bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase 1/2 study of NS-87/CPX-351 (cytarabine and daunorubicin liposome) in Japanese patients with high-risk acute myeloid leukemia
Authors: Usuki Kensuke , Miyamoto Toshihiro , Yamauchi Takuji , Ando Kiyoshi , Ogawa Yoshiaki , Onozawa Masahiro , Yamauchi Takahiro , Kiyoi Hitoshi , Yokota Akira , Ikezoe Takayuki , Katsuoka Yuna , Takada Satoru , Aotsuka Nobuyuki , Morita Yasuyoshi , Ishikawa Takayuki , Asada Noboru , Ota Shuichi , Dohi Atsushi , Morimoto Kensaku , Imai Shunji , Kishimoto Umi , Akashi Koichi , Miyazaki Yasushi ,   The Study Group for NS-87/CPX-351, Kuroda Junya , Iida Hiroatsu , Sekiguchi Naohiro , Takenaka Katsuto , Kawakita Toshiro , Imada Kazunori , Suzuki Takahiro , Miyawaki Shuichi , Usui Noriko , Asou Norio , Muta Masakazu , Tsuruda Kazuto , Taniwaki Masafumi , Fujita Masatoshi , Makishima Hideki , Nakanishi Yoko , Tajima Masaya , Masutomi Yutaka , Chiba Masahiro , Hokazomo Mayuna , Hirooka Shihomi , Mikasa Taisuke , Okamoto Moemi , Kawase Akitaka , Yamada Akane , Shimizu Yuto , Isogaya Kento , Ichikawa Tomohiko 
Published: March 2024

Abstract
Objectives
NS-87/CPX-351 is a dual-drug liposomal encapsulation of cytarabine and daunorubicin. NS-87/CPX-351 exerts antileukemic action by maintaining a synergistic molar ratio of cytarabine to daunorubicin of 5:1 within the liposome while in circulation. Patients with high-risk acute myeloid leukemia (AML), which includes therapy-related AML and AML with myelodysplasia-related changes (AML-MRC), have poorer outcomes than those with other AML.

Methodology
This open-label phase 1/2 (P1/2) study was conducted in 47 Japanese patients aged 60–75 years with newly diagnosed high-risk AML to evaluate the pharmacokinetics, safety, and efficacy of NS-87/CPX-351.

Results
In the 6 patients enrolled in the P1 portion, no dose-limiting toxicities (DLTs) were reported, and 100 units/m2 during the induction cycle was found to be acceptable. Cytarabine and daunorubicin had a long half-life in the terminal phase (32.8 and 28.7 h, respectively). In the 35 patients enrolled in the P2 portion, composite complete remission (CRc; defined as complete remission [CR] or CR with incomplete hematologic recovery [CRi]) was achieved in 60.0% (90% CI: 44.7–74.0) of the patients. Adverse events due to NS-87/CPX-351 were well tolerated.

Outcomes
NS-87/CPX-351 can be considered as a frontline treatment option for Japanese patients with high-risk AML.
Sedimentological and sequence-stratigraphic analyses of the Tithonian Hith Anhydrite Formation in the Dahal Hit outcrop, Saudi Arabia
Authors: Wolpert Philipp J. , Bartenbach Martin , Aigner Thomas , Wilson Augustus O. , Al-Husseini Moujahed I. , Petrovic Alexander , Dirks Heiko , Rausch Randolf 
Published: March 2024

AbstractThe Dahal Hit cavern in Central Saudi Arabia is the only locality where the Tithonian Hith Anhydrite Formation is exposed in the Middle East. In 2010, a 28.5-m interval in the 90-m-thick Hith Formation was logged and described in the cavern as part of a study to evaluate its sedimentological and sequence-stratigraphic architecture and to identify potential high-permeability layers within the seal of the world’s most prolific petroleum system. Seven facies types were interpreted as reflecting sabkha (subaerial) or salina (subaqueous) settings, and their vertical stacking patterns revealed that the logged interval consists of three transgressive–regressive cycles and part of a fourth cycle. The cavern was revisited in 2016 but only to find that the water level had risen by about 50 m rendering further geological studies impossible. The higher level of the water suggests that the cavern was flooded by the flow in the subsurface of treated sewage water released into a former quarry. The quarry is situated about 10 km southeast of the cavern, and the storage of water in it started in 2008. The flow pathways to the Dahal Hit cavern are apparently well-connected karsts, caverns, and high-permeability flow zones present in dolomite layers.
The duality of reputation portability: Investigating the demand effect of imported ratings across online labor markets
Authors: Tran Nhat Diana , Thäter Laura , Teubner Timm 
Published: March 2024

