bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cancer risk following onset of type 2 diabetes in New Zealanders with impaired glucose tolerance over 25 years: a matched prospective cohort study
Authors: Wang Zheng , Yu Dahai , Osuagwu Uchechukwu Levi , Pickering Karen , Baker John , Cutfield Richard , Cai Yamei , Orr-Walker Brandon J. , Sundborn Gerhard , Qu Bingjie , Zhao Zhanzheng , Simmons David 
Published: July 2024

Abstract
Background
In people with prediabetes, the link between developing type 2 diabetes (T2D) and cancer risk among those with impaired glucose tolerance (IGT) remains uncertain. We examined this association in IGT individuals from primary care in South and West Auckland, New Zealand, spanning 1994–2019, assessing 5- and 10-year cancer risks.

Methods
Study cohorts were extracted from the Diabetes Care Support Service in Auckland, New Zealand, linking it with national registries for death, cancer, hospital admissions, pharmaceutical claims, and socioeconomic status. We compared cancer risks in individuals with IGT newly diagnosed with or without T2D within a 1–5-year exposure window. Employing tapered matching and landmark analysis to address potential confounding effects, we formed comparative IGT cohorts. Weighted Cox regression models were then employed to assess the association between T2D onset and 5- and 10-year cancer risks.

Results
The study included 26,794 patients with IGT, with 629 newly diagnosed with T2D within 5 years and 13,007 without such a diagnosis. Those progressing to T2D had similar 5-year cancer risk but significantly higher 10-year risk (HR 1.35; 95% CI 1.09–1.68). This association was stronger in older individuals, the socioeconomically deprived, current smokers, those with worse metabolic measures, and lower renal function. Patients with IGT of NZ European ethnicity had lower 10-year cancer risk.

Conclusions
T2D diagnosis influences cancer risk in individuals with IGT. Developing risk scores for high-risk IGT individuals and implementing cancer screening and structured diabetes prevention, especially in deprived or minority ethnic populations, is essential.
Safety of first-line systemic therapy in patients with metastatic colorectal cancer: a network meta-analysis of randomized controlled trials
Authors: Zhan Yanrong , Cheng Xianwen , Mei Pingping , Tan Shufa , Feng Wenzhe , Jiang Hua 
Published: July 2024

Abstract
Objective
To evaluate the safety of first-line systemic therapy for metastatic colorectal cancer through network meta-analysis.

Methods
The literature from PubMed, Embase, Web of Science, and Cochrane Library databases was searched from the inception of the databases to August 15, 2023, and strict inclusion and exclusion criteria were applied to screen studies. The Cochrane Bias Risk Assessment Tool (RoB 2.0) was used to evaluate the quality of the included literature. Network meta-analysis was conducted using Stata 15.0 and R4.3.1 software to compare the incidence of adverse events (AEs) among different treatment regimens.

Results
A total of 53 randomized controlled trials, involving 17,351 patients with metastatic colorectal cancer (mCRC), were ultimately included, encompassing 29 different therapeutic approaches. According to SUCRA rankings, the CAPOX regimen is most likely to rank first in terms of safety, while the FOLFOXIRI + panitumumab regimen is most likely to rank last. In terms of specific AEs, the CAPOX regimen, whether used alone or in combination with targeted drugs (bevacizumab and cetuximab), is associated with a reduced risk of neutropenia and febrile neutropenia, as well as an increased risk of thrombocytopenia and diarrhea. The FOLFOX regimen, with or without bevacizumab, is linked to an increased risk of neutropenia and peripheral sensory neuropathy. The FOLFIRI/CAPIRI + bevacizumab regimen is associated with a reduced risk of peripheral sensory neuropathy. S-1 and S-1 + oxaliplatin are well-tolerated in terms of gastrointestinal reactions. The FOLFOXIRI regimen, whether used alone or in combination with targeted drugs, is associated with various AEs.

