bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Pivotal Role of Germline BRCA2 Pathogenic Variants in “Apparently Sporadic” Pancreatic Cancer
Authors: Brody Jonathan R. , Klein Alison P. 
Published: September 2024

Abstract
In 1996, Goggins and colleagues demonstrated the importance of germline BRCA2 pathogenic variants in the development of apparently sporadic pancreatic ductal adenocarcinoma (PDAC). Previously, the group identified homozygous deletion of the 13q region in PDACs, enabling the identification of the BRCA2 gene. This 1996 article first revealed loss of BRCA2, both germline and somatic, as a key driver of PDAC at a time when there was still doubt if PDAC even had an inherited component. Contrary to the prevailing wisdom, not all individuals with inherited pathogenic BRCA2 variants had a family history of cancer. The innovative bedside-to-bench nature of this work revealed that individuals with these variants would be missed if genetic testing was limited only to those meeting the family history criteria. Therefore, Goggins and colleagues advocated that universal genetic testing may be indicated for pancreatic cancer at a time when genetic testing was in its infancy. Twenty-three years later, in 2019, universal testing for pancreatic cancer became standard of care in the United States. Additionally, this work and future-related publications by the Kern Laboratory set the stage for targeting BRCA2 and related DNA repair mutations in pancreatic cancer via a synthetic lethal therapeutic approach. The provocative discussion initiated by this team in this publication is still inspiring the field today. In this seminal publication, Goggins and colleagues profoundly impacted the direction of pancreatic cancer research, leading to a more sophisticated approach to designing earlier detection and precision treatment strategies for pancreatic cancer.
See related article by Goggins and colleagues, Cancer Res 1996;56:5360–4
Clinical and Genomic Features of Classical and Basal Transcriptional Subtypes in Pancreatic Cancer
Authors: Singh Harshabad , Xiu Joanne , Kapner Kevin S. , Yuan Chen , Narayan Raja R. , Oberley Matthew , Farrell Alex , Surana Rishi , Huffman Brandon M. , Perez Kimberly , Cleary James M. , Jordan Alexander C. , Dias Costa Andressa , Williams Hannah L. , Raghavan Srivatsan , Weinberg Benjamin , Pishvaian Michael J. , Shroff Rachna T. , Goel Sanjay , Dougan Stephanie K. , Nowak Jonathan A. , Spetzler David , Sledge George , Wolpin Brian M. , Aguirre Andrew J. 
Published: September 2024

Abstract

Purpose:
Transcriptional profiling of pancreatic cancers has defined two main transcriptional subtypes: classical and basal. Initial data suggest shorter survival for patients with basal tumors and differing treatment sensitivity to FOLFIRINOX and gemcitabine plus nab-paclitaxel by transcriptional subtype.

Experimental Design:
We examined 8,743 patients with RNA sequencing from pancreatic cancers performed at Caris Life Sciences. Classical and basal subtypes were identified using purity independent subtyping algorithm on RNA sequencing, and two cohorts were analyzed: (i) the biomarker cohort included patients with complete molecular profiling data (n = 7,250) and (ii) the outcome cohort included patients with metastatic disease with available survival outcomes (n = 5,335). A total of 3,842 patients were shared between the two cohorts. Kaplan–Meier curves and Cox proportional hazards regression were used to assess patient survival.

Results:
In the biomarker cohort, 3,063 tumors (42.2%) were strongly classical (SC) and 2,015 tumors (27.8%) were strongly basal (SB). SC and SB tumors showed strong associations with histologic phenotypes and biopsy sites. SB tumors had higher rates of KRAS, TP53, and ARID1A mutations, lower rates of SMAD4 mutation, and transcriptional evidence of epithelial-mesenchymal transition. Sixty of 77 cases (78%) maintained their transcriptional subtype between temporally and/or spatially disparate lesions. In the outcome cohort, the SB subtype was associated with shorter overall survival time, regardless of whether they received FOLFIRINOX or gemcitabine plus nab-paclitaxel as first-line chemotherapy. The mutant KRAS allele type was prognostic of outcomes; however, this impact was restricted to SC tumors, whereas all mutant KRAS alleles had similarly poor outcomes in SB tumors.