AbstractOnline labor platforms have been criticized for fueling precarious working conditions. Due to their platform-bound reputation systems, switching costs are prohibitively high and workers are locked-in to the platforms. One widely discussed approach to addressing this issue and improving workers’ position is the portability of reputational data. In this study, we conduct an online experiment with 239 participants to test the effect of introducing reputation portability and to study the demand effect of imported ratings. We find that the volume of imported ratings stimulates demand, although to a lower degree than onsite ratings. Specifically, the effect of imported ratings corresponds to about 35% of the effect of onsite ratings. The results imply the possibility of unintended cross-market demand concentration effects that especially favor workers with high rating volumes (“superstars”).
Perspectives of Women of Reproductive Age Regarding Sexuality During Their Menstruation Period
Authors: Demirtaş Fatma Aslan , Oskay Ümran 
Published: March 2024

Abstract
Introduction
This study aimed to determine the views and experiences of women of reproductive age regarding their sexuality and sexual life during their menstrual period.

Methods
A qualitative, interpretive, phenomenological design was used. The study sample consisted of 16 women of reproductive age (18–49), who volunteered to participate and came to gynecology outpatient clinic appointments at a research hospital in Istanbul, Turkey. Data were collected online through in-depth individual interviews.

Results
The research was composed of six themes: “symptoms of the menstruation period,” “duration and severity of symptoms during menstruation,” “effect of the menstrual period on sexual life,” “sexual desire during the menstrual period,” “opinions about sexual life during menstruation,” and “spouses’ opinions about sexual life during menstruation.”

Conclusions
The women in the study noted that they experienced physiological and psychological symptoms during their menstrual period. Although some of the women stated that they do not have changes in sexual desire during this period, most of them think that they should not engage in sexual intercourse due to the symptoms they experience during their menstrual period, religious beliefs, and sociocultural values.

Policy Implications
Nurses should counsel couples about the possible advantages and disadvantages of sexual intercourse during menstruation without displaying a judgmental attitude.
Marked Spatial Point Processes: Current State and Extensions to Point Processes on Linear Networks
Authors: Eckardt Matthias , Moradi Mehdi 
Published: March 2024

AbstractWithin the applications of spatial point processes, it is increasingly becoming common that events are labelled by marks, prompting an exploration beyond the spatial distribution of events by incorporating the marks in the undertaken analysis. In this paper, we first consider marked spatial point processes in$$\mathbb {R}^2$$R2, where marks are either integer-valued, real-valued, or object-valued, and review the state-of-the-art to analyze the spatial structure and type of interaction/correlation between marks. More specifically, we review cross/dot-type summary characteristics, mark-weighted summary characteristics, various mark correlation functions, and frequency domain approaches. We also propose novel cross/dot-type higher-order summary characteristics, mark-weighted summary characteristics, and mark correlation functions for marked point processes on linear networks. Through a simulation study, we show that ignoring the underlying network gives rise to erroneous conclusions about the interaction/correlation between marks. Finally, we consider two applications: the locations of two different proteins on the membranes of cells infected with the influenza virus and the locations of public trees along the street network of Vancouver, Canada, where trees are labelled by their diameters at breast height.
Influential biosorption of lead ions from aqueous solution using sand leek (Allium scorodoprasum L.) biomass: kinetic and isotherm study
Authors: Şenol Zeynep Mine , Arslanoğlu Hasan 
Published: March 2024

