bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selpercatinib for treating recurrent mixed medullary and follicular cell-derived thyroid carcinoma: a case report
Authors: Kadoya Mei , Suganuma Nobuyasu , Matsubara Yuka , Takase Hiroki , Kumagai Eita , Toda Soji , Yamazaki Haruhiko , Masudo Katsuhiko , Fujii Satoshi , Saito Aya 
Published: April 2024

Abstract
Background
Mixed medullary and follicular cell-derived thyroid carcinoma (MMFCC) is characterized by the coexistence of follicular and C cell–derived tumour cell populations within the same lesion. Due to its rarity, its etiology and clinical course remain unclear, and treatment for advanced or recurrent cases has not been established.

Case presentation
We report a case of MMFCC treated with selpercatinib. The patient was a 69-year-old male presenting with tumors in the right thyroid lobe and in the upper mediastinum. Fine-needle aspiration (FNA) cytology of the right thyroid lobe tumor revealed a medullary carcinoma; germline RET mutations were not detected. After resection of the right thyroid lobe with central node dissection, rapid intraoperative diagnosis of the mediastinal mass confirmed malignancy, leading to total thyroidectomy with excision of the upper mediastinal tumor. Histologically, the tumor in the right thyroid lobe and the pretracheal lymph node revealed a mixture of medullary and follicular carcinoma components, diagnosed as MMFCC. The mediastinal lymph node exhibited only medullary carcinoma components. At 11 months postoperatively, computed tomography scans showed enlargement of the right supraclavicular and upper mediastinal lymph nodes. FNA cytology of the right supraclavicular lymph node suggested the recurrence of medullary thyroid carcinoma. The gene panel testing (The Oncomine Dx Target Test Multi-CDx system®, Thermo Fisher SCIENTIFIC) of metastatic lymph node revealed RET somatic mutation (M918T). Treatment with selpercatinib was initiated, and both the cervical and mediastinal lymph nodes showed a reduction in size.

Conclusions
We report a rare case of selpercatinib use for MMFCC. Since RET mutations may occur frequently in MMFCC, selpercatinib could be effective in treating MMFCC.
Multimodal exercise training to reduce frailty in people with multiple sclerosis: study protocol for a pilot randomized controlled trial
Authors: Zanotto Tobia , Kumar Danya Pradeep , Tabatabaei Abbas , Lynch Sharon G. , He Jianghua , Herda Trent J. , Devos Hannes , Thiyagarajan Ramkumar , Chaves Lee , Seldeen Kenneth , Troen Bruce R. , Sosnoff Jacob J. 
Published: April 2024

Abstract
Background
Frailty, a syndrome characterized by decreased reserve and resistance to stressors across multiple physiologic systems, is highly prevalent in people living with multiple sclerosis (pwMS), independent of age or disability level. Frailty in MS is strongly associated with adverse clinical outcomes, such as falls, and may aggravate MS-related symptoms. Consequently, there is a pressing necessity to explore and evaluate strategies to reduce frailty levels in pwMS. The purpose of this pilot randomized controlled trial (RCT) will be to examine the feasibility and preliminary efficacy of a multimodal exercise training program to reduce frailty in pwMS.

Methods
A total of 24 participants will be randomly assigned to 6 weeks of multimodal exercise or to a waitlist control group with a 1:1 allocation. PwMS aged 40–65 years and living with frailty will be eligible. The multimodal exercise program will consist of cognitive-motor rehabilitation (i.e., virtual reality treadmill training) combined with progressive, evidence-based resistance training. At baseline and post-intervention, participants will complete the Evaluative Frailty Index for Physical Activity (EFIP), measures of fall risk, and quality of life. Frailty-related biomarkers will also be assessed. In addition, the feasibility of the multimodal exercise program will be systematically and multidimensionally evaluated.

Discussion
To date, no RCT has yet been conducted to evaluate whether targeted exercise interventions can minimize frailty in MS. The current study will provide novel data on the feasibility and preliminary efficacy of multimodal exercise training as a strategy for counteracting frailty in pwMS.

