bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modelling disease course in amyotrophic lateral Sclerosis: pseudo-longitudinal insights from cross-sectional health-related quality of life data
Authors: Prell Tino , Gaur Nayana , Steinbach Robert , Witte Otto W. , Grosskreutz Julian 
Published: May 2020

Abstract
Background
Amyotrophic Lateral Sclerosis (ALS) is a rapidly progressive neurodegenerative disorder with limited robust disease-modifying therapies presently available. While several treatments are aimed at improving health-related quality of life (HRQoL), longitudinal data on how QoL changes across the disease course are rare.

Objectives
To explore longitudinal changes in emotional well-being and HRQoL in ALS.

Methods
Of the 161 subjects initially recruited, 39 received 2 subsequent follow-up assessments at 6 and 12 months after baseline. The ALS Functional Rating Scale-Revised (ALSFRS-R) was used to assess physical impairment. HRQoL was assessed using the ALS Assessment Questionnaire (ALSAQ-40). The D50 disease progression model was applied to explore longitudinal changes in HRQoL.

Results
Patients were primarily in the early semi-stable and early progressive model-derived disease phases. Non-linear correlation analyses showed that the ALSAQ-40 summary index and emotional well-being subdomain behaved differently across disease phases, indicating that the response shift occurs early in disease. Both the ALSFRS-R and ALSAQ-40 significantly declined at 6- and 12-monthly follow-ups.

Conclusion
ALSAQ-40 summary index and emotional well-being change comparably over both actual time and model-derived phases, indicating that the D50 model enables pseudo-longitudinal interpretations of cross-sectional data in ALS.
Transcultural adaptation and validation of a Korean version of the Oxford Ankle Foot Questionnaire for children
Authors: Cho Seong Hee , Chung Chin Youb , Park Moon Seok , Lee Kyoung Min , Sung Ki Hyuk 
Published: May 2020

Abstract
Background
The purpose of this study was to translate and transculturally adapt the original English version of the Oxford Ankle Foot Questionnaire (OAFQ) into a Korean version, and to evaluate its psychometric properties.

Methods
A Korean OAFQ for children was developed according to established guidelines. To test validity, 169 consecutive patients with foot and ankle problems and their caregivers each completed the OAFQ. The children also completed a Korean version of the KIDSCREEN-52 health related quality of life questionnaire (KIDSCREEN-52 HRQOL). To validate the Korean version of the OAFQ, reliability (child–parent agreement and internal consistency), feasibility (floor and ceiling effects), and construct validity were evaluated, and factor analysis was performed.

Results
In terms of reliability, Cronbach’s α values were > 0.7 in all subscales of the OAFQ (0.765 to 0.901). Child–parent agreement was confirmed by high intraclass correlation coefficients for all subscales (0.791 to 0.863). In terms of construct validity, there were moderate correlations between the subscales of the OAFQ and the subscales of the KIDSCREEN-52 HRQOL. Factor analysis revealed a three-component solution for both the child/adolescent and parent-proxy version, by combining the school and play, and footwear items into one subscale. In terms of feasibility, no floor effects were found for all subscales. However, ceiling effects were observed for the school and play, and emotional subscales for child/adolescent and parent-proxy versions.

Conclusions
The OAFQ was successfully translated and transculturally adapted into the Korean language; the Korean version of the OAFQ represents a reliable and valid instrument for evaluating children’s foot or ankle problems. However, factor analysis suggested the use of a three-subscale questionnaire.
Domestication of aromatic medicinal plants in Mexico: Agastache (Lamiaceae)—an ethnobotanical, morpho-physiological, and phytochemical analysis
Authors: Carrillo-Galván Guadalupe , Bye Robert , Eguiarte Luis E. , Cristians Sol , Pérez-López Pablo , Vergara-Silva Francisco , Luna-Cavazos Mario 
Published: May 2020