AbstractIn this study, a zero-cost, naturally effective adsorbent, sand leek (Allium scorodoprasum L.), was used for the effective removal of lead ions from an aqueous solution. This natural adsorbent was characterized by FT-IR, SEM–EDX, and PZC analyses. Batch studies were conducted at one factor at a time to explore maximum removal efficiency in terms of pH, initial lead(II) ion concentration, contact time, adsorbent dosage, and temperature for efficient adsorption. The maximum lead(II) ion uptake capacity for SAC was obtained at pH 4.5, initial lead(II) ion concentration at 1000 mg/L, operation time of 1440 min, adsorbent dosage of 10 g, and temperature of 25 °C. The adsorption data were well-fitted by the Freundlich isotherm model, with an R2 value of 1.000, indicating a good fit. The kinetic study revealed that the adsorption of lead(II) ions followed a pseudo-first-order kinetic model, with an R2 value of 0.9746. Furthermore, the thermodynamic parameters including Gibbs-free energy change (ΔG°), enthalpy change (ΔH°), and entropy change (ΔS°) were calculated to demonstrate that the adsorption of lead(II) ions onto natural adsorbent was endothermic and spontaneous.
Legume seed system performance in sub-Saharan Africa: barriers, opportunities, and scaling options. A review
Authors: Breen Caitlin , Ndlovu Noel , McKeown Peter C. , Spillane Charles 
Published: March 2024

AbstractAs a fundamental pillar of food security in sub-Saharan Africa (SSA), ensuring seed security is critical to empowering farmers in cultivating food and livestock feed, thereby fostering income generation from agricultural outputs. Among the crops cultivated by smallholders, legumes have the potential to deliver multifaceted benefits. Legumes are nutrient-dense and enhance soil health through their nitrogen-fixing qualities. However, in many instances, the development, release, and supply of improved legume varieties are insufficient to meet the needs of smallholder farmers in SSA. Here, we systematically reviewed the literature to (i) identify and categorize existing legume seed systems, (ii) map legume varieties available to smallholders, (iii) identify barriers hindering the adoption of various legume varieties, and (iv) identify potential strategies and opportunities for strengthening legume seed systems in SSA. Our results demonstrate the coexistence of formal and informal seed systems within legume seed supply chains in SSA, each employing unique seed distribution channels. Smallholders, however, are shown to predominantly depend on the informal seed system to source most legume seeds except for commercially available varieties. We also identified a diverse range of legume varieties available to smallholders in the region, with farmers having varying trait preferences based on crop type and gender. Notably, high yield and abiotic stress tolerance were the most preferred traits. The adoption of these varieties, however, is influenced by various factors, including lack of timely access to seeds in adequate quantities from the formal seed system, high seed costs, and limited information on new varieties. The reviewed literature highlighted that utilizing improved legume varieties had a positive effect on smallholders, leading to improved welfare, food security, dietary diversity, and income. We conclude that the effective scaling of legume systems in SSA is contingent upon the presence of supportive policy frameworks and well-established technical support structures.
Graphical Abstract
Packets of legume seeds within a legume germplasm and breeding program at the University of Zambia (Photo by Caitlin Breen, 2022).
Use of nebulized liposomal amphotericin B and posaconazole as antifungal prophylaxis in patients with severe SARS-CoV2 infection in intensive care unit
Authors: Fumarola Benedetta , Signorini Liana , Lorenzotti Silvia , Lanza Paola , Saccani Barbara , Van Hauwermeiren Evelyn , Mulè Alice , Piva Simone , Rota Matteo , Zuccalà Francesco , Rasulo Francesco Antonio , Filippini Matteo , Bertazzoli Alberto , Del Fabro Giovanni , Matteelli Alberto 
Published: March 2024

Abstract
Purpose
COVID-19 associated pulmonary aspergillosis (CAPA) is common and linked with high fatality rates. To assess the impact on the incidence and outcome of CAPA of an antifungal prophylaxis (AFP) we compared two cohorts of COVID-19 patients admitted to intensive care units (ICU) in Brescia, Italy, from January to August 2021.

Methods
The study cohort included all mechanically ventilated patients observed between April 2021 and August 2021 with SARS-CoV-2-pneumonia, who received AFP with oral posaconazole (200 mg every 6 h) and nebulized liposomal amphotericin B (50 mg every 2 weeks) from ICU admission to 7 days after discharge or, if applicable, until tracheostomy removal. The control cohort included COVID-19 patients admitted to the same ICU between January and March 2021 who did not receive any AFP. Subjects with CAPA at ICU admission were excluded.

Results
We included 270 patients, of whom 64 (23.7%) received AFP. In patients in the study group, CAPA-related mortality was significantly reduced (29% vs. 48% p = 0.04), as well as the incidence of CAPA (3.1% vs 12.1%, p = 0.03). Patients who developed CAPA were older (mean of 70-y-old vs 63-y-old, p < 0.001). One subject discontinued posaconazole due to an adverse reaction. Among the 46 patients who received it, only one patient reached an effective plasma concentration of posaconazole.