Trial registration
ClinicalTrials.gov, NCT06042244 (registered in September 2023).
Astaxanthin suppresses the malignant behaviors of nasopharyngeal carcinoma cells by blocking PI3K/AKT and NF-κB pathways via miR-29a-3p
Authors: Xu Yajia , Jiang Chengyi 
Published: April 2024

Abstract
Background
As a natural extraction, astaxanthin is gaining increasing attention because of its safety and anti-tumor properties. It has been reported to participate in the progression of various types of cancer such as gastric cancer and ovarian cancer. Nevertheless, the role of astaxanthin in nasopharyngeal carcinoma (NPC) has not been investigated.

Object
The study aimed to explore the anticancer mechanism of astaxanthin in regulating NPC cell proliferation, cell cycle progression, apoptosis, migration, and invasion.

Methods
Human NPC cells (C666-1) were treated with different concentrations of astaxanthin (0, 1, 10, 20 mg/mL) followed by detection of cell viability. Then, C666-1 cell proliferation, apoptosis, cell cycle progression, invasion, and migration in response to 10 mg/mL astaxanthin, LY294002 (PI3K/AKT inhibitor) or parthenolide (PTL; NF-κB inhibitor) treatment were measured using cell counting kit-8 assay, colony forming assay, flow cytometry analyses, Transwell assay, and wound healing assay, respectively. Western blotting was performed to quantify protein levels of factors involved in PI3K/AKT and NF-κB signaling pathways, cell cycle phase markers (Cyclin D1, p21) and apoptotic markers (Bcl-2 and Bax).

Results
C666-1 cell proliferation, invasion, and migration were significantly suppressed by astaxanthin while cell apoptosis and cell cycle arrest at G1 phase were effectively enhanced in the context of 10 mg/mL astaxanthin. Protein levels of p-AKT, p-P65 and p-IκB levels were suppressed by astaxanthin treatment. After LY294002 or PTL treatment, the suppressive impact of astaxanthin on C666-1 cell process was strengthened, accompanied by the more obvious decrease in cell activity and cell colony number, more enhanced cell apoptosis and G1 phase arrest, and further inhibited cell migration and invasion. Moreover, the inhibitory effect of astaxanthin on Cyclin D1 and Bcl-2 protein levels as well as the promoting impact of astaxanthin on p21 and Bax were also amplified in combination with LY294002 or PTL treatment.

Conclusions
Astaxanthin significantly suppresses NPC cell proliferation, cell cycle arrest, migration, invasion while promoting cell apoptosis by inactivating PI3K/AKT and NF-κB pathways. The study first reveals the anticancer role of astaxanthin in NPC, providing a potential candidate for NPC treatment.
Efficacy of combined formulation of bromadiolone and cholecalciferol in reducing rodent population and damage in agricultural crop fields
Authors: Saggi Diksha , Singla Neena 
Published: April 2024

Abstract
Background
Field rodents cause significant damage to standing crops in agroecosystems at vulnerable stages. Of all the methods available, chemical rodent control is the most practical and economically feasible. Laboratory studies demonstrate the potential of synergistic bait formulations containing bromadiolone and cholecalciferol. This study is the first multi-site multi-crop trial to assess the efficacy of cereal bait formulations containing lower than standard doses of bromadiolone (0.0025 and 0.001%) and cholecalciferol (0.02 and 0.04%) compared to presently recommended bait formulations of zinc phosphide (2.0%) and bromadiolone (0.005%) to protect wheat, rice and sugarcane crop fields against rodent attack.

Results
Rodent control success was highest (74.21–88.80%) in fields treated with a combination bait formulation containing bromadiolone (0.0025%) and cholecalciferol (0.04%), which led to a significant reduction in crop damage (from 6.82 to 26.56% cut tillers/canes and 251.75–1448.00 kg/ha yield loss (in reference block) to 1.18–6.18% cut tillers/canes and 46.67–745.00 kg/ha yield loss (in treated blocks).

