bluuebunny/crossref_metadata_2025_split huggingface dataset:
Methodology of the SORENTO clinical trial: a prospective, randomised, active-controlled phase 3 trial assessing the efficacy and safety of high exposure octreotide subcutaneous depot (CAM2029) in patients with GEP-NET
Authors: Singh Simron , Ferone Diego , Capdevila Jaume , Chan Jennifer Ang , de Herder Wouter W. , Halperin Daniel , Mailman Josh , Hellström Lisa , Liedman Hanna , Svedberg Agneta , Tiberg Fredrik 
Published: January 2024

Abstract
Background
The current standard of care (SoC) for the initial treatment of unresectable or metastatic well-differentiated gastroenteropancreatic neuroendocrine tumours (GEP-NET) requires initiation of first-generation somatostatin receptor ligand (SRL) therapy, octreotide and lanreotide, which provide safe and efficacious tumour/symptom control in most patients. However, disease progression can occur with SoC SRL treatment and the optimal dose response of SRL remains unknown. Octreotide subcutaneous depot (CAM2029) is a novel, long-acting, high-exposure formulation that has shown greater bioavailability and improved administration than octreotide long-acting release (LAR) with a well-tolerated safety profile. Retrospective data have highlighted a potential benefit of high-exposure SRL for improved disease control in patients who did not adequately respond to the current SoC SRL treatment. This trial will investigate the efficacy and tolerability of CAM2029 compared to the current SoC, including octreotide LAR and lanreotide autogel (ATG).

Methods
SORENTO is a prospective, multicentre, randomised, active-controlled, open-label phase 3 trial aiming to demonstrate superiority of treatment with 20 mg octreotide subcutaneous depot (CAM2029) every 2 weeks (Q2W) compared to treatment with the Investigator’s choice of SRL therapy at standard doses for tumour control (octreotide LAR 30 mg or lanreotide ATG 120 mg every 4 weeks [Q4W]) as assessed by progression-free survival (PFS) in approximately 300 patients with unresectable/metastatic and well-differentiated GEP-NET. Upon confirmation of disease progression (determined by a Blinded Independent Review Committee [BIRC] and defined as per RECIST 1.1), patients may enter an open-label extension treatment period with once weekly dosing, to investigate the effects of higher frequency dosing. Overall survival follow-up will end a maximum of 2 years after primary analysis. The primary endpoint will be analysed after 194 confirmed PFS events.

Discussion
This is the first trial investigating the efficacy of CAM2029 versus SoC SRL therapy using a head-to-head, superiority trial design. It is expected to be the first trial to investigate the efficacy of increased dosing frequency of a high-exposure SRL. A BIRC will limit bias and measurement variability and ensure high-quality efficacy data. Additionally, inclusion of patients with well-differentiated Grade 3 NET may elucidate treatment strategies for this rarely investigated patient population.

Trial registration
ClinicalTrials.gov NCT05050942. Registered on 21st September 2021.
Evaluation of the efficiency of nanomicellar formulation of fat-soluble vitamins in patients with cystic fibrosis: the study protocol for a randomized controlled trial
Authors: Soleimanzadeh Mahsa , Talebi Saeedeh , Jaafari Mahmoud Reza , Sayedi Seyed Javad , Emadzadeh Maryam , Kianifar Hamid Reza 
Published: January 2024

Abstract
Background
Cystic fibrosis is an inherited disease, which is caused by the CFTR protein defects due to mutations in the CFTR gene. Along with CFTR dysfunction, exocrine pancreatic insufficiency plays a key role in persistent fat malabsorption in CF patients; therefore, deficiency of fat-soluble vitamins (A, D, E, and K) is still a therapeutic challenge. Even with efficient pancreatic enzyme medication and CF-specific vitamins, many patients with CF have fat-soluble vitamins deficiency. The present study aims to evaluate the efficiency of nanomicelle formulation of fat-soluble vitamins in children with CF in order to achieve the appropriate serum levels of these vitamins.

