bluuebunny/crossref_metadata_2025 huggingface dataset:
Favourable neurological outcome following paediatric out-of-hospital cardiac arrest: a retrospective observational study
Authors: Fuchs Alexander , Bockemuehl Deliah , Jegerlehner Sabrina , Both Christian P. , Cools Evelien , Riva Thomas , Albrecht Roland , Greif Robert , Mueller Martin , Pietsch Urs
Published: December 2023

Background

Out-of-hospital cardiac arrest (OHCA) in children is rare and can potentially result in severe neurological impairment. Our study aimed to identify characteristics of and factors associated with favourable neurological outcome following the resuscitation of children by the Swiss helicopter emergency medical service.

Materials and methods

This retrospective observational study screened the Swiss Air-Ambulance electronic database from 01-01-2011 to 31-12-2021. We included all primary missions for patients ≤ 16 years with OHCA. The primary outcome was favourable neurological outcome after 30 days (cerebral performance categories (CPC) 1 and 2). Multivariable linear regression identified potential factors associated with favourable outcome (odd ratio – OR).

Results

Having screened 110,331 missions, we identified 296 children with OHCA, which we included in the analysis. Patients were 5.0 [1.0; 12.0] years old and 61.5% (n = 182) male. More than two-thirds had a non-traumatic OHCA (67.2%, n = 199), while 32.8% (n = 97) had a traumatic OHCA. Thirty days after the event, 24.0% (n = 71) of patients were alive, 18.9% (n = 56) with a favourable neurological outcome (CPC 1 n = 46, CPC 2 n = 10). Bystander cardiopulmonary resuscitation (OR 10.34; 95%CI 2.29–51.42; p = 0.002) and non-traumatic aetiology (OR 11.07 2.38–51.42; p = 0.002) were the factors most strongly associated with favourable outcome. Factors associated with an unfavourable neurological outcome were initial asystole (OR 0.12; 95%CI 0.04–0.39; p < 0.001), administration of adrenaline (OR 0.14; 95%CI 0.05–0.39; p < 0.001) and ongoing chest compression at HEMS arrival (OR 0.17; 95%CI 0.04–0.65; p = 0.010).

Conclusion

In this study, 18.9% of paediatric OHCA patients survived with a favourable neurologic outcome 30 days after treatment by the Swiss helicopter emergency medical service. Immediate bystander cardiopulmonary resuscitation and non-traumatic OHCA aetiology were the factors most strongly associated with a favourable neurological outcome. These results underline the importance of effective bystander and first-responder rescue as the foundation for subsequent professional treatment of children in cardiac arrest.
A classification system for identifying patients dead on ambulance arrival: a prehospital medical record review
Authors: Petersen Markus , Kjeldtoft Fredderick Georg , Christensen Erika Frischknecht , Bøggild Henrik , Lindskou Tim Alex
Published: December 2023

Background

Patients dead before arrival of the ambulance or before arrival at hospital may be in- or excluded in mortality analyses, making comparison of mortality difficult. Often only physicians are allowed to declare death, thereby impeding uniform registration of prehospital death. Many studies do not report detailed definitions of prehospital mortality. Our aim was to define criteria to identify and categorize prehospital patients’ vital status, and to estimate the proportion of these groups, primarily the proportion of patients dead on ambulance arrival.

Methods

Prehospital medical records review for patients receiving an ambulance in the North Denmark Region from 2019 to 2021 and registered dead on the same or the following day. We defined three vital status categories: (1) Dead on Ambulance Arrival (DOAA), (2) Out-of-Hospital Cardiac Arrest (OHCA) divided into OHCA Basic Life Support (OHCA BLS) and OHCA Advanced treatment, and 3) Alive on Ambulance Arrival.

Results

Among 3 174 dead patients, DOAA constituted 28.8%, OHCA BLS 13.4%, OHCA Advanced treatment 31.3%, and Alive on Ambulance Arrival 26.6%.

Conclusion

We defined exhaustive and mutually exclusive criteria to define vital status, DOAA, OHCA, and Alive on Ambulance Arrival based on prehospital medical records. More than one out of four patients receiving an ambulance and registered dead on the same or the following day were dead already at ambulance arrival. Adding OHCA BLS where resuscitation was terminated without defibrillation or other treatment, increased the proportion of patients dead on ambulance arrival to 42%. We recommend reporting similar categories of vital status to improve valid comparisons of prehospital mortality rates.
Benchmarking splice variant prediction algorithms using massively parallel splicing assays
Authors: Smith Cathy , Kitzman Jacob O.
Published: December 2023

Background

Variants that disrupt mRNA splicing account for a sizable fraction of the pathogenic burden in many genetic disorders, but identifying splice-disruptive variants (SDVs) beyond the essential splice site dinucleotides remains difficult. Computational predictors are often discordant, compounding the challenge of variant interpretation. Because they are primarily validated using clinical variant sets heavily biased to known canonical splice site mutations, it remains unclear how well their performance generalizes.

