bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interpretability of radiomics models is improved when using feature group selection strategies for predicting molecular and clinical targets in clear-cell renal cell carcinoma: insights from the TRACERx Renal study
Authors: Orton Matthew R. , Hann Evan , Doran Simon J. , Shepherd Scott T. C. , Ap Dafydd Derfel , Spencer Charlotte E. , López José I. , Albarrán-Artahona Víctor , Comito Francesca , Warren Hannah , Shur Joshua , Messiou Christina , Larkin James , Turajlic Samra ,   on behalf of the TRACERx Renal Consortium, Koh Dow-Mu 
Published: August 2023

AbstractBackgroundThe aim of this work is to evaluate the performance of radiomics predictions for a range of molecular, genomic and clinical targets in patients with clear cell renal cell carcinoma (ccRCC) and demonstrate the impact of novel feature selection strategies and sub-segmentations on model interpretability.MethodsContrast-enhanced CT scans from the first 101 patients recruited to the TRACERx Renal Cancer study (NCT03226886) were used to derive radiomics classification models to predict 20 molecular, histopathology and clinical target variables. Manual 3D segmentation was used in conjunction with automatic sub-segmentation to generate radiomics features from the core, rim, high and low enhancing sub-regions, and the whole tumour. Comparisons were made between two classification model pipelines: a Conventional pipeline reflecting common radiomics practice, and a Proposed pipeline including two novel feature selection steps designed to improve model interpretability. For both pipelines nested cross-validation was used to estimate prediction performance and tune model hyper-parameters, and permutation testing was used to evaluate the statistical significance of the estimated performance measures. Further model robustness assessments were conducted by evaluating model variability across the cross-validation folds.ResultsClassification performance was significant (p < 0.05, H0:AUROC = 0.5) for 11 of 20 targets using either pipeline and for these targets the AUROCs were within ± 0.05 for the two pipelines, except for one target where the Proposed pipeline performance increased by > 0.1. Five of these targets (necrosis on histology, presence of renal vein invasion, overall histological stage, linear evolutionary subtype and loss of 9p21.3 somatic alteration marker) had AUROC > 0.8. Models derived using the Proposed pipeline contained fewer feature groups than the Conventional pipeline, leading to more straightforward model interpretations without loss of performance. Sub-segmentations lead to improved performance and/or improved interpretability when predicting the presence of sarcomatoid differentiation and tumour stage.ConclusionsUse of the Proposed pipeline, which includes the novel feature selection methods, leads to more interpretable models without compromising prediction performance.Trial registrationNCT03226886 (TRACERx Renal)
In vitro characterisation of [177Lu]Lu-DOTA-C595 as a novel radioimmunotherapy for MUC1-CE positive pancreatic cancer
Authors: Hull Ashleigh , Hsieh William , Tieu William , Bartholomeusz Dylan , Li Yanrui , Bezak Eva 
Published: August 2023

Abstract
Background
Pancreatic ductal adenocarcinoma (PDAC) continues to be a malignancy with an unmet clinical demand. Development of radioimmunoconjugates which target cancer-specific receptors provides an opportunity for radioimmunotherapy of both metastatic and primary PDAC. In this study, we characterised the in vitro behaviour of a novel beta-emitting radioimmunoconjugate [177Lu]Lu-DOTA-C595 as a therapeutic agent against PDAC. [177Lu]Lu-DOTA-C595 is designed to target cancer-specific mucin 1 epitopes (MUC1-CE) overexpressed on most epithelial cancers, including PDAC.

Results
A series of in vitro experiments were performed on PDAC cell lines (PANC-1, CAPAN-1, BxPC-3 and AsPC-1) exhibiting strong to weak MUC1-CE expression. [177Lu]Lu-DOTA-C595 bound to all cell lines relative to their expression of MUC1-CE. [177Lu]Lu-DOTA-C595 was also rapidly internalised across all cell lines, with a maximum of 75.4% of activity internalised within the PANC-1 cell line at 48 h. The expression of γH2AX foci and clonogenic survival of PANC-1 and AsPC-1 cell lines after exposure to [177Lu]Lu-DOTA-C595 were used to quantify the in vitro cytotoxicity of [177Lu]Lu-DOTA-C595. At 1 h post treatment, the expression of γH2AX foci exceeded 97% in both cell lines. The expression of γH2AX foci continued to increase in PANC-1 cells at 24 h, although expression reduced in AsPC-1. Clonogenic assays showed a high level of cell kill induced by [177Lu]Lu-DOTA-C595.

