bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prospective pharmacotyping of urothelial carcinoma organoids for drug sensitivity prediction – feasibility and real world experience
Authors: Melzer Michael Karl , Ma Yanchun , Lindenmayer Jessica , Morgenstern Clara , Wezel Felix , Zengerling Friedemann , Günes Cagatay , Gaisa Nadine Therese , Kleger Alexander , Bolenz Christian 
Published: November 2024

AbstractUrothelial carcinoma (UC) of the urinary bladder has significant challenges in treatment due to its diverse genetic landscape and variable response to systemic therapy. In recent years, patient-derived organoids (PDOs) emerged as a novel tool to model primary tumors with higher resemblance than conventional 2D cell culture approaches. However, the potential of organoids to predict therapy response in a clinical setting remains to be evaluated. This study explores the clinical feasibility of PDOs for pharmacotyping in UC. Initially, we subjected tumor tissue specimens from 50 patients undergoing transurethral resection or radical cystectomy to organoid propagation, of whom 19 (38%) yielded PDOs suitable for drug sensitivity assessment. Notably, whole transcriptome-based analysis indicated that PDOs may show phenotypes distinct from their parental tumor tissue. Pharmacotyping within a clinically relevant timeframe [mean of 35.44 and 55 days for non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC), respectively] was achieved. Drug sensitivity analyses revealed marked differences between NMIBC and MIBC, with MIBC-derived organoids demonstrating higher chemosensitivity toward clinically relevant drugs. A case study correlating organoid response with patient treatment outcome illustrated the complexity of predicting chemotherapy efficacy, especially considering the rapid acquisition of drug resistance. We propose a workflow of prospective organoid-based pharmacotyping in UC, enabling further translational research and integration of this approach into clinical practice.
A 18F-FDG PET/CT-based deep learning-radiomics-clinical model for prediction of cervical lymph node metastasis in esophageal squamous cell carcinoma
Authors: Yuan Ping , Huang Zhen-Hao , Yang Yun-Hai , Bao Fei-Chao , Sun Ke , Chao Fang-Fang , Liu Ting-Ting , Zhang Jing-Jing , Xu Jin-Ming , Li Xiang-Nan , Li Feng , Ma Tao , Li Hao , Li Zi-Hao , Zhang Shan-Feng , Hu Jian , Qi Yu 
Published: November 2024

Abstract
Background
To develop an artificial intelligence (AI)-based model using Radiomics, deep learning (DL) features extracted from 18F-fluorodeoxyglucose (18F-FDG) Positron emission tomography/Computed Tomography (PET/CT) images of tumor and cervical lymph node with clinical feature for predicting cervical lymph node metastasis (CLNM) in patients with esophageal squamous cell carcinoma (ESCC).

Methods
The study included 300 ESCC patients from the First Affiliated Hospital of Zhengzhou University who were divided into a training cohort and an internal testing cohort with an 8:2 ratio. Another 111 patients from Shanghai Chest Hospital were included as the external cohort. For each sample, we extracted 428 PET/CT-based Radiomics features from the gross tumor volume (GTV) and cervical lymph node (CLN) delineated layer by layer and 256 PET/CT-based DL features from the maximum cross-section of GTV and CLN images We input these features into seven different machine learning algorithms and ultimately selected logistic regression (LR) as the model classifier. Subsequently, we evaluated seven models (Clinical, Radiomics, Radiomics-Clinical, DL-Clinical, DL-Radiomics, DL-Radiomics-Clinical) using Radiomics features, DL features and clinical feature.

Results
The DL-Radiomics-Clinical (DRC) model demonstrated higher AUC of 0.955 and 0.916 compared to the other six models in both internal and external testing cohorts respectively. The DRC model achieved the highest accuracy among the seven models in both the internal and external test sets, with scores of 0.951 and 0.892, respectively.

Conclusions
Through the combination of Radiomics features and DL features from PET/CT imaging and clinical feature, we developed a predictive model exhibiting exceptional classification capabilities. This model can be considered as a non-invasive method for predication of CLNM in patients with ESCC. It might facilitate decision-making regarding to the extend of lymph node dissection, and to select candidates for postoperative adjuvant therapy.
Volumetric changes of porcine collagen matrix and free gingival grafts for soft-tissue grafting to increase the width of keratinized tissue around dental implants: a retrospective clinical study
Authors: Ramanauskaite Ausra , Müller Katharina Melissa , Schliephake Carla , Obreja Karina , Begic Amira , Dahmer Iulia , Parvini Puria , Schwarz Frank 
Published: November 2024

Abstract
Aim
To compare three-dimensional changes of aporcine derived collagen matrix (CM) and free gingival grafts (FGG) for increasing keratinized tissue (KT) at dental implants over a 24-month follow-up period.