Results

We benchmark eight widely used splicing effect prediction algorithms, leveraging massively parallel splicing assays (MPSAs) as a source of experimentally determined ground-truth. MPSAs simultaneously assay many variants to nominate candidate SDVs. We compare experimentally measured splicing outcomes with bioinformatic predictions for 3,616 variants in five genes. Algorithms’ concordance with MPSA measurements, and with each other, is lower for exonic than intronic variants, underscoring the difficulty of identifying missense or synonymous SDVs. Deep learning-based predictors trained on gene model annotations achieve the best overall performance at distinguishing disruptive and neutral variants, and controlling for overall call rate genome-wide, SpliceAI and Pangolin have superior sensitivity. Finally, our results highlight two practical considerations when scoring variants genome-wide: finding an optimal score cutoff, and the substantial variability introduced by differences in gene model annotation, and we suggest strategies for optimal splice effect prediction in the face of these issues.

Conclusion

SpliceAI and Pangolin show the best overall performance among predictors tested, however, improvements in splice effect prediction are still needed especially within exons.
Identification of Trichinella taxa by ITS-1 amplicon next-generation sequencing with an improved resolution for detecting underrepresented genotypes in mixed natural infections
Authors: Lobanov Vladislav A. , Konecsni Kelly A. , Scandrett W. Brad , Jenkins Emily J.
Published: December 2023

Background

Amplicon-based next-generation sequencing (NGS) has rapidly gained popularity as a powerful method for delineating taxa in complex communities, including helminths. Here, we applied this approach to identify species and genotypes of zoonotic nematodes of the Trichinella genus. A known limitation of the current multiplex PCR (mPCR) assay recommended by the International Commission on Trichinellosis is that it does not differentiate Trichinella nativa from T. chanchalensis.

Methods

The new assay entails deep sequencing of an amplified variable fragment of the ribosomal cistron's (rDNA) internal transcribed spacer 1 using the Illumina platform. The assay was evaluated using first-stage larvae (L1) of select laboratory strains of various Trichinella taxa mixed in known proportions and then validated using archived L1 from 109 wildlife hosts. The species/genotypes of these L1 isolates from wildlife were previously determined using mPCR.

Results

NGS data analysis for Trichinella laboratory strains selected as representative of North American fauna revealed a sequence representation bias. Trichinella pseudospiralis, a non-encapsulated species, was the most underrepresented when mixed with T. spiralis, T. murrelli, T. nativa and Trichinella T6 in equal quantities. However, five L1 of T. pseudospiralis were readily revealed by NGS in a mix with 2000 L1 of T. nativa (1:400 ratio). From naturally infected wildlife, all Trichinella taxa revealed by mPCR were also identified by NGS in 103 of 107 (96.3%) samples amplified on both assays. NGS identified additional taxa in 11 (10.3%) samples, whereas additional taxa were revealed by mPCR in only four (3.7%) samples. Most isolates comprised single or mixed infections of T. nativa and Trichinella T6. On NGS, T. chanchalensis (T13) was detected in combination with Trichinella T6 in a wolverine (Gulo gulo) and in combination with T. nativa and Trichinella T6 in a marten (Martes americana) from the Northwest Territories, Canada.

Conclusions

This new NGS assay demonstrates strong potential as a single assay for identifying all recognised Trichinella taxa as well as improved sensitivity for detecting under-represented and novel genotypes in mixed infections. In addition, we report a new host record for T. chanchalensis in American marten.

Graphical Abstract
Cross-cultural differences in self-reported and behavioural emotional self-awareness between Japan and the UK
Authors: Huggins Charlotte F. , Williams Justin H. G. , Sato Wataru
Published: December 2023

Objective

How we express and describe emotion is shaped by sociocultural norms. These sociocultural norms may also affect emotional self-awareness, i.e., how we identify and make sense of our own emotions. Previous studies have found lower emotional self-awareness in East Asian compared to Western samples using self-report measures. However, studies using behavioural methods did not provide clear evidence of reduced emotional self-awareness in East Asian groups. This may be due to different measurement tools capturing different facets of emotional self-awareness.

Results

To investigate this issue further, we compared the emotional self-awareness of Japanese (n = 29) and United Kingdom (UK) (n = 43) adults using the self-report Toronto Alexithymia Scale (TAS-20), alongside two behavioural measures – the Emotional Consistency Task (EC-Task) and the Photo Emotion Differentiation Task (PED-Task). Japanese adults showed higher TAS-20 scores than UK participants, indicating greater self-reported difficulties with emotional self-awareness. Japanese participants also had lower EC-Task scores than UK adults, indicating a lower ability to differentiate between levels of emotional intensity. PED-Task performance did not show clear group differences. These findings suggest that cross-cultural differences in emotional self-awareness vary with the task used, because different tasks assess distinct aspects of this ability. Future research should attempt to capture these different aspects of emotional self-awareness.
Chromatin accessibility analysis suggested vascular induction of the biliary epithelium via the Notch signaling pathway in the human liver
Authors: Yoshihara Masaharu , Nakayama Takahiro , Takahashi Satoru
Published: December 2023

