bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adopting Consensus Terms for Testing in Precision Medicine
Authors: Martin Nikki A. , Tepper Joel E. , Giri Veda N. , Stinchcombe Thomas E. , Cheng Heather H. , Javle Milind M. , Konnick Eric Q. 
Published: October 2021

PURPOSEDespite the well-understood benefits of biomarker and genetic testing in precision medicine, uptake remains low, particularly for patients with low socioeconomic status and minority ethnic backgrounds. Patients report having limited familiarity with testing terminology and may not be able to accurately explain testing's role in treatment decisions. Patient confusion and lack of understanding is exacerbated by a multiplicity of overlapping terms used in communicating about testing. A LUNGevity Foundation–led working group composed of five professional societies, 23 patient advocacy groups, and 19 industry members assessed and recommended specific terms for communicating with patients on testing for tumor characteristics and germline mutations.METHODSMembers completed a precision oncology testing framework analysis (biomarkers, germline variants, testing modalities, biospecimen, and commonly used testing terms) for nine solid tumors and blood cancers. The evaluation was segmented into terms that distinguish between somatic and germline testing. Additional data were captured in a comprehensive survey (1,650 respondents) led by FORCE (Facing Our Risk of Cancer Empowered) on patient preferences on germline testing terms.RESULTSThirty-three terms were noted in patient education related to biomarker, genetic, and genomic testing. Biomarker testing was selected as the preferred term for testing for somatic (acquired) alterations and other biomarkers. Genetic testing for an inherited mutation and genetic testing for inherited cancer risk were selected as the preferred terms for testing for germline variants.CONCLUSIONDemocratizing comprehension about precision oncology testing through intentional use of plain language and common umbrella terminology by oncology health care providers and others in the oncology ecosystem may help improve understanding and communication, and facilitate shared decision making about the role of appropriate testing in treatment decisions and other aspects of oncology care.
Different Fumarate Hydratase Gene Variants Are Associated With Distinct Cancer Phenotypes
Authors: Kamihara Junne , Horton Carrie , Tian Yuan , Zhou Jing , Richardson Marcy , LaDuca Holly , Rana Huma Q. 
Published: October 2021

PURPOSE Whether individuals with monoallelic FH pathogenic variants (PVs) associated with autosomal recessive fumarate hydratase (FH) deficiency are also at risk of autosomal dominant FH-associated tumors is of paramount clinical importance. METHODS A retrospective study of individuals with a PV in the FH gene identified via multigene panel testing from 2012 to 2019 through a single testing laboratory was performed. Cancer histories of individuals with PVs in FH ( FH PV) were compared to those with PVs associated only with autosomal recessive FH deficiency (FH-d PV) and to FH-negative controls. Cancer histories of individuals with truncating versus nontruncating FH PV were also compared. RESULTS Individuals with FH PV were more likely to have kidney cancer than those with FH-d PV (odds ratio, 9.0; 95% CI, 4.4 to 20.0; P < .001) or FH-negative controls (odds ratio, 7.6; 95% CI, 5.2 to 11.2; P value < .001). The FH PV cohort had kidney cancer at a significantly younger age (median age: 35.0 years; interquartile range, 26.0-45.0 years) than the FH-d PV cohort (median age: 44.5 years; interquartile range, 43.5-53.5 years; P = .011). Within the FH PV cohort, there were no differences in the frequency or age at kidney cancer between those with truncating versus nontruncating PV. CONCLUSION Unlike FH PV, FH-d PV are not associated with kidney cancers at early ages of onset. The FH-d PV cohort had a cancer phenotype that resembled FH-negative controls. These data may inform genetic counseling and risk assessment of individuals with FH-d PV.
Neoplastic Etiology and Natural Course of Pituitary Stalk Thickening
Authors: Kim Dong Yeong , Kim Pyeong Hwa , Jung Ah Young , Choi Jin-Ho , Cho Young Ah , Yoon Hee Mang , Lee Jin Seong 
Published: October 2021

Abstract

Context
Pituitary stalk thickening (PST) is often identified on magnetic resonance imaging (MRI), either incidentally or during diagnostic workup of hypopituitarism. However, the neoplastic etiology and natural course of PST are not fully understood, although this knowledge is required to establish diagnostic and surveillance strategies.

Objective
This work aimed to investigate the neoplastic etiology and natural course of PST.

