bluuebunny/crossref_metadata_2025_split huggingface dataset:
72206 - Overall Survival after Isolated Hepatic Perfusion in Combination with Ipilimumab and Nivolumab in Patients with Uveal Melanoma (SCANDIUM II trial)
Authors: Nelson Axel , Shafazand Amir , Cahlin Christian , Carneiro Ana , Helgadottir Hildur , Levin Max , Rizell Magnus , Ullenhag Gustav , Wirén Sara , Lindnér Per , Nilsson Jonas A , Ny Lars , Bagge Roger Olofsson 
Published: August 2024

Abstract

Introduction
Uveal melanoma (UM) is a rare disease with a propensity for liver metastases and a poor prognosis. Isolated hepatic perfusion (IHP) using high-dose melphalan has demonstrated a 40% response rate in patients with liver metastases from UM, while the combination of ipilimumab 3 mg/kg and nivolumab 1 mg/kg (IPI3/NIVO1) yields response rates of 11-18%. However, the impact on overall survival (OS) of combining these treatments is unknown.

Method
This multicenter, open-label, randomized, controlled phase Ib trial enrolled patients with liver-dominant metastatic UM, randomized to receive either IHP with melphalan 1 mg/kg followed by combination immunotherapy (four cycles of IPI3/NIVO1) (Arm A) or one cycle of IPI3/NIVO1 before IHP followed by three cycles of IPI3/NIVO1 (Arm B). The primary endpoint was safey and has been reported previously, here we present data on overall survival.

Result
Eighteen patients were included, with 9 in each arm. Seventy-eight percent were treatment-naïve, and 72% had isolated liver metastases. Three patients did not undergo planned IHP. The overall response rate was 38%, with 57% in Arm A and 22% in Arm B, and a median response duration of 11.9 months. At a minimum 18-month follow-up, overall survival was 50%, with 56% in Arm A and 44% in Arm B. Median OS was 18.2 months in Arm A and 17.2 months in Arm B.

Discussion
The numerically higher response rate in Arm A warrants a randomized study designed to detect differences between IPI/NIVO with or without IHP.
72224 - Characteristics and management of locally advanced breast cancer – a retrospective register study from Breast Cancer DataBase Sweden (BCBaSe) 3.0
Authors: Waller Elisabet , Wennstig Anna-Karin , Garmo Hans , Nilsson Greger , Karlsson Per , Fredriksson Irma , Wadsten Charlotta 
Published: August 2024

Abstract

Introduction
Locally advanced breast cancer (LABC) refers to large primary breast tumours (T3), tumours of any size with chest wall/skin involvement (T4), and/or extensive lymph node involvement (N2-3). LABC may be a consequence of delayed presentation or aggressive tumour biology. The aim of the study was to explore patient characteristics, treatment, and time trends of LABC in a Swedish population-based cohort.

Method
The study cohort was retrieved from BCBaSe 3.0 including 94 271 patients with invasive breast cancer diagnosed 2008-2019 after exclusion of those with distant metastasis at diagnosis or within 3 months. Comparisons were made between non-LABC (T0-2N0-1) and LABC subcategorized by T-stage (T≥3) and N-stage (N≥2).

Result
Of all BC, 6565 (7.0 %) were LABC, with a fairly constant proportion over time. A higher proportion of LABC was seen both among the youngest (&lt;40 y; 11.9 %) and among the oldest (80+ y; 15.7 %), and in those with a low level of education (9.5 %). Lobular BC was overrepresented among LABC (16.0 % vs 11.1 % in non-LABC), as were the Her2-positive (17.3 % vs 10.2 %) and triple-negative subtypes (11.0 % vs 7.3 % in non-LABC). On average, 47.2 % of LABC underwent primary surgery, 44.2 % received neoadjuvant treatment ranging from 26.7 % for T0-2N2 to 83.0 % for inflammatory BC, whereas 8.6 % received no treatment. Of those undergoing neoadjuvant treatment, 71.8 % proceeded to surgery.

Discussion
LABC encompasses a wide range of tumours, comprising both primarily operable and non-operable tumours, with notable distinctions observed between different subgroups of LABC.
72301 - Breast cancer recurrence detection in relation to surveillance - applications on personalized follow-up
Authors: Sartor Hanna , Hagberg Oskar , Hemmingsson Oskar , Lång Kristina , Wadsten Charlotta 
Published: August 2024

Abstract

Introduction
The effectiveness of current follow-up guidelines after breast cancer (BC) treatment is uncertain. A tailored surveillance according to patient age and tumour characteristics may be more adequate. The aim of this study was to assess the frequency of and the risk factors for detection of ipsilateral locoregional recurrences (LR) and second primary breast cancers (SP) outside of scheduled surveillance in patients with recurrent BC.

