Miracle-dz/UniFAR-FTUs huggingface dataset:
28. TWO SEISMIC REFRACTION PROFILES IN THE WEST PHILIPPINE SEA

The results of two reversed refraction profiles made in the west Philippine Sea by Thomas Washington on Cruise Tasaday V in September 1973 are presented. SSQ-41 expendable military sonobuoys were used as receivers and explosives as a sound source on both stations. Station 5-2 was purposely located over Leg 31 DSDP Sites 294/295 where drilling had only been successful to the bottom of the thin sediment cover, about 150 meters maximum (Site Report Chapter 6, this volume). It is an area of relatively smooth bottom topography (100 m maximum relief along Station 5-2) with an average water depth of 5.75 km. Station 5-3 was located approximately 290 km to the southwest of Sites 294/295, just south of the Central Basin fault. The topography is hilly (800 m relief along Station 5-3) with an average water depth of 5.50 km (Figure 1).
Novel Plastid Genome Characteristics in Fugacium kawagutii and the Trend of Accelerated Evolution of Plastid Proteins in Dinoflagellates

Abstract Typical (peridinin-containing) dinoflagellates possess plastid genomes composed of small plasmids named “minicircles”. Despite the ecological importance of dinoflagellate photosynthesis in corals and marine ecosystems, the structural characteristics, replication dynamics, and evolutionary forcing of dinoflagellate plastid genomes remain poorly understood. Here, we sequenced the plastid genome of the symbiodiniacean species Fugacium kawagutii and conducted comparative analyses. We identified psbT-coding minicircles, features previously not found in Symbiodiniaceae. The copy number of F. kawagutii minicircles showed a strong diel dynamics, changing between 3.89 and 34.3 copies/cell and peaking in mid-light period. We found that F. kawagutii minicircles are the shortest among all dinoflagellates examined to date. Besides, the core regions of the minicircles are highly conserved within genus in Symbiodiniaceae. Furthermore, the codon usage bias of the plastid genomes in Heterocapsaceae, Amphidiniaceae, and Prorocentraceae species are greatly influenced by selection pressure, and in Pyrocystaceae, Symbiodiniaceae, Peridiniaceae, and Ceratiaceae species are influenced by both natural selection pressure and mutation pressure, indicating a family-level distinction in codon usage evolution in dinoflagellates. Phylogenetic analysis using 12 plastid-encoded proteins and five nucleus-encoded plastid proteins revealed accelerated evolution trend of both plastid- and nucleus-encoded plastid proteins in peridinin- and fucoxanthin-dinoflagellate plastids compared to plastid proteins of nondinoflagellate algae. These findings shed new light on the structure and evolution of plastid genomes in dinoflagellates, which will facilitate further studies on the evolutionary forcing and function of the diverse dinoflagellate plastids. The accelerated evolution documented here suggests plastid-encoded sequences are potentially useful for resolving closely related dinoflagellates.
Discovery and Mechanistic Elucidation of a Class of PDI Inhibitors for the Treatment of Glioblastoma

Protein disulfide isomerase (PDI) is overexpressed in glioblastoma, the most aggressive form of brain cancer, and folds nascent proteins responsible for the progression and spread of the disease. Herein, we describe a novel, nanomolar PDI inhibitor, pyrimidotriazinedione 35G8, that is toxic in a panel of human glioblastoma cell lines. We performed a medium throughput 20,000compound screen of a diverse subset of 1,000,000 compounds to identify cytotoxic small molecules. Cytotoxic compounds were screened for PDI inhibition, and, from the screen, 35G8 emerged as the most cytotoxic inhibitor of PDI. Bromouridine-labeling and sequencing (Bru-seq) of nascent RNA revealed that 35G8 induced Nrf2 (nuclear factor-like 2) antioxidant response, endoplasmic reticulum stress response, and autophagy. Specifically, 35G8 upregulated heme oxygenase 1 and SLC7A11 (solute carrier family 7 member 11) transcription and protein expression and repressed PDI target genes such as TXNIP (thioredoxin-interacting protein 1) and EGR1 (early growth response 1). Interestingly, 35G8-induced cell death did not proceed via apoptosis or necrosis, but by a mixture of autophagy and ferroptosis. Cumulatively, our data demonstrate a mechanism for a novel PDI inhibitor as a chemical probe to validate PDI as a target for brain cancer.
Oligocene bivalve faunas from the Silesian Nappe, Polish Outer Carpathians: Evidence for the early history of the Paratethys

