bluuebunny/crossref_metadata_2025_split huggingface dataset:
CUPCOMP: A multi-site UK trial in carcinoma of unknown primary: A comparison across tissue and liquid biomarkers.
Authors: Conway Alicia-Marie , Robinson Matthew , Concannon Matthew , Clive Sally , Tillett Tania , Shiu Kai-Keen , Medley Louise C. , Dasgupta Sonali , Ahmed Eliyaz , Warrington Kelly , Zair Zoulikha , Gillham Tess , Davis Aaron , Scott Julie-Anne , Taylor Alison , Stares Mark , Mitchell Claire , Oliveria Pedro , Burghel George , Cook Natalie 
Published: June 2024

3059 Background: Cancer of Unknown Primary (CUP) is a difficult to treat cancer entity for which the tumour origins remain elusive. There is emerging evidence to support a precision medicine approach to aid treatment decisions, however scarcity of tumour tissue for molecular profiling remains a challenge. CUPCOMP sought to compare the feasibility of molecular profiling from both tissue and blood in patients (pts) diagnosed with CUP. Methods: A non-randomised prospective feasibility clinical trial conducted across 7 UK sites between 06/2021-02/2023. Eligible pts had a histological confirmed diagnosis of favourable/unfavourable CUP based on clinical, radiological, and pathological review at a CUP Multi-Disciplinary Team meeting and ESMO Guidelines for CUP. Pts had mutation profiling performed from circulating tumour DNA (ctDNA) (FoundationOne Liquid CDx) and tumour tissue (FoundationOne CDX or whole genome sequencing (WGS)). All results were discussed at a dedicated Molecular Tumour Board (MTB) to evaluate the activation state of oncogenic pathways. Results: Baseline characteristics of the 117 pts recruited are shown (Table). 114/117 (97%) pts had successful blood (109/117; 93% pts) or tissue (69/117; 59% pts) molecular profiling; both methods were performed in 64/117 (55%) pts. WGS was only successful in 15/21 pts where repeat biopsy was obtained. Where targeted tissue and blood profiling was performed using the same panel (49/117; 42%): 421/550 (77%) Single Nucleotide Variants (SNVs) found in tissue were concordant in ctDNA. ctDNA tumour fraction was ≥10% in 41/109 (35%) pts. In ctDNA, 1556 SNVs, across 271 genes, and 42 rearrangements were identified. 73/114 (64%) of cases carried an actionable alteration in blood or tissue, as determined by MTB. The most frequently reported actionable gene alterations were: KRAS (n=11; 10%); ATM (n=9; 8%); ARID1A (n=9; 8%); PIK3CA (n=10; 9%); NF2 (n=7; 6%); BRAF (n=7; 6%); FGFR2-fusion (n=7; 6%). A tumour mutational burden (TMB) of ≥10 mutations/Mb was detected in 25/117 (22%) of pts. Potential germline variants were found in 8% of pts. 80/114 (70%) pts were alive 6 months after consent to trial. Conclusions: Successful tissue-based molecular profiling is challenging in pts with CUP; achieved in only 59% of pts in this cohort. ctDNA analysis was feasible (93% successful) and reliably concordant with tissue. Potentially actionable alterations were found in 64% of pts. ctDNA molecular profiling should be considered as a reliable alternative to tissue-based testing in pts diagnosed with CUP. Clinical trial information: NCT04750109 . [Table: see text]
Non-invasive colorectal cancer detection using multimodal deep learning ensemble classifier.
Authors: Hong Seung Wook , Park Juntae , Lee Junnam , Ki Chang-Seok , Kim Dasom , Lee Tae-Rim , Ahn Jin Mo , Wang Mengchi , Carson Andrew , Lee Byung-In , Byeon Jeong-Sik , Cho Eunhae 
Published: June 2024