Conclusion
[177Lu]Lu-DOTA-C595 has favourable in vitro characteristics to target and treat MUC1-CE positive PDAC. Further investigations to characterise the in vivo effects and potential value of [177Lu]Lu-DOTA-C595 in other MUC1-CE expressing malignancies such as lung, ovarian and colorectal adenocarcinoma are warranted.
Evaluation of the pharmacokinetics, dosimetry, and therapeutic efficacy for the α-particle-emitting transarterial radioembolization (αTARE) agent [225Ac]Ac-DOTA-TDA-Lipiodol® against hepatic tumors
Authors: Josefsson Anders , Cortez Angel G. , Rajkumar Harikrishnan , Latoche Joseph D. , Jaswal Ambika P. , Day Kathryn E. , Zarisfi Mohammadreza , Rigatti Lora H. , Huang Ziyu , Nedrow Jessie R. 
Published: August 2023

Abstract
Background
The liver is a common site for metastatic disease for a variety of cancers, including colorectal cancer. Both primary and secondary liver tumors are supplied through the hepatic artery while the healthy liver is supplied by the portal vein. Transarterial radioembolization (TARE) using yttrium-90 glass or resin microspheres have shown promising results with reduced side-effects but have similar survival benefits as chemoembolization in patients with hepatocellular carcinoma (HCC). This highlights the need for new novel agents against HCC. Targeted alpha therapy (TAT) is highly potent treatment due to the short range (sparing adjacent normal tissue), and densely ionizing track (high linear energy transfer) of the emitted α-particles. The incorporation of α-particle-emitting radioisotopes into treatment of HCC has been extremely limited, with our recent publication pioneering the field of α-particle-emitting TARE (αTARE). This study focuses on an in-depth evaluation of the αTARE-agent [225Ac]Ac-DOTA-TDA-Lipiodol® as an effective therapeutic agent against HCC regarding pharmacokinetics, dosimetry, stability, and therapeutic efficacy.

Results
[225Ac]Ac-DOTA-TDA was shown to be a highly stable with bench-top stability at ≥ 95% radiochemical purity (RCP) over a 3-day period and serum stability was ≥ 90% RCP over 5-days. The pharmacokinetic data showed retention in the tumor of [225Ac]Ac-DOTA-TDA-Lipiodol® and clearance through the normal organs. In addition, the tumor and liver acted as suppliers of the free daughters, which accumulated in the kidneys supplied via the blood. The dose limiting organ was the liver, and the estimated maximum tolerable activity based on the rodents whole-body weight: 728–3641 Bq/g (male rat), 396–1982 Bq/g (male mouse), and 453–2263 Bq/g (female mouse), depending on an RBE-value (range 1–5). Furthermore, [225Ac]Ac-DOTA-TDA-Lipiodol® showed significant improvement in survival for both the male and female mice (median survival 47-days) compared with controls (26-days untreated, and 33–35-days Lipiodol® alone).

Conclusions
This study shows that [225Ac]Ac-DOTA-TDA-Lipiodol® is a stable compound allowing for centralized manufacturing and distribution world-wide. Furthermore, the result of this study support the continue development of evaluation of the αTARE-agent [225Ac]Ac-DOTA-TDA-Lipiodol® as a potential treatment option for treating hepatic tumors.
Needs and contents of a customized digital tool for retention in care and medication adherence among pregnant and breastfeeding women living with HIV in Kilimanjaro
Authors: Maro Rehema Anenmose , Ngowi Kennedy , Martin Haikael , Dillip Angel , Masika Lyidia , Mtenga Alan , Mtesha Benson , Boer Marion Sumari-de 
Published: August 2023

Abstract
Background
Retention in care and adherence to medication among pregnant and breastfeeding women living with HIV (PBWLH) are crucial for preventing mother-to-child transmission (PMTCT) of HIV. Wide coverage of mobile phones, digital tools, including internet-enabled medication dispensers and short message service (SMS), have been recommended as potential interventions to improve adherence to medication by PBWLH. The main objective of the study was to understand the needs and contents for a customized digital tool for retention in care and medication adherence among PBWLH.

Method
A mixed-methods study was conducted from September 2021 to March 2022 at five health facilities in the Kilimanjaro region. We interviewed 142 pregnant and breastfeeding women, receiving PMTCT services, using a semi-structured questionnaire. Among the interviewed, twenty breastfeeding women were purposively selected and enrolled to use an internet-enabled Wisepill medication dispenser for one month. They received different types of SMS reminders for one month, and feedback on their adherence patterns was received after one month using an adherence graph from the Wisepill digital tool. Later, exit and in-depth interviews were conducted to explore the needs and contents of a future customized digital adherence tool. Descriptive analyses for quantitative data and thematic content analyses for qualitative data were also done.