The study is focused on the taxonomic inventory of an intriguing bivalve fauna from the Lower Oligocene Menilite Beds (Dynow Marls) within the Silesian Nappe, Polish Outer Carpathians. Sixteen bivalve species have been identified within the material collected in two small quarries in Jablonica Polska near Krosno. Stratigraphic and geographic distributions of all recognized species are considered. This assemblage, the first of this kind in Poland and one of three recognized in the Outer Carpathians, shows clear affinities to coeval typical Solenovian faunas from Ukraine to Kazakhstan, with particular comparison made to bivalve faunas from the Menilite Formation (Subchert Member) within the Boryslav-Pokuttya Nappe, Ukrainian Outer Carpathians. Moreover, this study presents an overview of the main aspects and definitions of the date of the Paratethys origin. The main criterion used to define the time of the Paratethys birth is the distinct faunal turnover from the moderately diverse boreal or Tethyan bivalve faunas populating particular basins of the Northern Peri-Tethys in the earliest Oligocene to the uniform, highly endemic fauna inhabiting the newly formed semi-closed basin. This vast inland sea, named Paratethys, was populated by representatives of eight euryhaline bivalve families. They are characterized by extinct Paratethyan genera, such as Bessia Kojumdgieva et Sapungieva, Merklinicardium Popov, Korobkoviella Merklin, Urbnisia Goncharova, Ergenica G. Popov and Janschinella Merklin
Association of a Heart Failure Management Incentive in Primary Care With Clinical Outcomes: A Retrospective Cohort Study

Background We aim to examine the association between primary care physicians' billing of Q050A, a pay‐for‐performance heart failure (HF) management incentive fee code, and the composite outcome of mortality, hospitalization, and emergency department visits. Methods and Results This population‐based cohort study linked administrative health databases in Ontario, Canada, for patients with HF aged >66 years between January 1, 2008, and March 31, 2020. Cases were patients with HF who had a Q050A fee code billed. Cases and controls were matched 1:1 on age, sex, patient status on being rostered to a primary care physician, cardiologist, or internist visit in the 6 months before study enrollment, Johns Hopkins Adjusted Clinical Group resource use bands, days between HF diagnosis and study enrollment (±2 years), and the logit of the propensity score. A Cox proportional hazards model assessed the association of Q050A with the outcome. A total of 59 664 cases had a Q050A billed, whereas 244 883 patients did not. Before matching, patients who had a Q050A billed were more likely to be men (52% versus 49%), were rostered to a primary care physician (100% versus 96%), had a higher Charlson Comorbidity Index, and had higher health care costs. The mean follow‐up was 481 days for cases and 530 days for controls. The composite outcome (hazard ratio, 1.11 [95% CI, 1.09–1.12]) was significantly higher for cases than controls. Conclusions The Q050A incentive improved financial compensation for primary care physicians managing patients with HF but was not associated with improvements in the outcome. Research on promoting evidence‐based HF management is warranted.
Multilevel Petri net‐based ticket assignment and IT management for improved IT organization support

The problem of incident management has been well studied and the ticketing has been handled by various approaches. Still, the methods suffer to produce higher growth in IT service management towards the development of IT organizations. To solve this issue, a multilevel Petri net‐based ticket assignment scheme has been proposed. The method maintains different services in different levels. According to the ticket identified, the ticket has been assigned through number of services in different levels. At each level, the status of service and ticket has been collected and maintained. Similarly, the number of ticket and service states has been generated. For each level and for each service, the method computes the popularity based on their previous ticket management support measure and the error rate. Finally, a single set of services has been selected for the assignment of ticket. At the selected composite service, the six sigma has been applied and validated for the quality of output. Based on the error rate identified, the process has been iterated until an optimal service has been identified. The proposed algorithm identifies an efficient set of services to be assigned for the ticket and improves the performance of ticket management. In addition, the proposed algorithm improves performance of organizational support greatly.
The Hydrodynamics of the Gulf of Cadiz and the Exchange of Water Masses Through the Gibraltar Strait