Method
Patients with surgically treated stage I-III BC from Malmö Diet and Cancer Study (MDCS) 1991-2014 (n=1095) and region Västernorrland 2009-2018 (n=1930) were included. Data on the index BC and recurrences were retrieved from medical records. Recurrent events were defined as symptomatic when detected at a patient-initiated visit or breast imaging outside of scheduled annual mammography surveillance.

Result
Median follow-up time was 6.5 years (Interquartile range: 3.8-10.0). In total, 262 patients had a relapse. The most common first event was distant metastasis (46%) followed by LR (22%) and SP (18%). Fifty-four per cent of LR and 27 % of SP were detected outside of scheduled surveillance. Logistic regression analysis showed that lymph node positive BC (HR 2.12; 95%CI, 1.00-4.60), BC of HER2 positive subtype (HR 5.13; 95%CI, 1.37-25.32) and young age (HR 2.25; 95%CI, 0.98-5.47) were associated with increased probability of having a symptomatically detected recurrence.

Discussion
Most recurrent events are detected outside of scheduled surveillance. Risk-based tailored surveillance might be more appropriate for subsets of patients.
72309 - Postoperative complications after breast cancer surgery and effect on recurrence and survival – a large population-based cohort study
Authors: Adwall Linda , Fredriksson Irma , Hultin Hella , Mani Maria , Norlén Olov 
Published: August 2024

Abstract

Introduction
This study aimed to assess the risk of systemic breast cancer recurrence after surgical site infection (SSI) and also the impact of SSI on locoregional recurrence, overall survival (OS), and breast cancer-specific survival (BCSS).

Method
This nationwide cohort study included patients who underwent surgery for primary breast cancer in Sweden between January 2008 and September 2019. The study cohort was identified in BCBaSe 3.0, a database linking the National Breast Cancer Quality Register to national population-based health care registers held by the National Board of Health and Welfare and Statistics Sweden. The primary exposure was SSI within 90 days from surgery, and the primary outcome was systemic recurrence of breast cancer. Secondary outcomes included locoregional recurrence, OS and BCSS. Multivariable Cox regression analysis was performed to assess the association between exposure, predictors and outcomes.

Result
Of the 82 102 patients included in the study, 15.7% experienced an SSI within 90 days from surgery. SSI was not significantly associated with systemic recurrence, locoregional recurrence or BCSS after adjustment for confounding variables. SSI was significantly associated with worse OS, but the significant association disappeared in a sensitivity analysis excluding all patients with any kind of malignancy before breast cancer diagnosis.

Discussion
SSI does not significantly increase the risk of systemic recurrence. But still, it is important to strive to reduce complications after breast cancer surgery.
71935 - Endoscopic screening for anal high grade squamous intraepithelial dysplasia in HIV-positive men who have sex with men
Authors: Borch-Johnsen Peter , Schmidt Peter Thelin , Filén Finn , Storgärd Elisabet , Nygren Jonas 
Published: August 2024

Abstract

Introduction
Anal Squamous Intraepithelial Lesions (ASIL) are precursors to anal cancer. The highest risk is found in HIV-positive men having sex with men (MSM). The aim of the study is to evaluate flexible endoscopy as a screening method for ASIL.

Method
304 HIV-positive MSM were included. At inclusion, anal samples were taken for HPV-PCR, cytology, chlamydia and gonorrhea. Previous chlamydia/gonorrhea infections, smoking habits, years with HIV, nadir CD4 count, initiation of antiretroviral therapy, previous ASIL/condyloma and symptoms from the anal canal were collected. A diagnostic endoscopy was performed using underwater technique. Number of lesions and morphology were documented. Detected lesions were removed with diathermy-snare after submucosal injection of lidocaine in un-anesthetized patients.

Result
Presently, we have performed anal endoscopy in 283 individuals. Macroscopic lesions were found in 230 cases (81%). Endoscopic resection in 189 cases with findings of one case (0,5 %) of squamous cell carcinoma, surgical R0 resection, no oncologic treatment necessary. 74 patients (39 %) with HSIL, 47 (25%) with LSIL, 7 (4 %) indeterminate for LSIL/HSIL and 60 (32 %) without dysplasia. Swabs for cytology had a sensitivity for SCC/HSIL of 12%, specificity of 50% and for HPV-PCR a sensitivity for SCC/HSIL of 61%, specificity of 42%.Possible correlation with nadir CD4, duration of HIV infections, tobacco use, and number of previous anal chlamydia/gonorrhea remain to be analyzed.

