bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of moxifloxacin in canine and non‐human primate telemetry assays: Comparison of QTc interval prolongation by timepoint and concentration‐QTc analysis
Authors: Chui Ray W. , Baublits Joel , Chandra Fiona A. , Jones Zack W. , Engwall Michael J. , Vargas Hugo M. 
Published: June 2021

AbstractThe in vivo correct QT (QTc) assay is used by the pharmaceutical industry to characterize the potential for delayed ventricular repolarization and is a core safety assay mentioned in International Conference on Harmonization (ICH) S7B guideline. The typical telemetry study involves a dose‐response analysis of QTc intervals over time using a crossover (CO) design. This method has proven utility but does not include direct integration of pharmacokinetic (PK) data. An alternative approach has been validated and is used routinely in the clinical setting that pairs pharmacodynamic (PD) responses with PK exposure (e.g., concentration‐QTc (C‐QTc) analysis. The goal of our paper was to compare the QTc sensitivity of two experimental approaches in the conscious dog and non‐human primate (NHP) QTc assays. For timepoint analysis, a conventional design using eight animals (8 × 4 CO) to detect moxifloxacin‐induced QTc prolongation was compared to a PK/PD design in a subset (N = 4) of the same animals. The findings demonstrate that both approaches are equally sensitive in detecting threshold QTc prolongation on the order of 10 ms. Both QTc models demonstrated linearity in the QTc prolongation response to moxifloxacin dose escalation (6 to 46 ms). Further, comparison with human QTc findings with moxifloxacin showed agreement and consistent translation across the three species: C‐QTc slope values were 0.7‐ (dog) and 1.2‐ (NHP) fold of the composite human value. In conclusion, our data show that dog and NHP QTc telemetry with an integrated PK arm (C‐QTc) has the potential to supplement clinical evaluation and improve integrated QTc risk assessment.
Severe and complex youth depression: Clinical and historical features of young people attending a tertiary mood disorders clinic
Authors: Rice Simon M. , McKechnie Ben , Cotton Susan , Brooker Abi , Pilkington Vita , Youzchalveen Belinsha , Schmaal Lianne , Davey Christopher G. 
Published: June 2021

AbstractAimThe concept of severe and complex youth depression has evolved from clinical experience. Here we conducted a file audit study to evaluate supporting data for the construct.MethodsA retrospective file audit was undertaken with 84 consecutively discharged patients over 6‐months from Orygen's Youth Mood Clinic (YMC; 50% female).ResultsOver a third (36.9%) were disengaged from vocation and education, with exposure to traumatic events common (84.5%). Almost all patients (91.7%) reported past 2‐week suicidal ideation at clinic entry. Hospital emergency departments were the most frequent referral source (31.0%). Most (72.6%) had received previous mental health treatment. Multimorbidity was frequently observed. The presence of a substance use disorder, or ≥ 3 comorbidities were both associated with a greater likelihood of prior suicide attempt.ConclusionsThese data highlight the clinical needs associated with severe and complex depression. Findings have implications for youth experiencing mood disorders attending tertiary and community mental health settings.
European guideline and expert statements on the management of narcolepsy in adults and children
Authors: Bassetti Claudio L. A. , Kallweit Ulf , Vignatelli Luca , Plazzi Giuseppe , Lecendreux Michel , Baldin Elisa , Dolenc‐Groselj Leja , Jennum Poul , Khatami Ramin , Manconi Mauro , Mayer Geert , Partinen Markku , Pollmächer Thomas , Reading Paul , Santamaria Joan , Sonka Karel , Dauvilliers Yves , Lammers Gert J. 
Published: June 2021

SummaryBackground and aimNarcolepsy is an uncommon hypothalamic disorder of presumed autoimmune origin that usually requires lifelong treatment. This paper aims to provide evidence‐based guidelines for the management of narcolepsy in both adults and children.MethodsThe European Academy of Neurology (EAN), European Sleep Research Society (ESRS) and European Narcolepsy Network (EU‐NN) nominated a task force of 18 narcolepsy specialists. According to the EAN recommendations, 10 relevant clinical questions were formulated in PICO format. Following a systematic review of the literature (performed in Fall 2018 and updated in July 2020) recommendations were developed according to the GRADE approach.ResultsA total of 10,247 references were evaluated, 308 studies were assessed and 155 finally included. The main recommendations can be summarized as follows: (i) excessive daytime sleepiness in adults—scheduled naps, modafinil, pitolisant, sodium oxybate (SXB), solriamfetol (all strong), methylphenidate, amphetamine derivates (both weak); (ii) cataplexy in adults—SXB, venlafaxine, clomipramine (all strong) and pitolisant (weak); (iii) excessive daytime sleepiness in children—scheduled naps, SXB (both strong), modafinil, methylphenidate, pitolisant, amphetamine derivates (all weak); (iv) cataplexy in children—SXB (strong), antidepressants (weak). Treatment choices should be tailored to each patient’s symptoms, comorbidities, tolerance and risk of potential drug interactions.ConclusionThe management of narcolepsy involves non‐pharmacological and pharmacological approaches with an increasing number of symptomatic treatment options for adults and children that have been studied in some detail.
Can plantar fibroblast implantation protect amputees from skin injury? A recipe for skin augmentation
Authors: Boyle Colin J. , Higgins Claire A. 
Published: June 2021