Methods
MEDLINE/PubMed and EMBASE databases were searched up to February 2021 to identify original research investigating the etiologies of PST. The proportion of neoplastic etiology in patients with PST was meta-analytically pooled. Supplementary analysis exploring factors suggesting neoplasm was also performed. For initially indeterminate cases without confirmed diagnosis, the proportion of patients showing progression of PST during follow-up was evaluated.

Results
Eighteen studies covering 1368 patients with PST were included. The pooled proportion of neoplasm was 45.2% (95% CI, 33.3%-57.8%), with substantial heterogeneity across studies (I2 = 93%). The most common neoplasm was germ cell tumor (14.0% of study population), followed by Langerhans cell histiocytosis (10.2%) and metastasis (4.7%). The studies on pediatric populations and those with more than 50% of patients having at least one pituitary hormone deficiency tended to show a higher proportion of neoplasm. The pituitary stalk was thicker in neoplasms, but the difference was not significant (pooled mean difference, 2.08 mm; P = .08). In initially indeterminate cases, 18.5% (95% CI, 7.6%-38.3%) showed progression of PST during follow-up.

Conclusion
PST was commonly confirmed to be neoplastic, especially in pediatric populations. As isolated PST frequently progresses, follow-up imaging is essential in initially indeterminate cases.
Evaluation of Diagnostic Workup and Etiology of Hypercalcemia of Malignancy in a Cohort of 167 551 Patients Over 20 Years
Authors: Sheehan Michael T , Li Ya-Huei , Doi Suhail A , Onitilo Adedayo A 
Published: October 2021

Abstract

Context
Hypercalcemia of malignancy (HCM) has not been studied in a fashion to determine all possible mechanisms of hypercalcemia in any given patient.

Objective
The 2 objectives were to assess the completeness of evaluation and to determine the distribution of etiologies of HCM in a contemporary cohort of patients.

Methods
A retrospective analysis was performed of patients with cancer who developed hypercalcemia over 20 years at a single health system. Laboratory data were electronically captured from medical records to identify cases of parathyroid hormone (PTH)-independent hypercalcemia. The records were then manually reviewed to confirm the diagnosis of HCM, document the extent of evaluation, and determine underlying etiology(ies) of HCM in each patient.

Results
The initial data set included 167 551 adult patients with malignancy, of which 11 589 developed hypercalcemia. Of these, only a quarter (25.4%) had assessment of PTH with a third of the latter (30.9%) indicating PTH-independent hypercalcemia. Of those with PTH-independent hypercalcemia, a third (31.6%) had assessment of PTH-related peptide (PTHrP) and/or 1,25-dihydroxy (1,25-OH) vitamin D and constituted the 153 cases of HCM examined in this study. Eighty-three of these patients had an incomplete evaluation of their HCM. The distribution of etiologies of HCM was therefore determined from the remaining 70 patients who had assessment of all 3 possible etiologies (PTHrP, 1,25-OH vitamin D, and skeletal imaging) and was as follows: PTHrP, 27%; osteolytic metastases, 50%; and 1,25-OH vitamin D, 39%, with combinations of etiologies being common (approximately 20%).

Conclusion
HCM is incompletely evaluated in many patients. The distribution of etiologies of HCM in this report differs significantly from the previous literature, warranting further study to determine whether its causes have indeed changed over time.
Managing risky assets – mitophagy in vivo
Authors: Narendra Derek P. 
Published: October 2021

ABSTRACT
Mitochondria, which resemble their α-proteobacteria ancestors, are a major cellular asset, producing energy ‘on the cheap’ through oxidative phosphorylation. They are also a liability. Increased oxidative phosphorylation means increased oxidative stress, and damaged mitochondria incite inflammation through release of their bacteria-like macromolecules. Mitophagy (the selective macroautophagy of mitochondria) controls mitochondria quality and number to manage these risky assets. Parkin, BNIP3 and NIX were identified as being part of the first mitophagy pathways identified in mammals over a decade ago, with additional pathways, including that mediated by FUNDC1 reported more recently. Loss of Parkin or PINK1 function causes Parkinson's disease, highlighting the importance of mitophagy as a quality control mechanism in the brain. Additionally, mitophagy is induced in idiopathic Parkinson's disease and Alzheimer's disease, protects the heart and other organs against energy stress and lipotoxicity, regulates metabolism by controlling mitochondrial number in brown and beige fat, and clears mitochondria during terminal differentiation of glycolytic cells, such as red blood cells and neurons. Despite its importance in disease, mitophagy is likely dispensable under physiological conditions. This Review explores the in vivo roles of mitophagy in mammalian systems, focusing on the best studied examples – mitophagy in neurodegeneration, cardiomyopathy, metabolism, and red blood cell development – to draw out common themes.
A Robust Superhydrophobic Perfluoropolysiloxane and Self-doped Polyaniline/Epoxy Resin Composite Coating with Excellent Performance
Authors: Xu Haidong , Miao Congcong , Wang Luyao , Zhang Liang , Feng Huixia , Qiu Jianhui 
Published: October 2021