Methods
This prospective, single-blind control trial will be conducted at the Akbar Children’s Hospital in Mashhad, Iran. Patients with CF will be enrolled based on the eligibility criteria. The control group will receive the standard formulation of fat-soluble vitamins similar to the routine CF treatment, and for the intervention group, the nanomicelle formulation of fat-soluble vitamins will be administered for 3 months. The primary outcome of this study is the measurement of serum levels of fat-soluble vitamins. The secondary outcomes are clinical assessment by the Shwachman-Kulczycki score, anthropometrics, and quality of life. Outcomes will be assessed before and after 3 months.

Discussion
Due to persistent fat-soluble vitamin deficiency in CF disease, the nanomicelle formulation could be proposed as a new delivery method of fat-soluble vitamins in the treatment of cystic fibrosis.

Trial registration
Iranian Registry of Clinical Trials IRCT20220415054541N1. Registered on July 23, 2022.
Former Soviet Union middle class: how entrepreneurs are shaping a new stratum and pattern of socio-economic behavior
Authors: Otar Elmira , Salikzhanov Rinat , Akhmetova Aigul , Issakhanova Assel , Mukhambetova Kuralay 
Published: January 2024

AbstractThe purpose of this study is to create a representative socio-economic profile of entrepreneurs operating in the former Soviet Union (FSU) states as a pillar of the new middle-class stratum. This study explored middle-class entrepreneurship from multiple perspectives, encompassing statistical analysis of microdata about households and firms. The aim was to gauge entrepreneurship within a national framework and examine its associations with social and economic factors. The study adopted the Doing Business tool as a novel paradigm to establish a quantitative correlation between the economic system in the post-Soviet space and the investigated variables. The analysis revealed that prospective entrepreneurs are members of the younger generation between the ages of 25 and 34; a critical factor in the development of entrepreneurship is highly educated human capital; and typical representatives of entrepreneurship intending to operate in the FSU states establish their own business as a means of subsistence, not as a means of advancement in the social stratum. In general, an entrepreneur of the middle class in the new economies of the post-Soviet space does not demonstrate a high level of entrepreneurial activity and, as a pillar of the middle-class stratum, is in the formation stage.
Structural Performance Assessment of Derailment Containment Provision for Railway using a Grid Steel Frame
Authors: Kim Tae-Hoon , Kang Yun-Suk , Bang Choon-Seok 
Published: January 2024

AbstractThe structural performance of derailment containment provision (DCP) was investigated using a grid steel frame. The DCP which was installed within the gauge of a track was capable of resisting the impact loading in the case of derailed wheels. It was also possible to control the excessive lateral movement of the derailed train. In this study, the structural performance of DCP with a post-installed anchor to a railway concrete sleeper was evaluated. For this purpose, a total of nine specimens were manufactured and static tests were conducted to investigate the structural performance. Furthermore, the shear resistance of the connecting anchor was also evaluated using grid steel frame specimens. The initial test indicated that the developed DCP for railway using grid steel frames had sufficient load-carrying capacity and performance equivalent to about 150% of the design load. The developed DCP also demonstrated sufficient load-carrying capacity up to about 140% of the designed load in combination tests that simulated conceivable boundary conditions. As analytical results, the overall DCP behavior for the specimen railway that utilized grid steel frames was appropriately tracked, and detailed information was presented.
Weather-dependent changes in habitat use by Alpine chamois
Authors: Anderwald Pia , Buchmann Sven , Rempfler Thomas , Filli Flurin 
Published: January 2024

Abstract
Background
Alterations in weather patterns due to climate change are accelerated in alpine environments, but mountains also provide a wide range of niches and potential refuge areas. In order to identify future critical habitat for mountain ungulates for effective protection, it is important to understand their spatial responses to changing weather conditions without movement constraints by human disturbance.

Methods
Using integrated step selection functions, we investigated fine-scale changes in seasonal habitat use in response to weather and time of day for 55 GPS-collared adult Alpine chamois in summer and 42 individuals in winter in a strictly protected area.

Results
Chamois reacted to increasing precipitation and wind speeds primarily by moving to lower elevations in summer and winter. However, reactions to high summer temperatures predominantly involved preferences for increasing tree cover density and northerly slopes. Snow depth had little effect on habitat choice, and southerly slopes were preferred in winter regardless of temperature. At night, chamois moved to steeper slopes and lower elevations than during daytime in both seasons, and to more open areas in summer. Steeper slopes were also preferred with increasing tree cover density.

