bluuebunny/crossref_metadata_2025_split huggingface dataset:
Making predictions under interventions: a case study from the PREDICT-CVD cohort in New Zealand primary care
Authors: Lin Lijing , Poppe Katrina , Wood Angela , Martin Glen P. , Peek Niels , Sperrin Matthew 
Published: April 2024

BackgroundMost existing clinical prediction models do not allow predictions under interventions. Such predictions allow predicted risk under different proposed strategies to be compared and are therefore useful to support clinical decision making. We aimed to compare methodological approaches for predicting individual level cardiovascular risk under three interventions: smoking cessation, reducing blood pressure, and reducing cholesterol.MethodsWe used data from the PREDICT prospective cohort study in New Zealand to calculate cardiovascular risk in a primary care setting. We compared three strategies to estimate absolute risk under intervention: (a) conditioning on hypothetical interventions in non-causal models; (b) combining existing prediction models with causal effects estimated using observational causal inference methods; and (c) combining existing prediction models with causal effects reported in published literature.ResultsThe median absolute cardiovascular risk among smokers was 3.9%; our approaches predicted that smoking cessation reduced this to a median between a non-causal estimate of 2.5% and a causal estimate of 2.8%, depending on estimation methods. For reducing blood pressure, the proposed approaches estimated a reduction of absolute risk from a median of 4.9% to a median between 3.2% and 4.5% (both derived from causal estimation). Reducing cholesterol was estimated to reduce median absolute risk from 3.1% to between 2.2% (non-causal estimate) and 2.8% (causal estimate).ConclusionsEstimated absolute risk reductions based on non-causal methods were different to those based on causal methods, and there was substantial variation in estimates within the causal methods. Researchers wishing to estimate risk under intervention should be explicit about their causal modelling assumptions and conduct sensitivity analysis by considering a range of possible approaches.
Case report: EBV-related eye orbits and sinuses lymphohistiocytic infiltration responsive to rituximab in a patient with X lymphoproliferative syndrome type 1
Authors: Giardino Giuliana , Lanni Vittoria , Mascolo Massimo , Russo Daniela , Cirillo Emilia , Romano Roberta , Cillo Francesca , Grilli Laura , Prencipe Maria Rosaria , Iuliano Adriana , Uccello Giovanni , De Fusco Carmela , Menna Giuseppe , Scalia Giulia , Portella Giuseppe , Pignata Claudio 
Published: April 2024

Background and aimsX lymphoproliferative syndrome type 1 (XLP1) is a rare inborn error of immunity due to mutations of SH2D1A, encoding for slam-associated protein (SAP). The clinical phenotype includes severe mononucleosis, hemophagocytic lymphohistiocytosis (HLH), and B-cell lymphomas.MethodsWe report the case of a child affected with XLP1 who presented with an incomplete HLH, triggered by Epstein–Barr virus (EBV) and treated with rituximab, involving orbits and paranasal sinuses.ResultsThe lesion was indistinguishable from lymphoma, complicating diagnosis and treatment. In addition, considering the high incidence of lymphoma in patients with XLP1, histology helped define its nature, driving therapeutic choices.ConclusionWe described an unusual presentation of incomplete HLH in a patient affected with XLP1: an EBV-driven infiltration of the orbits and paranasal sinuses. This led us to a challenging differential diagnosis of lymphoma-associated hemophagocytic syndrome, which can be frequently observed in patients with XLP1. Considering the extremely poor prognosis of this clinical finding, we sought for a prompt diagnosis and managed to obtain it and to immediately establish the right treatment on the basis of the pathological finding.
The development and validation of automated machine learning models for predicting lymph node metastasis in Siewert type II T1 adenocarcinoma of the esophagogastric junction
Authors: Lu Chenghao , Liu Lu , Yin Minyue , Lin Jiaxi , Zhu Shiqi , Gao Jingwen , Qu Shuting , Xu Guoting , Liu Lihe , Zhu Jinzhou , Xu Chunfang 
Published: April 2024