3066 Background: The demand for alternative, non-invasive methods for colorectal cancer (CRC) screening is substantial. Cell-free DNA (cfDNA) whole genome sequencing (WGS) offers a promising avenue, utilizing diverse fragmentomic data. We aimed to develop a new approach: integrating fragment end motif by size (FEMS) with genomic coverage (COV) of cfDNA to enhance CRC screening. Methods: Participants were comprised of 1,506 colonoscopy verified normal samples, 130 advanced adenoma (AA) patients, 302 CRC patients (stage I: 28.5%, stage II: 25.5%, stage III: 31.1%, stage IV: 14.2%, unknown: 0.7%). We generated low depth cfDNA-WGS data (a minimum 40 million reads per sample) using the Novaseq 6000 sequencer. We minimized batch bias by normalizing with the same samples for each experimental batch. The development set comprised 1,332 samples (1,023 normal, 103 AA, and 206 CRC), while the validation set consisted of 606 samples (483 normal, 27 AA, and 96 CRC). Results: Our new algorithm achieved 84.0% sensitivity (95% CI: 81%-86%) for CRC and 69.9% (95% CI: 66%-81%) for AA in the development set, with a specificity of 90.0%. These findings were consistent in the external set with 84.9% specificity (95% CI: 82%-88%) and sensitivities of 80.2% (95% CI: 72%-88%) and 63.0% (95% CI: 44%-82%) for CRC and AA, respectively. The sensitivities across stages (Stage I: 80%, Stage II: 86.8%, Stage III: 78.8%, Stage IV: 96.7%) were similarly reflected in the validation sets (Stage I: 74%, Stage II: 83%, Stage III: 79%, Stage IV: 92%). Conclusions: Our multimodal deep learning model shows promise for accurate non-invasive colon cancer and AA detection using low-coverage cfDNA WGS. Its strong performance in detecting not only CRC but also AA lesions suggests its potential for early intervention and improved patient outcomes. The use of colonoscopy-verified normal samples strengthens the study's credibility and paves the way for future clinical translation.
Targeting rare variants of a pan-cancer target: The landscape of BRAF non-v600 mutations and BRAFfusions from 172,005 adult patients with cancer.
Authors: Coleman Niamh , Subbiah Vivek 
Published: June 2024

3113 Background: BRAF is a recognized pan-cancer target, with dabrafenib in combination with trametinib receiving FDA accelerated approval for unresectable metastatic solid tumors with BRAF V600E mutation. BRAF fusions and mutations at codons aside from V600 (non-V600) activate the MAP kinase/ERK-signaling pathway, however the spectrum of these alterations is not yet well-defined. Preclinical data suggests that BRAF non-v600 mutations are diverse, with evidence of alternate signaling, requiring dimerization to function, while BRAFV600E tumors activate the pathway as monomers. We include a comprehensive analysis of non- BRAF V600 mutations and BRAF fusions in pan-cancer adult malignancies. Methods: 198,041 samples from 172,005 patients available from AACR Project GENIE v.15 (1) database were analyzed for the prevalence of non-V600 BRAF mutations, fusions and copy number alterations in a range of cancer types. Results: A total of 6374 separate non-V600 BRAF alterations were identified in 5876 samples (2.97%), including 1176 fusions (18.4%), 4435 missense mutations (69.6%), 299 truncating mutations (4.7%), and 245 in-frame mutations (3.8%), splice variants (3.4%). Most frequent tumors included lung (19%), melanoma (14%), colorectal (9.7%) glioma (5%), thyroid (1.4%). BRAF fusions were observed in 0.7% of tumor samples, most identified in glioma, prostate, lung, thyroid, and colorectal cancer (20%, 7.3%, 6.1%; 4%, 4% of identified BRAF fusions, respectively). Most fusions were considered driver events (1123, 95.5%); frequent fusion gene partners included KIAA1549, intragenic fusions, SND1, AGK, MKRN1 (39.9%, 15%, 4%, 3.3%, 2.4% of 1176 samples respectively). Of 4435 missense mutations identified, most were considered driver events (2734, 62%); 1701 missense mutations were variants of uncertain significance (VUS) using OncoKB database (38%). Missense mutations occurred across codons, most frequently involving codon 469 (n=584, 13.2%, G469A/V/R/E/S/L/K/I), 466 (n=310, 10.5%, G466V/E/A/R), 594 (n=506, 11.4%, D594G/N/A/E/H/Y/V/F), 601 (n=279, 6.3%, K601E/N/I/T/_S602delinsNT), 581 (n=231, 5.2%, N581S/I/Y/H/T/D/K) 597 (n=118; 2.7%, L597R/Q/S/V/P/H/I). BRAF amplification occurred in 0.14% of samples. Conclusions: While BRAF fusions are rare events across cancers, non-v600 BRAF alterations occur in 3% of malignancies. Atypical non-V600 BRAFalterations and BRAF fusions represent a distinct molecular cohort across cancers. Most BRAF fusion events and non-V600 missense mutations are characterized as oncogenic, underlining the spectrum of BRAF inhibition, and the urgent need to expand agents beyond the current BRAFV600 indications. Functional characterization of atypical BRAF variants is therefore crucial, together with enrolling patients with these rare alterations on rationally designed clinical trials. 1. Cancer Discov. 2017.
Efficacy and safety of CalliSpheres drug-eluting beads for bronchial arterial chemoembolization combined with intravenous chemotherapy for extensive-stage small cell lung cancer.
Authors: Cai Daxia , Tu Jianfei , Wang Yonghui 
Published: June 2024