Conclusions:
The SB subtype is a strong independent predictor of worse outcomes, regardless of the up-front chemotherapy regimen used. Clinical trials should further investigate pancreatic cancer transcriptional subtypes as a prognostic and predictive biomarker.
High Mechanical Conditioning by Tumor Extracellular Matrix Stiffness Is a Predictive Biomarker for Antifibrotic Therapy in HER2-Negative Breast Cancer
Authors: Quintela-Fandino Miguel , Bermejo Begoña , Zamora Esther , Moreno Fernando , García-Saenz José Ángel , Pernas Sonia , Martínez-Jañez Noelia , Jiménez Desirée , Adrover Encarna , de Andrés Raquel , Mourón Silvana , Bueno Maria J. , Manso Luis , Viñas Gemma , Alba Emilio , Llombart-Cussac Antonio , Cortés Javier , Tebar Cristina , Roe Denise J. , Grant Adam , Watson Adam , Colomer Ramon , Mouneimne Ghassan 
Published: September 2024

Abstract

Purpose:
Tumor progression has been linked to stiffening of the extracellular matrix caused by fibrosis. Cancer cells can be mechanically conditioned by stiff extracellular matrix, exhibiting a 1,004-gene signature [mechanical conditioning (MeCo) score]. Nintedanib has demonstrated antifibrotic activity in idiopathic pulmonary fibrosis. This study explores nintedanib’s antifibrotic effect on breast cancer outcomes.

Experimental Design:
We present long-term follow-up and analysis of a neoadjuvant randomized phase II trial in early HER2-negative breast cancer. Patients (N = 130) underwent a baseline biopsy and received 12 paclitaxel courses alone (control arm) or in combination with nintedanib (experimental arm). The tumor MeCo score was determined by RNA sequencing. The primary aim was to assess nintedanib’s impact on event-free survival based on MeCo scores.

Results:
Follow-up data were retrieved from 111 patients; 75 baseline and 24 post-run-in phase samples were sequenced. After median follow-up of 9.67 years, median event-free survival was not statistically different between arms (P = 0.37). However, in the control arm, high- versus low-MeCo patients had a statistically higher relapse risk: HR = 0.21; P = 0.0075. This risk was corrected by nintedanib in the experimental arm: HR = 0.37; P = 0.16. Nintedanib demonstrated pharmacodynamic engagement, reducing the MeCo score by 25% during the run-in phase (P &lt; 0.01). Patients with low MeCo after run-in had the best long-term prognosis (HR = 0.087; P = 0.03).

Conclusions:
High MeCo is predictive of poor outcomes in HER2-negative early breast cancer, although this risk can be mitigated by nintedanib, which is able to specifically reduce MeCo.
Identifying Transfer Learning in the Reshaping of Inductive Biases
Authors: Székely Anna , Török Balázs , Kiss Mariann , Janacsek Karolina , Németh Dezső , Orbán Gergő 
Published: September 2024

Abstract
Transfer learning, the reuse of newly acquired knowledge under novel circumstances, is a critical hallmark of human intelligence that has frequently been pitted against the capacities of artificial learning agents. Yet, the computations relevant to transfer learning have been little investigated in humans. The benefit of efficient inductive biases (meta-level constraints that shape learning, often referred as priors in the Bayesian learning approach), has been both theoretically and experimentally established. Efficiency of inductive biases depends on their capacity to generalize earlier experiences. We argue that successful transfer learning upon task acquisition is ensured by updating inductive biases and transfer of knowledge hinges upon capturing the structure of the task in the inductive bias that can be reused in novel tasks. To explore this, we trained participants on a non-trivial visual stimulus sequence task (Alternating Serial Response Times, ASRT); during the Training phase, participants were exposed to one specific sequence for multiple days, then on the Transfer phase, the sequence changed, while the underlying structure of the task remained the same. Our results show that beyond the acquisition of the stimulus sequence, our participants were also able to update their inductive biases. Acquisition of the new sequence was considerably sped up by earlier exposure but this enhancement was specific to individuals showing signatures of abandoning initial inductive biases. Enhancement of learning was reflected in the development of a new internal model. Additionally, our findings highlight the ability of participants to construct an inventory of internal models and alternate between them based on environmental demands. Further, investigation of the behavior during transfer revealed that it is the subjective internal model of individuals that can predict the transfer across tasks. Our results demonstrate that even imperfect learning in a challenging environment helps learning in a new context by reusing the subjective and partial knowledge about environmental regularities.
Lung Ultrasound as an Adjunct to Pulse Oximetry and Respiratory Symptoms in the Diagnosis of Freediving-Induced Pulmonary Syndrome
Authors: Yu Elaine , Silva Fernando , Lussier Anna , Lindholm Peter 
Published: September 2024