BackgroundLymph node metastasis (LNM) is considered an essential prognosis factor for adenocarcinoma of the esophagogastric junction (AEG), which also affects the treatment strategies of AEG. We aimed to evaluate automated machine learning (AutoML) algorithms for predicting LNM in Siewert type II T1 AEG.MethodsA total of 878 patients with Siewert type II T1 AEG were selected from the Surveillance, Epidemiology, and End Results (SEER) database to develop the LNM predictive models. The patients from two hospitals in Suzhou were collected as the test set. We applied five machine learning algorithms to develop the LNM prediction models. The performance of predictive models was assessed using various metrics including accuracy, sensitivity, specificity, the area under the curve (AUC), and receiver operating characteristic (ROC) curve.ResultsPatients with LNM exhibited a higher proportion of male individuals, a poor degree of differentiation, and submucosal infiltration, with statistical differences. The deep learning (DL) model demonstrated relatively good accuracy (0.713) and sensitivity (0.868) among the five models. Moreover, the DL model achieved the highest AUC (0.781) and sensitivity (1.000) in the test set.ConclusionThe DL model showed good predictive performance among five AutoML models, indicating the advantage of AutoML in modeling LNM prediction in patients with Siewert type II T1 AEG.
The role of volatile organic compounds for assessing characteristics and severity of non-cystic fibrosis bronchiectasis: an observational study
Authors: Gu Shu-Yi , Lu Hai-Wen , Bai Jiu-Wu , Yang Jia-Wei , Mao Bei , Yu Li , Xu Jin-Fu 
Published: April 2024

BackgroundHypoxic conditions and Pseudomonas aeruginosa (P. aeruginosa) infection are significant factors influencing the prognosis and treatment of patients with bronchiectasis. This study aimed to explore the potential for breath analysis to detect hypoxic conditions and P. aeruginosa infection in bronchiectasis patients by analyzing of volatile organic compounds (VOCs) in exhaled breath condensate (EBC).MethodsEBC samples were collected from stable bronchiectasis patients and analyzed using solid phase microextraction-gas chromatography-mass spectrometry (SPME-GCMS). The association of VOCs with bronchiectasis patients' phenotypes including hypoxic conditions and P. aeruginosa isolation was analyzed, which may relate to the severity of bronchiectasis disease.ResultsLevels of 10-heptadecenoic acid, heptadecanoic acid, longifolene, and decanol in the hypoxia group were higher compared to the normoxia group. Additionally, the levels of 13-octadecenoic acid, octadecenoic acid, phenol, pentadecanoic acid, and myristic acid were increased in P. aeruginosa (+) group compared to the P. aeruginosa (–) group. Subgroup analysis based on the bronchiectasis severity index (BSI)reveled that the levels of 10-heptadecenoic acid, heptadecanoic acid, decanol, 13-octadecenoic acid, myristic acid, and pentadecanoic acid were higher in the severe group compared to the moderate group. Multivariate linear regression showed that 10-heptadecenoic acid and age were independent prognostic factors for bronchiectasis patients with hypoxia. Furthermore, octadecenoic acid, phenol and gender were identified as independent prognostic factors for bronchiectasis patients with P. aeruginosa isolation.ConclusionThe study provides evidence that specific VOCs in EBC are correlated with the severity of bronchiectasis, and 10-heptadecenoic acid is shown to be a predictive marker for hypoxia condition in bronchiectasis patients.
Associations between genomic aberrations, increased nuchal translucency, and pregnancy outcomes: a comprehensive analysis of 2,272 singleton pregnancies in women under 35
Authors: Huang Jia , Wu Dong , He Jia-Huan , Wang Jing-Yuan , Li Xi , Wang Zheng-Yuan , Wang Yue , Liu Hong-Yan 
Published: April 2024