Conclusion
In summary, the CAPOX regimen may be the safest option among the first-line systemic treatment regimens for mCRC patients, while the FOLFOXIRI + panitumumab regimen may be associated with a higher incidence of grade 3 or higher AEs.
A comparison between IBEX bone health applied to digital radiographs and dual-energy X-ray absorptiometry at the distal-third and ultra-distal regions of the radius
Authors: Lopez Ben , Meertens Robert , Gundry Mike , Scott Paul , Crone Mr Ben , McWilliam Richard 
Published: July 2024

Abstract
Background
In an ageing population, low impact fragility fractures are becoming increasingly common. However, fracture risk can be reduced where low bone density can be identified at an early stage. In this study we aim to demonstrate that IBEX Bone Health (IBEX BH) can provide a clinically useful prediction from wrist radiographs of aBMD and T-score at the ultra-distal (UD) and distal-third (DT) regions of the radius.

Methods
A 261-participant single-centre, non-randomised, prospective, study was carried out to compare a) IBEX BH, a quantitative digital radiography software device, to b) Dual-energy X-ray Absorptiometry (DXA). A total of 257 participants with wrist digital radiograph (DR), forearm DXA pairs were included in the analysis after exclusions.

Results
The adjusted R2 value for IBEX BH outputs to the radial areal bone mineral density (aBMD) produced by a GE Lunar DXA system for the UD region is 0.87 (99% Confidence Interval (CI) [0.84, 0.89]). The adjusted R2 value for IBEX BH outputs to aBMD for the DT region is 0.88 (99% CI [0.85, 0.90]). The Area Under the Receiver Operating Characteristic curve (AUC) for the forearm T-score ≤  − 2.5 risk prediction model at the UD region is 0.95 (99% CI [0.93, 0.98]). The AUC for the forearm T-score ≤  − 2.5 risk prediction model at the DT region is 0.98 (99% CI [0.97, 0.99]).

Conclusion
From a DR of the wrist, IBEX BH provides a clinically useful i) estimate of aBMD at the two regions of interest on the radius and ii) risk prediction model of forearm T-score ≤  − 2.5 at the UD and DT regions.
Pregnancies complicated with functioning adrenal adenomas causing severe obstetric outcomes: a 20-year experience at a tertiary center
Authors: Zhu Caixia , Cai Shiqin , Zhong Xue , Huang Linhuan 
Published: July 2024

Abstract
Background
Functioning adrenal adenoma during pregnancy is rare, and the diagnosis is challenging owing to unspecific symptoms and restricted investigations. The obstetric outcomes of patients who undergo surgery during pregnancy or who receive only medical treatment are poorly described.

Objective
The aim was to investigate the associations between functioning adrenal adenomas and obstetric outcomes.

Methods
A retrospective study was performed in a tertiary center over 20 years. The clinical characteristics, management and obstetric outcomes of the diagnosed pregnant women were reviewed.

Results
A total of 12 women were diagnosed with functioning adrenal adenomas during pregnancy from January 2002 to September 2022. Eight women had cortisol-secreting adrenal adenomas, two had excessive catecholamine secretion, and two had primary aldosteronism. The initial symptoms of adrenal adenoma during pregnancy included hypertension or preeclampsia, gestational diabetes mellitus or prepregnancy diabetes mellitus, hypokalemia and ecchymosis. Four women underwent adrenalectomy during pregnancy, while 8 women received only medical therapy. Preterm birth occurred in all patients who received medicine, whereas 1 patient who underwent surgery experienced preterm birth. Among the 8 women in the medical treatment group, 3 had neonates who died.

Conclusions
Once hypertension, hyperglycemia and hypokalemia occur during the 1st or 2nd trimester, pregnant women with adrenal adenomas should be evaluated via laboratory and imaging examinations. The maternal and fetal outcomes were unpredictable owing to the severity of adrenal adenoma, particularly in patients who received only medical treatment. Adrenalectomy should be recommended during pregnancy.
Causal effect of the age at first birth with depression: a mendelian randomization study
Authors: Guo Wanshu , Guo Yuanyuan , Song Shaokang , Huang Xuankai , Zhang Yu , Zhang Aizhen , Meng Fangrong , Chang Minghang , Wang Zhipeng 
Published: July 2024

Abstract
Background
This study aimed to explore the causal relationship between age at first birth (AFB) and depression.