Conclusion
AFP was associated with reduced incidence and mortality from CAPA and was well tolerated in patients with severe COVID-19. Posaconazole concentrations below the efficacy threshold in almost all patients may be attributable to drug interactions and prompt further studies to define its clinical significance.
Experiences, Perceptions and Attitudes Toward Bullying Among School-Going Adolescents: A Cross-Sectional Study from South India
Authors: Nedumpully Nayana Narayanan , Praharaj Samir Kumar , Rai Shweta 
Published: March 2024

AbstractBullying victimisation affects an estimated 30% of individuals worldwide. While the prevalence and risk factors of bullying have been studied in India, comprehensive research on the phenomenon of bullying itself remains scarce. Our objective was to study the experiences, perceptions, and attitudes towards bullying among seventh to ninth-grade students. The study included all seventh to ninth graders (N = 205) from two schools in the Udupi district of South India. To collect information on bullying, we used the Bully Survey - Student Version with appropriate modifications for our context. The mean age of the participants was 13 (1.05) years, with 58% being females. Our findings showed that almost half of the students had bullying roles. Students attending private schools and residing in urban areas were more likely to be victims, bullies, and bully-victims. Seventh and eighth graders experienced higher rates of bullying, whereas ninth graders were more likely to engage in bully behaviours or be bully-victims. Verbal bullying, including name calling, playing jokes, and making fun of others, was more prevalent. No gender differences were observed in verbal or physical bullying. School teachers, staff, and parents were unaware of bullying incidents almost half of the time. Anti-bullying programs should consider these aspects of bullying to be effective.
The discovery of archaea: from observed anomaly to consequential restructuring of the phylogenetic tree
Authors: Fry Michael 
Published: March 2024

AbstractObservational and experimental discoveries of new factual entities such as objects, systems, or processes, are major contributors to some advances in the life sciences. Yet, whereas discovery of theories was extensively deliberated by philosophers of science, very little philosophical attention was paid to the discovery of factual entities. This paper examines historical and philosophical aspects of the experimental discovery by Carl Woese of archaea, prokaryotes that comprise one of the three principal domains of the phylogenetic tree. Borrowing Kuhn’s terminology, this discovery of a major biological entity was made during a ‘normal science’ project of building molecular taxonomy for prokaryotes. Unexpectedly, however, an observed anomaly instigated the discovery of archaea. Substantiation of the existence of the new archaeal entity and consequent reconstruction of the phylogenetic tree prompted replacement of a long-held model of a prokarya and eukarya bipartite tree of life by a new model of a tripartite tree comprising of bacteria, archaea, and eukarya. This paper explores the history and philosophical implications of the progression of Woese’s project from normal science to anomaly-instigated model-changing discovery. It is also shown that the consequential discoveries of RNA splicing and of ribozymes were similarly prompted by unexpected irregularities during normal science activities. It is thus submitted that some discoveries of factual biological entities are triggered by unforeseen observational or experimental anomalies.
Design Principles and Mechanistic Understandings of Non-Noble-Metal Bifunctional Electrocatalysts for Zinc–Air Batteries
Authors: Gao Yunnan , Liu Ling , Jiang Yi , Yu Dexin , Zheng Xiaomei , Wang Jiayi , Liu Jingwei , Luo Dan , Zhang Yongguang , Shi Zhenjia , Wang Xin , Deng Ya-Ping , Chen Zhongwei 
Published: March 2024

AbstractZinc–air batteries (ZABs) are promising energy storage systems because of high theoretical energy density, safety, low cost, and abundance of zinc. However, the slow multi-step reaction of oxygen and heavy reliance on noble-metal catalysts hinder the practical applications of ZABs. Therefore, feasible and advanced non-noble-metal electrocatalysts for air cathodes need to be identified to promote the oxygen catalytic reaction. In this review, we initially introduced the advancement of ZABs in the past two decades and provided an overview of key developments in this field. Then, we discussed the working mechanism and the design of bifunctional electrocatalysts from the perspective of morphology design, crystal structure tuning, interface strategy, and atomic engineering. We also included theoretical studies, machine learning, and advanced characterization technologies to provide a comprehensive understanding of the structure-performance relationship of electrocatalysts and the reaction pathways of the oxygen redox reactions. Finally, we discussed the challenges and prospects related to designing advanced non-noble-metal bifunctional electrocatalysts for ZABs.
RebL1 is required for macronuclear structure stability and gametogenesis in Tetrahymena thermophila
Authors: Hao Huijuan , Lian Yinjie , Ren Chenhui , Yang Sitong , Zhao Min , Bo Tao , Xu Jing , Wang Wei 
Published: March 2024