The biliary epithelial cells (cholangiocytes) in the liver originate from undifferentiated liver parenchymal cells (hepatoblasts) that are located adjacent to the portal vein. This differentiation process is driven by Notch signaling, which is recognized for generating salt-and-pepper (fine-grained) patterns, in contrast to one- or two-cell layer (spatially confined) patterning in cholangiocyte differentiation. It is unclear how Notch signaling acts and localizes only in cholangiocytes. A computer simulation study suggested that low production rates of the ligands or receptors of Notch signaling are crucial for the spatially confined patterning, although biochemical examination is lacking. Here, we analyzed a publicly available single-cell ATAC-sequencing dataset from human fetal liver samples. We showed high chromatin accessibility for the ligands only in vascular cells, while that for the receptor is limited to a small population of hepatoblasts. This finding strengthens the previously proposed idea that low production rates of the ligands or receptors of Notch signaling enable vascular induction of cholangiocytes.
Amlodipine alleviates renal ischemia/reperfusion injury in rats through Nrf2/Sestrin2/PGC-1α/TFAM Pathway
Authors: Shirzad Hadi , Mousavinezhad Seyed Amin , Panji Mohammad , Ala Moin
Published: December 2023

Background

Previously, observational studies showed that amlodipine can mitigate calcineurin inhibitor- and contrast-induced acute kidney injury (AKI). Herein, we aimed to measure the effect of amlodipine on renal ischemia/reperfusion (I/R) injury and find the underlying mechanisms.

Materials and methods

Bilateral renal I/R was induced by clamping the hilum of both kidneys for 30 min. The first dose of amlodipine 10 mg/kg was gavaged before anesthesia. The second dose of amlodipine was administered 24 h after the first dose. Forty-eight hours after I/R, rats were anesthetized, and their blood and tissue specimens were collected.

Results

Amlodipine significantly decreased the elevated serum levels of creatinine and blood urea nitrogen (BUN) and mitigated tissue damage in hematoxylin & eosin (H&E) staining. Amlodipine strongly reduced the tissue levels of malondialdehyde (MDA), interleukin 1β (IL1β), and tumor necrosis factor α (TNF-α). Amlodipine enhanced antioxidant defense by upregulating nuclear factor erythroid 2-related factor 2 (Nrf2) and Sestrin2. Furthermore, amlodipine significantly improved mitochondrial biogenesis by promoting Sestrin2/peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α)/mitochondrial transcription factor A (TFAM) pathway. It also enhanced autophagy and attenuated apoptosis, evidenced by increased LC3-II/LC3-I and bcl2/bax ratios after renal I/R.

Conclusion

These findings suggest that amlodipine protects against renal I/R through Nrf2/Sestrin2/PGC-1α/TFAM Pathway.
In diabetic male Wistar rats, quercetin-conjugated superparamagnetic iron oxide nanoparticles have an effect on the SIRT1/p66Shc-mediated pathway related to cognitive impairment
Authors: Chamgordani Mahnaz Karami , Bardestani Akram , Ebrahimpour Shiva , Esmaeili Abolghasem
Published: December 2023

Background

Quercetin (QC) possesses a variety of health-promoting effects in pure and in conjugation with nanoparticles. Since the mRNA-SIRT1/p66Shc pathway and microRNAs (miRNAs) are implicated in the oxidative process, we aimed to compare the effects of QC and QC-conjugated superparamagnetic iron oxide nanoparticles (QCSPIONs) on this pathway.

Methods

Through the use of the chemical coprecipitation technique (CPT), SPIONs were synthesized, coated with dextran, and conjugated with quercetin. Adult male Wistar rats were given intraperitoneal injections of streptozotocin to look for signs of type 1 diabetes (T1D). The animals were randomized into five groups: the control group got deionized water (DI), free QC solution (25 mg/kg), SPIONs (25 mg/kg), and QCSPIONs (25 mg/kg), and all groups received repeat doses administered orally over 35 days. Real-time quantitative PCR was used to assess the levels of miR-34a, let-7a-p5, SIRT1, p66Shc, CASP3, and PARP1 expression in the hippocampus of diabetic rats.

Results

In silico investigations identified p66Shc, CASP3, and PARP1 as targets of let-7a-5p and miR-34a as possible regulators of SIRT1 genes. The outcomes demonstrated that diabetes elevated miR-34a, p66Shc, CASP3, and PARP1 and downregulated let-7a-5p and SIRT1 expression. In contrast to the diabetic group, QCSPIONs boosted let-7a-5p expression levels and consequently lowered p66Shc, CASP3, and PARP1 expression levels. QCSPIONs also reduced miR-34a expression, which led to an upsurge in SIRT1 expression.

Conclusion

Our results suggest that QCSPIONs can regulate the SIRT1/p66Shc-mediated signaling pathway and can be considered a promising candidate for ameliorating the complications of diabetes.
Caprock integrity at Çanakkale-Tuzla hydrothermal system inferred from magnetotelluric modeling using particle swarm optimization
Authors: Büyük Ersin , Karaman Abdullah
Published: December 2023