Introduction B-lines on lung ultrasound have been found in asymptomatic competitive breath-hold divers, but their significance and time to resolution are not well understood. We sought to investigate the relationship between B-lines, oxygen saturation, and respiratory symptoms after competitive dives to diagnose pulmonary injury. Methods We performed lung ultrasounds before (predive), immediately after (postdive), and within 1 h (follow-up) of a competitive dive. B-lines were counted in each intercostal space in the anterior, lateral, and posterior lung fields, and the highest number of B-lines within a space was recorded for each lung region. At follow-up, each diver's oxygen saturation and respiratory symptoms were recorded. Statistical analysis included the Kruskal–Wallis test, Spearman's correlation, and sensitivity and specificity calculations. Results Forty-four divers completed 143 individual dives of four different disciplines. The median number of B-lines was 0 (IQR inclusive=0) predive, 1 (IQR=3) postdive, and 0 (IQR=1) at follow-up. There was a significant difference in total B-lines between measurement times ( p<0.001). Sensitivity and specificity of hypoxemia, clinically significant B-lines, and both measures in tandem in detecting respiratory symptomatology were 52% and 76%, 24% and 92%, and 24% and 95%, respectively. Conclusions B-lines are a common phenomenon in competitive breath-hold divers on surfacing and decrease within 1 h, suggesting a physiologic fluid shift. B-lines are negatively correlated with oxygen saturation, indicating that extravascular fluid impairs gas exchange in the lung. Neither hypoxemia nor clinically significant B-lines were found to be reliable indicators for respiratory symptomatology, suggesting that there may be multiple phenotypes of freediving-induced pulmonary syndrome.
Using Group History-Taking and Individual Reasoning to Identify Shortcomings in Clinical Reasoning for Medical Students
Authors: Cheng Kuan-Hao , Lee Chi-Yu , Wu Yih-Jer , Lin Ching-Chung 
Published: September 2024

OBJECTIVE It is crucial that teaching faculties determine and remain informed of medical school learners’ clinical reasoning competence. We created an innovative assessment method for fourth-year medical students to identify deficiencies in various components of their clinical reasoning ability. METHODS This was a cross-sectional observational study of fourth-year medical students’ reasoning assessments from 2019 to 2022. Teams of four–five trainees questioned standardized patients in clinical scenarios, including fever, abdominal pain, and weight loss. They then individually documented key information to reflect comprehension of patient problems. Trainees were tasked with differentiating diagnoses and associated statuses and reaching the most likely diagnosis along with two tentative diagnoses. The correlations observed between 2020 and 2022 for abdominal pain were analyzed using student t-tests. RESULTS A total of 177 students participated in this study. Across the scenarios, there was no significant difference in key information representation scores (56%–58%). Reasoning ability scores were 49% for fever, 57% for abdominal pain, and 61% for weight loss. A comparison between 2020 and 2022 revealed a significant improvement in the objective structured clinical examination scores and differential diagnoses ( P < .01). Shortcomings included brief chief complaint duration, lack of detailed presentation, and insufficient description of negative information. Differential diagnosis and diagnostic justification were inadequate for acute and chronic conditions, and disease location clarity within the organ system was lacking. On average, students presented two correct diagnoses. CONCLUSIONS Fourth-year medical students exhibited inadequate reasoning abilities, particularly in fever and abdominal pain scenarios, with deficiencies in hypothesis generation and differential diagnosis. Group history-taking with individual reasoning assessment identified students’ shortcomings and provided faculty feedback to improve their teaching strategies.
Influence of the clay fractions from various horizons on the radiation shielding parameters of an Arenosol
Authors: Pires Luiz F. , Yanaguisawa Victor A. , Brinatti André M. , Saab Sérgio C. , Correchel Vladia 
Published: September 2024