Materials and methods
This retrospective study enrolled 25 patients exhibiting 41 implants with deficient KT width (i.e., < 2 mm) who underwent soft tissue augmentation using either CM (11 patients/15 implants) or FGG (14 patients/26 implants). The primary outcome was tissue thickness change (mm) at treated implant sites between 1- (S0), 12- (S1), and 24-months (S2). Secondary outcome was the changes of KT width over a 24-month follow-up period.

Results
Dimensional analyses from S0 to S1 and from S0 to S2 revealed a mean decrease in tissue thickness of -0.05 ± 0.35 mm and − 0.31 ± 0.41 mm in the CM group, and − 0.23 ± 0.38 mm and − 0.22 ± 0.81 mm in the FGG group, with no significant differences found between the groups (S0-S1: p = 0.14, S0-S2: p = 0.58). Within S1 and S2, the CM and FGG groups displayed comparable tissue thickness reduction (CM: -0.32 ± 0.53 mm, FGG: -0.02 ± 0.21 mm; p = 0.07). The FGG group exhibited a significantly greater KT gain 24-months compared to the CM group (CM: 1.50 ± 1.14 mm, FGG: 4.04 ± 1.65 mm; p < 0.001).

Conclusions
CM and FGG were associated with comparable three-dimensional thickness changes over a period of 24 months. A significantly wider KT band could be established in the FGG group.

Graphical Abstract
Patient perception of bowel urgency and remission in moderately to severely active Crohn’s disease or ulcerative colitis: a qualitative study
Authors: Gibble Theresa Hunter , Stassek Larissa , Harding Gale , Stefan Marissa , Fikre Tsion , Bleakman Alison Potts , Moses Richard , Dubinsky Marla 
Published: November 2024

Abstract
Background
Bowel urgency, the sudden and immediate need to have a bowel movement, is common in patients with ulcerative colitis (UC) and Crohn’s disease (CD). While its impact in UC is well established, less is known about its importance in CD. Further, what level of bowel urgency control patients with UC or CD would consider to be acceptable or in remission has not been established. This qualitative study aimed to understand perceptions of bowel urgency and remission in these patients.

Methods
Semi-structured combined concept elicitation and cognitive interviews were conducted to explore how adults with moderate-to-severe UC or CD and current or recent bowel urgency think about the concept of bowel urgency and its remission. The Urgency Numeric Rating Scale (UNRS) was used to examine different levels of bowel urgency severity and to investigate what level of bowel urgency patients would consider as representing remission.

Results
Forty adults (n = 19 UC, n = 21 CD) recruited from six US sites completed the study. Sociodemographic and clinical characteristics were similar in both groups. Both groups reported impacts of bowel urgency on physical, social, professional, and emotional aspects of their lives. Most participants (n = 15 UC, n = 18 CD) reported having experienced one or more incidents of urgency-related fecal incontinence. Most participants considered remission to be a state with a normal or reduced number of bowel movements and no or less frequent bowel urgency, and they noted that remission would increase their ability to engage in daily activities without fear of fecal incontinence. Participants were able to map different levels of severity of bowel urgency to UNRS score ranges (scale: 0–10), and they indicated that a mean UNRS score of 5 (UC) or 4 (CD) would be the highest point on the NRS at which they would still consider their bowel urgency to be in remission.

Conclusions
Bowel urgency is an important issue for patients with either moderate-to-severe UC or CD, and its remission would improve their lives. Further, these patients may still consider bowel urgency to be in remission even at UNRS scores as high as 4 or 5.
Efficiency of the fungi isolated from the tomato rhizosphere to control the north root-knot nematode Meloidogyne hapla Chitwood 1949
Authors: Nekoval Svetlana N. , Chernyakovich Maxim N. , Churikova Arina K. , Maskalenko Oksana A. , Muravyov Vyacheslav S. 
Published: November 2024

Abstract
Background
In the South of Russia, due to the large acreage of tomato crops (Solanum lycopersicum Mill.), there is an acute problem of plant protection against the obligate endoparasitic of the root system Meloidogyne hapla Chitwood 1949. The aim of this study was to assess the nematicidal activity of fungal strains isolated from the rhizosphere of tomato plants infected with root-knot nematodes (RKN) (Meloidogyne spp.).