The impermeable caprock within a geothermal system serves the purpose of effectively sealing the reservoir, resulting in the elevation of both pressure and temperature. This sealing mechanism plays a crucial role in the long-term preservation of the system, while also contributing to its overall sustainability. Caprock failure subsequent to seismic activity near a geothermal site can lead to the permeation of the caprock structure, resulting in diminished sealing capabilities and a decline in the reservoir temperature. Additionally, this process alters the geochemical composition of the water by creating a hydrothermal mixture zone that disrupts the resistivity structure of the caprock, which is typically characterized by low resistivity values due to its substantial clay content and mineral alteration. This study focuses on investigating the integrity of the caprock at ơnakkale-Tuzla geothermal field in Turkey, where the water temperature and conductivity were reported to have decreased after a moderate magnitude earthquake and subsequent aftershocks. For this purpose, we performed magnetotelluric (MT) measurements, a method known for its sensitivity to geochemical reactions. These measurements were conducted along two parallel profiles that encompassed a total of 32 stations. Particle swarm optimization (PSO) technique was employed to overcome subtle difficulties associated with conventional inversion methods when modeling the MT data of complex formations. This is the first study that overcomes the difficulties emanating from the caprock failure by modeling MT data using PSO. Our modeling approach produced resistivity images that we interpreted as the signature of the failed caprock following the earthquake at the study site. Our results appear to confirm the documented geochemical changes or hydrothermal mixture zone about caprock structure.
Postrift buried volcanoes and igneous plumbing systems along a continental ribbon: Insights from the Xisha massif, northwestern margin of the South China Sea
Authors: Wang Lijie , Zhang Ruwei , Li Fucheng , Liu Shengxuan , Li Fuyuan , Yao Yongjian , Gu Yuan , Zhuo Haiteng
Published: December 2023

Despite the prevalence of postrift volcanoes and underlying igneous plumbing systems in rifted basins at proximal and hyperextended crustal configurations, well-preserved volcanoes and related intrusions are rare within minimally stretched continental blocks (i.e., continental ribbon). It is now possible to investigate the size, age, and geographical distribution of the buried volcanoes from multibeam, single-, and multichannel seismic data recently collected beneath the South China Sea Xisha massif, which we argue is a continental ribbon. These data made it evident that the Middle Miocene volcanoes frequently generated massive volcanic fields that erupted along the rift fault zones in contrast to the Early Miocene volcanoes, which typically built clusters of small-volume volcanic cones in the rift half-graben. Details include the presence of numerous volcanoes above and to the side of the dome-shaped main edifice that constitutes the middle Miocene volcanic field. Intrusive sills beneath volcanoes are isolated and have a dispersed distribution pattern at different levels, whereas dikes beneath volcanoes are numerous and have vertical zones of disruption that connect to underlying faults or extend through the sediments to the crust. The relationship between the volcanoes and intrusions suggests that shallow igneous plumbing systems within the Xisha massif are most likely dike domains. The Xisha massif has favorable conditions, including a relatively thin sedimentary sequence over a slightly extended continental crust (20–28 km) that might provide sufficient magma pressure for an igneous plumbing system that is primarily fed by dikes. In addition, rifted faults in the upper crust and possibly subvertical foliations in the basement rock mass are thought to be viable routes for magma transport vertically. In conclusion, we emphasize the importance of crustal structure on the continental ribbon in controlling igneous plumbing styles and the distribution of postrift volcanic systems along magma-poor continental margins, including crustal thickness, preexisting faults, heterogeneous basement, and sediments.
The characteristics and distribution of the Moho reflections in the South China Sea Oceanic Basin
Authors: Geng Minghui , Chen Xi , Zhang Baojin , Zhao Bin , Zhang Ruwei , Bian Donghui , Lu Yunqian , Wang Lijie
Published: December 2023

The distribution and characteristics of the Moho reflections (M-reflections) in oceanic basins record the seafloor spreading process and provide crucial insights into the formation and evolution of the oceanic basins. Approximately 20,000 km of multichannel seismic reflection sections are used to characterize the M-reflections and the crustal structures in the South China Sea oceanic subbasins. The identified M-reflections are mainly distributed in the northwest subbasin, the east subbasin, and the northern and southern flanks of the southwest subbasin (SWSB). They exhibit a banded distribution pattern in two-way traveltime along the north–south direction, with shallower depths observed in the central region and gradually deepening toward the northern and southern sides. In addition, the M-reflection amplitudes generally weaken, and the reflection events become less continuous as the igneous oceanic crust thins along with the seafloor spreading prior to the second ridge jump event. Ultimately, the M-reflection becomes indistinguishable in proximity to fossil spreading centers. These observations suggest a decreasing magma supply toward the cessation of the spreading. Despite the significance of Moho interface imaging at the crust-mantle boundary, the distinct M-reflections are absent in the SWSB and the vicinity of the Zhenbei-Huangyan Seamounts Chain, which are attributed to several factors, especially the vague nature of Moho interfaces.
Detection of Medication Taking Using a Wrist-Worn Commercially Available Wearable Device
Authors: Laughlin Amy I. , Cao Quy , Bryson Richard , Haughey Virginia , Abdul-Salaam Rashad , Gonzenbach Virgilio , Rudraraju Mridini , Eydman Igor , Tweed Christopher M. , Fala Glenn J. , Patel Kash , Fox Kevin R. , Hanson C. William , Bekelman Justin E. , Shou Haochang
Published: December 2023

PURPOSE

Medication nonadherence is a persistent and costly problem across health care. Measures of medication adherence are ineffective. Methods such as self-report, prescription claims data, or smart pill bottles have been used to monitor medication adherence, but these are subject to recall bias, lack real-time feedback, and are often expensive.

METHODS

We proposed a method for monitoring medication adherence using a commercially available wearable device. Passively collected motion data were analyzed on the basis of the Movelet algorithm, a dictionary learning framework that builds person-specific chapters of movements from short frames of elemental activities within the movements. We adapted and extended the Movelet method to construct a within-patient prediction model that identifies medication-taking behaviors.