AbstractThis study examines the effects of the chemical composition of the clay fraction of various soil horizons on radiation shielding parameters. X-ray fluorescence (XRF) analysis did not reveal significant differences in the concentration of the most abundant oxides (Al2O3, SiO2, Fe2O3) among the various horizons. Consequently, the mass attenuation coefficient did not vary among the horizons in terms of the photon energies studied (15 keV–10 MeV). The mean free path (MFP), half-value layer (HVL) and tenth-value layer (TVL) did not differ for energies up to 100 keV. However, at higher energies, these parameters were mainly influenced by the differences in the densities of the soil horizons. The effective atomic number did not differ across the horizons for the various photon energies, nor did the mass attenuation coefficient. It is shown that slight differences in the chemical composition of the clay fraction of soil horizons do not affect radiation shielding parameters (MFL, HVL, TVL) for low photon energies (<500 keV). Density is more important for radiation shielding than the chemical composition of the various horizons of the same soil type for higher energies (>100 keV); hence, compacting the clay fraction might be more efficient for radiation shielding purposes at higher energies.
Dose-response relationship of high-intensity training on global cognition in older adults with mild cognitive impairment or dementia: a systematic review with meta-analysis - the ACHIEVE-Study
Authors: Afanador-Restrepo Diego Fernando , Casanova-Correa Alejandro , Martín-Ojeda Rita Inés , Aibar-Almazán Agustín , González-Martín Ana María , Hita-Contreras Fidel , del Carmen Carcelén-Fraile María , Castellote-Caballero Yolanda 
Published: September 2024

Abstract
Background
The prevalence of mild cognitive impairment (MCI) and its subsequent progression to dementia has increased progression to dementia has increased worldwide, making it a topic of interest. of interest, and it has been observed that approximately 23% of cases are avoidable through preventable through vigorous exercise.

Methods
A systematic review with meta-analysis was conducted by searching in the PubMed, Scopus, CINAHL, and Web of Science databases. For inclusion, studies had to incorporate High Intensity Training (HIT) as a primary or significant component of the overall intervention for older adults with MCI. Out of the 611 articles identified, 14 randomized clinical trials met the criteria for inclusion in the review.

Results
Fourteen trials were included in the systematic review, and seven were included in the meta-analysis. A total of 1839 participants were included in the studies, with 1014 receiving a high-intensity training-based intervention, and 998 were considered in the meta-analysis. Compared to usual care or sedentary activities, the high-intensity training interventions had a positive effect on cognition, either improving it or delaying the decline (g = 0.710 (95% CI: 0.191 — 1.229; p = 0.007). Additionally, the meta-analysis determined that a frequency of 3 sessions per week (g = 0.964, CI = 0.091 — 1.837, p = 0.030) of approximately 60 minutes (g = 0.756, CI = 0.052 — 1.460, p = 0.035) each was the best dose to obtain better effects on global cognition.

Conclusion
Low-frequency and short-duration high-intensity training interventions are sufficient to improve or at least delay the decline in global cognition.
Comparison of combination therapy with tamsulosin and dutasteride or finasteride in patients with benign prostatic hyperplasia: a randomized clinical trial
Authors: Basiri Abbas , Zare Rasool , Zahir Mazyar , Kashi Amir Hossein , Zobeiry Mahsa , Borumandnia Nasrin , Abedi Amir Reza , Golshan Shabnam 
Published: September 2024

Abstract
Background
Based on our observations at the largest outpatient urology clinic in Iran, patients for whom finasteride is prescribed as a secondary drug to tamsulosin tend to experience earlier and more severe sexual side effects without any difference in the amelioration of symptoms. This study aimed to compare the time lag, efficacy, and side effects of combination therapy with varying doses of dutasteride or finasteride added to tamsulosin for benign prostatic hyperplasia (BPH) treatment.