Methods
Using the univariable Mendelian randomization (UVMR) and multivariable Mendelian randomization (MVMR) methods to examine the potential correlation between age at first birth (AFB) and major depressive disorder and postpartum depression. A public database was used to obtain the genome-wide association studies (GWAS) summary data. We put inverse-variance-weighted (IVW) as the primary method in Mendelian randomization (MR) analysis and used sensitivity analysis to confirm the robustness of our result.

Results
We found a significant causal association between AFB and major depressive disorder by using the IVW algorithm (odd ratio [OR] 0.826; 95% confidence interval [CI] 0.793 − 0.861; P = 4.51 × 10− 20). MR-Egger, weighted median, simple mode and weighted mode method concluded the same result (P < 0.05). During the sensitivity analysis, the heterogeneity test (Q-value = 55.061, df = 48, P = 2.81 × 10− 01, I2 = 12.82%) and the leave-one-out plot analysis confirmed the stability of the results. The outcomes of the pleiotropy test (MR-Egger intercept = 8.932 × 10− 3. SE = 6.909 × 10− 3. P = 2.02 × 10− 01) and MR_PRESSO global test (P = 2.03 × 10− 01) indicated there is no pleiotropy.

Conclusion
There is solid evidence that a higher age at first birth is associated with a lower risk of major depressive disorder.
Producing recombinant proteins in Vibrio natriegens
Authors: Smith Matthew , Hernández José Sánchez , Messing Simon , Ramakrishnan Nitya , Higgins Brianna , Mehalko Jennifer , Perkins Shelley , Wall Vanessa E. , Grose Carissa , Frank Peter H. , Cregger Julia , Le Phuong Vi , Johnson Adam , Sherekar Mukul , Pagonis Morgan , Drew Matt , Hong Min , Widmeyer Stephanie R. T. , Denson John-Paul , Snead Kelly , Poon Ivy , Waybright Timothy , Champagne Allison , Esposito Dominic , Jones Jane , Taylor Troy , Gillette William 
Published: July 2024

AbstractThe diversity of chemical and structural attributes of proteins makes it inherently difficult to produce a wide range of proteins in a single recombinant protein production system. The nature of the target proteins themselves, along with cost, ease of use, and speed, are typically cited as major factors to consider in production. Despite a wide variety of alternative expression systems, most recombinant proteins for research and therapeutics are produced in a limited number of systems: Escherichia coli, yeast, insect cells, and the mammalian cell lines HEK293 and CHO. Recent interest in Vibrio natriegens as a new bacterial recombinant protein expression host is due in part to its short doubling time of ≤ 10 min but also stems from the promise of compatibility with techniques and genetic systems developed for E. coli. We successfully incorporated V. natriegens as an additional bacterial expression system for recombinant protein production and report improvements to published protocols as well as new protocols that expand the versatility of the system. While not all proteins benefit from production in V. natriegens, we successfully produced several proteins that were difficult or impossible to produce in E. coli. We also show that in some cases, the increased yield is due to higher levels of properly folded protein. Additionally, we were able to adapt our enhanced isotope incorporation methods for use with V. natriegens. Taken together, these observations and improvements allowed production of proteins for structural biology, biochemistry, assay development, and structure-based drug design in V. natriegens that were impossible and/or unaffordable to produce in E. coli.
Biosynthesis of a clickable pyoverdine via in vivo enzyme engineering of an adenylation domain
Authors: Puja Hélène , Bianchetti Laurent , Revol-Tissot Johan , Simon Nicolas , Shatalova Anastasiia , Nommé Julian , Fritsch Sarah , Stote Roland H. , Mislin Gaëtan L. A. , Potier Noëlle , Dejaegere Annick , Rigouin Coraline 
Published: July 2024