RESULTS

Using 15 activity features recorded from wrist-worn wearable devices of 10 patients with breast cancer on endocrine therapy, we demonstrated that medication-taking behavior can be predicted in a controlled clinical environment with a median accuracy of 85%.

CONCLUSION

These results in a patient-specific population are exemplar of the potential to measure real-time medication adherence using a wrist-worn commercially available wearable device.
Brain Drain in Cancer Care: The Shrinking Clinical Oncology Workforce in Nigeria
Authors: Chidebe Runcie C.W. , Orjiakor Tochukwu C. , Lasebikan Nwamaka , Joseph Adedayo , Toland Samantha , Simons Alison
Published: December 2023

PURPOSE

A recent estimate indicates that Nigeria has about 70 clinical oncologists (COs) providing care for 124,815 patients with cancer and its 213 million total population. This staggering deficit is likely to worsen as about 90% of Nigerian physicians are eager to leave the country for perceived greener pastures in the United States, the United Kingdom, Canada, etc. Previous studies have examined general physician migration abroad; however, the CO workforce in Nigeria has been barely considered in the workforce literature. This study examined the push and pull factors to stay or leave the CO workforce and Nigeria.

METHODS

Using a correlational design, 64 COs completed turnover intention (TI), workload, and satisfaction measures. Multiple linear regression was used for the data analysis.

RESULTS

The results show that CO workload (number of outpatients attended to; r = 0.30, P < .01) and satisfaction with the delivery of CO care ( r = 0.23, P < .05) were significantly related to TI. The number of outpatients seen was also positively linked to TI. Hence, the more outpatients a CO sees, the higher the intention to leave. The United States (31%), the United Kingdom (30%), and Canada (10%) were the top countries of destinations for Nigerian COs.

CONCLUSION

Higher CO workload is a push factor propelling the intention to leave CO practice and relocate to other countries. Nigeria's new National Cancer Control Plan and the Federal Ministry of Health need to explore innovative approaches to attract and retain the CO workforce, which would lead to improvement in cancer survival and outcomes. Increasing the number of CO programs and positions available, improving work conditions, and introducing work benefits may mitigate the shrinking CO workforce in Nigeria.
FDA Approval Summary: Olaparib in Combination With Abiraterone for Treatment of Patients With BRCA-Mutated Metastatic Castration-Resistant Prostate Cancer
Authors: Fallah Jaleh , Xu Jianjin , Weinstock Chana , Brave Michael H. , Bloomquist Erik , Fiero Mallorie H. , Schaefer Timothy , Pathak Anand , Abukhdeir Abdelrahmman , Bhatnagar Vishal , Chiu Haw-Jyh , Ricks Tiffany , John Christy , Hamed Salaheldin , Lee Christal , Pierce William F. , Kalavar Shyam , Philip Reena , Tang Shenghui , Amiri-Kordestani Laleh , Pazdur Richard , Kluetz Paul G. , Suzman Daniel
Published: December 2023

PURPOSE

This article summarizes the US Food and Drug Administration (FDA) review of the data leading to approval of olaparib plus abiraterone for the treatment of patients with deleterious or suspected deleterious BRCA-mutated ( BRCAm) metastatic castration-resistant prostate cancer (mCRPC), as determined by an FDA-approved companion diagnostic test.

PATIENTS AND METHODS

Approval was based on the results from PROpel, a double-blind trial that randomly assigned 796 patients with mCRPC to abiraterone plus prednisone or prednisolone with either olaparib or placebo. The primary end point was radiographic progression-free survival (rPFS) per investigator assessment.

RESULTS

There was a statistically significant improvement in rPFS for olaparib plus abiraterone versus placebo plus abiraterone, with a median rPFS of 25 versus 17 months and a hazard ratio (HR) of 0.66 (95% CI, 0.54 to 0.81) in the intention-to-treat population. In an exploratory analysis of the subgroup of 85 patients with BRCAm mCRPC, the HR for rPFS was 0.24 (95% CI, 0.12 to 0.45) and the HR for overall survival (OS) was 0.30 (95% CI, 0.15 to 0.59). In an exploratory analysis of the subgroup of 711 patients without an identified BRCA mutation, the HR for rPFS was 0.77 (95% CI, 0.63 to 0.96) and the HR for OS was 0.92 (95% CI, 0.74 to 1.14). Adding olaparib to abiraterone resulted in increased toxicity, including anemia requiring transfusion in 18% of patients.

CONCLUSION

In patients with mCRPC, efficacy of the combination of olaparib plus abiraterone was primarily attributed to the treatment effect in the BRCAm subgroup, the indicated population for the approval. For patients without BRCAm, the FDA determined that the modest rPFS improvement, combined with clinically significant toxicities, did not demonstrate a favorable risk/benefit assessment.
Exceptional Response to MEK Inhibition in a Patient With RAF1-Mutant Myxofibrosarcoma: Case Report and Mechanistic Overview
Authors: Özgü Eylül , Aydin Esranur , Adibi Ashkan , Tokat Ünal Metin , Tutar Onur , Hu Jiancheng , Demiray Irem , Kurzrock Razelle , Demiray Mutlu
Published: December 2023

Complete response to Trametinib in a heavily-pretreated sarcoma: RAF1 as a predictor of MEKi Response
Time Course of Body Composition Changes in Transgender Adolescents During Puberty Suppression and Sex Hormone Treatment
Authors: Boogers Lidewij Sophia , Reijtenbagh Sterre Johanna Petronella , Wiepjes Chantal Maria , van Trotsenburg Adrianus Sarinus Paulus , den Heijer Martin , Hannema Sabine Elisabeth
Published: December 2023

Context

Transgender adolescents can undergo puberty suppression (PS) and subsequent gender-affirming hormone therapy (GAHT) but little information is available on the expected rate of physical changes.