Studies on the exchange of water masses through the Gibraltar Strait, between the Atlantic Ocean and the Mediterranean Sea, are numerous, mainly in recent years. However, there is a lack of works of synthesis about the mechanism, distribution and nature of the water masses etc., based on more recent data. On the other hand, the establishment of temperature and salinity data for the waters partially covering the continental shelf near Câdiz, has demonstrated the presence, in this area, of North Atlantic Surface Water (NASW), to about 140 metres depth, with clear seasonal variations. At a deeper level, some North Atlantic Central Water (NACW) has been detected, but the presence of Mediterranean Water (MW), which circulates below 500 metres, in the continental slope, has not been observed.
From theoretical models to practical deployment: A perspective and case study of opportunities and challenges in AI-driven healthcare research for low-income settings

This paper critically explores the opportunities and challenges of deploying Artificial Intelligence (AI) in healthcare. This study has two parallel components: (1) A narrative literature summary, which assesses the capacity of AI to aid in addressing the observed disparity in healthcare between high- and low-income countries. Despite the development of machine learning models for a wide range of diseases, many are never deployed in practice. We highlight various challenges that contribute to the lack of deployed models. A main challenge that is not always sufficiently addressed in the literature is the evaluation of model generalisation. For example, by using a multi-site set-up with test sets that were collected separately to the train and validation sets, or by using evaluation metrics which are both understandable and clinically applicable. Moreover, we discuss how the emerging trend of human-centred deployment research is a promising avenue for overcoming barriers towards deployment. (2) A case study on developing and evaluating a predictive AI model tailored for low-income environments. The focus of this case study is heart murmur detection in rural Brazil. Our Binary Bayesian ResNet model leverages overlapping log mel spectrograms of patient heart sound recordings and integrates demographic data and signal features via XGBoost to optimise performance. We discuss the models limitations, its robustness, and the obstacles preventing its practical application. We especially highlight how our model, and other state-of-the-art models, struggle to generalise to out-of-distribution data. The research accentuates the transformative potential of AI-enabled healthcare, particularly affordable point-of-care monitoring systems, in low-income settings. It also emphasises the necessity for effective implementation and integration strategies to guarantee the successful deployment of these technologies.
Luminal B Breast Cancer Coexpressing p62 and ALDH1A3 Is Less Susceptible to Radiotherapy

Background/Aim: We have reported that p62 (also known as sequestosome 1) is needed for survival/proliferation and tumor formation by aldehyde dehydrogenase 1 (ALDH1) -positive cancer stem cells (CSCs) and that p62high ALDH1A3high expression is associated with a poor prognosis in luminal B breast cancer. However, the association between p62high ALDH1A3high and the benefit from radiotherapy in patients with luminal B breast cancer remains unclear. Materials and Methods: Datasets from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and The Cancer Genome Atlas (TCGA) were downloaded, and data from p62high ALDH1A3high luminal B patients treated without or with radiotherapy were analyzed by Kaplan–Meier and multivariate Cox regression analyses. We also performed an in vitro tumor sphere formation assay after X-ray irradiation using p62-knockdown ALDH1high luminal B BT-474 cells. Results: p62high ALDH1A3high patients had poorer clinical outcomes than other luminal B breast cancer patients treated with radiotherapy. The combination of p62 DsiRNA KD and X-ray irradiation suppressed in vitro tumor sphere formation by ALDH1high BT-474 cells. These results suggest that p62 is involved in the reduced effect of X-ray irradiation on ALDH1-positive luminal B breast CSCs. Conclusion: p62 and ALDH1A3 may serve as prognostic biomarkers for luminal B breast cancer patients treated with radiotherapy. Additionally, the combination of p62 inhibition and radiotherapy could be useful for targeted strategies against ALDH1-positive luminal B breast CSCs.
Clinical Impact of Preoperative Neutrophil-to-Lymphocyte Ratio in Surgical Patients With Pancreatic Cancer