AbstractHistone modification and nucleosome assembly play important roles in chromatin-related processes. Histone chaperones form different complexes and coordinate histone transportation and assembly. Various histone chaperone complexes have been identified in different organisms. The ciliate protozoa (ciliates) have various chromatin structures and different nuclear morphology. However, histone chaperone components and functions of different subunits remain unclear in ciliates. Tetrahymema thermophila contains a transcriptionally active macronucleus (MAC) and a transcriptionally inactive micronucleus (MIC) which exhibit multiple replication and various chromatin remodeling progresses during vegetative growth and sexual developmental stages. Here, we found histone chaperone RebL1 not only localized evenly in the transcriptionally active MAC but also dynamically changed in the MIC during vegetative growth and sexual developmental stages. REBL1 knockdown inhibited cellular proliferation. The macronuclear morphology became bigger in growing mutants. The abnormal macronuclear structure also occurred in the starvation stage. Furthermore, micronuclear meiosis was disturbed during sexual development, leading to a failure to generate new gametic nuclei. RebL1 potentially interacted with various factors involved in histone-modifying complexes and chromatin remodeling complexes in different developmental stages. REBL1 knockdown affected expression levels of the genes involved in chromatin organization and transcription. Taken together, RebL1 plays a vital role in maintaining macronuclear structure stability and gametogenesis in T. thermophila.
Recent Status of Phase I Clinical Trials for Brain Tumors: A Regulatory Science Study of Exploratory Efficacy Endpoints
Authors: Watanabe Shinya , Nonaka Takahiro , Maeda Makoto , Yamada Masanobu , Sugii Narushi , Hashimoto Koichi , Takano Shingo , Koyanagi Tomoyoshi , Arakawa Yoshihiro , Ishikawa Eiichi 
Published: March 2024

Abstract
Background
Appropriate exploratory efficacy data from Phase I trials are vital for subsequent phases. Owing to the uniqueness of brain tumors (BTs), use of different strategies to evaluate efficacy is warranted. We studied exploratory efficacy evaluation in Phase I trials involving BTs.

Methods
Using Clarivate’s Cortellis™, 42 Phase I trials of BT interventions conducted from 2020 to 2022 were analyzed for efficacy endpoints, which were set as primary endpoints (PEs) or secondary endpoints (SEs). Additionally, these metrics were compared in two subgroups: trials including only BTs (Group-A) and those including BTs among mixed solid tumors (Group-B).

Results
Selected studies included a median of 1.5 PEs (range, 1–6) and 5 SEs (range, 0–19). Efficacy endpoints were included as PEs and SEs in 2 (5%) and 31 (78%) trials, respectively. Among the latter 31 trials that included 94 efficacy endpoints, 24, 22, 20, 9, and 8 reflected overall response rate (ORR), progression-free survival (PFS), overall survival (OS), duration of response (DOR), and disease control rate (DCR), respectively. ORR for BT was determined using various methods; however, the Response Evaluation Criteria in Solid Tumors (RECIST) was used less frequently in Group-A than in Group-B (p = 0.0039).

Conclusions
Recent Phase I trials included efficacy endpoints as SEs, with ORR, PFS, or OS included in ~ 50% trials and DOR or DCR in ~ 25%. No established criteria exist for imaging evaluation of BTs. Phase I trials involving mixed solid tumor cohorts revealed challenges in designing methods to assess the exploratory efficacy of BTs.
AI: the future of humanity
Authors: Rawas Soha 
Published: March 2024

AbstractArtificial intelligence (AI) is reshaping humanity's future, and this manuscript provides a comprehensive exploration of its implications, applications, challenges, and opportunities. The revolutionary potential of AI is investigated across numerous sectors, with a focus on addressing global concerns. The influence of AI on areas such as healthcare, transportation, banking, and education is revealed through historical insights and conversations on different AI systems. Ethical considerations and the significance of responsible AI development are addressed. Furthermore, this study investigates AI's involvement in addressing global issues such as climate change, public health, and social justice. This paper serves as a resource for policymakers, researchers, and practitioners understanding the complex link between AI and humans.