Results
After conducting route surveys, 10 soil samples were selected from the rhizosphere of tomato plants affected by RKN. Fifteen isolates of fungi belonging to different species were isolated from the soil samples. The species composition of the isolated fungal strains was determined: Metarhizium anisopliae IG01, Penicillium citrinum IG02, Trichoderma harzianum IG03, Aspergillus niger IG04, Trichoderma ghanense IG05, Trichoderma harzianum IG06, Trichoderma atroviride IG07, Aspergillus awamori IG08, Trichoderma atroviride IG09, Paramyrothecium roridum IG10, Trichoderma atroviride IG11, Trichoderma hamatum IG12, Beauveria bassiana IG13, Aspergillus ochraceus IG14, Purpureocillium lilacinum IG15. After initial screening in the laboratory, strains with the greatest nematicidal activity and safe for humans were selected: M. anisopliae ИГ01, T. harzianum IG03, T. ghanense IG05, T. atroviride IG07, T. atroviride IG09. The mortality rate of RKN when using these fungal strains varied from 79.4 ± 1.8 to 93.9 ± 3.1%. In the greenhouse, the fungal strains M. anisopliae IG01, T. harzianum IG03, T. ghanense IG05, T. atroviride IG07, T. atroviride IG09 showed high results in reducing the number of galls on the roots of tomato plants, and their biological efficacy was 71.4–83.0%.

Conclusion
Work on the study of the nematicidal activity of fungi, in vitro and in vivo, allows us to conclude that strains isolated from the rhizosphere of plants can be effective in combating the north RKN (M. hapla). In the future, it is planned to establish the compatibility of M. anisopliae IG01, T. harzianum IG03, T. ghanense IG05, T. atroviride IG07, T. atroviride IG09 with each other and selecting the ratios of the studied strains to obtain mixtures to create an effective biological nematicide.
Prevalence of comorbid autoimmune diseases and antibodies in newly diagnosed multiple sclerosis patients
Authors: Jendretzky Konstantin Fritz , Lezius Lisa-Marie , Thiele Thea , Konen Franz Felix , Huss André , Heitmann Lena , Güzeloglu Yunus Emre , Schwenkenbecher Philipp , Sühs Kurt-Wolfram , Skuljec Jelena , Wattjes Mike Peter , Witte Torsten , Kleinschnitz Christoph , Pul Refik , Tumani Hayrettin , Gingele Stefan , Skripuletz Thomas 
Published: November 2024

Abstract
Background
Diagnosing multiple sclerosis (MS) is challenging due to diverse symptoms and the absence of specific biomarkers. Concurrent autoimmune diseases (AID) or non-specific antibodies further complicate diagnosis, progression monitoring, and management. Data on AID prevalence in MS patients are sparse. This study aims to identify concurrent AIDs alongside MS.

Methods
In this retrospective single-center study, we analyzed patient records at our university hospital from 2010 to 2017, focusing on cases suspected of inflammatory demyelinating disease. The 2017 McDonald criteria were applied. Additionally, we measured neurofilament light (NfL) levels from available CSF samples in our biobank.

Results
We identified a total of 315 patients, of whom 66% were women. In total, 13.7% of all patients had concurrent AID, while 20.3% had isolated antibody findings without AID. The most common AID was autoimmune thyroiditis (8.9%), followed by chronic inflammatory skin diseases (1.6%), arthritis (1%), type 1 diabetes (1%), Sjögren’s syndrome (0.6%), and inflammatory bowel diseases (0.6%). Cardiolipin antibodies were the most frequent isolated antibody finding (8.6%). Our data showed that, from the perspective of the initial demyelinating event, neither comorbid AID nor isolated antibodies significantly influenced relapses or MS progression over a median follow-up of 9 months. Standard CSF parameters and NfL levels were similar between the groups at the time of MS diagnosis.

