bluuebunny/crossref_metadata_2025_split huggingface dataset:
The pharmaceuticalisation of life? A fictional case report of insomnia with a thought experiment
Authors: Bäckryd Emmanuel 
Published: October 2021

Abstract
Background
The safety of sleeping pills has increased dramatically during the last 100 years, from barbiturates to bensodiazepines to modern day so-called Z-drugs.

Methods
The circumstances of prescribing sleeping pills in the early 20th century are illustrated by summarizing the main storyline of a novel by Swedish writer Vilhelm Moberg. This is followed by a thought experiment and a theoretical discussion.

Results
In his 1937 novel Sömnlös (Swedish for sleepless) Vilhelm Moberg portrayed existential and relational distress in relation to insomnia. In a thought experiment, past progresses in sleeping pills safety are projected into the future. Thereby, it is claimed that important issues in the area of philosophy of medicine come to the fore. This leads to a theoretical discussion about broader questions concerning the role of the physician, the goals of medicine (as described by Lennart Nordenfelt), the concept of pharmaceuticalisation (as described notably by sociologist of sleep Simon J. Williams and co-workers), and health enhancement (c.f. Carl Elliott and the alleged wish to be better than well).

Conclusion
Insomnia is a prism through which important philosophical and sociological questions related to the practice of medicine can be asked.
The susceptibility of the aortic root: porcine aortic rupture testing under cardiopulmonary bypass
Authors: Surman Timothy Luke , Abrahams John Matthew , Manavis Jim , Finnie John , Christou Chris , Williams Georgia Kate , Walls Angela , Frantzis Peter , Adams Mark , Edwards James , Worthington Michael George , Beltrame John 
Published: October 2021

AbstractBackgroundIn our earlier study on the functional limits of the aneurysmal aortic root we determined the pig root is susceptible to failure at high aortic pressures levels. We established a pig rupture model using cardiopulmonary bypass to determine the most susceptible region of the aortic root under the highest pressures achievable using continuous flow, and what changes occur in these regions on a macroscopic and histological level. This information may help guide clinical management of aortic root and ascending aorta pathology.MethodsFive pigs underwent 4D flow MRI imaging pre surgery to determine vasopressor induced wall sheer stress and flow parameters. All pigs were then placed on cardiopulmonary bypass (CPB) via median sternotomy, and maximal aortic root and ascending aorta flows were initiated until rupture or failure, to determine the most susceptible region of the aorta. The heart was explanted and analysed histologically to determine if histological changes mirror the macroscopic observations.ResultsThe magnetic resonance imaging (MRI) aortic flow and wall sheer stress (WSS) increased significantly in all regions of the aorta, and the median maximal pressures obtained during cardiopulmonary bypass was 497 mmHg and median maximal flows was 3.96 L/m. The area of failure in all experiments was the non-coronary cusp of the aortic valve. Collagen and elastin composition (%) was greatest in the proximal regions of the aorta. Collagen I and III showed greatest content in the inner aortic root and ascending aorta regions.ConclusionsThis unique porcine model shows that the aortic root is most susceptible to failure at high continuous aortic pressures, supported histologically by different changes in collagen content and subtypes in the aortic root. With further analysis, this information could guide management of the aortic root in disease.
Neurobehavioral alternations of the female offspring born to polycystic ovary syndrome model rats administered by Chinese herbal medicine
Authors: Zhang Xian , You Lifang , Zhang Xiaohui , Wang Fangfang , Wang Yi , Zhou Jue , Liu Chang , Qu Fan 
Published: October 2021