Conclusions
This study therefore found that cereal bait formulation containing bromadiolone (0.0025%) and cholecalciferol (0.04%) can be effectively used to manage rodent population in agricultural crop fields and it is suggested that consideration be given to registering this combination rodenticide formulation to improve global food security.
Effect size varies based on calculation method and may affect interpretation of treatment effect: an illustration using randomised clinical trials in osteoarthritis
Authors: Schnitzer Thomas J. , Conaghan Philip G. , Berenbaum Francis , Abraham Lucy , Cappelleri Joseph C. , Bushmakin Andrew G. , Viktrup Lars , Yang Ruoyong , Brown Mark T. 
Published: April 2024

Abstract
Background
To illustrate how (standardised) effect sizes (ES) vary based on calculation method and to provide considerations for improved reporting.

Methods
Data from three trials of tanezumab in subjects with osteoarthritis were analyzed. ES of tanezumab versus comparator for WOMAC Pain (outcome) was defined as least squares difference between means (mixed model for repeated measures analysis) divided by a pooled standard deviation (SD) of outcome scores. Three approaches to computing the SD were evaluated: Baseline (the pooled SD of WOMAC Pain values at baseline [pooled across treatments]); Endpoint (the pooled SD of these values at the time primary endpoints were assessed); and Median (the median pooled SD of these values based on the pooled SDs across available timepoints). Bootstrap analyses were used to compute 95% confidence intervals (CI).

Results
ES (95% CI) of tanezumab 2.5 mg based on Baseline, Endpoint, and Median SDs in one study were − 0.416 (− 0.796, − 0.060), − 0.195 (− 0.371, − 0.028), and − 0.196 (− 0.373, − 0.028), respectively; negative values indicate pain improvement. This pattern of ES differences (largest with Baseline SD, smallest with Endpoint SD, Median SD similar to Endpoint SD) was consistent across all studies and doses of tanezumab.

Conclusion
Differences in ES affect interpretation of treatment effect. Therefore, we advocate clearly reporting individual elements of ES in addition to its overall calculation. This is particularly important when ES estimates are used to determine sample sizes for clinical trials, as larger ES will lead to smaller sample sizes and potentially underpowered studies.

Trial Registration
Clinicaltrials.gov NCT02697773, NCT02709486, and NCT02528188.
A prospective open-label study to evaluate the effectiveness of intravenous ketamine as an adjunct in treating severe depression
Authors: Thatisetti Venkata Pavan Kumar , Bolla Divya , Donthu Raj Kiran , Pathak Anzory , Gudimetla Amrutha 
Published: April 2024

Abstract
Background
Ketamine, an emerging pharmacotherapeutic agent for depression, has demonstrated rapid and substantial improvement in mood and suicidal ideation, particularly in severe cases. While previous studies have established its efficacy, the current study aims to delve into the effectiveness of intravenous ketamine in treating severe depression.

Methods
An open-label prospective study enrolled 49 consecutive patients with severe depression. Baseline assessments using the Hamilton Depression Rating Scale (HAMD), Montgomery-Asberg Depression Rating Scale (MADRS), and Modified Scale for Suicidal Ideation (MSSI) were conducted. Intravenous (IV) ketamine, administered at 0.5 mg/kg in 100-ml normal saline over 40 min, was given during sessions spaced on alternate days. Each patient received at least five sessions alongside their regular antidepressants. Close monitoring occurred during the infusion, and disease rating scale scores were recorded. Data was analyzed; employed paired Student t-test and graphical were used for visual clarity.

Results
Following the initiation of IV ketamine, a significant reduction in scores was observed from baseline. Response rates were achieved in over half of the patients by the third session and in nearly all by the end of fifth session. Remission rates were attained in nearly half of the patients by the fourth session and in almost all by the fifth session.

Conclusions
IV ketamine could be considered as an adjunct to antidepressants in treating severe depression especially among those with suicidal ideations to obtain rapid improvement. However, the need for long-term studies is emphasized to determine the duration of its effect.
Radio-anatomical evaluation of clinical and radiomic profile of multi-parametric magnetic resonance imaging of de novo glioblastoma multiforme
Authors: Ahmed H. Shafeeq , Devaraj Trupti , Singhvi Maanini , Dasan T. Arul , Ranganath Priya 
Published: April 2024

Abstract
Background
Glioblastoma (GBM) is a fatal, fast-growing, and aggressive brain tumor arising from glial cells or their progenitors. It is a primary malignancy with a poor prognosis. The current study aims at evaluating the neuroradiological parameters of de novo GBM by analyzing the brain multi-parametric magnetic resonance imaging (mpMRI) scans acquired from a publicly available database analysis of the scans.