AbstractBackgroundMost reports of domesticated plants that involve a domestication gradient or inter-specific hybridization in Mexico have focused on those used as food. This study provides knowledge about these processes in two aromatic medicinal plants,Agastache mexicana(Lamiaceae) andA. m.subsp.xolocotziana, widely used in Mexican traditional medicine for the treatment of gastrointestinal ailments and for their sedative effect. Different populations ofA.mexicanaalong a gradient of domestication are found in the foothills of the Popocatepetl volcano of central Mexico, while in this same area the subsp.xolocotzianagrows only in the cultivation, possibly a product of hybridization betweenA.mexicanaandAgastache palmeri. This study links ethnobotanical, morpho-physiological, and phytochemical evidence to document the domestication of both taxa as well as elucidates the possible hybrid origin of the subsp.xolocotziana.MethodWe analyze three groups of data derived from (1) 80 semi-structured interviews aimed at documenting the selection criteria related to the use and management ofA.mexicana; (2) a cultivation experiment under homogeneous conditions, evaluating 21 floral, vegetative, and seed characters (that were important according to ethnobotanical information) in 97 plants corresponding to 13 populations of the taxa under study; and (3) the chemical profiles of the essential oils of these plants by means of a thin-layer chromatography.ResultsBy linking the three types of evidence, two evolutionary processes are distinguished: (1)A.mexicanaoccurs in the encouraged-cultivated phases of the domestication gradient and (2)A.m.subsp.xolocotzianamay have originated through inbreeding depression or hybridization. These two cultivated plants show a domestication syndrome based upon organoleptic differentiation due to their dissimilar phytochemical composition and gigantism in flowers, seeds, and rhizomes (the last enhancing their asexual reproductive capacity). In addition to this,A.mexicanaexhibits more intense floral pigmentation and foliar gigantism while subsp.xolocotzianapresents floral albinism and partial seed sterility.ConclusionTwo divergent evolutionary processes are reported for the domestication ofA.mexicanaas a result of the intensification of its use and management. The selection processes of these plants have resulted in alternation of the organoleptic properties based upon the divergence of the phytochemical composition. Also, gigantism has been selected in culturally preferred plant parts and in correlated structures. The preceding characteristics reinforce the joint use of these plants in infusion in Mexican traditionalmedicine for the treatment of gastrointestinal diseases and for their sedative effects.
Commercialisation and commodification of breastfeeding: video diaries by first-time mothers
Authors: Taylor Alison M. , Alexander Jo , van Teijlingen Edwin , Ryan Kath M. 
Published: May 2020

AbstractsBackgroundMany of aspects of our lives became increasingly commercialised in post-modern society. Although breastfeeding is perhaps a late comer to this process in recent years, it too has seen significant commercialisation facilitated by social media and our obsession with celebrity culture. This paper explores how the commercialisation and commodification of breastfeeding impacts mothers’ experiences of breastfeeding.MethodsIn a qualitative study, five mothers in the United Kingdom recorded their real-time breastfeeding experiences in video diaries. Using a multi-modal method of analysis, incorporating both visual and audio data, a thematic approach was applied.FindingsWomen preparing for breastfeeding are exposed to increasing commercialisation. When things do not go to plan, women are even more exposed to commercial solutions. The impact of online marketing strategies fuelled their need for paraphernalia so that their dependence on such items became important aspects of their parenting and breastfeeding experiences.ConclusionsThe audio-visual data demonstrated the extent to which “essential” paraphernalia was used, offering new insights into how advertising influenced mothers’ need for specialist equipment and services. Observing mothers in their video diaries, provided valuable insights into their parenting styles and how this affected their breastfeeding experience.
An optimized histological proceeding to study the female gametophyte development in grapevine
Authors: Moreno-Sanz P. , D’Amato E. , Nebish A. , Costantini L. , Grando M. S. 
Published: May 2020