AbstractThe engineering of non ribosomal peptide synthetases (NRPS) for new substrate specificity is a potent strategy to incorporate non-canonical amino acids into peptide sequences, thereby creating peptide diversity and broadening applications. The non-ribosomal peptide pyoverdine is the primary siderophore produced by Pseudomonas aeruginosa and holds biomedical promise in diagnosis, bio-imaging and antibiotic vectorization. We engineered the adenylation domain of PvdD, the terminal NRPS in pyoverdine biosynthesis, to accept a functionalized amino acid. Guided by molecular modeling, we rationally designed mutants of P. aeruginosa with mutations at two positions in the active site. A single amino acid change results in the successful incorporation of an azido-l-homoalanine leading to the synthesis of a new pyoverdine analog, functionalized with an azide function. We further demonstrated that copper free click chemistry is efficient on the functionalized pyoverdine and that the conjugated siderophore retains the iron chelation properties and its capacity to be recognized and transported by P. aeruginosa. The production of clickable pyoverdine holds substantial biotechnological significance, paving the way for numerous downstream applications.
Lifestyles associated with malaria in pregnancy in northwest Colombia: a mixed study from Latin American critical epidemiology
Authors: Cardona-Arias Jaiberth Antonio , Higuita-Gutiérrez Luis Felipe , Carmona-Fonseca Jaime 
Published: July 2024

Abstract
Background
In the scientific literature on Malaria in Pregnancy (MiP), no studies have been conducted on lifestyles based on critical theory. The objective of this study was to analyse the lifestyles or singular processes of social determination of health in MiP in northwestern Colombia.

Methods
Mixed QUAN-QUAL convergent triangulation study. In the quantitative component, a psychometric evaluation and a cross-sectional design were conducted in 400 pregnant women to whom the Pender-Walker lifestyle scale and a survey on MiP prevention were applied. In the qualitative study, a critical ethnography was conducted with 46 pregnant women in whom their narratives and practices regarding lifestyles at home and healthcare were described.

Results
The frequency of MiP was 9%, and a higher occurrence of the disease was identified in those who did not control stagnant water (29%), did not use insecticide-treated net (16%) and went to the hospital (14%) or the microscopist (20%) when they had fever. This coincides with the presence of unhealthy lifestyles, little knowledge about malaria, and a low perception of the risk of getting sick, as well as meanings and experiences about MiP, maternity, and pregnancy that show a high clinical, cultural, and socioeconomic burden for the women studied.

Conclusion
This epidemiological profile and the approach to lifestyles based on the postulates of critical theory in health evidence that pregnant women exposed to malaria suffer serious social, cultural and health injustices that are not possible to impact with the current health model of malaria control in Colombia guided by aetiopathogenic, biomedical, positivist and utilitarian theories.
Malaria and typhoid fever co-infection: a retrospective analysis of University Hospital records in Nigeria
Authors: Olowolafe Tubosun A. , Agosile Oluwaseyi F. , Akinpelu Adekemi O. , Aderinto Nicholas , Wada Ojima Z. , Olawade David B. 
Published: July 2024

Abstract
Background
Studies have long documented the presence of malaria and typhoid fever in sub-Saharan Africa (SSA). However, studies on these diseases have primarily concentrated on rural settings, neglecting the potential impact on urban areas. This knowledge gap hinders effective surveillance and intervention strategies. To bridge this gap, this study investigated the prevalence of malaria and typhoid co-infections in an urban environment.

Methods
This study, conducted at Lead City University Hospital in Ibadan, Nigeria (West Africa’s largest metropolis), analysed medical records of over 3195 patients seen between April and June 2023. Descriptive statistics and chi-square tests were used to understand how these co-infections were distributed across different age and gender groups.

Results
The prevalence of co-infection peaked in May (9.7%), followed by June (8.9%) and April (5.7%). Notably, children aged 6–12 years exhibited the highest co-infection rate (18.5%), while those under five had the lowest (6.3%). Gender analysis indicated a slight difference, with 8.8% of females and 7.1% of males co-infected. Malaria prevalence was highest at the beginning of the rainy season and significantly decreased over time. Conversely, typhoid fever displayed the opposite trend, increasing with the rainy season. Children under five years old were most susceptible to malaria, while typhoid fever predominantly affected adults over 25 years old, with prevalence decreasing significantly with age.