Objective

To investigate the time course of body composition changes during PS and GAHT.

Methods

In this study, retrospective data of 380 trans boys and 168 trans girls treated with PS prior to GAHT from a gender identity clinic were included. Total lean and fat mass Z-scores using birth-assigned sex as reference were determined using dual-energy X-ray absorptiometry.

Results

In trans boys, lean mass Z-scores decreased (−0.32, 95% CI −0.41; −0.23) and fat mass Z-scores increased (0.31, 95% CI 0.21; 0.41) in the first year of PS and remained stable thereafter. Lean mass Z-scores increased (0.92, 95% CI 0.81; 1.04) and fat mass Z-scores decreased (−0.43, 95% CI −0.57; −0.29) only during the first year of testosterone,. In trans girls, both lean and fat mass Z-scores gradually changed over 3 years of PS (respectively −1.13, 95% CI −1.29; −0.98 and 1.06, 95% CI 0.90; 1.23). In the first year of GAHT, lean mass Z-scores decreased (−0.19, 95% CI −0.36; −0.03) while fat mass Z-scores remained unchanged after 3 years (−0.02, 95% CI −0.20; 0.16).

Conclusion

Compared with peers, trans girls experienced ongoing lean mass decrease and fat mass increase during 3 years of PS while in trans boys smaller changes were observed that stabilized after 1 year. A large increase in lean mass Z-scores occurred only during the first year of testosterone treatment. In trans girls, body composition changed only slightly during GAHT. This information can improve counseling about treatment effects.
The Interaction of Duchenne Muscular Dystrophy and Insulin Resistance
Authors: Krishna Swathy , Quindry John C. , Valentine Rudy J. , Selsby Joshua T.
Published: December 2023

Duchenne muscular dystrophy (DMD), caused by deficiency of functional dystrophin protein, is a fatal, progressive muscle disease that frequently includes metabolic dysregulation. Herein, we explore the physiologic consequences of dystrophin deficiency within the context of obesity and insulin resistance. We hypothesized that dystrophin deficiency increases the frequency of insulin resistance, and insulin resistance potentiates muscle pathology caused by dystrophin deficiency.
A Burial of the Early Christian Period in the Sanctuary at Symi
Authors: McGeorge Tina
Published: December 2023

The burial is an extended inhumation in a stone-lined cist, unearthed in 1997, parallel to and in contact with the north wall of the more recent and smaller of two chapels of the Early Christian period, located in the northwest sector of the area of the sanctuary at Symi.. The East-West orientation of the deceased, placed supine in the grave with the head at the west facing east, dates the burial to the Christian era and the archaeological context dates it specifically to the 6th c. AD. The inhumation was that of a woman, at least 35 years old and 160.3 cm tall. Lesions on both shoulder joints may have been caused by repetitive trauma in the course of arduous daily tasks. Since the right shoulder was more severely affected than the left, she was probably right-handed. Dental hypoplasia shows that she had suffered from poor health in childhood when her teeth were being formed. The teeth, which were severely worn, also showed a build-up of dental calculus on the roots of the third molar indicating that she suffered from gingivitis in addition to caries. She also suffered from osteoporosis, perhaps as a result of a chronic infection caused by tuberculosis or brucellosis, compounded by pregnancy. When nutrition is inadequate, an expectant mother’s body is depleted of its reserves of calcium in order to sustain the foetus, which is in a parasitic relationship with the mother. The existence of an infant buried with the adult connects the infant to the woman. It would be too much of a coincidence for a woman and a child to be buried simultaneously unless they were related. So they are presumed to be mother and child. The woman’s death was probably the result of complications in childbirth, a common event in the poorest countries of the world today.
Inhaltsverzeichnis
Authors: Schlaepfer Aline
Published: December 2023

Inhaltsverzeichnis
CRIMINOLOGICAL FEATURES ORGANIZED COUNTERFEITING IN THE DIGITAL AGE
Authors: Umakhanov Jamaludin Kh. , Dieva Maya G.
Published: December 2023

Relevance. In recent years, in the field of counterfeiting, organized groups have been using the possibilities of digital technologies, which contributes to changing the structure of crime in this category, associated with erasing the criminal relationship and personal interaction of accomplices.

In the digital age, as at any historical stage, legal means fulfill the most important task of social regulation – the protection of the monetary sphere from criminal encroachments. In the context of the development of new technologies, legal means are doubling their importance in the system of countering organized counterfeiting.

Purpose and methods. The purpose of the study is to analyze the legal foundations of state policy in the field of countering organized counterfeiting in the digital age. To achieve this goal, dialectical and historical methods, sociological methods, and the method of expert assessments were used in the framework of the study.