Results
Among 142 women interviewed, 42(30%) were pregnant and 100 (70%) were breastfeeding. Most 136 (95%) had access to mobile phones and used SMS daily, while 90% were interested in receiving reminder messages. Qualitative findings revealed more insights into reminders’ content and educational SMS. Most people preferred neutral SMS, which does not contain the word “medication”. Health educational SMS content was preferred to be on breastfeeding, opportunistic diseases, nutrition and entrepreneurship education. Overall, SMSs were regarded as helpful to remind clients of medication time and the medication dispenser provided them with privacy and safe storage for their medication.

Conclusions
This study's findings will help construct useful content for future digital adherence tools to support the health of pregnant and breastfeeding women living with HIV.
Consensus on pediatric epilepsy surgery for young children: an investigation by the China Association Against Epilepsy task force on epilepsy surgery
Authors: Cai Lixin , Zhang Kai , Zhou Wenjing , Shao Xiaoqiu , Guan Yuguang , Yu Tao , Wu Ye , Chen Shuhua , Zhao Rui , Liang Shuli , Wu Xun , Luan Guoming , Jiang Yuwu , Zhang Jianguo , Liu Xiaoyan 
Published: August 2023

AbstractResearchers have widely acknowledged the therapeutic value of epilepsy surgery for drug-resistant epilepsy. Nonetheless, there is a substantial gap in the surgical treatment for appropriate candidates owing to several factors, particularly in the population of young children. To standardize the protocols of preoperative evaluation and surgery of young children for epilepsy surgery, the China Association Against Epilepsy has appointed an expert task force to standardize the protocols of preoperative evaluation and surgery in pediatric epilepsy patients. It adopted the modified Delphi method and performed two rounds of surveys through an anonymous inquiry among 75 experts from four subgroups including pediatric neurologists, epileptologists, pediatric epilepsy surgeons, and functional neurosurgeons. The survey contents contained: (1) the participants, comprising children aged ≤ 6 years; (2) adopted DRE definition proposed by the International League Against Epilepsy in 2010; and (3) investigated epilepsy surgery, principally referring to curative epilepsy surgeries. The neuromodulation therapies were excluded because of the differences in treatment mechanisms from the above-mentioned surgeries. According to the Delphi process, a consensus was achieved for most aspects by incorporating two rounds of surveys including preoperative assessment, surgical strategies and techniques, and perioperative and long-term postoperative management, despite controversial opinions on certain items. We hope the results of this consensus will improve the level of surgical treatment and management of intractable epilepsy in young children.
Factors associated with recurrent endometriomas after surgical excision
Authors: Atwa Khaled A. , Ibrahim Zakia M. , Bassuony Eman M. El , Taha Omima T. 
Published: August 2023

Abstract
Background
Endometriosis affects women in reproductive age and causes a great impact on their lives. When affecting the ovary, excision represents the main management option. However, recurrence represents a challenging situation for patients and physicians. This study aimed to determine factors contributing to endometriomas recurrence after surgical excision.

Results
This was a quasi-experimental study recruiting 60 patients with ovarian endometrioma. The mean age was 30.33 ± 7.95 years. The mean parity was 1.27 ± 0.69. The recurrence rate after excision was 11/60 (18.3%) after a mean follow-up period of 22.62 ± 4.96 months. None of the patients’ characteristics or endometriosis-related characteristics were significant factors contributing to cyst recurrence (age, parity, history of infertility, preoperative endometrioma diameter, preoperative AFC, preoperative AMH, degree of pelvic pain, degree of dysmenorrhea, degree of dyspareunia, pelvic tenderness, and induration) (p value > 0.05).