e20137 Background: We aim to explore the efficacy and tolerability of Drug-Eluting Bead Bronchial Arterial Chemotherapy Embolization (DEB-BACE) combined with intravenous chemotherapy in the treatment of patients with initially diagnosed extensive-stage small cell lung cancer (SCLC). Methods: We collected data from 24 patients with extensive-stage small cell lung cancer who received DEB-BACE combined with intravenous chemotherapy (DEB-BACE-V) and initially diagnosed at our hospital between 2013 and 2022. Among them, nine patients received BACE combined with intravenous chemotherapy from the first-line (first-line DEB-BACE-V), ten patients from the third-line (third -line DEB-BACE-V), and five patients from the second-line (second -line DEB-BACE-V). Then, the treatment response (objective response rate and rate of cancer regression) and tumor marker levels were evaluated at the first month and third month after treatment. The quality of life was assessed using the EORTC QLQ-C30 scale. Overall survival (OS) was also evaluated. First, compare the first-line DEB-BACE-V group with the second-line DEB-BACE-V group. Then, compare the first-line DEB-BACE-V group with third-line DEB-BACE-V group. Lastly, compare the second-line DEB-BACE-V group with the third-line DEB-BACE-V group. Results: In initially diagnosed extensive-stage SCLC patients treated with DEB-BACE combined with intravenous chemotherapy, first and third month post treatment, the objective response rates were 58.33% and 79.17%, respectively; and the rates of cancer regression were 75% and 91.67%, respectively. In addition, the neuron-specific enolase (NSE) and progastrin-releasing peptide levels were reduced at the third and sixth month. Quality of life assessed by EORTC QLQ-C30 scale, which included subscales of general health status, functional domains, symptom domains, and single domains except for financial difficulty, was markedly improved in first and third month of post treatment. Adverse reactions were mild and manageable, the most common being chest pain and low fever. Median values of OS in first-line DEB-BACE-V, second -line DEB-BACE-V and third -line DEB-BACE-V were 15.7 (95% CI: 9.1595-20.759) months, 29.63 (95% CI: 20.5684-36.268) months 16.92 (95% CI: 10.4044-21.871) months, and respectively. Conclusions: Due to its favorable therapeutic response, quality of life, survival benefits, and safety profile, DEB-BACE combined with intravenous chemotherapy may become a treatment option for patients with extensive-stage SCLC, particularly as second-line therapy.
“Women Work Particularly Well in Community Organizations”
Authors: Plutshack Victoria , Merck Ashton 
Published: June 2024