AbstractBackgroundChinese herbal medicine (CHM) has significant effects that improve the reproductive functions of patients with polycystic ovary syndrome (PCOS). However, the intergenerational effects of CHM on offspring and the underlying mechanism of CHM remain unclear. This study aimed to explore the effects and the underlying mechanism of CHM, specifically the Bu-Shen-Tian-Jing formula (BSTJF), on model rats with polycystic ovary syndrome (PCOS) and the neurobehavioral alterations of female offspring born to PCOS rats administered BSTJF.MethodsHigh-performance liquid chromatography-mass spectrometry (HPLC–MS) and network pharmacology analysis were performed to identify the active ingredients and potential targets of BSTJF. Moreover, PCOS model rats were used to validate the role of BSTJF in reproduction and progeny neural development and to confirm the network pharmacological targets.ResultsA total of 91 constituents were characterized from BSTJF. The 20 most significant KEGG pathways and the high-frequency genes of these pathways were predicted to be putative targets of these molecules. The rat experiment showed that the downregulation of FOS protein expression in the ovarian granulosa cells of the PCOS group was reversed by BSTJF. The target residence time of the 5-week-old female offspring of the BSTJF group was higher than that of the PCOS group in the water maze experiment. Compared to the PCOS group, the changes in dendritic spine density, ultrastructure of neurons and synapses, and Gabrb1 and Grin2b protein expression levels in the hippocampus of female offspring were partially reversed in the BSTJF group.ConclusionsBSTJF can effectively improve ovarian follicle development in PCOS rats and has positive effects on pubertal neurobehavioral alterations in the female offspring of these rats by reversing dendritic spine density, the ultrastructure of neurons and synapses, and the Gabrb1 and Grin2b protein expression levels in the hippocampus.
Cognitive–behavioral therapy for management of mental health and stress-related disorders: Recent advances in techniques and technologies
Authors: Nakao Mutsuhiro , Shirotsuki Kentaro , Sugaya Nagisa 
Published: October 2021

AbstractCognitive–behavioral therapy (CBT) helps individuals to eliminate avoidant and safety-seeking behaviors that prevent self-correction of faulty beliefs, thereby facilitating stress management to reduce stress-related disorders and enhance mental health. The present review evaluated the effectiveness of CBT in stressful conditions among clinical and general populations, and identified recent advances in CBT-related techniques. A search of the literature for studies conducted during 1987–2021 identified 345 articles relating to biopsychosocial medicine; 154 (45%) were review articles, including 14 systemic reviews, and 53 (15%) were clinical trials including 45 randomized controlled trials. The results of several randomized controlled trials indicated that CBT was effective for a variety of mental problems (e.g., anxiety disorder, attention deficit hypersensitivity disorder, bulimia nervosa, depression, hypochondriasis), physical conditions (e.g., chronic fatigue syndrome, fibromyalgia, irritable bowel syndrome, breast cancer), and behavioral problems (e.g., antisocial behaviors, drug abuse, gambling, overweight, smoking), at least in the short term; more follow-up observations are needed to assess the long-term effects of CBT. Mental and physical problems can likely be managed effectively with online CBT or self-help CBT using a mobile app, but these should be applied with care, considering their cost-effectiveness and applicability to a given population.
Humans and machines in biomedical knowledge curation: hypertrophic cardiomyopathy molecular mechanisms’ representation
Authors: Glavaški Mila , Velicki Lazar 
Published: October 2021

Abstract
Background
Biomedical knowledge is dispersed in scientific literature and is growing constantly. Curation is the extraction of knowledge from unstructured data into a computable form and could be done manually or automatically. Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease, with genotype–phenotype associations still incompletely understood. We compared human- and machine-curated HCM molecular mechanisms’ models and examined the performance of different machine approaches for that task.

Results
We created six models representing HCM molecular mechanisms using different approaches and made them publicly available, analyzed them as networks, and tried to explain the models’ differences by the analysis of factors that affect the quality of machine-curated models (query constraints and reading systems’ performance). A result of this work is also the Interactive HCM map, the only publicly available knowledge resource dedicated to HCM. Sizes and topological parameters of the networks differed notably, and a low consensus was found in terms of centrality measures between networks. Consensus about the most important nodes was achieved only with respect to one element (calcium). Models with a reduced level of noise were generated and cooperatively working elements were detected. REACH and TRIPS reading systems showed much higher accuracy than Sparser, but at the cost of extraction performance. TRIPS proved to be the best single reading system for text segments about HCM, in terms of the compromise between accuracy and extraction performance.