Conclusion
Our study shows that AIDs, particularly autoimmune thyroiditis, frequently occur at the onset of MS. The proportion of AIDs commonly treated with immunomodulatory therapy in our cohort was similar to that observed in the general population. Comorbid AID did not affect NfL levels, indicating similar disease activity. Future research should explore new AID emergence during the course of MS, especially considering the increased incidence of rheumatic diseases later in life.
JCCG ALL-B12: Evaluation of Intensified Therapies With Vincristine/Dexamethasone Pulses and Asparaginase and Augmented High-Dose Methotrexate for Pediatric B-ALL
Authors: Kato Motohiro , Okamoto Yasuhiro , Imamura Toshihiko , Kada Akiko , Saito Akiko M. , Iijima-Yamashita Yuka , Deguchi Takao , Ohki Kentaro , Fukushima Takashi , Anami Kenichi , Sanada Masashi , Taki Tomohiko , Hashii Yoshiko , Inukai Takeshi , Kiyokawa Nobutaka , Kosaka Yoshiyuki , Yoshida Nao , Yuza Yuki , Yanagimachi Masakatsu , Watanabe Kenichiro , Sato Atsushi , Imai Chihaya , Taga Takashi , Adachi Souichi , Horibe Keizo , Manabe Atsushi , Koh Katsuyoshi 
Published: November 2024

PURPOSE
The JCCG ALL-B12 clinical trial aimed to evaluate the effectiveness of unvalidated treatment phases for pediatric ALL and develop a safety-focused treatment framework.

PATIENTS AND METHODS
Patients age 1-19 years with newly diagnosed B-ALL were enrolled in this study. These patients were stratified into standard-risk (SR), intermediate-risk (IR), and high-risk (HR) groups. Randomized comparisons assessed the effectiveness of vincristine (VCR)/dexamethasone pulses in the SR group, evaluated the effects of L-asparaginase (ASP) intensification in the IR group, and compared standard consolidation including block-type treatment with experimental consolidation with high-dose methotrexate (HD-MTX) intensified with VCR and ASP in the HR group.

RESULTS
Of 1,936 patients enrolled, 1,804 were eligible for the experimental treatment. The overall 5-year event-free survival and overall survival rates were 85.2% (95% CI, 83.5 to 86.8) and 94.3% (95% CI, 93.1 to 95.3), respectively. The cumulative incidence of relapse and postremission nonrelapse mortality was 13.2% (95% CI, 11.6 to 14.8) and 0.6% (95% CI, 0.3 to 1.0), respectively. Random assignment in the SR group showed no significant benefit from pulse therapy. In the IR group, ASP intensification had limited effects. In the HR group, standard block therapy and HD-MTX yielded equivalent outcomes.

CONCLUSION
The ALL-B12 trial achieved favorable outcomes in a nationwide cohort by stratifying treatment on the basis of risk and balancing treatment intensity. This study not only demonstrated that existing standard of care can be further refined but also indicated that improvement in outcomes with intensified chemotherapy has reached a plateau.
Blood Pressure Decreases in Overweight Elderly Individuals on Vitamin D: A Randomized Trial
Authors: Rahme Maya , Al-Shaar Laila , Tamim Hani , El-Hajj Fuleihan Ghada 
Published: November 2024

Abstract

Context
Evidence for a beneficial role of vitamin D on blood pressure (BP) outcomes is inconclusive.

Objective
This work aimed to investigate the effect of 2 doses of cholecalciferol (vitamin D3) supplementation coadministered with calcium on systolic blood pressure (SBP) and diastolic blood pressure (DBP).

Methods
Exploratory analyses were conducted from a 1-year, multicenter, double-blind, randomized controlled trial (RCT). Total of 221 ambulatory older overweight individuals received calcium dose and oral vitamin D3, at the equivalent of 600 IU/day or 3750 IU/day.

Results
SBP and DBP decreased significantly in the overall group, and in the high-dose group at 6 and 12 months. Similar trends were observed in the low-dose group, but did not achieve statistical significance. In participants with a body mass index (BMI) greater than 30, SBP decreased significantly in both treatment groups whereas DBP significantly decreased in the high-dose group only. In the subgroups of hypertensive participants (N = 143), there was a decrease in SBP and DBP at 6 and 12 months, with both vitamin D doses and independently of BMI levels. Using multivariate linear mixed models with random effects in the overall group of participants, SBP at 6 and 12 months was significantly predicted by BMI (β = .29; P = .05) and by baseline SBP (β = .16; P &lt; .001), but not by vitamin D treatment dose.

Conclusion
Vitamin D and calcium decrease SBP and DBP in overweight older individuals, but more is not necessarily better. This effect is seen in individuals with BMI greater than 30, in hypertensive patients, and seems to be largely independent of dose.
Improved Clinical Outcomes During Long-term Osilodrostat Treatment of Cushing Disease With Normalization of Late-night Salivary Cortisol and Urinary Free Cortisol
Authors: Newell-Price John , Fleseriu Maria , Pivonello Rosario , Feelders Richard A , Gadelha Mônica R , Lacroix André , Witek Przemysław , Heaney Anthony P , Piacentini Andrea , Pedroncelli Alberto M , Biller Beverly M K 
Published: November 2024

Abstract

Purpose
To assess whether simultaneous normalization of late-night salivary cortisol (LNSC) and mean urinary free cortisol (mUFC) in patients with Cushing disease treated with osilodrostat is associated with better clinical outcomes than control of mUFC or LNSC alone.