Methods
The dataset used was the mpMRI scans for de novo glioblastoma (GBM) patients from the University of Pennsylvania Health System, called the UPENN-GBM dataset. This was a collection from The Cancer Imaging Archive (TCIA), a part of the National Cancer Institute. The MRIs were reviewed by a single diagnostic radiologist, and the tumor parameters were recorded, wherein all recorded data was corroborated with the clinical findings.

Results
The study included a total of 58 subjects who were predominantly male (male:female ratio of 1.07:1). The mean age with SD was 58.49 (11.39) years. Mean survival days with SD were 347 (416.21) days. The left parietal lobe was the most commonly found tumor location with 11 (18.96%) patients. The mean intensity for T1, T2, and FLAIR with SD was 1.45E + 02 (20.42), 1.11E + 02 (17.61), and 141.64 (30.67), respectively (p =  < 0.001). The tumor dimensions of anteroposterior, transverse, and craniocaudal gave a z-score (significance level = 0.05) of − 2.53 (p = 0.01), − 3.89 (p < 0.001), and 1.53 (p = 0.12), respectively.

Conclusion
The current study takes a third-party database and reduces physician bias from interfering with study findings. Further prospective and retrospective studies are needed to provide conclusive data.
SKZC: self-distillation and k-nearest neighbor-based zero-shot classification
Authors: Sun Muyang , Jia Haitao 
Published: April 2024

AbstractZero-shot learning represents a formidable paradigm in machine learning, wherein the crux lies in distilling and generalizing knowledge from observed classes to novel ones. The objective is to identify unfamiliar objects that were not included in the model’s training, leveraging learned patterns and knowledge from previously encountered categories. As a crucial subtask of open-world object detection, zero-shot classification can also provide insights and solutions for this field. Despite its potential, current zero-shot classification models often suffer from a performance gap due to limited transfer ability and discriminative capability of learned representations. In pursuit of advancing the subpar state of zero-shot object classification, this paper introduces a novel model for image classification which can be applied to object detection, namely, self-distillation and k-nearest neighbor-based zero-shot classification method. First, we employ a diffusion detector to identify potential objects in images. Then, self-distillation and distance-based classifiers are used for distinguishing unseen objects from seen classes. The k-nearest neighbor-based cluster heads are designed to cluster the unseen objects. Extensive experiments and visualizations were conducted on publicly available datasets on the efficacy of the proposed approach. Precisely, our model demonstrates performance improvement of over 20% compared to contrastive clustering. Moreover, it achieves a precision of 0.910 and a recall of 0.842 on CIFAR-10 datasets, a precision of 0.737, and a recall of 0.688 on CIFAR-100 datasets for the macro average. Compared to a more recent model (SGFR), our model realized improvements of 10.9%, 13.3%, and 7.8% in Sacc, Uacc, and H metrics, respectively. This study aims to introduce fresh ideas into the domain of zero-shot image classification, and it can be applied to open-world object detection tasks. Our code is available at https://www.github.com/CmosWolf1/Code_implementation_for_paper_SKZC.
Compressive loading and response time behavior of concrete containing refractory brick coarse aggregates
Authors: Deti Deti , Tjaronge Muhammad Wihardi , Caronge Muhammad Akbar 
Published: April 2024

AbstractThis research aimed to determine compressive stress and response time of using refractory brick waste as alternative natural coarse aggregates combined with blended cement in manufacturing sustainable concrete. The experiment was conducted by adding 15–50% aggregates volume of refractory bricks coarse aggregate (RBCA) to concrete mix in order to determine the suitability as coarse aggregates. The results showed that the slump values for the combination of standard concrete (SC) with all RBCA satisfied the design value of ± 20 cm and this showed easy handling and workability of the fresh concrete produced. Moreover, the peak stress and toughness were reduced as RBCA increased from 15 to 50% at both w/c of 0.52 and 0.49. The relationship between compressive stress and response time also showed that the travel time at the elastic, peak, and ultimate stages decreased as RBCA increased from 15 to 50% at both w/c. It was concluded that concrete mix with 50% RBCA did not meet the required criteria at w/c of 0.49 but those with 15–50% RBCA satisfied the minimum requirements at w/c of 0.52.
Explainable Machine Learning Model to Preoperatively Predict Postoperative Complications in Inpatients With Cancer Undergoing Major Operations
Authors: Hernandez Matthew C. , Chen Chen , Nguyen Andrew , Choong Kevin , Carlin Cameron , Nelson Rebecca A. , Rossi Lorenzo A. , Seth Naini , McNeese Kathy , Yuh Bertram , Eftekhari Zahra , Lai Lily L. 
Published: April 2024