Conclusions
Different approaches in curation can produce models of the same disease with diverse characteristics, and they give rise to utterly different conclusions in subsequent analysis. The final purpose of the model should direct the choice of curation techniques. Manual curation represents the gold standard for information extraction in biomedical research and is most suitable when only high-quality elements for models are required. Automated curation provides more substance, but high level of noise is expected. Different curation strategies can reduce the level of human input needed. Biomedical knowledge would benefit overwhelmingly, especially as to its rapid growth, if computers were to be able to assist in analysis on a larger scale.
Epigenetic dynamics shaping melanophore and iridophore cell fate in zebrafish
Authors: Jang Hyo Sik , Chen Yujie , Ge Jiaxin , Wilkening Alicia N. , Hou Yiran , Lee Hyung Joo , Choi You Rim , Lowdon Rebecca F. , Xing Xiaoyun , Li Daofeng , Kaufman Charles K. , Johnson Stephen L. , Wang Ting 
Published: October 2021

AbstractBackgroundZebrafish pigment cell differentiation provides an attractive model for studying cell fate progression as a neural crest progenitor engenders diverse cell types, including two morphologically distinct pigment cells: black melanophores and reflective iridophores. Nontrivial classical genetic and transcriptomic approaches have revealed essential molecular mechanisms and gene regulatory circuits that drive neural crest-derived cell fate decisions. However, how the epigenetic landscape contributes to pigment cell differentiation, especially in the context of iridophore cell fate, is poorly understood.ResultsWe chart the global changes in the epigenetic landscape, including DNA methylation and chromatin accessibility, during neural crest differentiation into melanophores and iridophores to identify epigenetic determinants shaping cell type-specific gene expression. Motif enrichment in the epigenetically dynamic regions reveals putative transcription factors that might be responsible for driving pigment cell identity. Through this effort, in the relatively uncharacterized iridophores, we validatealx4aas a necessary and sufficient transcription factor for iridophore differentiation and present evidence onalx4a’s potential regulatory role in guanine synthesis pathway.ConclusionsPigment cell fate is marked by substantial DNA demethylation events coupled with dynamic chromatin accessibility to potentiate gene regulation through cis-regulatory control. Here, we provide a multi-omic resource for neural crest differentiation into melanophores and iridophores. This work led to the discovery and validation of iridophore-specificalx4atranscription factor.
A phase I/II dose-escalation multi-center study to evaluate the safety of infusion of natural killer cells or memory T cells as adoptive therapy in coronavirus pneumonia and/or lymphopenia: RELEASE study protocol
Authors: García-García I. , Guerra-García P. , Ferreras C. , Borobia A. M. , Carcas A. J. , Queiruga-Parada J. , Vicario J. L. , Mirones I. , Solano C. , Eguizabal C. , Soria B. , Pérez-Martínez A. 
Published: October 2021

Abstract
Background
Moderate/severe cases of COVID-19 present a dysregulated immune system with T cell lymphopenia and a hyper-inflammatory state.
This is a study protocol of an open-label, multi-center, double-arm, randomized, dose-finding phase I/II clinical trial to evaluate the safety, tolerability, alloreactivity, and efficacy of the administration of allogeneic memory T cells and natural killer (NK) cells in COVID-19 patients with lymphopenia and/or pneumonia. The aim of the study is to determine the safety and the efficacy of the recommended phase 2 dose (RP2D) of this treatment for patients with moderate/severe COVID-19.

Methods
In the phase I trial, 18 patients with COVID-19-related pneumonia and/or lymphopenia with no oxygen requirement or with an oxygen need of ≤ 2.5 liters per minute (lpm) in nasal cannula will be assigned to two arms, based on the biology of the donor and the patient. Treatment of arm A consists of the administration of escalating doses of memory T cells, plus standard of care (SoC). Treatment of arm B consists of the administration of escalating doses of NK cells, plus SoC.
In the phase II trial, a total of 182 patients with COVID-19-related pneumonia and/or lymphopenia requiring or not oxygen supplementation but without mechanical ventilation will be allocated to arm A or B, considering HLA typing. Within each arm, they will be randomized in a 1:1 ratio. In arm A, patients will receive SoC or RP2D for memory T cells plus the SoC. In arm B, patients will receive SoC or RP2D for NK cells plus the SoC.

Discussion
We hypothesized that SARS-CoV-2-specific memory T-lymphocytes obtained from convalescent donors recovered from COVID-19 can be used as a passive cell immunotherapy to treat pneumonia and lymphopenia in moderate/severe patients. The lymphopenia induced by COVID-19 constitutes a therapeutic window that may facilitate donor engraftment and viral protection until recovery.