Background/Aim: The prognosis of patients with pancreatic cancer remains poor, despite recent advances in surgical techniques, perioperative care, neoadjuvant and adjuvant chemotherapy. This study aimed to investigate the preoperative neutrophil-to-lymphocyte ratio (NLR) as a prognostic factor and determine the optimal cutoff value in surgical patients with pancreatic cancer. Patients and Methods: We retrospectively enrolled 461 patients with pancreatic cancer who underwent resection between January 2013 and December 2022 in the Department of Gastrointestinal Surgery at Kanagawa Cancer Center. The association between continuous or categorical variables and NLR was analyzed using the Mann–Whitney U-test and Fisher’s exact test. Overall survival (OS) and relapse-free survival (RFS) rates were calculated using the Kaplan–Meier method. Univariate and multivariate analyses were performed using Cox proportional-hazard regression models. Results: The optimal cutoff value for the preoperative NLR was 3.2. The NLR≥3.2 was associated with a large tumor size (p=0.005), poor histological differentiation (p=0.002), and less adjuvant chemotherapy (p=0.048). The NLR≥3.2 had an important influence on the decreased OS (21.6 vs. 25.8 months), and RFS (10.3 vs. 14.3 months). In univariate and multivariate analyses, the preoperative NLR was an independent prognostic factor for OS (p=0.022) and RFS (p=0.002). Conclusion: Preoperative NLR (cutoff value: 3.2) within two weeks before surgery is a prognostic factor for OS and RFS in surgical patients with pancreatic cancer. This study could help establish evidence on the immune system’s impact and a unified treatment strategy pre-surgery, potentially improving the prognosis for patients with pancreatic cancer.
Simvastatin Enhances the Radiosensitivity of Androgen-independent Prostate Cancer Cells via Inhibition of RAD51 Expression

Background/Aim: Statins exert antitumor effects via various mechanisms. Additionally, the recurrence rate of prostate cancer after radiation therapy is lower in patients taking statins. This study investigated the efficacy of combination therapy with statins and irradiation in androgen-independent prostate cancer cells. Materials and Methods: PC-3 and LNCaP human prostate cancer cell lines were used in this study. We developed androgen-independent LNCaP cells (LNCaP-LA) by gradually replacing fetal bovine serum (FBS) with charcoal-stripped FBS. Microarray analysis was performed, followed by Ingenuity Pathway Analysis. Cell viability was determined using the MTS assay. Results: Simvastatin alters gene expressions in PC-3 cells. Microarray data showed that the number of differentially expressed genes was the highest in the pathway of “Role of BRCA1 in DNA Damage Response”. In the validation, the expression of RAD51, listed in “Role of BRCA1 in DNA Damage Response”, decreased significantly by simvastatin in PC-3 cells. Reduction in RAD51 expression following siRNA transfection increased the cytocidal effects of X-ray therapy in PC-3 and LNCaP-LA cells. The combination of simvastatin and irradiation further inhibited cell proliferation compared with monotherapy with either therapy in PC-3 or LNCaP-LA cells. In addition, compared with X-ray monotherapy, the combination of simvastatin and irradiation further enhanced the expression of γH2AX, which is reported to be one of the accurate markers of DNA damage in PC-3 cells. Conclusion: Simvastatin decreased the expression of RAD51 in androgen-independent prostate cancer cells. The combination of irradiation and drugs that reduce RAD51 expression can potentially affect androgen-independent prostate cancer growth.
Geriatric Nutritional Risk Index Is an Independent Prognostic Factor for Patients With Esophageal Cancer Who Receive Curative Treatment