Abstract
A robust superhydrophobic perfluoropolysiloxane and self-doped polyaniline/epoxy resin composite coating (EPAN-RA-POS) was prepared. The structure is composed of the internal self-doped polyaniline/epoxy resin layer and the outer superhydrophobic perfluoropolysiloxane layer. The contact angle (CA) and sliding angle (SA) of EPAN-RA-POS are 165.0° ± 1.5 and 1.2° ± 0.7, respectively, the protection efficiency and immersion durability of EPAN-RA-POS reach 99.99% and 408 h, the superhydrophobicity is only lost after 330 peeling experiments.
Trans-lymphatic contrast-enhanced ultrasound with sentinel lymph node biopsy for detecting cervical skip metastasis to lymph nodes in early-stage oral tongue squamous cell carcinoma
Authors: Huang Jian , Wu Song-song , Zheng Song , Gao Hong , Wu Zhi-yuan , Xu Jun-wu 
Published: October 2021

Objectives: The purpose of this study was to assess whether trans-lymphatic contrast-enhanced ultrasound (CEUS) combined with sentinel lymph node biopsy can be used to assess the status of cervical lymph nodes and skip metastasis in patients with early squamous cell carcinoma (SCC) of the oral tongue. Methods: This study included 21 subjects with early oral tongue SCC who received multiple intramucosal peritumoral injections of Sonazoid. CEUS examinations were performed immediately after Sonazoid injection to identify sentinel lymph nodes (SLNs). The SLNs were excised for histological examination to determine if the lymph nodes has metastases. Results: Thirty-five SLNs were detected by CEUS after Sonazoid injection in the subjects. SLNs were identified in 20 of the total 21 subjects. Four participants had metastasis to lymph nodes, and one had skip metastasis in level Ⅲ. In one subject, SLNs were successfully detected in level Ⅳ without skip metastasis. Conclusions: Trans-lymphatic CEUS combined with sentinel lymph node biopsy showed high accuracy for evaluating cervical lymph node status. This could be a reliable approach for detecting cervical skip metastases of lymph nodes in early-stage oral cancer patients.
Caracterización y factores de riesgo de caídas en un hospital de alta complejidad de Bogotá (Colombia)
Authors: Rodríguez Ibagué Luis Fernando , Gallego Ardila Andres Daniel , Quiroga Ardila Yudy Jazmín , Molina Eslava Helga Idaly 
Published: October 2021

Introducción
Las caídas intrahospitalarias están dentro de las prioridades nacionales e internacionales en cuanto a calidad asistencial. Aunque se reconocen elementos intrínsecos y extrínsecos al paciente con la presencia de caídas, en Colombia existe poca evidencia al respecto. El objetivo es caracterizar las caídas de pacientes ocurridas entre el 2013 y 2016, y sus factores asociados en un hospital de alta complejidad de Bogotá, Colombia.
Materiales y métodos
Estudio observacional retrospectivo basado en el registro de caídas que ocurrieron en el periodo de análisis en un hospital de alta complejidad de Bogotá, Colombia. Se utilizó estadística descriptiva y análisis de regresión logística binaria.
Resultados
De 951 caídas que ocurrieron entre el 2013 y 2016, el 63,1% se clasificaron como eventos adversos. Según la gravedad, el 54,2% fueron “moderados” y “severos”. De la muestra de pacientes, el 53,0% fueron hombres, el 65,5% tenía 65 o más años (mediana=71 años, mínimo=16 años, máximo=98 años), el 23,2% tenían enfermedad del sistema circulatorio. Se asoció con un mayor riesgo para una caída que culmina en evento adverso: ser mujer (IC95%OR=1,08–1,87), el turno laboral noche (IC95%=1,09-2,03) y las especialidades clínicas (IC95%=1,36-4,84) y quirúrgicas (IC95%=1,14-4,46).
Conclusión
Las caídas de pacientes son un evento adverso importante de intervenir en las instituciones hospitalarias. Se identificaron elementos intrínsecos, principalmente la edad, y extrínsecos, el turno laboral y la especialidad médica, relacionados con la probabilidad de generar un daño en el paciente ante una caída.
On the Exact Solution of Prize-Collecting Steiner Tree Problems
Authors: Rehfeldt Daniel , Koch Thorsten 
Published: October 2021