AbstractBackgroundReproductive success in seed plants depends on a healthy fruit and seed set. Normal seed development in the angiosperms requires the production of functional female gametophytes. This is particularly evident in seedless cultivars where defects during megagametophyte’s developmental processes have been observed through cytohistological analysis. Several protocols for embryo sac histological analyses in grapevine are reported in literature, mainly based on resin- or paraffin-embedding approaches. However their description is not always fully exhaustive and sometimes they consist of long and laborious steps. The use of different stains is also documented, some of them, such as hematoxylin, requiring long oxidation periods of the dye-solution before using it (from 2 to 6 months) and/or with a differentiation step not easy to handle. Paraffin-embedding associated to examination with light microscope is the simplest methodology, and with less requirements in terms of expertise and costs, achieving a satisfactory resolution for basic histological observations. Safranin O and fast green FCF is an easy staining combination that has been applied in embryological studies of several plant species.ResultsHere we describe in detail a paraffin-embedding method for the examination of grapevine ovules at different phenological stages. The histological sample preparation process takes 1 day and a half. Sections of 5 µm thickness can be obtained and good contrast is achieved with the safranin O and fast green FCF staining combination. The method allows the observation of megasporogenesis and megagametogenesis events in the different phenological stages examined.ConclusionsThe histological sample preparation process proposed here can be used as a routine procedure to obtain embedded ovaries or microscope slides that would require further steps for examination. We suggest the tested staining combination as a simple and viable technique for basic screenings about the presence in grapevine of a normally and fully developed ovule with embryo sac cells, which is therefore potentially functional.
Risk factors for esophagitis after hypofractionated palliative (chemo) radiotherapy for non-small cell lung cancer
Authors: Nieder Carsten , Imingen Kristian S. , Mannsåker Bård , Yobuta Rosalba , Haukland Ellinor 
Published: May 2020

Abstract
Introduction
Esophagitis influences quality of life and might cause treatment interruption and hospitalization. Previous studies of risk factors focused on curative treatment for non-small cell lung cancer (NSCLC), which often involves concomitant chemoradiation (CRT). Given the uncertainty around extrapolation of dose constraints, we analyzed risk factors in patients treated with hypofractionated palliative regimens.

Patients and methods
A retrospective review of 106 patients treated with palliative radiotherapy or CRT between 2009 and 2017 was performed. Inclusion criteria: prescribed total dose 30–54 Gy, dose per fraction 2.5–4 Gy, esophageal dose > 1 Gy. Uni- and multivariate analyses were performed in 97 eligible patients to identify predictive factors for acute esophagitis grade ≥ 1 (CTCAE 5.0).

Results
Forty percent of patients were treated with 15 fractions of 2.8 Gy (42 Gy) and 28% also received chemotherapy according to the CONRAD study regimen (induction and concomitant Carboplatin/Vinorelbine) published by the Norwegian Lung Cancer Group. Thirty-four percent were treated with 10 fractions of 3 Gy. Stage IV NSCLC was present in 47%. Esophagus Dmax was 39 Gy (population median) and Dmean 15 Gy. Overall 31% of patients developed esophagitis (26% grade 2–3, no grade 4–5). Several dosimetric parameters correlated with the risk of esophagitis (Dmax, Dmean, D5cc, V20, V30, V35, V40). Dmax outperformed other dosimetric variables in multivariate analysis. Furthermore, concomitant chemotherapy significantly increased the risk of esophagitis, while oral steroid medication reduced it. In patients with Dmax ≥40 Gy a reduced Dmean (≤20 Gy) was beneficial.

Conclusion
In order to reduce esophagitis after hypofractionated palliative treatment lower doses than those recommended in curative NSCLC settings are preferable. Besides esophageal dose, CRT is the main risk factor for esophagitis. Additional work is needed to confirm that steroids are able to modify the risk (or to rule out confounding effects of baseline variables not included in our database).
Niosomes of active Fumaria officinalis phytochemicals: antidiabetic, antineuropathic, anti-inflammatory, and possible mechanisms of action
Authors: Raafat Karim M. , El-Zahaby Sally A. 
Published: May 2020

Abstract
Background
Fumaria officinalis (F. officinalis, FO) has been used in many inflammatory and painful-ailments. The main aim of this work is to perform an in-depth bio-guided phytochemical investigation of F. officinalis by identifying its main-active ingredients. Optimizing pharmacokinetics via niosomal-preparation will also be done to enhance their in vivo antineuropathic and anti-inflammatory potentials, and to explore their possible-mechanism of actions.