Conclusions
Chamois employ adaptive fine-scale adjustments in their habitat choice consistent with respect to efficient thermoregulation and protection from both weather extremes and predation risk in summer and winter. Movement responses to climate change are therefore expected to be far more complex than simple altitudinal changes in distribution. Particularly the role of forest cover must not be underestimated, as it appears to provide important thermal refuge habitat from high summer temperatures.
Unclassifiable CNS tumors in DNA methylation-based classification: clinical challenges and prognostic impact
Authors: Drexler Richard , Brembach Florian , Sauvigny Jennifer , Ricklefs Franz L. , Eckhardt Alicia , Bode Helena , Gempt Jens , Lamszus Katrin , Westphal Manfred , Schüller Ulrich , Mohme Malte 
Published: January 2024

AbstractDNA methylation analysis has become a powerful tool in neuropathology. Although DNA methylation-based classification usually shows high accuracy, certain samples cannot be classified and remain clinically challenging. We aimed to gain insight into these cases from a clinical perspective. To address, central nervous system (CNS) tumors were subjected to DNA methylation profiling and classified according to their calibrated score using the DKFZ brain tumor classifier (V11.4) as “≥ 0.84” (score ≥ 0.84), “0.3–0.84” (score 0.3–0.84), or “< 0.3” (score < 0.3). Histopathology, patient characteristics, DNA input amount, and tumor purity were correlated. Clinical outcome parameters were time to treatment decision, progression-free, and overall survival. In 1481 patients, the classifier identified 69 (4.6%) tumors with an unreliable score as “< 0.3”. Younger age (P < 0.01) and lower tumor purity (P < 0.01) compromised accurate classification. A clinical impact was demonstrated as unclassifiable cases (“< 0.3”) had a longer time to treatment decision (P < 0.0001). In a subset of glioblastomas, these cases experienced an increased time to adjuvant treatment start (P < 0.001) and unfavorable survival (P < 0.025). Although DNA methylation profiling adds an important contribution to CNS tumor diagnostics, clinicians should be aware of a potentially longer time to treatment initiation, especially in malignant brain tumors.
Limitation of life sustaining measures in neurocritical care: sex, timing, and advance directive
Authors: Bögli Stefan Yu , Stretti Federica , Utebay Didar , Hitz Ladina , Hertler Caroline , Brandi Giovanna 
Published: January 2024

Abstract
Background
The limitation of life sustaining treatments (LLST) causes ethical dilemmas even in patients faced with poor prognosis, which applies to many patients admitted to a Neurocritical Care Unit (NCCU). The effects of social and cultural aspects on LLST in an NCCU population remain poorly studied.

Methods
All NCCU patients between 01.2018 and 08.2021 were included. Medical records were reviewed for: demographics, diagnosis, severity of disease, and outcome. Advance directives (AD) and LLST discussions were reviewed evaluating timing, degree, and reason for LLST. Social/cultural factors (nationality, language spoken, religion, marital status, relationship to/sex of legal representative) were noted. Associations between these factors and the patients’ sex, LLST timing, and presence of AD were evaluated.

Results
Out of 2975 patients, 12% of men and 10.5% of women underwent LLST (p = 0.30). Women, compared to men, more commonly received withdrawal instead of withholding of life sustaining treatments (57.5 vs. 45.1%, p = 0.028) despite comparable disease severity. Women receiving LLST were older (73 ± 11.7 vs. 69 ± 14.9 years, p = 0.005) and often without a partner (43.8 vs. 25.8%, p = 0.001) compared to men. AD were associated with female sex and early LLST, but not with an increased in-hospital mortality (57.1 vs. 75.2% of patients with and without AD respectively).

Conclusions
In patients receiving LLST, the presence of an AD was associated with an increase of early LLST, but not with an increased in-hospital mortality. This supports the notion that the presence of an AD is primarily an expression of the patients’ will but does not per se predestine the patient for an unfavorable outcome.
Biotransformation of 2-keto-4-hydroxybutyrate via aldol condensation using an efficient and thermostable carboligase from Deinococcus radiodurans
Authors: Jeong Yeon-Ju , Seo Min-Ju , Sung Bong Hyun , Kim Jeong-Sun , Yeom Soo-Jin 
Published: January 2024