Abstract
From 1939 to 1941, the US Rural Electrification Administration conducted a nationwide educational campaign to share the benefits of electricity with rural Americans, known as the Electric Farm Equipment Show. A key part of the show was a series of appliance schools, which were run by female home economists and designed for a female audience. This article examines an appliance school organized for one REA women's club and the efforts of officials like REA chief home electrification specialist Clara O. Nale to navigate the disconnect between the official REA project, which assumed a gendered division of labor, and the real needs of the farm women they served. Through the Comanche County REA Women's Club, the article explores how REA administrators imagined that women would participate in its cooperative-led electrification efforts, women's engagement with and resistance to the REA's programming, and how technology adoption was ultimately mediated through women's priorities.
Long-Term Resistance Trained Human Muscles Have More Fibers, More Myofibrils, and Tighter Myofilament Packing Than Untrained
Authors: MAEO SUMIAKI , BALSHAW THOMAS G. , MÄRZ BENJAMIN , ZHOU ZHAOXIA , HAUG BILL , MARTIN NEIL R. W. , MAFFULLI NICOLA , FOLLAND JONATHAN P. 
Published: June 2024

ABSTRACT

Introduction
Increases in skeletal muscle size occur in response to prolonged exposure to resistance training that is typically ascribed to increased muscle fiber size. Whether muscle fiber number also changes remains controversial, and a paucity of data exists about myofibrillar structure. This cross-sectional study compared muscle fiber and myofibril characteristics in long-term resistance-trained (LRT) versus untrained (UNT) individuals.

Methods
The maximal anatomical cross-sectional area (ACSAmax) of the biceps brachii muscle was measured by magnetic resonance imaging in 16 LRT (5.9 ± 3.5 yr’ experience) and 13 UNT males. A muscle biopsy was taken from the biceps brachii to measure muscle fiber area, myofibril area, and myosin spacing. Muscle fiber number, and myofibril number in total and per fiber were estimated by dividing ACSAmax by muscle fiber area or myofibril area, and muscle fiber area by myofibril area, respectively.

Results
Compared with UNT, LRT individuals had greater ACSAmax (+70%, P < 0.001), fiber area (+29%, P = 0.028), fiber number (+34%, P = 0.013), and myofibril number per fiber (+49%, P = 0.034) and in total (+105%, P < 0.001). LRT individuals also had smaller myosin spacing (−7%, P = 0.004; i.e., greater packing density) and a tendency toward smaller myofibril area (−16%, P = 0.074). ACSAmax was positively correlated with fiber area (r = 0.526), fiber number (r = 0.445), and myofibril number (in total r = 0.873 and per fiber r = 0.566), and negatively correlated with myofibril area (r = −0.456) and myosin spacing (r = −0.382) (all P < 0.05).

Conclusions
The larger muscles of LRT individuals exhibited more fibers in cross-section and larger muscle fibers, which contained substantially more total myofibrils and more packed myofilaments than UNT participants, suggesting plasticity of muscle ultrastructure.
Routing and Staffing in Customer Service Chat Systems with Generally Distributed Service and Patience Times
Authors: Long Zhenghua , Tezcan Tolga , Zhang Jiheng 
Published: June 2024