Methods
Bio-guided phytochemical-investigations including fractionation, isolation, chromatographic-standardization, and identification of the most active compound(s) were done. Optimized niosomal formulations of F. officinalis most active compound(s) were prepared and characterized. An in vivo biological-evaluation was done exploring acute, subchronic, and chronic alloxan-induced diabetes and diabetic-neuropathy, and carrageenan-induced acute inflammatory-pain and chronic-inflammatory edema.

Results
In-vivo bio-guided fractionation and chromatographic phytochemical-analysis showed that the alkaloid-rich fraction (ARF) is the most-active fraction. ARF contained two major alkaloids; Stylopine 48.3%, and Sanguinarine 51.6%. In-vitro optimization, analytical, and in vivo biological-investigations showed that the optimized-niosome, Nio-2, was the most optimized niosomal formulation. Nio-2 had particle size 96.56 ± 1.87 nm and worked by improving the pharmacokinetic-properties of ARF developing adequate entrapment-efficiency, rapid-degradation, and acceptable stability in simulated GI conditions. FO, ARF, and Nio 2 were the most potent antidiabetic and anti-inflammatory compounds. The reduction of the pro-inflammatory tumor necrosis factor-alpha (TNF-alpha) and Interleukin 6 (IL-6), and elevation the anti-inflammatory factor IL-10 levels and amelioration of the in vivo oxidative-stress might be the main-mechanism responsible for their antinociceptive and anti-inflammatory activities.

Conclusions
Fumaria officinalis most-active fraction was identified as ARF. This study offers an efficient and novel practical oral formulation ameliorating various inflammatory conditions and diabetic complications especially neuropathic-pain.
Cyclin-dependent kinases and CDK inhibitors in virus-associated cancers
Authors: Tavakolian Shaian , Goudarzi Hossein , Faghihloo Ebrahim 
Published: May 2020

AbstractThe role of several risk factors, such as pollution, consumption of alcohol, age, sex and obesity in cancer progression is undeniable. Human malignancies are mainly characterized by deregulation of cyclin-dependent kinases (CDK) and cyclin inhibitor kinases (CIK) activities. Viruses express some onco-proteins which could interfere with CDK and CIKs function, and induce some signals to replicate their genome into host’s cells. By reviewing some studies about the function of CDK and CIKs in cells infected with oncoviruses, such as HPV, HTLV, HERV, EBV, KSHV, HBV and HCV, we reviewed the mechanisms of different onco-proteins which could deregulate the cell cycle proteins.
Health status of rescued people by the NGO Open Arms in response to the refugee crisis in the Mediterranean Sea
Authors: Cañardo Guillermo , Gálvez Jesús , Jiménez Juanfe , Serre Núria , Molina Israel , Bocanegra Cristina 
Published: May 2020

Abstract
Background
The migration over the Mediterranean has become one of the deadliest sea voyages in last few years. The NGO Open Arms works in the area since 2015, with the objectives of protecting and reporting human rights at sea. This paper aims to give an overview on characteristics and health conditions of rescued people by the NGO in the Central Mediterranean.

Methods
A descriptive retrospective population study was conducted, including people who were rescued from distress at sea by the NGO Open Arms from 1st July 2016 to 31st December 2018.

Results
In this period of time 22,234 people were rescued from sea. Among them 2234 (22.7%) were minors, and 177 (0.8%) pregnant women. The most frequent countries of origin were Nigeria (1278–13.1%), Eritrea (1215–12.3%) and Bangladesh (981–9.9%). Among all people rescued, 4516 (20.3%) reported symptoms. Scabies was the most frequent pathology, being suspected in 1817 (8.2%) people. Other infectious diseases were diagnosed in 91 (0.4%). Thirty-five (0.16%) patients suffered some complication from their chronic diseases. Acute injuries due to trauma, burns, aggressions, and bullet or bladed weapon wound were reported in 135 (0.6%) cases. Seventy-four corpses were recovered.