AbstractThe bioconversion of 4-hydroxy-2-keto acid derivatives via aldol condensation of formaldehyde and pyruvate has received substantial attention as potential source of chemicals for production of amino acids, hydroxy carboxylic acids, and chiral aldehydes. We developed an environmentally friendly biocatalyst consisting of a novel thermostable class II pyruvate aldolase from Deinococcus radiodurans with maltose-binding protein (MBP-DrADL), which has specific activity of 46.3 µmol min–1 mg–1. Surprisingly, MBP-DrADL maintained over 60% of enzyme activity for 4 days at 50 to 65 °C, we used MBP-DrADL as the best candidate enzyme to produce 2-keto-4-hydroxybutyrate (2-KHB) from formaldehyde and pyruvate via aldol condensation. The optimum reaction conditions for 2-KHB production were 50 °C, pH 8.0, 5 mM Mg2+, 100 mM formaldehyde, and 200 mM pyruvate. Under these optimized conditions, MBP-DrADL produced 76.5 mM (8.94 g L–1) 2-KHB over 60 min with a volumetric productivity of 8.94 g L–1 h–1 and a specific productivity of 357.6 mg mg-enzyme–1 h–1. Furthermore, 2-KHB production was improved by continuous addition of substrates, which produced approximately 124.8 mM (14.6 g L–1) of 2-KHB over 60 min with a volumetric productivity and specific productivity of 14.6 g L–1 h–1 and 583.4 mg mg-enzyme–1 h–1, respectively. MBP-DrADL showed the highest specific productivity for 2-KHB production yet reported. Our study provides a highly efficient biocatalyst for the synthesis of 2-KHB and lays the foundation for large-scale production and application of high-value compounds from formaldehyde.
Graphical Abstract
Bacterial wilt affects the structure and assembly of microbial communities along the soil-root continuum
Authors: Liang Jinchang , Wei Chengjian , Song Xueru , Wang Rui , Shi Heli , Tan Jun , Cheng Dejie , Wang Wenjing , Wang Xiaoqiang 
Published: January 2024

Abstract
Background
Beneficial root-associated microbiomes play crucial roles in enhancing plant growth and suppressing pathogenic threats, and their application for defending against pathogens has garnered increasing attention. Nonetheless, the dynamics of microbiome assembly and defense mechanisms during pathogen invasion remain largely unknown. In this study, we aimed to investigate the diversity and assembly of microbial communities within four niches (bulk soils, rhizosphere, rhizoplane, and endosphere) under the influence of the bacterial plant pathogen Ralstonia solanacearum.

Results
Our results revealed that healthy tobacco plants exhibited more diverse community compositions and more robust co-occurrence networks in root-associated niches compared to diseased tobacco plants. Stochastic processes (dispersal limitation and drift), rather than determinism, dominated the assembly processes, with a higher impact of drift observed in diseased plants than in healthy ones. Furthermore, during the invasion of R. solanacearum, the abundance of Fusarium genera, a known potential pathogen of Fusarium wilt, significantly increased in diseased plants. Moreover, the response strategies of the microbiomes to pathogens in diseased and healthy plants diverged. Diseased microbiomes recruited beneficial microbial taxa, such as Streptomyces and Bacilli, to mount defenses against pathogens, with an increased presence of microbial taxa negatively correlated with the pathogen. Conversely, the potential defense strategies varied across niches in healthy plants, with significant enrichments of functional genes related to biofilm formation in the rhizoplane and antibiotic biosynthesis in the endosphere.

Conclusion
Our study revealed the varied community composition and assembly mechanism of microbial communities between healthy and diseased tobacco plants along the soil-root continuum, providing new insights into niche-specific defense mechanisms against pathogen invasions. These findings may underscore the potential utilization of different functional prebiotics to enhance plants’ ability to fend off pathogens.
A Photo Album's Redrawn Color Line: On Black Freedom in Japan, 1947–1949
Authors: Boone Emilie 
Published: January 2024