Conclusion
The patient’s related factors and endometrioma characteristics did not predict its recurrence.
Critical variables affecting the layering method of pelletization
Authors: Maniyar Drashti , Kadu Pramod , Baig Mirza Ilyas Rahim 
Published: August 2023

AbstractThe oral route of delivery is the most preferred route for administering most of the drugs. Pellets have gained importance since they offer numerous advantages like decreased dose dumping, improved patient compliance since dosing frequency is reduced, and ease of administering multiple chemically incompatible drugs immediately without the possibility of them interacting with each other. The critical variables related to process and equipment are identified and what impact they have on the quality of pellets formed is discussed. The position of the spray nozzle also affects the pellets and their yield. A complete guideline has been drawn which makes the process of pelletization using the Wurster method easier. The process variables affecting the pelletization process include inlet and product temperature, relative humidity, batch size; spray rate, and atomization air pressure and the equipment variables include column height, air distribution plate, a type of filter, and shaking interval. All these variables have a low, medium, or high impact on the process and they all together contribute to the quality of pellets formed. This review article focuses on critical process and equipment variables affecting the process of pelletization and the quality of pellets formed when using the Wurster equipment. The main objective is to review critical variables affecting the layering method of palletization and to sketch some basic problems encountered during pelletization and their troubleshooting.
Feasibility of the pupillary pain index as a guide for depth of analgesia during opioid-sparing anesthesia with continuous infusion of dexmedetomidine
Authors: Stefanini Martino , Cagnazzi Elena , Calza Stefano , Latronico Nicola , Rasulo Francesco A. 
Published: August 2023

Abstract
Background
The pupillary dilation reflex (PDR) is an objective indicator of analgesic levels in anesthetized patients. Through measurement of the PDR during increasing tetanic stimulation (10–60 mA), it is possible to obtain the pupillary pain index (PPI), a score that assesses the level of analgesia.

Objectives
The depth of analgesia during opioid-sparing anesthesia (OSA) with continuous infusion of dexmedetomidine in addition to general anesthesia was assessed.

Design
Observational prospective feasibility pilot study

Setting
This study was performed in the operating rooms of the Spedali Civili University-affiliated hospital of Brescia, Italy.

Patients
Forty-five adults who underwent elective open (5-cm incision) surgery under general anesthesia (78% inhalation anesthesia), from Feb. 18th to Aug. 1st, 2019, were enrolled. Exclusion criteria were as follows: implanted pacemaker or ICD, ophthalmological comorbidities, chronic opioid use, peripheral neuropathy, other adjuvant drugs, epidural analgesia, or locoregional block.

Main outcome measures
The first aim was to verify the feasibility of applying a study protocol to evaluate the depth of analgesia during intraoperative dexmedetomidine administration using an instrumental pupillary evaluation. The secondary outcome was to evaluate appropriate analgesia, drug dosage, anesthesia depth, heart rate, blood pressure, transient side effects, postoperative nausea and vomiting (PONV), and pain numerical rating scale (NRS) score.

Results
Thirty out of 50 patients (60%) treated with dexmedetomidine during the study period were included in the DEX group (8 males, age 42 ± 13 years, BMI 45 ± 8), and 15 other patients were included in the N-DEX group (8 males, age 62 ± 13 years, BMI 26 ± 6). Patients who underwent bariatric, abdominal, or plastic surgery were enrolled. At least 3 pupillary evaluations were taken for each patient. PPI ≤ 3 was observed in 97% of patients in the DEX group and 53% in the N-DEX group. Additionally, the DEX group received less than half the remifentanil dose than the N-DEX group (0.13 ± 0.07 vs 0.3 ± 0.11 mcg kg−1 min−1). The average dose of dexmedetomidine administered was 0.17 ± 0.08 mcg kg−1 h−1.

Conclusion
The feasibility of applying the protocol was verified. An OSA strategy involving dexmedetomidine may be associated with improved analgesic stability: a randomized controlled trial is necessary to verify this hypothesis.

Trial registration
Trial.gov registration number: NCT05785273
High-stress surgery in severely frail patients: a case report of personalized and multidisciplinary shared decision-making
Authors: Sanna Andrea , Miori Sara , Lassola Sergio , Umbrello Michele , De Rosa Silvia , Bellani Giacomo 
Published: August 2023

AbstractWe report the case of a 65-year-old severely disabled man diagnosed with advanced renal neoplasm who was scheduled for major urologic surgery. Through a multidisciplinary approach, a shared decision-making process and mutual listening of all the health professionals involved, it was decided not to have major surgery due to the high risk of worsening the patient’s health and quality of life.
Germline EGFR Mutations and Familial Lung Cancer
Authors: Oxnard Geoffrey R. , Chen Ruthia , Pharr Jennifer C. , Koeller Diane R. , Bertram Arrien A. , Dahlberg Suzanne E. , Rainville Irene , Shane-Carson Kate , Taylor Kelly A. , Sable-Hunt Alicia , Sholl Lynette M. , Teerlink Craig C. , Thomas Alun , Cannon-Albright Lisa A. , Fay André P. , Ashton-Prolla Patrícia , Yang Hao , Salvatore Mary M. , Addario Bonnie J. , Jänne Pasi A. , Carbone David P. , Wiesner Georgia L. , Garber Judy E. 
Published: August 2023