Trial registration
ClinicalTrials.govNCT04578210. First Posted : October 8, 2020
Immunomodulation for primary prevention of urinary tract infections in patients with spinal cord injury during primary rehabilitation: protocol for a randomized placebo-controlled pilot trial (UROVAXOM-pilot)
Authors: Krebs Jörg , Stoyanov Jivko , Wöllner Jens , Valido Ezra , Pannek Jürgen 
Published: October 2021

Abstract
Background
Urinary tract infections (UTIs) are common in individuals with neurogenic lower urinary tract dysfunction (NLUTD) following spinal cord injury (SCI). They are not only a great burden for affected individuals, but also cause considerable health costs. Furthermore, recurrent antibiotic treatments of UTIs contribute to the growing problem of bacterial resistance to antimicrobial compounds. Even though there is a multitude of different measures to prevent UTIs in individuals with NLUTD, no clear evidence exists for any of these. Oral immunomodulation with UTI-relevant Escherichia coli lysate may be a promising preventative measure with a good safety profile in individuals with NLUTD. However, currently available data are sparse.

Methods
This is a randomized, quasi-blinded, placebo-controlled, mono-centric pilot trial investigating the feasibility of a main trial regarding the effects of a lyophilized lysate of E. coli strains for oral application (Uro-Vaxom®, OM Pharma SA, Meyrin, Switzerland). There will be two parallel groups of 12 participants each. Individuals with acute SCI (duration SCI ≤ 56 days) from 18 to 70 years of age admitted for primary rehabilitation will be eligible. Blood and urine samples will be taken prior to intervention start, at the end of the intervention, and 3 months after intervention termination. The trial intervention will last 90 days. The participants will not be informed regarding the treatment allocation (quasi-blinded). The nursing staff will prepare the daily dose of the allocated treatment from the original packaging. The trial personnel and the biostatistician will be blinded. Feasibility (e.g., recruitment rate, patient attrition), clinical (e.g., number of symptomatic UTIs), and laboratory parameters (e.g., urinary culture, urinary proteo- and microbiome, blood cell counts) as well as adverse events will be collected.

Discussion
Effective and efficient measures for the prevention of UTIs in individuals with NLUTD are urgently needed. If the conclusion of this pilot is positive regarding feasibility, the effects of oral immunomodulation with a E. coli lysate will be investigated in a larger, sufficiently powered, multi-center trial.

Trial registration
ClinicalTrials.govNCT04049994. Registered on 8 August 2019
Analysis of septal spacing and septal crowding in Devonian and Carboniferous ammonoids
Authors: Beck Sophie Marie , De Baets Kenneth , Klug Christian , Korn Dieter 
Published: October 2021

AbstractSeptal crowding is widely known as a sign of maturity in conchs of ammonoids and nautiloids. However, reduced septal spacing may also occur as a consequence of adverse ecological conditions. Here, we address the question how septal spacing varied through ontogeny in representatives of some of the major clades of Devonian and Carboniferous ammonoids. We found that the degree of ontogenetic variation is similar between clades and that variation is only weakly linked with conch form. The results show that septal crowding alone is insufficient to identify adulthood in ammonoids; intermediate septal crowding is a common phenomenon and occurs in various growth stages. Changes in septal distances during ontogeny were, in addition to adulthood of the individuals, a passive reaction likely caused by fluctuating environmental conditions.
Long-term survival of mechanically ventilated patients with severe COVID-19: an observational cohort study
Authors: Peñuelas Oscar , del Campo-Albendea Laura , de Aledo Amanda Lesmes González , Añón José Manuel , Rodríguez-Solís Carmen , Mancebo Jordi , Vera Paula , Ballesteros Daniel , Jiménez Jorge , Maseda Emilio , Figueira Juan Carlos , Franco Nieves , Algaba Ángela , Avilés Juan Pablo , Díaz Ricardo , Abad Beatriz , Canabal Alfonso , Abella Ana , Gordo Federico , García Javier , Suarez Jessica García , Cedeño Jamil , Martínez-Palacios Basilia , Manteiga Eva , Martínez Óscar , Blancas Rafael , Bardi Tommaso , Pestaña David , Lorente José Ángel , Muriel Alfonso , Esteban Andrés , Frutos-Vivar Fernando 
Published: October 2021

Abstract
Background
Information is lacking regarding long-term survival and predictive factors for mortality in patients with acute hypoxemic respiratory failure due to coronavirus disease 2019 (COVID-19) and undergoing invasive mechanical ventilation. We aimed to estimate 180-day mortality of patients with COVID-19 requiring invasive ventilation, and to develop a predictive model for long-term mortality.