AbstractSkin injuries remain a persistent problem for users of lower‐limb prostheses despite sustained progress in prosthesis design. One factor limiting the prevention of skin injuries is that skin on the residual limb is not suited to bear the mechanical loads of ambulation. One part of the body that is suited to this task is the sole of the foot. Here, we propose a novel strategy to actively augment skin's tolerance to load, increasing its resistance to mechanically induced injuries. We hypothesise that the load tolerance of skin can be augmented by autologous transplantation of plantar fibroblasts into the residual limb dermis. We expect that introducing plantar fibroblasts will induce the overlying keratinocytes to express plantar‐specific keratins leading to a tougher epidermis. Using a computational finite element model of a weight‐bearing residual limb, we estimate that skin deformation (a key driver of pressure ulcer injuries) could be halved by reprogramming skin to a plantar‐like phenotype. We believe this strategy could yield new progress in pressure ulcer prevention for amputees, facilitating rehabilitation and improving quality of life for patients.
The role of the skin microbiota in the modulation of cutaneous inflammation—Lessons from the gut
Authors: Elias Abigail E. , McBain Andrew J. , O’Neill Catherine A. 
Published: June 2021

AbstractInflammation is a vital defense mechanism used to protect the body from invading pathogens, but dysregulation can lead to chronic inflammatory disorders such as psoriasis and atopic dermatitis. Differences in microbiota composition have been observed in patients with inflammatory skin conditions compared with healthy individuals, particularly within lesions. There is also increasing evidence accumulating to support the notion that the microbiome contributes to the onset or modulates the severity of inflammatory diseases. Despite the known protective effects of orally administered lactic acid bacteria against inflammation, few studies have investigated the potential protective effects of topical application of bacteria on skin health and even fewer have looked at the potential anti‐inflammatory effects of skin commensals. If lack of diversity and reduction in the abundance of specific commensal strains is observed in inflammatory skin lesions, and it is known that commensal bacteria can produce anti‐inflammatory compounds, we suggest that certain members of the skin microbiota have anti‐inflammatory properties that can be harnessed for use as topical therapeutics in inflammatory skin disorders.
Functional validation of a finding from a mouse genome‐wide association study shows that Azi2 influences the acute locomotor stimulant response to methamphetamine
Authors: Zhou Xinzhu , Barkley‐Levenson Amanda M. , Montilla‐Perez Patricia , Telese Francesca , Palmer Abraham A. 
Published: June 2021

AbstractIn a previous genome‐wide association study (GWAS) using outbred Carworth Farms White (CFW) mice, we identified a locus that influenced the stimulant response to methamphetamine and colocalized with an eQTL for Azi2. Based on those findings, we hypothesized that heritable differences in Azi2 expression were causally related to the differential response to methamphetamine. To test that hypothesis, we created a mutant Azi2 allele on an inbred C57BL/6J background. The mutant allele enhanced the locomotor response to methamphetamine. However, the GWAS had suggested that lower Azi2 would decrease the locomotor response to methamphetamine. We also sought to explore the mechanism by which Azi2 influenced methamphetamine sensitivity. A recent publication reported that the 3′UTR of Azi2 mRNA downregulates the expression of Slc6a3, which encodes the dopamine transporter, which is a key target of methamphetamine. We evaluated the relationship between Azi2, Azi2 3′UTR and Slc6a3 expression in the ventral tegmental area of wildtype, mutant Azi2 heterozygotes and mutant Azi2 homozygotes and in a new cohort of outbred CFW mice where both allele mapped in our prior GWAS were segregating. We did not observe any correlation between Azi2 and Slc6a3 in either cohort. However, RNA sequencing confirmed that the Azi2 mutation altered Azi2 expression and also revealed a number of potentially important genes and pathways that were regulated by Azi2, including the metabotropic glutamate receptor group III pathway and nicotinic acetylcholine receptor signaling pathway. Our results support a role for Azi2 in methamphetamine sensitivity; however, the exact mechanism does not appear to involve regulation of Slc6a3.
Association between frequency of snacking and all‐cause mortality among community‐dwelling young‐old adults: An age‐specific prospective cohort study
Authors: Kobayashi Tohru , Zhao Wenjing , Ukawa Shigekazu , Wakai Kenji , Tsushita Kazuyo , Kawamura Takashi , Ando Masahiko , Tamakoshi Akiko 
Published: June 2021