Discussion
Preliminary data from a still ongoing study indicate that flexible endoscopy is useful for screening high-risk individuals and for resection of dysplastic lesions. Anal cytology did not meet our expectations but HPV-PCR showed a more promising result.
71635 - Can prediction models aid in the process of selecting treatment for hyperthyroidism?
Authors: Mauritzson Daniel , Sjölin Gabriel , Persson Andreas 
Published: August 2024

Abstract

Introduction
Hyperthyroidism (HT) is treated with antithyroid drugs, radioactive iodine, or surgery. Previous studies have demonstrated that many patients undergo repeated treatment without remission and have impaired quality of life 6-10 years after diagnosis. This study aimed to evaluate different predictive machine learning models as a means of support in selecting treatment for HT.

Method
The study is based on a dataset of 2916 newly diagnosed HT patients between 2003-2005, who later were invited to participate in a 6-10 year follow-up study. This dataset underwent standard preprocessing for data representation and preparation for learning algorithms. Large Language Models were assessed as an alternative to encode medical records into sentence embeddings. Various regression models were trained and evaluated to predict the probability of a successful treatment based on nine features (Age, Sex, Diagnosis, thyroid-stimulating hormone receptor antibodies, T4-levels, TRAb (reference), TRAb (corrected), TRAb (positive), Thyroid-associated Ophthalmopathy.

Result
Two different multi-output regression models were trained and evaluated for each pre-processed dataset: Gradient-Boosting (GB) and Random Forest (RF). Root Mean Squared Error (RMSE) and the coefficient of determination, R2 score, were measured for evaluation metrics. RF trained on the traditionally pre-processed dataset showed best result, RMSE 0.1764 and R2 score 0.1460. However, the differences between both evaluated models and the approach in data preparation were negligible.

Discussion
This study show promising results in using prediction models for assessing the probability of successful treatment in individual patients. Further investigation is necessary regarding the choice of prediction models and how the data are prepared and represented.
Effect of short-term intensive design-based STEM learning on executive function: an fNIRS study of the left-behind children
Authors: Ding Keya , Wu Dandan , Shen Yining , Cao Simin , Liu Qianming , Wan Zhihong , Li Hui 
Published: August 2024

Abstract
Design-based STEM learning is believed to be an effective cross-disciplinary strategy for promoting children’s cognitive development. Yet, its impact on executive functions, particularly for disadvantaged children, still need to be explored. This study investigated the effects of short-term intensive design-based STEM learning on executive function among left-behind children. Sixty-one Grade 4 students from a school dedicated to the left-behind children in China were sampled and randomly assigned to an experimental group (10.70 ± 0.47 years old, n = 30) or a control group (10.77 ± 0.43 years old, n = 31). The experimental group underwent a two-week design-based STEM training program, while the control group participated in a 2-week STEM-related reading program. Both groups were assessed with the brain activation from 4 brain regions of interest using functional near-infrared spectroscopy (fNIRS) and behavioral measures during a Stroop task before and after the training. Analysis disclosed: (i) a significant within-group time effect in the experimental group, with posttest brain activation in Brodmann Area 10 and 46 being notably lower during neutral and word conditions; (ii) a significant between-group difference at posttest, with the experimental group showing considerably lower brain activation in Brodmann Area 10 and Brodmann Area 46 than the control group; and (iii) a significant task effect in brain activity among the three conditions of the Stroop task. These findings indicated that this STEM learning effectively enhanced executive function in left-behind children. The discrepancy between the non-significant differences in behavioral performance and the significant ones in brain activation implies a compensatory mechanism in brain activation. This study enriches current theories about the impact of Science, Technology, Engineering, and Mathematics (STEM) learning on children’s executive function development, providing biological evidence and valuable insights for educational curriculum design and assessment.
Treatment Outcomes Among Patients With a PositiveCandidaCulture Close to Randomization Receiving Rezafungin or Caspofungin in the ReSTORE Study
Authors: Soriano Alex , Honore Patrick M , Cornely Oliver A , Chayakulkeeree Methee , Bassetti Matteo , Haihui Huang , Dupont Hervé , Kim Young Keun , Kollef Marin , Kullberg Bart Jan , Manamley Nick , Pappas Peter , Pullman John , Sandison Taylor , Dignani Cecilia , Vazquez Jose A , Thompson George R 
Published: August 2024