Conclusion. The study of organizational and criminological aspects of organized counterfeiting in the digital age has shown that a significant part of the acts of this category is committed in a virtual environment. Block-network transnational organized crime in the field of counterfeiting is spreading in the digital space.

Digital systems and computer programs have become a tool and a means of making counterfeit money and counterfeit securities. In the digital world, non-cash money has become the subject of organized counterfeiting. Significant changes in the structure of organized counterfeiting dictate certain requirements for its prevention system. The paper proposes some organizational and criminological measures to counter organized digital counterfeiting.
АКТУАЛЬНЫЕ ТЕНДЕНЦИИ РАЗВИТИЯ ПРАВОВОГО И ПОЛИТИЧЕСКОГО ЗНАНИЯ НА СТРАНИЦАХ ЖУРНАЛА RUSSIAN STUDIES IN LAW AND POLITICS
Authors: Большакова В. М.
Published: December 2023

Вниманию научной общественности и заинтересованных лиц представляется третий номер седьмого тома научно-практического и общественно-политического рецензируемого журнала по праву и политологии Russian Studies in Law and Politics. Журнал включен в актуальный Перечень рецензируемых научных изданий, в которых должны быть опубликованы основные научные результаты диссертаций на соискание ученой степени кандидата наук, на соискание ученой степени доктора наук по научным специальностям (5.1.2. Публично-правовые (государственно-правовые) науки (юридические науки); 5.1.3. Частно-правовые (цивилистические) науки (юридические науки); 5.5.3. Государственное управление и отраслевые политики (политические науки).

Знаковым событием для дальнейшего эффективного функционирования журнала и повышения внимания к нему со стороны научно-академического сообщества является включение Russian Studies in Law and Politics в международную базу научных и академических журналов с открытым доступом Directory of Open Access Journals (DOAJ). Входящие в названную базу научные издания представляют свое содержание открытым образом, без взимания платы за любое законное использование этих материалов, не выдвигают требований по регистрации или авторизации пользователей, и отвечают самым высоким стандартам качества, что обеспечивается сплошной научно-экспертной оценкой поступающих на рассмотрение работ.

Настоящий номер журнала посвящен интересным для научной общественности разработкам в области норм права и проблемных аспектов их реализации в социальной практике. В номере рассмотрена общая характеристика договоров, заключаемых в торговом обороте, исследованы меры поощрения, применяемые в отношении государственных гражданских служащих и являющихся основанием для публичных расходов.

Также на страницах журнала изучены вопросы разграничения полномочий федерального центра и субъектов Российской Федерации в области физической культуры и спорта. Обращает на себя внимание рецензия на книгу «Уголовно-правовые гарантии суверенитета государства (сравнительно-правовое исследование)» через призму устойчивости статуса государства в условиях кризиса глобализации.

Научно-практическое пособие «Уголовно-правовые гарантии суверенитета государства (сравнительно-правовое исследование)» подготовленное научным коллективом из известных специалистов Института законодательства и сравнительного правоведения при Правительстве Российской Федерации обладает для читателей широким гносеологическим потенциалом и раскрывает перспективы познания правовых отношений в обществе и на международной арене.

Обращаю внимание потенциальных авторов журнала на высокие редакционные требования к оригинальности публикации, обоснованности положений и выводов работ, научности и достоверности основных научных результатов публикаций. Эти требования реализуются путем сплошного двойного слепого рецензирования поступающих статей и обсуждением их на редакционной коллегии.
GENDER-SPECIFIC LIFE SCENARIOS IN INDIVIDUALS WITH DIFFERENT LEVELS OF TOLERANCE TO UNCERTAINTY
Authors: Smorkalova Tatyana L. , Tarasova Lyudmila V. , Solodukhina Olga S.
Published: December 2023

Purpose. Currently, the scenario line of research in personality psychology seems to be particularly promising, since this line of research allows us to identify the specific features of the transformation of the conscious construction of human life paths under changing conditions of uncertainty. The aim of the study is to determine the gender specificity of life scenarios in individuals with different levels of tolerance to uncertainty.

Materials and Methods. The sampling consisted of 200 people with different levels of tolerance towards uncertainty. The methods of the study included the semantic differential Lifestyle by V.P. Serkin and the New Questionnaire of Tolerance Towards Uncertainty by T.V. Kornilova. The data obtained were processed by means of factor analysis with the help of the program IBM SPSS Statistics 23.

Results. The results showed that the life scenarios of people with different levels of tolerance to uncertainty are gender-specific: men with a high tolerance to uncertainty show predominant characteristics of the scenario associated with an active life position and the search for novelty, whereas women show a scenario aimed at activity in the social sphere (the desire to actively participate in the fate of others, to help and support). Men with a low tolerance towards uncertainty show such scenario patterns as striving for security, stability and predictability of events, while women – in addition to striving for a convenient, comfortable life – show tactical patterns: emotional restraint and calculation.