The prize-collecting Steiner tree problem (PCSTP) is a well-known generalization of the classic Steiner tree problem in graphs, with a large number of practical applications. It attracted particular interest during the 11th DIMACS Challenge in 2014, and since then, several PCSTP solvers have been introduced in the literature. Although these new solvers further, and often drastically, improved on the results of the DIMACS Challenge, many PCSTP benchmark instances have remained unsolved. The following article describes further advances in the state of the art in exact PCSTP solving. It introduces new techniques and algorithms for PCSTP, involving various new transformations (or reductions) of PCSTP instances to equivalent problems, for example, to decrease the problem size or to obtain a better integer programming formulation. Several of the new techniques and algorithms provably dominate previous approaches. Further theoretical properties of the new components, such as their complexity, are discussed. Also, new complexity results for the exact solution of PCSTP and related problems are described, which form the base of the algorithm design. Finally, the new developments also translate into a strong computational performance: the resulting exact PCSTP solver outperforms all previous approaches, both in terms of runtime and solvability. In particular, it solves several formerly intractable benchmark instances from the 11th DIMACS Challenge to optimality. Moreover, several recently introduced large-scale instances with up to 10 million edges, previously considered to be too large for any exact approach, can now be solved to optimality in less than two hours. Summary of Contribution: The prize-collecting Steiner tree problem (PCSTP) is a well-known generalization of the classic Steiner tree problem in graphs, with many practical applications. The article introduces and analyses new techniques and algorithms for PCSTP that ultimately aim for improved (practical) exact solution. The algorithmic developments are underpinned by results on theoretical aspects, such as fixed-parameter tractability of PCSTP. Computationally, we considerably push the limits of tractibility, being able to solve PCSTP instances with up to 10 million edges. The new solver, which also considerably outperforms the state of the art on smaller instances, will be made publicly available as part of the SCIP Optimization Suite.
Product Selling vs. Pay-Per-Use Service: A Strategic Analysis of Competing Business Models
Authors: Ladas Konstantinos , Kavadias Stylianos , Loch Christoph 
Published: October 2021

We present a model that suggests possible explanations for the observed proliferation of “pay-per-use” (PPU) business models over the last two decades. Delivering “fractions” of a product as a service offers a cost advantage to customers with lower usage but requires extra delivery costs. Previous research focused on information goods (with negligible production costs) and predicted that PPU, when arising as a differentiation to selling in equilibrium, would fundamentally achieve lower profits than selling. We extend the theory by covering goods with any production cost in duopolistic competition. We show that PPU business models can be more profitable than selling (especially at midrange production costs), as long as their delivery costs are not too high, a requirement that is more easily fulfilled as new technologies reduce these costs. Moreover, if firms are imperfectly informed about their customers’ usage profiles, PPU’s effective pricing of customers’ varying usage offers an additional advantage over selling. This requires companies to employ accounting methods that do not inappropriately allocate production costs over stochastic usage levels. If PPU service provision suffers from queueing inefficiencies, this does not fundamentally change the relative profitability of the PPU and selling models, provided that PPU providers can attract sufficiently high demand to benefit from pooling economies.This paper was accepted by Charles Corbett, operations management.
Controllable ablative machining of Al/Ti and Ti/Al nano-layers on a Si substrate by single-pulse femtosecond laser irradiation
Authors: Gaković B. , Kudryashov S. I. , Danilov P. A. , Milovanović D. , Panjan P. , Bezhanov S. G. , Uryupin S. A. , Ionin A. A. 
Published: October 2021