AimWe aimed to clarify whether snacking habits decrease the risk of all‐cause mortality in an older Japanese population.MethodsThe study participants were 64‐ or 65‐year‐old community‐dwelling residents recruited each survey year from 1996 through 2005. Data on the frequency of snacking and other lifestyle factors were obtained during the baseline survey using self‐administered questionnaires, and the participants were followed up annually until the end of 2017. In total, 2943 participants (1484 men and 1459 women) were eligible. All‐cause mortality was compared among participants grouped by frequency of snacking (no snacking, one to four times/week, or every day).ResultsThe number of deaths recorded over the study period of 43 204 person‐years was 357 (24.1%) for men and 173 (11.9%) for women. The mean ± standard deviations for the follow‐up period were 14.2 ± 4.9 years in men and 15.2 ± 4.5 years in women. Cox proportional hazard regression analyses showed that after adjusting for potential confounding factors, the hazard ratios for women were 0.64 (95% confidence interval [CI], 0.43–0.94) in the group that had a habit of snacking one to four times/week, and 0.93 (95% CI 0.63–1.36) in the group that had a habit of snacking every day compared with those in the no snacking group. These associations were not observed among men.ConclusionsA moderate frequency of snacking slightly decreases the risk of all‐cause mortality among women. Our findings might be useful for improving the nutrition statuses in older female adults. Geriatr Gerontol Int 2021; 21: 697–704.
Competing for seafaring labour: Social security and agency employment in Chinese shipping
Authors: Chen Gang , Tang Lijun 
Published: June 2021

AbstractThis paper discusses one strategy that Chinese crewing agencies adopt to compete with each other in the global seafarer labour supplying market. This strategy is related to Chinese seafarers’ social insurance participation. It shows that crewing agencies utilised a dual workforce – ‘company‐owned seafarers’ and ‘externally hired seafarers’. Externally hired seafarers, though in precarious employment, are offered higher salaries in place of social insurance coverage. By contrast, company‐owned seafarers are paid less, though enjoy social insurance arranged by agencies. This strategy serves to segment the seafarer labour market, conceal the level playing field and help agencies recruit seafarers cost‐effectively, though in violation of labour rights. This paper argues that this strategy grows out of the competitive landscape co‐shaped by the national regulatory and institutional settings and the global structure of the shipping industry.
Effect of photobiomodulation on post‐operative symptoms in teeth with asymptomatic apical periodontitis treated with foraminal enlargement: A randomized clinical trial
Authors: Guimarães Ludmila da Silva , da Silva Erlange Andrade Borges , Hespanhol Fernanda Garcias , Fontes Karla Bianca Fernandes da Costa , Antunes Livia Azeredo Alves , Antunes Leonardo Santos 
Published: June 2021

AbstractAimTo assess the efficacy of photobiomodulation in reducing post‐operative symptoms and use of analgesics in teeth with asymptomatic apical periodontitis treated with foraminal enlargement in a single visit.MethodologyThis prospective double‐blind, controlled, superiority, randomized clinical trial enrolled 70 patients requiring root canal treatment of one single‐rooted tooth with asymptomatic apical periodontitis. The participants were randomized into one of the following two groups: 35 patients in the control group (C.G) – root canal treatment with foraminal enlargement, without any additional treatment and 35 patients in the photobiomodulation group (PBM.G) – root canal treatment with foraminal enlargement associated with photobiomodulation (antimicrobial photodynamic therapy and low‐level laser therapy). The outcome variables were post‐operative pain, tenderness, oedema and the use of analgesics. Pain intensity was measured using a visual analogue scale (recorded every day for 7 days, then the 14th and 30th days after root canal treatment). Facial oedema was assessed subjectively by two independent evaluators using photographs taken by one of the researchers at 48 h, 72 h and 7 days after the procedures. Data were tabulated and analysed using the Mann–Whitney U, Chi‐Square, Fisher`s Exact, Student T and Ordinal Logistic Regression by Generalized Estimating Equations tests in SPSS software.ResultsThere were no significant differences in post‐operative pain and tenderness between the groups at any observation period (p > .05). Photobiomodulation (beta = −0.77 / p = .01), time (beta = −0.23 / p < .01), and male gender (beta = −1.20 / p < .01) were associated with decreased post‐operative pain. Only time (beta: −0.10; p < .01) and male gender (beta: −1.04; p < .01) were associated with decreased tenderness. For oedema and use of analgesics, there was no difference between the groups (p > .05).ConclusionsPhotobiomodulation had no significant effect on post‐operative pain, tenderness, oedema and the use of analgesics after root canal treatment with foraminal enlargement, in single‐rooted teeth treated in a single visit.Register of Clinical Trials: NCT03704857.Research Ethics Committee: no 2.353.996 / CAAE 74185417.9.0000.5626.
Is it possible to repigment iatrogenic and traumatic hypochromic lesions? A case series using the MMP® drug delivery technique with 5‐fluorouracil and bleomycin
Authors: Arbache Samir , Arbache Samia T. , Hirata Sergio H. 
Published: June 2021