Conclusion
This study sheds light on the previously overlooked risk of malaria and typhoid co-infections in urban settings. These findings highlight the need for enhanced surveillance and targeted public health interventions, particularly for vulnerable groups like young children during peak transmission seasons.
Orlistat for the treatment of antipsychotic-induced weight gain: an eight-week multicenter, randomized, placebo-controlled, double-blind trial
Authors: Xie Peng , Shao Tiannan , Long Yujun , Xie Weiwei , Liu Yangjun , Yang Ye , Huang Yuyan , Wu Renrong , Deng Qijian , Tang Hui 
Published: July 2024

Abstract
Background
Weight gain and metabolic disorders are commonly induced by antipsychotics. Orlistat is a lipase inhibitor used for weight control. The effect of orlistat on weight gain and metabolic disturbances in people (especially women) treated with antipsychotics has not been sufficiently studied. This study aimed to investigate the efficacy of orlistat in mitigating antipsychotic-induced weight gain and abnormal glycolipid metabolism.

Methods
Patients with schizophrenia or bipolar disorder with a weight gain ≥ 7% after taking antipsychotics were recruited. Participants were randomly allocated to two groups: one received eight weeks of orlistat (360 mg/day) and the other received a placebo. Anthropometric and fasting serum biochemical parameters were measured at baseline, week 4 and week 8.

Results
Sixty individuals (orlistat:placebo = 32:28) participated in the study. After controlling for the study center, the eight-week changes in body mass index (BMI), cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-CH) and low-density lipoprotein cholesterol (LDL-CH) were significantly different between the groups. According to the mixed linear models, CHOL and LDL-CH were significantly lower in the orlistat group than in the control group at week 8. The week 0-to-8 slopes of BMI, CHOL and LDL-CH were also significantly lower in the orlistat group.

Conclusions
These findings suggested that orlistat is an effective intervention for attenuating weight gain and serum lipid disturbances in antipsychotic-treated patients.

Trial registration
ClinicalTrials.gov NCT03451734.
Spatial dynamics of tertiary lymphoid aggregates in head and neck cancer: insights into immunotherapy response
Authors: Sadeghirad Habib , Monkman James , Tan Chin Wee , Liu Ning , Yunis Joseph , Donovan Meg L. , Moradi Afshin , Jhaveri Niyati , Perry Chris , Adams Mark N. , O’Byrne Ken , Warkiani Majid E. , Ladwa Rahul , Hughes Brett G.M. , Kulasinghe Arutha 
Published: July 2024

Abstract
Background
Recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) generally has a poor prognosis for patients with limited treatment options. While incorporating immune checkpoint inhibitors (ICIs) has now become the standard of care, the efficacy is variable, with only a subset of patients responding. The complexity of the tumor microenvironment (TME) and the role of tertiary lymphoid structures (TLS) have emerged as critical determinants for immunotherapeutic response.

Methods
In this study, we analyzed two independently collected R/M HNSCC patient tissue cohorts to better understand the role of TLS in response to ICIs. Utilizing a multi-omics approach, we first performed targeted proteomic profiling using the Nanostring GeoMx Digital Spatial Profiler to quantify immune-related protein expression with spatial resolution. This was further characterized by spatially resolved whole transcriptome profiling of TLSs and germinal centers (GCs). Deeper single-cell resolved proteomic profiling of the TLSs was performed using the Akoya Biosciences Phenocycler Fusion platform.

Results
Our proteomic analysis revealed the presence of T lymphocyte markers, including CD3, CD45, and CD8, expressing cells and upregulation of immune checkpoint marker PD-L1 within tumor compartments of patients responsive to ICIs, indicative of ‘hot tumor’ phenotypes. We also observed the presence of antigen-presenting cells marked by expression of CD40, CD68, CD11c, and CD163 with upregulation of antigen-presentation marker HLA-DR, in patients responding to ICIs. Transcriptome analysis of TLS and GCs uncovered a marked elevation in the expression of genes related to immune modulation, diverse immune cell recruitment, and a potent interferon response within the TLS structure. Notably, the distribution of TLS-tumor distance was found to be significantly different across response groups (H = 9.28, p = 0.026). The proximity of TLSs to tumor cells was found to be a critical indicator of ICI response, implying that patients with TLSs located further from tumor cells have worse outcomes.

Conclusion
The study underscores the multifaceted role of TLSs in modulating the immunogenic landscape of the TME in R/M HNSCC, likely influencing the efficacy of ICIs. Spatially resolved multi-omics approaches offer valuable insights into potential biomarkers for ICI response and highlight the importance of profiling the TME complexity when developing therapeutic strategies and patient stratification.