Problem definition: We study customer service chat (CSC) systems, in which agents can serve multiple customers simultaneously, with generally distributed service and patience times. The multitasking capability of agents introduces idiosyncratic challenges when making routing and staffing decisions. Methodology/results: To determine the dynamic matching of arriving customers with available agents, we first formulate a routing linear program (LP) based on system primitives. Inspired by the optimal solution of the routing LP, we design a parsimonious dynamic routing policy that is independent of arrival rate and service capacity information. We also use the optimal solution to develop closed-form approximations for crucial performance metrics and show that a similar LP can be utilized to make staffing decisions. Through extensive simulation experiments, we showcase the efficacy of our approximations and staffing decisions. Furthermore, under our proposed policy, the CSC system exhibits a unique stationary fluid model in which the steady-state performance measures align with our approximations. Managerial implications: The extant literature primarily focuses on Markovian systems with exponential distributions. In this paper, customers’ service and patience times are allowed to be generally distributed to agree with practical settings. Our findings indicate that the distributions have a significant impact on routing policies, staffing decisions, and system performance. Funding: Z. Long was supported by the National Natural Science Foundation of China [Grants 72101112, 72132005, and 72271119] and Jiangsu Province, China [Grant BK20210171]. J. Zhang was supported by the Hong Kong Research Grants Council, General Research Fund [Grants 16208120 and 16214121]. Supplemental Material: The online appendix is available at https://doi.org/10.1287/msom.2022.0114 .
OS PROBLEMAS ESTRUTURAIS QUE IMPACTAM AS AULAS DE EDUCAÇÃO FÍSICA NAS ESCOLAS PÚBLICAS
Authors: Bispo dos Santos Paulo Victor , Nascimento Pereira Ana Carolina , Alves Nogueira Souza Suzana 
Published: June 2024

Este estudo tem como objetivo analisar quais são os problemas estruturais mais marcantes e presentes nas escolas públicas e que impactam a organização do trabalho pedagógico nas aulas de Educação Física, para que, dessa forma, seja possível contribuir com as discussões acerca de reformulação de novas propostas nas escolas. A partir de uma revisão bibiográfica, de caráter descritivo e abordagem qualitativa, discute-se aqui, como as questões estruturais são vistas pelos professores de Educação Física das escolas públicas e quais desdobramentos e possibilidades aparecem ou têm que aparecer nessas circunstâncias, visto que a evasão desses contextos contribui com a disseminação de uma perspectiva pejorativa quanto à Educação Física como componente curricular. Foi evidenciada também a importância da promoção de uma mobilização social do corpo docente em vista de atingir melhores parâmetros estruturais. As dificuldades estruturais estão presente na maioria das escolas públicas, elas são um fator limitante para a práxis qualificada; entretanto, não devem ser vistas como um pretexto para abdicar do ensino de qualidade.
NGF effects promote the maturation of rat pancreatic beta cells by regulating GLUT2 levels and distribution, and glucokinase activity
Authors: Samario-Román Jazmín , Velasco Myrian , Larqué Carlos , Cárdenas-Vázquez René , Ortiz-Huidobro Rosa Isela , Hiriart Marcia 
Published: June 2024

The nerve growth factor (NGF) participates in cell survival and glucose-stimulated insulin secretion (GSIS) processes in rat adult beta cells. GSIS is a complex process in which metabolic events and ionic channel activity are finely coupled. GLUT2 and glucokinase (GK) play central roles in GSIS by regulating the rate of the glycolytic pathway. The biphasic release of insulin upon glucose stimulation characterizes mature adult beta cells. On the other hand, beta cells obtained from neonatal, suckling, and weaning rats are considered immature because they secrete low levels of insulin and do not increase insulin secretion in response to high glucose. The weaning of rats (at postnatal day 20 in laboratory conditions) involves a dietary transition from maternal milk to standard chow. It is characterized by increased basal plasma glucose levels and insulin levels, which we consider physiological insulin resistance. On the other hand, we have observed that incubating rat beta cells with NGF increases GSIS by increasing calcium currents in neonatal cells. In this work, we studied the effects of NGF on the regulation of cellular distribution and activity of GLUT2 and GK to explore its potential role in the maturation of GSIS in beta cells from P20 rats. Pancreatic islet cells from both adult and P20 rats were isolated and incubated with 5.6 mM or 15.6 mM glucose with and without NGF for 4 hours. Specific immunofluorescence assays were conducted following the incubation period to detect insulin and GLUT2. Additionally, we measured glucose uptake, glucokinase activity, and insulin secretion assays at 5.6 mM or 15.6 mM glucose concentrations.
We observed an age-dependent variation in the distribution of GLUT2 in pancreatic beta cells and found that glucose plays a regulatory role in GLUT2 distribution independently of age. Moreover, NGF increases GLUT2 abundance, glucose uptake, and GSIS in P20 beta cells and GK activity in adult beta cells.
Our results suggest that besides increasing calcium currents, NGF regulates metabolic components of the GSIS, thereby contributing to the maturation process of pancreatic beta cells.
Democracy in Aotearoa New Zealand: A Survival Guide, Geoffrey Palmer and Gwen Palmer Steeds (2022)
Authors: Wilson John F. 
Published: June 2024