Results concerning the controllable ablation of nano-layered thin films (NLTF) by femtosecond laser pulses are presented. Investigated samples were titanium-aluminum bilayers, deposited on a silicon substrate, with the top titanium or aluminum layer of variable thickness on the surface. Irradiation was done in ambient air with single femtosecond laser pulses under standard laboratory conditions. The samples were analyzed by complementary methods of optical and scanning electron microscopy and optical profilometry, exhibiting laser-fluence-dependent ablative removal either of the top layer or the entire bilayer or even partial ablation of the underlying silicon substrate. The removal (spallation) threshold fluences for the topmost layer are scalable versus its thickness almost irrespectively of its material, being rather selective for the Ti-coated samples and much less selective for the Al-coated samples. The removal of the entire bilayers was found to be strongly influenced by electronic properties of the underlying metallic layer, dictating the NLTF-Si adhesion, heat conduction, and capacity in the NLTFs toward the NLTF-Si interface and beyond, as well as by their thermophysical characteristics, e.g., almost twice higher melting temperature and enthalpy for Ti. As a result, precise fs-laser machining of the entire NLTFs is pronounced and selective for the samples with the fusible Al at the low-adhesion Al-Si interfaces, compared with the incomplete NLTF removal from the high-adhesion and refractory Ti-Si interfaces.
A novel xenonucleic acid-mediated molecular clamping technology for early colorectal cancer screening
Authors: Sun Qing , Pastor Larry , Du Jinwei , Powell Michael J. , Zhang Aiguo , Bodmer Walter , Wu Jianzhong , Zheng Shu , Sha Michael Y. 
Published: October 2021

Background
Colorectal cancer (CRC) is one of the leading causes of cancer-related death. Early detection is critical to reduce CRC morbidity and mortality. In order to meet this need, we developed a molecular clamping assay called the ColoScape TM assay for early colorectal cancer diagnostics.

Methods
Nineteen mutations in four genes (APC, KRAS, BRAF and CTNNB1) associated with early events in CRC pathogenesis are targeted in the ColoScapeTM assay. Xenonucleic Acid (XNA)-mediated qPCR clamping technology was applied to minimize the wild-type background amplification in order to improve assay sensitivity of CRC mutation detection. The assay analytical performance was verified and validated, cfDNA and FFPE CRC patient samples were evaluated, and an ROC curve was applied to evaluate its performance.

Results
The data showed that the assay analytical sensitivity was 0.5% Variant Allele Frequency, corresponding to ~7–8 copies of mutant DNA with 5 ng total DNA input per test. This assay is highly reproducible with intra-assay CV of <3% and inter-assay CV of <5%. We have investigated 380 clinical samples including plasma cfDNA and FFPE samples from patients with precancerous and different stages of CRC. The preliminary assay clinical specificity and sensitivity for CRC cfDNA were: 100% (95% CI, 80.3–97.5%) and 92.2% (95% CI, 94.7–100%), respectively, with AUC of 0.96; 96% specificity (95% CI, 77.6–99.7%) and 92% sensitivity (95% CI, 86.1–95.6%) with AUC of 0.94 for CRC FFPE; 95% specificity (95% CI, 82.5%–99.1%) and 62.5% sensitivity (95% CI, 35.8%–83.7%) with AUC of 0.79 for precancerous lesions cfDNA.

Conclusions
The XNA-mediated molecular clamping assay is a rapid, precise, and sensitive assay for the detection of precancerous lesions cfDNA and CRC cfDNA or FFPE samples.
COVID-19 pandemic preparedness period through healthcare workers’ eyes: A qualitative study from a Romanian healthcare facility
Authors: Stoichitoiu Laura Elena , Baicus Cristian 
Published: October 2021

Introduction
Healthcare providers represent a limited resource, and their mental health is crucial for patient care and for ensuring containment of the pandemics. We aimed to explore how healthcare workers experienced the preparedness period of COVID-19 pandemic, in order to ascertain the perceived weaknesses and strengths.

Methods
Interviews were conducted with 17 participants encompassing senior physicians, residents, and nurses. They were audio-recorded, and the transcription was verbatim. We used thematic analysis.

Results
We identified four themes, with subsequent subthemes: dealing with the unknown, human versus doctors, sense of helplessness, and a bridge to heaven, which explore how healthcare workers experienced the lack of knowledge, their feeling of losing control, and how they managed their internal fights. The disappointment provoked by the authorities and their colleagues was further evaluated. We identified factors involved in their well-being.

Conclusions
COVID-19 pandemic represented and will still pose a challenge for healthcare workers (HCWs) from all over the world. They felt unprepared for such a crisis. Further measures should be implemented in every hospital to maintain HCWs awareness and to prevent physical imbalance. Appropriate standards of care should be further stated by the authorities so that the healthcare providers may find easier a balance between their safety and their patients’ needs. Conducting qualitative research involving HCWs during pandemic times may help in informing more significant policy decisions.