Conclusions
Main diagnoses on board were directly related to the precarious living conditions through migratory route, violence and complications of chronic diseases due to lack of care. The large number of people rescued highlights the catastrophic effect on migrants’ health of European policies, which overlap the desire to restrict migratory movements on the humanitarian and health issues. An integrated information system and a coordinated response are basic to improve the situation in the area.
Time-dependent changes in FT4 and FT3 levels measured using mass spectrometry after an acute ingestion of excess levothyroxine in a case with hypothyroidism
Authors: Ito Yuko , Suzuki Satoru , Matsumoto Yoshiko , Ohkouchi Chiyo , Suzuki Satoshi , Iwadate Manabu , Midorikawa Sanae , Yokoya Susumu , Suzuki Shinichi , Shimura Hiroki 
Published: May 2020

Abstract
Background
Thyrotoxicosis is common disorder among endocrine dysfunctions. It is not rare that the free thyroid hormone level exceeds the measurement range of immunoassay. Such extreme high concentration of free thyroid hormone is generally considered to be impossible to measure correctly because of changes in the balance between free hormones and binding proteins by dilution of serum. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), however, higher concentrations are able to be determined.

Case presentation
We present a case of a 21-year-old female with congenital hypothyroidism who had taken a total of 5 mg levothyroxine over three consecutive days following discontinuance of the medication for a month. Immunoassay performed 3 hours after the last ingestion showed that the patient’s free thyroxine (FT4) was over 100 pmol/L and her free triiodothyronine (FT3) was 24.5 pmol/L. With a temporary cessation of levothyroxine, the patient was kept for observation without any other medication. Two days after the last ingestion, FT4 was still over 100 pmol/L and FT3 was increased to 28.8 pmol/L. After an additional 4 days, both FT4 and FT3 levels decreased. Through this period, no thyrotoxic symptom or physical sign had appeared. We also measured FT4 and FT3 levels in her cryopreserved serum by ultrafiltration LC-MS/MS. Her FT4 level measured by ultrafiltration LC-MS/MS on the visiting day and 2 days later were 160.0 and 135.5 pmol/L, respectively, indicating that the toxic dose of levothyroxine was partly changed to T3 during the 2 days. The FT3/FT4 ratios were revealed to be low, accounting for the patient’s benign clinical course despite temporal toxic exposure to levothyroxine. It is implied that prior discontinuation of supplementary levothyroxine increases potential vacant binding sites for thyroid hormone as a buffer to prevent toxic T3 effect.

Conclusion
It was helpful to clarify the time dependent changes in free thyroid hormone levels by ultrafiltration LC-MS/MS in discussing the clinical course in this case. Though mass spectrometry has a disadvantage in speed for routine laboratory use, its accurate measurement, particularly of levels exceeding the measurable range of the immunoassay, provides valuable information for more appropriate management of extreme thyrotoxicosis.
Mimicking tumor hypoxia and tumor-immune interactions employing three-dimensional in vitro models
Authors: Bhattacharya Somshuvra , Calar Kristin , de la Puente Pilar 
Published: May 2020

AbstractThe heterogeneous tumor microenvironment (TME) is highly complex and not entirely understood. These complex configurations lead to the generation of oxygen-deprived conditions within the tumor niche, which modulate several intrinsic TME elements to promote immunosuppressive outcomes. Decoding these communications is necessary for designing effective therapeutic strategies that can effectively reduce tumor-associated chemotherapy resistance by employing the inherent potential of the immune system.While classic two-dimensional in vitro research models reveal critical hypoxia-driven biochemical cues, three-dimensional (3D) cell culture models more accurately replicate the TME-immune manifestations. In this study, we review various 3D cell culture models currently being utilized to foster an oxygen-deprived TME, those that assess the dynamics associated with TME–immune cell penetrability within the tumor-like spatial structure, and discuss state of the art 3D systems that attempt recreating hypoxia-driven TME-immune outcomes. We also highlight the importance of integrating various hallmarks, which collectively might influence the functionality of these 3D models.This review strives to supplement perspectives to the quickly-evolving discipline that endeavors to mimic tumor hypoxia and tumor-immune interactions using 3D in vitro models.