ObjectivesRegarding increased nuchal translucency (NT), the cutoff values used are heterogeneous in clinical practice, this study aims to assess the efficacy of prenatal detection for chromosomal abnormalities and pregnancy outcomes in fetuses with varying NT thicknesses, in order to provide data that supports informed prenatal diagnosis and genetic counseling for such cases.MethodsWe included 2,272 pregnant women under 35 with singleton pregnancies who underwent invasive prenatal diagnosis between 2014 and 2022. The cohort comprised 2,010 fetuses with increased NT (≥2.5 mm) and 262 fetuses with normal NT but exhibiting a single soft marker. Prenatal diagnoses were supported by chromosomal microarray (CMA) and copy number variation sequencing (CNV-seq) analyses.ResultsThe detection rates of numerical chromosomal abnormalities were 15.4% (309/2,010) and 17.3% (297/1,717) in the NT ≥2.5 and ≥ 3.0 groups, respectively. Pathogenic/likely pathogenic CNV incidence increased with NT thickness (χ2 = 8.60, p &lt; 0.05), peaking at 8.7% (22/254) in the NT 4.5–5.4 mm group. Structural defects were found in 18.4% of fetuses with NT values between 2.5 mm and 2.9 mm. Chromosomal abnormality rates in the isolated increased NT groups of 2.5–2.9 mm and 3.0–3.4 mm were 6.7% (16/239) and 10.0% (47/470), respectively, with no statistical significance (χ2 = 2.14, p &gt; 0.05). Fetuses with NT thickness between 2.5 and 2.9 mm combined with the presence of soft markers or non-lethal structural abnormalities exhibited a significantly higher chromosomal abnormality risk (19.0%) compared to fetuses with isolated increased NT ranging from 3.5 to 4.4 mm (13.0%). Pregnancy termination rates increased with NT thickness (χ2 = 435.18, p &lt; 0.0001), ranging from 12.0% (30/249) in the NT 2.5–2.9 mm group to 87.0% (141/162) in the NT ≥ 6.5 mm group.ConclusionCMA or CNV-seq exhibited good performance in identifying genomic aberrations in pregnancies with increased NT thickness. NT ranging from 2.5 mm to 2.9 mm elevated the risk of fetal chromosomal abnormalities, particularly when combined with other soft markers.
Causal relationship between gut microbiota and chronic renal failure: a two-sample Mendelian randomization study
Authors: Liu Xingzheng , Mo Jinying , Yang Xuerui , Peng Ling , Zeng Youjia , Zheng Yihou , Song Gaofeng 
Published: April 2024

BackgroundObservational studies and some experimental investigations have indicated that gut microbiota are closely associated with the incidence and progression of chronic renal failure. However, the causal relationship between gut microbiota and chronic renal failure remains unclear. The present study employs a two-sample Mendelian randomization approach to infer the causal relationship between gut microbiota and chronic renal failure at the genetic level. This research aims to determine whether there is a causal effect of gut microbiota on the risk of chronic renal failure, aiming to provide new evidence to support targeted gut therapy for the treatment of chronic renal failure.MethodsEmploying genome-wide association study (GWAS) data from the public MiBioGen and IEU OpenGWAS platform, a two-sample Mendelian randomization analysis was conducted. The causal relationship between gut microbiota and chronic renal failure was inferred using five different methods: Inverse Variance Weighted, MR-Egger, Weighted Median, Simple Mode, and Weighted Mode. The study incorporated sensitivity analyses that encompassed evaluations for pleiotropy and heterogeneity. Subsequently, the results of the Mendelian randomization analysis underwent a stringent correction for multiple testing, employing the False Discovery Rate method to enhance the validity of our findings.ResultsAccording to the results from the Inverse Variance Weighted method, seven bacterial genera show a significant association with the outcome variable chronic renal failure. Of these, Ruminococcus (gauvreauii group) (OR = 0.82, 95% CI = 0.71–0.94, p = 0.004) may act as a protective factor against chronic renal failure, while the genera Escherichia-Shigella (OR = 1.22, 95% CI = 1.08–1.38, p = 0.001), Lactococcus (OR = 1.1, 95% CI = 1.02–1.19, p = 0.013), Odoribacter (OR = 1.23, 95% CI = 1.03–1.49, p = 0.026), Enterorhabdus (OR = 1.14, 95% CI = 1.00–1.29, p = 0.047), Eubacterium (eligens group) (OR = 1.18, 95% CI = 1.02–1.37, p = 0.024), and Howardella (OR = 1.18, 95% CI = 1.09–1.28, p &lt; 0.001) may be risk factors for chronic renal failure. However, after correction for multiple comparisons using False Discovery Rate, only the associations with Escherichia-Shigella and Howardella remain significant, indicating that the other genera have suggestive associations. Sensitivity analyses did not reveal any pleiotropy or heterogeneity.ConclusionOur two-sample Mendelian randomization study suggests that the genera Escherichia-Shigella and Howardella are risk factors for chronic renal failure, and they may serve as potential targets for future therapeutic interventions. However, the exact mechanisms of action are not yet clear, necessitating further research to elucidate their precise roles fully.
Dysexecutive difficulty and subtle everyday functional disabilities: the digital Trail Making Test
Authors: Libon David J. , Swenson Rod , Tobyne Sean , Jannati Ali , Schulman Daniel , Price Catherine C. , Lamar Melissa , Pascual-Leone Alvaro 
Published: April 2024