Methods
Pooled data from two phase III osilodrostat studies (LINC 3 and LINC 4) were analyzed. Both comprised a 48-week core phase and an optional open-label extension. Changes in cardiovascular/metabolic-related parameters, physical manifestations of hypercortisolism, and quality of life (QoL) were evaluated across the following patient subgroups: both LNSC and mUFC controlled, only mUFC controlled, only LNSC controlled, and neither controlled.

Results
Of 160 patients included in the analysis, 85.0% had both LNSC and mUFC uncontrolled at baseline. At week 72, 48.6% of patients had both LNSC and mUFC controlled; these patients generally exhibited greater improvements in cardiovascular/metabolic-related parameters than those with only mUFC controlled or both LNSC and mUFC uncontrolled: systolic/diastolic blood pressure, −7.4%/−4.9%, −6.0%/−5.5%, and 2.3%/0.8%, respectively; fasting plasma glucose, −5.0%, −4.8%, and 1.9%; glycated hemoglobin, −5.1%, −4.8%, and −1.3%. Weight, waist circumference, and body mass index improved with control of LNSC and/or mUFC; physical manifestations of hypercortisolism generally improved regardless of LNSC/mUFC control. Patients with both LNSC and mUFC controlled or only mUFC controlled had the greatest improvement from baseline to week 72 in QoL.

Conclusion
In osilodrostat-treated patients with Cushing disease, normalization of LNSC and mUFC led to improvements in long-term outcomes, indicating that treatment should aim for normalization of both parameters for optimal patient outcomes.

Clinical trial identifiers
NCT02180217 (LINC 3); NCT02697734 (LINC 4)
Direct Aspiration Versus Combined Technique for Anterior Distal, Medium Vessel Occlusions Stroke: The JET Distal Vessel Occlusion Study
Authors: Palmisano Vitanio , Simonetti Luigi , Marotti Nicola , Reverberi Lorenzo , Comai Alessio , Ganimede Maria Porzia , Comelli Simone , Taglialatela Francesco , Zini Andrea , Paolucci Matteo , Sponza Massimo , Ciardi Chiara , Verganti Luca , Vallone Stefano , Gorgatti Tommaso , Franchini Enrica , Marrazzo Antonio , Paladini Andrea , della Malva Giuseppina , Barone Michele , Briatico Vangosa Alessandra , Di Stasi Carmine , Burdi Nicola , Semeraro Vittorio 
Published: November 2024

BACKGROUND AND OBJECTIVES:
The optimal mechanical thrombectomy technique for distal, medium vessel occlusion (DMVO) stroke remains unknown. We aimed to compare the safety and efficacy of 2 thrombectomy first-line approaches, direct aspiration (DA), and combined technique (CT) in patients with DMVOs.

METHODS:
We conducted a retrospective review of a prospectively collected multicenter database of patients with DMVOs (at or distal to M2 and A1), who underwent mechanical thrombectomy with JET D reperfusion catheters between January 2020 and December 2021. The primary end point was the rate of first-pass complete recanalization, defined as modified treatment in cerebral infarction (mTICI) 3. The hemorrhagic complications, the 90 days functional independence rate (modified Rankin Scale 0-2), and mortality were also evaluated.

RESULTS:
A total of 171 consecutive patients were enrolled (95 in DA and 76 in CT cohort). The 2 groups had comparable demographics and baseline characteristics. The DA group had a higher rate of first-pass effect (40.0% vs 10.5%, P < .001), final mTICI 2b-3 (89.5% vs 71.1%, P = .003) and final mTICI 3 (58.9% vs 28.9%, P < .001), shorter groin to reperfusion time (65 ± 43 min vs 101 ± 60 min, P < .001), and higher rate of 90-day functional independence (63.7% vs 36.1%; P = .001) compared with the CT group. There were no significant differences in hemorrhagic complications between the 2 groups. The DA group showed a lower rate of 90-day mortality (9.9% vs 27.8%; P = .004).

CONCLUSION:
In patients with DMVOs, DA with a distal dedicated reperfusion catheter appears to demonstrate better safety and efficacy when compared with the CT using the same catheter.