PURPOSE The genomic underpinnings of inherited lung cancer risk are poorly understood. This prospective study characterized the clinical phenotype of patients and families with germline EGFR pathogenic variants (PVs). METHODS The Investigating Hereditary Risk from T790M study (ClinicalTrials.gov identifier: NCT01754025 ) enrolled patients with lung cancer whose tumor profiling harbored possible germline EGFR PVs and their relatives, either in person or remotely, providing germline testing and follow-up. RESULTS A total of 141 participants were enrolled over a 5-year period, 100 (71%) remotely. Based upon previous genotyping, 116 participants from 59 kindreds were tested for EGFR T790M, demonstrating a pattern of Mendelian inheritance with variable lung cancer penetrance. In confirmed or obligate carriers of a germline EGFR PV from 39 different kindreds, 50/91 (55%) were affected with lung cancer with 34/65 (52%) diagnosed by age 60 years. Somatic testing of lung cancers in carriers revealed that 35 of 37 (95%) had an EGFR driver comutation. Among 36 germline carriers without a cancer diagnosis, 15 had computed tomography (CT) imaging and nine had lung nodules, including a 28-year-old with >10 lung nodules. Given geographic enrichment of germline EGFR T790M in the southeast United States, genome-wide haplotyping of 46 germline carriers was performed and identified a 4.1-Mb haplotype shared by 41 (89%), estimated to originate 223-279 years ago. CONCLUSION To our knowledge, this is the first prospective description of familial EGFR-mutant lung cancer, identifying a recent founder germline EGFR T790M variant enriched in the Southeast United States. The high prevalence of EGFR-driver lung adenocarcinomas and lung nodules in germline carriers supports effort to identify affected patients and family members for investigation of CT-based screening for these high-risk individuals.
Serum Klotho Modifies the Associations of 25-Hydroxy Vitamin D With All-Cause and Cardiovascular Mortality
Authors: Chen Zhuohui , Liu Menghui , Xu Xingfeng , He Lixiang , Wang Peng , Cai Xiaojie , Huang Rihua , Zhang Shaozhao , Xu Xinghao , Lai Yuhui , Huang Yiquan , Li Miaohong , Lin Yifen , Xie Peihan , Liao Xinxue , Zhuang Xiaodong , Guo Yue 
Published: August 2023

Abstract

Background
The association between 25-hydroxyvitamin D and mortality remains controversial. Klotho, a biomarker of vitamin D activation and metabolism, may play a key role in this association. However, it is unclear whether the association between vitamin D deficiency and mortality risk is modified by klotho levels. Therefore, this study investigated the joint association of serum 25-hydroxyvitamin D [25(OH)D] and klotho with mortality risk in American community-dwelling adults.

Methods
A total of 9870 adults from the National Health and Nutrition Examination Survey (2007-2016) were included in our study. Mortality data were ascertained by linking participants to National Death Index records. Cox proportional hazards models were used to assess the association among serum 25(OH)D, serum klotho, and all-cause and cardiovascular disease (CVD) mortality.

Results
We found a significant interaction between klotho and serum 25(OH)D in all-cause mortality (P = .028). With klotho &gt; 848.4 pg/mL (risk threshold on mortality), no significant all-cause and CVD mortality risk was observed at any level of serum 25(OH)D. However, with klotho &lt; 848.4 pg/mL, a significant all-cause and CVD mortality risk was observed with serum 25(OH)D &lt; 50 nmol/L [hazards ratio (HR), 1.36; 95% confidence interval (CI), 1.10-1.69; HR, 1.78; 95% CI, 1.16-3.45) and serum 25(OH)D of continuous variable (HR, 0.98; 95% CI, .97-.99; HR, 0.98; 95% CI, .98-.99). In addition, vitamin D metabolism disruption accessed by the combination of decreasing serum 25(OH)D (&lt;50 nmol/L) and klotho (&lt;848.4 pg/mL) was associated with significant all-cause mortality (HR, 1.48; 95% CI, 1.11-1.96) and CVD mortality (HR, 2.36; 95% CI, 1.48-3.75).

Conclusions
Vitamin D-associated mortality risk is observed only with concurrently decreasing klotho, indicating that vitamin D metabolism dysfunction increases the risk of mortality. Klotho levels could help predict long-term mortality outcomes and thus may be useful concurrently for guiding vitamin D supplementation therapy decision-making in populations with vitamin D deficiency.