AbstractBackgroundRezafungin, a novel, once-weekly echinocandin for the treatment of candidemia and/or invasive candidiasis (IC) was noninferior to caspofungin for day 30 all-cause mortality (ACM) and day 14 global cure in the phase 3 ReSTORE trial (NCT03667690). We conducted preplanned subgroup analyses for patients with a positive culture close to randomization in ReSTORE.MethodsReSTORE was a multicenter, double-blind, double-dummy, randomized trial in patients aged ≥18 years with candidemia and/or IC treated with once-weekly intravenous rezafungin (400 mg/200 mg) or once-daily intravenous caspofungin (70 mg/50 mg). This analysis comprised patients with a positive blood culture drawn between 12 hours before and 72 hours after randomization or a positive culture from another normally sterile site sampled between 48 hours before and 72 hours after randomization. Efficacy endpoints included day 30 ACM, day 14 global cure rate, and day 5 and 14 mycological response. Adverse events were evaluated.ResultsThis analysis included 38 patients randomized to rezafungin and 46 to caspofungin. In the rezafungin and caspofungin groups, respectively, day 30 ACM was 26.3% and 21.7% (between-group difference [95% confidence interval], 4.6% [−13.7%, 23.5%]), day 14 global response was 55.3% and 50.0% (between-group difference, 5.3% [−16.1%, 26.0%]), and day 5 mycological eradication was 71.1% and 50.0% (between-group difference, 21.1% [−0.2%, 40.2%]). Safety was comparable between treatments.ConclusionsThese findings support the efficacy and safety of rezafungin compared with caspofungin for the treatment of candidemia and/or IC in patients with a positive culture close to randomization, with potential early treatment benefits for rezafungin.
A Comparative Analysis of Clinical Symptoms and Modified Pouchitis Disease Activity Index Among Endoscopic Phenotypes of the J Pouch in Patients With Inflammatory Bowel Disease
Authors: Akiyama Shintaro , Cohen Nathaniel A , Ollech Jacob E , Traboulsi Cindy , Rodriguez Tina , Rai Victoria , Glick Laura R , Yi Yangtian , Runde Joseph , Cohen Russell D , Skowron Kinga B , Hurst Roger D , Umanskiy Konstantin , Shogan Benjamin D , Hyman Neil H , Rubin Michele A , Dalal Sushila R , Sakuraba Atsushi , Pekow Joel , Chang Eugene B , Rubin David T 
Published: August 2024

Abstract

Background
The modified pouchitis disease activity index (mPDAI) based on clinical symptoms and endoscopic findings is used to diagnose pouchitis, but validated instruments to monitor pouchitis are still lacking. We recently established an endoscopic classification that described 7 endoscopic phenotypes with different outcomes. We assessed symptoms and compared mPDAIs among phenotypes in inflammatory bowel disease (IBD).

Methods
We retrospectively reviewed pouchoscopies and classified them into 7 main phenotypes: normal (n = 25), afferent limb (AL) involvement (n = 4), inlet involvement (n = 14), diffuse (n = 7), focal inflammation of the pouch body (n = 25), cuffitis (n = 18), and pouch-related fistulas (n = 10) with a single phenotype were included. Complete-case analysis was conducted.

Results
One hundred and three IBD patients were included. The median mPDAI was 0 (IQR 0-1.0) in patients with a normal pouch. Among inflammatory phenotypes, the highest median mPDAI was 4.0 (IQR 2.25-4.75) in cuffitis, followed by 3.0 (IQR 2.5-4.0) in diffuse inflammation, 2.5 (IQR 1.25-4.0) in inlet involvement, 2.5 (IQR 2.0-3.5) in AL involvement, 2.0 (IQR 1.0-3.0) in focal inflammation, and 1.0 (IQR 0.25-2.0) in the fistula phenotype. Perianal symptoms were frequently observed in pouch-related fistulas (8/10, 80%) and cuffitis (13/15, 87%). Among patients with cuffitis, all had incomplete emptying (6/6, 100%).

Conclusions
We correlated the mPDAI with the endoscopic phenotypes and described the limited utility of symptoms in distinguishing between inflammatory phenotypes. Further studies are warranted to understand which symptoms should be monitored for each phenotype and whether mPDAI can be minimized after pouch normalization.
An acute coronary syndrome in an unusual patient: analysing cisplatin toxicity—a case report and review of the literature
Authors: Erquicia Peralt Josu , Fernandez Gonzalez Luis , Garcia San Román Koldobika , Astorga Burgo Juan Carlos , Acín Labarta Aida 
Published: August 2024

Abstract

Background
Germ cell tumours (GCT) are the most common malignancy affecting young adult men. The introduction of cisplatin-based chemotherapy in recent decades has significantly changed the prognosis of these malignant tumours into highly curable cancer, even in the setting of advanced disease. However, in the last decade, the success of these chemotherapy regimens in curing GCTs has been slowed by a growing recognition of their important late toxicities, such as cardiovascular disease.