Abstract
While art historians have highlighted the reputed freedoms afforded to African Americans—such as painters and sculptors—who traveled abroad to escape racism in the United States, little attention has been paid to vernacular photography or to places beyond a few storied locations. Made partly within the context of the American military base of Camp Gifu, an album by a woman named Darlene Littleton brings attention to the vernacular photographs of Black life in Japan under the US Occupation following World War II. The album serves as a creative practice in which Black visual production is propelled by a range of circumstances distinctly marked by alternate modes of freedom—moments loosened from the logic of race, gender, and class commonly known to the United States.
Nociceptive Processing of Elite Athletes Varies Between Sport-Specific Loads: An EEG-based Study Approach
Authors: Dreismickenbecker Elias , Fleckenstein Johannes , Walter Carmen , Enax-Krumova Elena K. , Fischer Michael J. M. , Kreuzer Matthias , Zinn Sebastian , Anders Malte 
Published: January 2024

ABSTRACT

Introduction
For the downstream nociceptive processing of elite athletes recent studies indicate that athletes probably tolerate more pain as compared to a normally active population. Phenotyping the nociceptive processing of athletes in different types of endurance sports can provide insight into training-specific effects, which may help in understanding the long-term effects of specific exercise.

Methods
26 elite endurance athletes from the disciplines of rowing, triathlon and running, and 26 age and sex-matched, recreationally active control subjects the subjective pain perception and processing of standardized noxious stimuli were investigated by EEG. This included standardized heat pain thresholds (HPT) and contact heat-evoked potentials (CHEPS) from heat stimulation, measured with EEG as well as pinprick-evoked potentials (PEP) from mechanical stimulation.

Results
Following noxious stimulation, athletes showed a higher activation of the event-related spectral perturbation (ERSP) patterns in the N2P2 EEG response at the Cz Electrode compared to the controls. Following noxious contact heat stimulation, triathletes had a higher ERSP activation compared to the controls, while the rowers had a higher ERSP activation following noxious mechanical stimulation. Also, HPTs in triathletes were increased despite their increased central activation following thermal stimulation. We found a correlation between increased HPTs and training hours and years, though athletes did not differ within these variables.

Conclusions
Although we were able to identify differences between athletes of different endurance sports, the reasons and implications of these differences remain unclear. The study of sport-specific somatosensory profiles may help to understand the mechanisms of exercise-related long-term effects on pain processing and perception. Furthermore, sport-specific somatosensory effects may support the personalization of exercise interventions and identify risk factors for chronic pain in elite athletes.
Injury Incidence, Severity and Type across the Menstrual Cycle in Female Footballers: A Prospective Three Season Cohort Study
Authors: Barlow Ally , Blodgett Joanna M. , Williams Sean , Pedlar Charles R. , Bruinvels Georgie 
Published: January 2024

ABSTRACT

Purpose
The aim of the study was to assess the influence of menstrual cycle phase on injury incidence, severity and type in elite female professional footballers over three seasons.

Methods
Time-loss injuries and menstrual cycle data were prospectively recorded for 26 elite female football players across three seasons. The menstrual cycle was categorised into four phases using a standardised model: menstruation (phase 1; P1), remainder of follicular phase (phase 2; P2), early luteal (phase 3; P3), and pre-menstrual phase (phase 4; P4). Injury incidence rates (IRR) and ratios (IIRR) were calculated for overall injuries, injury severity, type, contact vs non-contact and game/training.

Results
593 cycles across 13,390 days were tracked during the study and 74 injuries from 26 players were eligible for analysis. When comparing IRR between phases (reference: P1), overall injury rates were highest in P4 (IIRR: 2.30 [95% CI: 0.99-5.34; p = 0.05]). When examining rates by injury severity and type, IRR were also highest in P4 for ≤7 days’ time-loss (4.40 [0.93-20.76; p = 0.06]), muscle-specific (6.07 [1.34-27.43; p = 0.02]) and non-contact (3.05 [1.10-8.50; p = 0.03]) injuries. Muscle-specific (IIRR P3:P1: 5.07 [1.16-22.07; p = 0.03]) and ≤ 7 days’ time-loss (4.47 [1.01-19.68; p = 0.05]) injury risk was also significantly higher in P3. Muscle injuries were the most prevalent sub-type (n = 41). No anterior cruciate ligament injuries were recorded across the monitoring period.

Conclusions
Injury risk was significantly elevated during the luteal phase of the menstrual cycle (P3 and P4) among elite female professional footballers. Further research is urgently needed to better understand the influence of the menstrual cycle on injury risk and to develop interventions to mitigate risk.