BackgroundDigital neuropsychological tests reliably capture real-time, process-based behavior that traditional paper/pencil tests cannot detect, enabling earlier detection of neurodegenerative illness. We assessed relations between informant-based subtle and mild functional decline and process-based features extracted from the digital Trail Making Test-Part B (dTMT-B).MethodsA total of 321 community-dwelling participants (56.0% female) were assessed with the Functional Activities Questionnaire (FAQ) and the dTMT-B. Three FAQ groups were constructed: FAQ = 0 (unimpaired); FAQ = 1–4 (subtle impairment); FAQ = 5–8 (mild impairment).ResultsCompared to the FAQ-unimpaired group, other groups required longer pauses inside target circles (p &lt; 0.050) and produced more total pen strokes to complete the test (p &lt; 0.016). FAQ-subtle participants required more time to complete the entire test (p &lt; 0.002) and drew individual lines connecting successive target circles slower (p &lt; 0.001) than FAQ-unimpaired participants. Lines connecting successive circle targets were less straight among FAQ-mild, compared to FAQ-unimpaired participants (p &lt; 0.044). Using stepwise nominal regression (reference group = FAQ-unimpaired), pauses inside target circles classified other participants into their respective groups (p &lt; 0.015, respectively). Factor analysis using six dTMT-B variables (oblique rotation) yielded a two-factor solution related to impaired motor/cognitive operations (48.96% variance explained) and faster more efficient motor/cognitive operations (28.88% variance explained).ConclusionDigital assessment technology elegantly quantifies occult, nuanced behavior not previously appreciated, operationally defines critical underlying neurocognitive constructs related to functional abilities, and yields selected process-based scores that outperform traditional paper/pencil test scores for participant classification. When brought to scale, the dTMT-B test could be a sensitive tool to detect subtle-to-mild functional deficits in emergent neurodegenerative illnesses.
Comparative efficacy and safety of targeted therapy and immunotherapy for HER2-positive breast cancer: a systematic review and network meta-analyses
Authors: Gu Suyu , Liu Yuting , Huang Yufan , Lin Wenzheng , Li Ke 
Published: April 2024

BackgroundIn recent years, novel therapies targeting specific molecular pathways and immunotherapies have exhibited promising outcomes for treating human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Our work aimed to assess the effectiveness and safety of these emerging treatment regimens for this disease.Material and methodsWe systematically searched databases including PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials their inception to August 2023 to identify relevant randomized controlled trials (RCTs). The quality of eligible RCTs was evaluated with the Cochrane risk-of-bias tool, version 2 (RoB2). Investigated outcomes encompassed progression-free survival (PFS), overall survival (OS), disease-free survival (DFS), pathologic complete remission (pCR), and adverse events (AEs). They were expressed as hazard ratio (HR) with 95% conference intervals (CI) or risk ratio (RR) with 95% CI.ResultsOur analysis identified a total of 28 RCTs suitable for inclusion in the NMA. Regarding the PFS, all these treatment regimens exhibited comparable effectiveness. In terms of OS, Capecitabine+Trastuzumab, Lapatinib+Trastuzumab and Pyrotinib+Capecitabine exhibited better effect compared to other treatments. Regarding pCR and AEs, all these treatment regimens exhibited comparable effectiveness, especially Lapatinib+Trastuzumab and Pyrotinib+Capecitabine.ConclusionOur study highlights the prominent role of targeted therapies and immunotherapies in treating HER2-positive breast cancer. The efficacy of trastuzumab-containing regimens was superior to other treatment options, while maintaining a comparable safety profile. Based on these findings, trastuzumab-containing regimens emerge as a preferable and recommended choice in clinical practice for managing HER2-positive breast cancer.Systematic Review RegistrationPROSPERO, identifier CRD42023414348.
Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy and intraoperative radiation therapy in the management of gallbladder cancer: a case report
Authors: Alaswad Marwan , Otry Abdullah Al , Alhosainy Ziad , Elkordy Fadwa , Sabbah Belal Nedal , Arabi Tarek Ziad , Abdulkader Humzah , Ghanayem Obaida Fadi , Azzam Ayman Zaki , Amin Tarek 
Published: April 2024