Case summary
We present the case of a 23-year-old male, recently diagnosed with a mixed non-seminomatous testicular germinal tumour, on stage IIIA (pT3 cN2 cM1a), with retroperitoneal adenopathies and pulmonary metastases. After performing a right inguinal orchiectomy, he started chemotherapy treatment with cisplatin + etoposide. Shortly after starting treatment, the patient presented an ST-elevation acute coronary syndrome. The cardiac catheterization revealed a non-occlusive thrombus in the middle segment of the right coronary artery. Intracoronary imaging techniques were used to study the arterial wall, which revealed the presence of atherosclerotic plaque that could have ruptured, with the consequent response of platelet aggregation and thrombus formation. Barely 7 months after this event, the patient was again admitted to hospital for pulmonary thromboembolism with pulmonary infarction.

Discussion
To date, there are two hypotheses linking the association between cisplatin-based chemotherapy and cardiovascular disease. The direct hypothesis argues for the presence of direct chemotherapy-induced vascular damage. The indirect hypothesis, on the other hand, is based on the induction and development of cardiovascular risk factors by chemotherapy. This cardiovascular toxicity of chemotherapy is aggravated by a cancer-induced proinflammatory and prothrombotic state.
Towns and Princely Rebellion in Fifteenth-Century France: The War of the Public Weal, 1465
Authors: Murphy Neil 
Published: August 2024

Abstract
The historiography of fifteenth-century France overwhelmingly finds that towns worked with the monarchy against rebellious princes in pursuit of a centralised royal state. Focusing on the War of the Public Weal of 1465, this article demonstrates instead that urban communities played a central role in the rebellion and that there was considerable urban support for the league. This evidence suggests both that we need to re-evaluate the view that the princes lacked popular support in their rebellions against the Crown in fifteenth-century France and that we need to reconsider the current model of town–Crown relations. The article begins by highlighting regional patterns of support for the king and the princes during the war, before moving on to examine ideology and the reasons why towns favoured one side over the other. It then goes on to consider what townspeople hoped to gain from their actions during the War of the Public Weal, taking particular account of the presence of urban factions and the competition for urban privileges. A study of urban participation in the War of the Public Weal thus contributes to debates on the wider narratives of European state formation in the later Middle Ages, when increasingly powerful monarchs sought to break the power of their overmighty subjects by co-opting urban populations to join their cause, and highlights the ongoing limitations of French royal power at the end of the Middle Ages.
Overexpression of TIAM2S, a Critical Regulator for the Hippocampal–Medial Prefrontal Cortex Network, Progresses Age-Related Spatial Memory Impairment
Authors: Chu Chun-Hsien , Su Chia-Hao , Hsiao Ya-Hsin , Yu Chun-Chieh , Liao Yi-Chun , Mao Pin-Cheng , Chen Jia-Shing , Sun H Sunny 
Published: August 2024

Abstract
TIAM Rac1-associated GEF 2 short-form protein (TIAM2S) is abundant in specific brain tissues, especially in the hippocampus, a brain region critical for processing and consolidation of spatial memory. However, how TIAM2S plasticizes the microstructure and circuits of the hippocampus to shape spatial memory as a neuroplastic regulator during aging remains to be determined. In this study, transgenic mice overexpressing human TIAM2S protein (TIAM2S-TG mice) were included, and interdisciplinary approaches, such as spatial memory tests and multiparametric magnetic resonance imaging sequences, were conducted to determine the role and the mechanism of TIAM2S in age-related spatial memory deficits. Despite no changes in their neural and glial markers and neuropathological hallmark expression of the hippocampus, behavioral tests showed that the TIAM2S-TG mice, and not wild-type (WT) mice, developed spatial memory impairment at 18 months old. The T2-weighted and diffusion tensor image analyses were performed to further study the possible role of TIAM2S overexpression in altering the hippocampal structure or neuronal circlets of the mice, increasing their vulnerability to developing spatial memory deficits during aging. The results revealed that the 12-month-old TIAM2S-TG mice had hippocampal dysplasticity, with larger volume, increased fiber numbers, and changed mean fractional anisotropy compared to those in the age-matched WT mice. The fiber tractography analysis exhibited significantly attenuated structural connectivity between the hippocampus and medial prefrontal cortex in the TIAM2S-TG mice. In conclusion, overexpression of TIAM2S, a detrimental factor affecting hippocampus plasticity, causes attenuation of the connectivity within hippocampus–mPFC circuits, leading to age-related spatial memory impairment.