Background/Aim: The perioperative nutritional status has recently been reported to influence the prognosis of various types of cancer. We investigated the relationship between the Geriatric Nutritional Risk Index (GNRI) and overall survival (OS) and recurrence-free survival (RFS) in patients with esophageal cancer who received radical and adjuvant therapy. Patients and Methods: Patients who underwent radical resection for esophageal cancer at our hospital (n=187) were included. Background characteristics, surgical factors, and OS were examined retrospectively. The GNRI was calculated using preoperative values, with GNRI <98 classified as low-GNRI. Results: Seventy-five and 112 patients were classified into the GNRI-low and -high groups, respectively. The 3- and 5-year OS rates were 75.7% and 66.7%, respectively, in the GNRI-high group and 43.2% and 36.7% in the GNRI-low group; the difference was statistically significant (p<0.001). In the univariate and multivariate analyses, low-GNRI was selected as a risk factor for OS. The hazard ratio for low-GNRI was 2.184 (95% confidence interval=1.361-3.508, p=0.001). The 5-year RFS rate in the high- and low-GNRI groups was 54.6% and 25.0%, respectively (p=0.001). In the univariate and multivariate analyses, low-GNRI was a risk factor for RFS. The hazard ratio for low-GNRI was 1.704 (95%CI=1.121-2.590, p=0.013). Regarding the type of recurrence, lymph node recurrence was significantly more common in the low-GNRI group (p=0.008). Conclusion: Low-GNRI was an independent risk factor for OS and RFS after radical resection of esophageal cancer. The preoperative GNRI may be a useful prognostic factor after esophageal cancer surgery.
Gonadotropins in the Management of Couple Infertility: Toward the Rational Use of an Empirical Therapy

Abstract Although epidemiology shows that both men and woman can experience infertility, the female partner usually experiences most of the diagnostic and therapeutic burden. Thus, management of couple infertility is a unique example of gender inequality. The use of exogenous gonadotropins in assisted reproductive technology (ART) to induce multifollicular growth is well consolidated in women, but the same is not done with the same level of confidence and purpose in infertile men. Indeed, the treatment of idiopathic male infertility is based on an empirical approach that involves administration of the follicle-stimulating hormone (FSH) in dosages within the replacement therapy range. This treatment has so far been attempted when the endogenous FSH serum levels are within the reference ranges. According to the most recent evidence, a “substitutive” FSH administration may not be effective enough, while a stimulatory approach could boost spermatogenesis over its basal levels without adverse extragonadal effects. This article aims to describe the rationale behind the empirical application of gonadotropins in couple infertility, highlighting the need for a change in the therapeutic approach, especially for the male partner.
Experience shapes initial exploration for non-generalizable spatial learning

Experience can change how individuals learn. Learning to solve a new problem can be accelerated by generalizing known rules in the new context, but the impact of experience on solving problems where generalization cannot be applied remains unclear. To study the impact of experience on solving new problems that are distinct from previously learned tasks, we examined how rats learned a new spatial navigation task after having previously learned different sets of spatial navigation tasks. The new task differed from the previous tasks in spatial layout and navigation rule, and could not be solved by applying previously learned rules. We found that different experience histories did not impact task performance in the new task. However, by examining navigation choices made by rats, we found exploration patterns during the early stage of learning in the new task was dependent on experience history. We identified these behavioral differences by analyzing each rat’s navigation choices and by modeling their choice sequences with a modified distance dependent Chinese restaurant process. We further pinpointed the behavioral difference to sequential turn/no turn decisions made at choice points. Our results indicate that experience can influence problem-solving strategies when learning to solve new problems. Individuals with distinct experience histories can approach new problems from different starting points but converge on the same solution.
Contrasting urban adaptations of seed dispersal traits in two closely-related plant species

Urbanisation has largely altered city landscapes, resulting in habitat loss, fragmentation, and environmental degradation. City plants often have adapting traits and ecologies to such urban habitat environments. The existing literature on urban adaptation has often focused on species that shrink the abundances in urban areas compared to rural areas. Meanwhile, the studies on species that expand their range in cities remain limited, although they would exhibit different trait responses to urban environments, particularly in dispersal-related traits. In this study, we compared seed dispersal-related traits between Youngia japonica subsp. japonica (Y.j. japonica), which is expanding its range in urban areas and its closely-relative Y.j. elstonii, which is contracting its range in urban areas along an urban-rural gradient of the Osaka-Kobe megacity area. We also examined relationships between seed traits and terminal velocity which influences seed dispersal ability. We found that achene length increased with the degree of urbanisation only in Y.j. japonica, while pappus length decreased only in Y.j. elstonii. The terminal velocity had a significant relationship only with pappus length in Y. japonica. Seed traits of two subspecies with different urban distributions showed different responses to urbanisation. Our results suggest that species expanding their distribution in urban areas has increased seed competitiveness while maintaining dispersal ability. In contrast, species that has shrunk in urban areas likely showed a passive response to urban fragmentation, indicating a loss of seed dispersal ability.