Gallbladder cancer (GBC) is a rare and highly aggressive malignancy, often characterized by nonspecific clinical presentations and late diagnosis, which contribute to its poor prognosis. It is commonly detected at advanced stages, leading to low survival rates. Surgical resection is the primary treatment, with the extent of surgery depending on the T stage of the cancer. In advanced cases, surgery is only considered if it can potentially be curative. Despite various treatment approaches for advanced GBC, survival outcomes remain poor. In our case series, we introduce a novel treatment approach combining cytoreductive surgery, intraoperative radiation therapy, and hyperthermic intraperitoneal chemotherapy. Remarkably, we observed a 100% one-year survival rate, with one patient achieving eight years of disease-free survival without recurrence or metastasis. This aggressive treatment strategy did not lead to increased morbidity or mortality, suggesting its safety and feasibility. However, larger-scale studies are required to draw definitive conclusions.
Clinical outcomes of intermittent panitumumab based-therapy for previously treated older patient with metastatic colorectal cancer: a case report and review of literature
Authors: Rosati Gerardo , Annunziata Luigi , Scarano Enrico , Dapoto Francesca , Bilancia Domenico 
Published: April 2024

BackgroundMetastatic colorectal cancer is one of the most common causes of cancer death worldwide, and its incidence increases with age. Treating an older RAS and BRAF wild-type patient represents a challenge for the medical oncologist, even more so for those patients defined as “vulnerable” and undergoing at least two lines of therapy. In this context, recent evidence supports the role of retreatment with anti-EGFR inhibitors and the use of liquid biopsy. However, frequent skin toxicity constitutes a limitation of therapy, especially in older people. Since it has been described that continuous administration of these monoclonal antibodies leads to acquired resistance to anti-EGFRs, with consequent therapeutic failure, an intermittent strategy with chemotherapy plus an anti-EGFR could help maintain the efficacy of the treatment over time, delaying the resistance and improving patients’ quality of life.Case presentationIn this case report, we describe the case of an older RAS and BRAF wild-type patient reporting a clinical response after first-line chemotherapy with FOLFOX + panitumumab, subsequently interrupted in the absence of disease progression. After radiological worsening and two additional lines of therapy, the reintroduction of panitumumab plus 5-fluorouracil, administered with a stop-and-go strategy, allowed the patient to benefit from the same drugs for 2 years from diagnosis, to achieve a clinical response during fourth-line treatment lasting more than 3 years, to delay resistance and to avoid unacceptable anti-EGFR skin toxicity. This patient, who died from a myocardial infarction more than 5 years after diagnosis, represents the case of a good synergy between molecular profile of disease and reintroduction of an anti-EGFR with intermittent strategy.
Hypoxic preacclimatization combining intermittent hypoxia exposure with physical exercise significantly promotes the tolerance to acute hypoxia
Authors: Xie Jiaxin , Xie Shenwei , Zhong Zhifeng , Dong Huaping , Huang Pei , Zhou Simin , Tian Huaijun , Zhang Jijian , Wu Yu , Li Peng 
Published: April 2024

Background: Both hypoxia exposure and physical exercise before ascending have been proved to promote high altitude acclimatization, whether the combination of these two methods can bring about a better effect remains uncertain. Therefore, we designed this study to evaluate the effect of hypoxic preacclimatization combining intermittent hypoxia exposure (IHE) and physical exercise on the tolerance to acute hypoxia and screen the optimal preacclimatization scheme among the lowlanders.Methods: A total of 120 Han Chinese young men were enrolled and randomly assigned into four groups, including the control group and three experimental groups with hypoxic preacclimatization of 5-day rest, 5-day exercise, and 3-day exercise in a hypobaric chamber, respectively. Main physical parameters for hypoxia acclimatization, AMS incidence, physical and mental capacity were measured for each participant in the hypobaric chamber simulated to the altitude of 4500 m in the effect evaluation stage. The effect was compared between different schemes.Results: During the effect evaluation stage, SpO2 of the 5-day rest group and 5-day exercise group was significantly higher than that of the control group (p = 0.001 and p = 0.006, respectively). The participants with 5-day rest had significantly lower HR than the controls (p = 0.018). No significant differences of AMS incidence were found among the four groups, while the proportion of AMS headache symptom (moderate and severe vs. mild) was significantly lower in the 3-day exercise group than that in the control group (p = 0.002). The 5-day exercise group had significantly higher VO2max, than the other three groups (p = 0.033, p &lt; 0.001, and p = 0.023, respectively). The 5-day exercise group also had significantly higher digital symbol and pursuit aiming test scores, while shorter color selection reaction time than the control group (p = 0.005, p = 0.005, and p = 0.004, respectively).Conclusion: Hypoxic preacclimatization combining IHE with physical exercise appears to be efficient in promoting the tolerance to acute hypoxia. Hypoxia duration and physical exercise of moderate intensity are helpful for improvement of SpO2 and HR, relief of AMS headache symptoms, and enhancement of mental and physical operation capacity.