaxis strategy for Chinese MM patients.
Exploring the design and utility of an integrated web-based chatbot for young adults to support healthy eating: a qualitative study
Authors: Ashton Lee M , Adam Marc TP , Whatnall Megan , Rollo Megan E , Burrows Tracy L , Hansen Vibeke , Collins Clare E 
Published: October 2023

Abstract
Background
There is a lack of understanding of the potential utility of a chatbot integrated into a website to support healthy eating among young adults. Therefore, the aim was to interview key informants regarding potential utility and design of a chatbot to: (1) increase young adults’ return rates and engagement with a purpose-built healthy eating website and, (2) improve young adults’ diet quality.

Methods
Eighteen qualitative, semi-structured interviews were conducted across three stakeholder groups: (i) experts in dietary behaviour change in young adults (n = 6), (ii) young adult users of a healthy eating website (n = 7), and (iii) experts in chatbot design (n = 5). Interview questions were guided by a behaviour change framework and a template analysis was conducted using NVivo.

Results
Interviewees identified three potential roles of a chatbot for supporting healthy eating in young adults; R1: improving healthy eating knowledge and facilitating discovery, R2: reducing time barriers related to healthy eating, R3: providing support and social engagement. To support R1, the following features were suggested: F1: chatbot generated recommendations and F2: triage to website information or externally (e.g., another website) to address current user needs. For R2, suggested features included F3: nudge or behavioural prompts at critical moments and F4: assist users to navigate healthy eating websites. Finally, to support R3 interviewees recommended the following features: F5: enhance interactivity, F6: offer useful anonymous support, F7: facilitate user connection with content in meaningful ways and F8: outreach adjuncts to website (e.g., emails). Additional ‘general’ chatbot features included authenticity, personalisation and effective and strategic development, while the preferred chatbot style and language included tailoring (e.g., age and gender), with a positive and professional tone. Finally, the preferred chatbot message subjects included training (e.g., would you like to see a video to make this recipe?), enablement (e.g., healthy eating doesn’t need to be expensive, we’ve created a budget meal plan, want to see?) and education or informative approaches (e.g., “Did you know bananas are high in potassium which can aid in reducing blood pressure?”).

Conclusion
Findings can guide chatbot designers and nutrition behaviour change researchers on potential chatbot roles, features, style and language and messaging in order to support healthy eating knowledge and behaviours in young adults.