PURPOSE Preoperative prediction of postoperative complications (PCs) in inpatients with cancer is challenging. We developed an explainable machine learning (ML) model to predict PCs in a heterogenous population of inpatients with cancer undergoing same-hospitalization major operations. METHODS Consecutive inpatients who underwent same-hospitalization operations from December 2017 to June 2021 at a single institution were retrospectively reviewed. The ML model was developed and tested using electronic health record (EHR) data to predict 30-day PCs for patients with Clavien-Dindo grade 3 or higher (CD 3+) per the CD classification system. Model performance was assessed using area under the receiver operating characteristic curve (AUROC), area under the precision recall curve (AUPRC), and calibration plots. Model explanation was performed using the Shapley additive explanations (SHAP) method at cohort and individual operation levels. RESULTS A total of 988 operations in 827 inpatients were included. The ML model was trained using 788 operations and tested using a holdout set of 200 operations. The CD 3+ complication rates were 28.6% and 27.5% in the training and holdout test sets, respectively. Training and holdout test sets’ model performance in predicting CD 3+ complications yielded an AUROC of 0.77 and 0.73 and an AUPRC of 0.56 and 0.52, respectively. Calibration plots demonstrated good reliability. The SHAP method identified features and the contributions of the features to the risk of PCs. CONCLUSION We trained and tested an explainable ML model to predict the risk of developing PCs in patients with cancer. Using patient-specific EHR data, the ML model accurately discriminated the risk of developing CD 3+ complications and displayed top features at the individual operation and cohort level.
Implication of Pappalysins and Stanniocalcins in the Bioavailability of IGF-I in Children With Type 1 Diabetes Mellitus
Authors: Güemes María , Martín-Rivada Álvaro , Corredor Beatriz , Enes Patricia , Canelles Sandra , Barrios Vicente , Argente Jesús 
Published: April 2024

Abstract

Context
Anomalies in the growth hormone (GH)/insulin-like growth factor (IGF) axis, are common in children with type 1 diabetes mellitus (T1DM), even in those reaching a normal or near-normal final height. However, concentrations of the IGF bioavailability regulatory factors (pappalysins [PAPP-As] and stanniocalcins [STCs]) have not been reported in children with T1DM.

Objective
To determine serum concentrations of PAPP-As and STCs in children at diagnosis of T1DM and after insulin treatment and the correlation of these factors with other members of the GH/IGF axis, beta-cell insulin reserve, auxology, and nutritional status.

Methods
A single-center prospective observational study including 47 patients (59.5% male), with T1DM onset at median age of 9.2 years (interquartile range: 6.3, 11.9) was performed. Blood and anthropometric data were collected at diagnosis and after 6 and 12 months of treatment.

Results
At 6 and 12 months after T1DM diagnosis, there was improvement in the metabolic control (decrease in glycated hemoglobin [HbA1c] at 12 months −3.66 [95% CI: −4.81, −2.05], P = .001), as well as in body mass index SD and height SD (not statistically significant). STC2 increased (P &lt; .001) and PAPP-A2 decreased (P &lt; .001) at 6 and 12 months of treatment onset (P &lt; .001), which was concurrent with increased total IGF-I and IGF-binding protein concentrations, with no significant modification in free IGF-I concentrations. HbA1c correlated with PAPP-A2 (r = +0.41; P &lt; .05) and STC2 (r = −0.32; P &lt; .05).

Conclusion
Implementation of insulin treatment after T1DM onset modifies various components of the circulating IGF system, including PAPP-A2 and STC2. How these modifications modulate linear growth remains unknown.