Methods
In this study 165 were randomized into 5 groups (each N = 33); receiving tamsulosin 0.4mg plus either of A: finasteride 3mg, B: placebo, C: dutasteride 0.25mg, D: finasteride 5mg or E: dutasteride 0.5mg. During the 6-month period of the study, International Prostate Symptom Score (IPSS), post-void residual urine (PVR), International Index of Erectile Function (IIEF-5), prostate volume (PV), prostate specific antigen (PSA) and maximum urinary flow rate (Qmax) were evaluated at baseline and at the 1st, 3rd and 6th month. The differences between each time point and baseline were then compared between groups.

Results
At 3-month follow-up, group E exhibited a higher decrease in PSA but a greater increase in Qmax compared to group A (p = 0.047 and 0.006, respectively). Group C showed higher Qmax increase compared to group A at 3 and 6 months (p = 0.003 and 0.014) and concurrently a more pronounced PV decrease at 1 and 3 months (p = 0.047 and 0.003, respectively). Group D had a significantly more decrease in their IIEF-5 compared to group A at one-month visit (p = 0.006).

Conclusions
In summary, at the sixth-month follow-up, dutasteride demonstrated superiority over finasteride solely in enhancing Qmax. Therefore, dutasteride may be marginally more beneficial as a secondary component of combination therapy in BPH.
Trial registration IRCT, IRCT20120516009772N2. Registered 18 January 2021 Retrospectively registered, https://irct.behdasht.gov.ir/search/result?query=IRCT20120516009772N2.
TRPV2: a universal regulator in cellular physiology with a yet poorly defined thermosensitivity
Authors: Fricke Tabea C. , Leffler Andreas 
Published: September 2024

AbstractTransient receptor potential (TRP) ion channels serve as sensors for variations in ambient temperature, modulating both thermoregulation and temperature responsive cellular processes. Among these, the vanilloid TRP subfamily (TRPV) comprises six members and at least four of these members (TRPV1-TRPV4) have been associated with thermal sensation. TRPV2 has been described as a sensor for noxious heat, but subsequent studies have unveiled a more complex role for TRPV2 beyond temperature perception. This comprehensive review aims to elucidate the intricate thermosensitivity of TRPV2 by synthesizing current knowledge on its biophysical properties, expression pattern and known physiological functions associated with thermosensation.
Literature review of comparative school-to-work research: how institutional settings shape individual labour market outcomes
Authors: Marczuk Anna 
Published: September 2024

AbstractComparative school-to-work research has long emphasised the role of institutions in shaping youth labour market integration. This paper provides an overview of this research stream, consisting of four main sections. The first section introduces a variety of labour market outcomes of young graduates within Europe and identifies country clusters with higher and lower outcomes; this empirical evidence has so far remained limited in the multivariate oriented research stream. The second section links these labour market outcomes to the institutional settings of the education systems prevalent in the country clusters. By considering a wide country sample, it introduces a reliable country classification of transition regimes (along the OLM–ILM continuum), which has so far been partly inconclusive in research. The third section links labour market outcomes in turn to labour market institutions of the country clusters. This section emphasizes why labour market institutions drive only particular individual outcomes. Finally, the fourth section connects the previous three: it describes how certain institutional complementarities affect the youth labour market integration in the identified European country clusters. The review further identifies theoretical inconclusiveness or data-related desiderata, for which recommendations and solutions are proposed. The paper thus aims to assist both familiar and unfamiliar researchers to access the research stream by offering a comprehensive introduction and clear country classifications, linking research streams, and providing solutions to identified issues.