Field of results application. The results of the study can be used in socio-psychological training and counselling to identify and correct an individual’s life scenario.
Investment strategy
Authors: Charaeva Marina
Published: December 2023

The evolution, modern interpretation of an organization's investment strategy, the mechanism of its financial support, risk and time factors, and their impact on investment management are considered. The features of project activities in the financial service of the corporation are highlighted. Currently, the issues of the content of the corporate investment strategy, its transformation in the context of innovation and financial constraints are becoming particularly relevant. The modeling of corporate investment decisions is investigated. Risk is comprehensively characterized as a category accompanying investment decision-making.
It complies with the Federal State Educational Standard of Higher Education of the third generation.
For students studying in economic and managerial fields of study, graduate students, teachers and trainees of the system of additional professional education.
The processes of preparation and preparation for the sale of hot dishes, culinary products, snacks of a complex assortment
Authors: Medved' Tat'yana
Published: December 2023

The textbook includes a detailed description of the content of laboratory work related to the processes of preparation and preparation for the sale of hot dishes, culinary products and snacks of a complex assortment, as well as recommendations for the organization of their implementation by students.
Meets the requirements of the federal state educational standards of secondary vocational education of the latest generation.
It is intended for students of the specialty 02/3/15 "Cooking and confectionery business", as well as for teachers of secondary vocational education working with students of this specialty.
A citizen as a subject of economic activity according to the legislation of Russia
Authors: Shapsugova Marietta
Published: December 2023

The monograph examines the role of citizens in the economic sphere and their impact on the development of the economy and legal regulation. The concept of a citizen as a subject of economic activity is analyzed, his rights and obligations are considered, as well as their relationship with economic processes.
The influence of legal regulation on the economic activity of citizens is studied in detail. The various forms in which citizens carry out economic activities are analyzed.
The issues of social responsibility of citizens in the economy, their contribution to sustainable development and well-being of society are also considered, various approaches to legal regulation of economic activity of citizens are analyzed and measures to improve its effectiveness are proposed.
For students, postgraduates and teachers of law schools, as well as a wide range of readers interested in the impact of citizens on the country's economy.
Old Believers in Russia: history and Modernity, economics, Ethics, social charity
Authors: Stolbov Vyacheslav
Published: December 2023

The monograph explores the phenomenon of Old Believers, the emergence of which is associated with the church reform of Patriarch Nikon, supported by Tsar Alexei Mikhailovich Romanov. The history of the Old Believers is full of dramatic pages of survival and, contrary to the will of the church and state authorities, the preservation of the beliefs of their ancestors and the way of economic life. Through their activities, the Old Believers have made a significant contribution to the Russian economy and to its socio-cultural development.
It is intended for a wide range of readers.
Modeling of the thermal state and calculation of the friction pairs of the basic heat-stressed parts of piston engines
Authors: Zarenbin Vladimir , Chaynov Nikolay , Russinkovskiy Sergey , Val'eho Mal'donado
Published: December 2023

The monograph presents modern methods for calculating the thermal state of thermally stressed basic parts of internal combustion engines, including calculations for jamming of movable conjugate elements of the cylinder piston group.
For engineering and technical workers involved in the design, calculation and manufacture of piston engines. It can be useful for graduate students and university students of relevant fields of study and specialties.
Combined technology in ecobiotechnological and environmental technologies
Authors: Ksenofontov Boris
Published: December 2023

The monograph outlines the theoretical foundations of the cultivation of microorganisms and the most common ecobiotechnological technologies, including biological water purification, biotechnology of soil and air purification, as well as aerobic and anaerobic treatment of sewage sludge and waste. Possible ways of generating electricity by anaerobic digestion of sewage sludge are analyzed.
It is intended for researchers and specialists of research and design organizations, graduate students, masters, bachelors, senior students studying in environmental areas of training and specialties.
Joint venture in the Russian renewable energy market
Authors: Dudnik Anna
Published: December 2023

In modern conditions of energy decarbonization, the activities of international business entities in the alternative energy sector in Russia are of particular scientific interest. Despite the aspirations of many States to develop low-carbon energy by creating special conditions, only a few countries have been able to achieve serious results, in particular through the use of the mechanism of international joint venture. The monograph attempts to identify what conditions are necessary for the effective functioning of enterprises with international participation in the industry, and to identify potential mechanisms for improving the efficiency of joint ventures in the renewable energy market in Russia.
For students, teachers and researchers who study the problems of joint entrepreneurship in the field of renewable energy.
Digital Contact Tracing for Pandemic Response: The Roles of Cultural Worldviews and Technology Awareness
Authors: Wang Jingguo , Li Yuan
Published: December 2023

Information technologies have been developed and used by government agencies and public authorities to address societal issues, but their effectiveness often hinges on public support and participation. This is evidenced in the use of digital contact tracing (DCT) technology to contain the spread of the coronavirus. Despite the efforts of public authorities and technology firms to develop and promote DCT, its adoption in the United States had been low and uneven. This research resolves the puzzle by showing that the public’s mixed views on DCT are caused by their cultural worldviews, which represent their values and attitudes toward collective responsibility in addressing personal needs as well as social hierarchies and established norms in regulating behaviors. These worldviews influence not only their perceptions of the risks and benefits of the technology but also how they interpret information about the technology. Being more aware of the technology may contribute to, rather than correct, the biases resulting from individuals’ prominent cultural worldviews. This research has practical implications for policymakers and technology developers, highlighting the importance of considering cultural worldviews in communication strategies and technology design. It offers a unique perspective on the interplay between worldviews, technology, and public perception, providing valuable insights for navigating the complex landscape of emerging technologies addressing diverse societal issues.