Methods
Retrospective, multicentre, national cohort study between March 8 and April 30, 2020 in 16 intensive care units (ICU) in Spain. Participants were consecutive adults who received invasive mechanical ventilation for COVID-19. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection detected in positive testing of a nasopharyngeal sample and confirmed by real time reverse-transcriptase polymerase chain reaction (rt-PCR). The primary outcomes was 180-day survival after hospital admission. Secondary outcomes were length of ICU and hospital stay, and ICU and in-hospital mortality. A predictive model was developed to estimate the probability of 180-day mortality.

Results
868 patients were included (median age, 64 years [interquartile range [IQR], 56–71 years]; 72% male). Severity at ICU admission, estimated by SAPS3, was 56 points [IQR 50–63]. Prior to intubation, 26% received some type of noninvasive respiratory support. The unadjusted overall 180-day survival rates was 59% (95% CI 56–62%). The predictive factors measured during ICU stay, and associated with 180-day mortality were: age [Odds Ratio [OR] per 1-year increase 1.051, 95% CI 1.033–1.068)), SAPS3 (OR per 1-point increase 1.027, 95% CI 1.011–1.044), diabetes (OR 1.546, 95% CI 1.085–2.204), neutrophils to lymphocytes ratio (OR per 1-unit increase 1.008, 95% CI 1.001–1.016), failed attempt of noninvasive positive pressure ventilation prior to orotracheal intubation (OR 1.878 (95% CI 1.124–3.140), use of selective digestive decontamination strategy during ICU stay (OR 0.590 (95% CI 0.358–0.972) and administration of low dosage of corticosteroids (methylprednisolone 1 mg/kg) (OR 2.042 (95% CI 1.205–3.460).

Conclusion
The long-term survival of mechanically ventilated patients with severe COVID-19 reaches more than 50% and may help to provide individualized risk stratification and potential treatments.
Trial registration: ClinicalTrials.gov Identifier: NCT04379258. Registered 10 April 2020 (retrospectively registered)
Deep learning-based optimal placement of a mobile HAP for common throughput maximization in wireless powered communication networks
Authors: Kim Hong-Sik , Joe Inwhee 
Published: October 2021

AbstractHybrid access point (HAP) is a node in wireless powered communication networks (WPCN) that can distribute energy to each wireless device and also can receive information from these devices. Recently, mobile HAPs have emerged for efficient network use, and the throughput of the network depends on their location. There are two kinds of metrics for throughput, that is, sum throughput and common throughput; each is the sum and minimum value of throughput between a HAP and each wireless device, respectively. Likewise, two types of throughput maximization problems can be considered, sum throughput maximization and common throughput maximization. In this paper, we focus on the latter to propose a deep learning-based methodology for common throughput maximization by optimally placing a mobile HAP for WPCN. Our study implies that deep learning can be applied to optimize a complex function of common throughput maximization, which is a convex function or a combination of a few convex functions. The experimental results show that our approach provides better performance than mathematical methods for smaller maps.
Two-hop cognitive DF relaying with wireless power transfer in time and power domains
Authors: Zheng Lina , Zhai Chao 
Published: October 2021

AbstractIn this paper, we consider a wireless powered cognitive relaying system with a secondary relay (SR) capable of harvesting wireless energy. Along with an access point (AP) continuously transmitting the primary data to a primary user (PU), a secondary source (SS) can transmit the secondary data to a secondary destination (SD) with the help of SR using the decode-and-forward (DF) protocol. SR can harvest energy from both SS and AP in both time and power domains using time-splitting and power-splitting techniques. The interference from primary data transmissions can help boost the amount of harvested energy at SR. The transmit power of SS is regulated by the interference threshold at PU and the allowable peak power. Despite the above two constraints, the transmit power of SR is further constrained by the amount of harvested energy. Once SR successfully decodes the data from SS, it will forward the data to SD using a constrained power. We analyze the approximate outage probabilities for both primary and secondary systems. Simulation results are provided to verify the effectiveness of our theoretical analysis and reveal the impacts of various parameters to the outage performance.