Review of: Democracy in Aotearoa New Zealand: A Survival Guide, Geoffrey Palmer and Gwen Palmer Steeds (2022)
Wellington: Te Herenga Waka University Press, 400 pp.,
ISBN 978 1 77692 016 7 (pbk), NZ$40
SADC Multilateral Approach for Sustainable Development in Cabo Delgado
Authors: Mpshane-Nkosi Mmakoena 
Published: June 2024

This article investigates the political stability of Cabo Delgado’s insurgency in Mozambique and the regional multilateral efforts of the South African Development Community (SADC) and international organisations. Since establishing the United Nations’ seventeen Sustainable Development Goals five years ago, recent studies have shown that governance sustainability is essential for peace and security. According to Meadowcroft (2007), sustainable governance refers to the socio-political governance systems established to achieve sustainable growth. Thus, sustainable governance is a foundation for ensuring the achievement of long-term governmental goals managed and operated by multiple actors within a system. Sustainable development promotes methodical and constructive planning of current and future usage of resources. Governance refers to how government manage and exercises the country’s economic and social resources for growth. While many scholars in the last two years, such as Bosman and Gruzd (2022), Sithole (2022), and Okunade et al. (2021), have indicated the conflict vulnerability to the Southern African region, the government and bloc’s slow response, particularly in dealing with the armed conflict; this study argues that the multilaterally the region responded on time and is ensuring sustainable development and peace and security. The article details the multilateral approach used for counterterrorism, mainly the use of military intervention and continuous discourse within political spaces. The qualitative method extrapolates how stability, safety and security were achieved and the sustainable development plans.
Keywords: Insurgency, Cabo Delgado, SADC, Mozambique, Multilateralism, Good Governance Theory
Influence of hypercapnia and hypercapnic hypoxia on the heart rate response to apnea
Authors: O'Croinin Benjamin R. , Young Desmond A. , Maier Lauren E. , van Diepen Sean , Day Trevor A. , Steinback Craig D. 
Published: June 2024

AbstractWe aimed to determine the relative contribution of hypercapnia and hypoxia to the bradycardic response to apneas. We hypothesized that apneas with hypercapnia would cause greater bradycardia than normoxia, similar to the response seen with hypoxia, and that apneas with hypercapnic hypoxia would induce greater bradycardia than hypoxia or hypercapnia alone. Twenty‐six healthy participants (12 females; 23 ± 2 years; BMI 24 ± 3 kg/m2) underwent three gas challenges: hypercapnia (+5 torr end tidal partial pressure of CO2 [PETCO2]), hypoxia (50 torr end tidal partial pressure of O2 [PETO2]), and hypercapnic hypoxia (combined hypercapnia and hypoxia), with each condition interspersed with normocapnic normoxia. Heart rate and rhythm, blood pressure, PETCO2, PETO2, and oxygen saturation were measured continuously. Hypercapnic hypoxic apneas induced larger bradycardia (−19 ± 16 bpm) than normocapnic normoxic apneas (−11 ± 15 bpm; p = 0.002), but had a comparable response to hypoxic (−19 ± 15 bpm; p = 0.999) and hypercapnic apneas (−14 ± 14 bpm; p = 0.059). Hypercapnic apneas were not different from normocapnic normoxic apneas (p = 0.134). After removal of the normocapnic normoxic heart rate response, the change in heart rate during hypercapnic hypoxia (−11 ± 16 bpm) was similar to the summed change during hypercapnia+hypoxia (−9 ± 10 bpm; p = 0.485). Only hypoxia contributed to this bradycardic response. Under apneic conditions, the cardiac response is driven by hypoxia.