AbstractObjectivesWe present the results of 11 patients with hypochromic lesions treated with antifibrotic agents delivered through the MMP® technique.MethodsEleven patients with hypochromic lesions because of external injuries were treated at a single clinic with 5‐fluorouracil (5‐FU) and/or bleomycin using the MMP® drug delivery technique. Treatment sessions were repeated at 30‐day intervals until patient satisfaction. The primary outcome was repigmentation of the lesions, assessed independently by two dermatologists and by the patient.ResultsThe MMP® technique injected 0.048 mg/cm2 of 5‐FU or 0.0028 U/cm2 of bleomycin. The accumulated 5‐FU and bleomycin density per patient ranged from 0.02 to 0.77 mg and 0.0022 to 0.2800 U/ml, respectively. Patients were treated with 1 to 6 MMP® sessions with 5‐FU (3 patients), bleomycin (6 patients), or both drugs (2 patients). After the last session, all patients had a significant improvement (>75%) of the lesions compared to baseline. There were no procedure‐related short‐ or long‐term adverse effects in any of the participants up to their last follow‐up visit.ConclusionsThe injection of antifibrotic agents using the MMP® technique was effective and safe in the treatment of hypochromic lesions. This can be a new therapeutic option for these lesions.
COVID‐19 and informal work: Evidence from 11 cities
Authors: CHEN Martha Alter , GRAPSA Erofili , ISMAIL Ghida , ROGAN Michael , VALDIVIA Marcela , ALFERS Laura , HARVEY Jenna , OGANDO Ana Carolina , REED Sarah Orleans , ROEVER Sally 
Published: June 2021

AbstractThis article presents the findings for 11 cities across five geographical regions from a study led by Women in Informal Employment: Globalizing and Organizing, investigating the impacts of the COVID‐19 crisis on different groups of informal workers and their households. Detailing impacts on work and income, food and hunger, care and other household responsibilities, and on the coping strategies of informal worker households, the article also compares the roles of government and informal worker organizations in providing relief and other support. Based on worker demands, the authors present guiding principles for a better deal for informal workers going forward.
Évolution de l'importance des emplois à vie au Royaume‐Uni
Authors: ST‐DENIS Xavier 
Published: June 2021

RésuméLes emplois à vie sont généralement présentés comme un trait dominant des marchés du travail de l'après‐guerre, en recul aujourd'hui. L'auteur cherche à vérifier ces affirmations avec une nouvelle méthode, qui permet d'estimer, à partir de données transversales, la probabilité d'occuper un emploi à vie selon la cohorte de naissance. Il montre que cette situation n'a concerné en réalité qu'une faible proportion des travailleurs britanniques de l'après‐guerre, avec des variations selon le groupe sociodémographique. En outre, si les emplois à vie ne disparaissent pas, les emplois de longue durée reculent chez les hommes des cohortes 1947–1966, notamment à cause d'une moindre stabilité des parcours professionnels plus tôt dans la carrière.
Libertéautravail,parle travail etfaceau travail: comment repenser les droits relatifs au travail
Authors: BUENO Nicolas 
Published: June 2021

RésuméLes droits relatifs au travail sont‐ils un instrument promouvant la liberté? L'auteur définit trois libertés: la libertéautravail,parle travail mais aussifaceau travail. Bien que certains courants du droit du travail analysent les liens entre droits relatifs au travail et liberté, ces droits se limitent traditionnellement à protéger les travailleuses et travailleurs sur le marché du travail plutôt qu'à étendre leurs libertés, notamment la liberté face au travail. L'auteur souligne à cet égard les limites des propositions actuelles en vue d'une émancipation du travail, dont le revenu de base. Lui‐même propose plutôt de créer de nouveaux droits dans un modèle dit de l'économie humaine.
Evolución de la prevalencia del empleo de por vida: nuevas estimaciones sobre el Reino Unido
Authors: ST‐DENIS Xavier 
Published: June 2021

ResumenFrente a la idea de que en la era fordista predominó el empleo de por vida, el autor utiliza un método novedoso para estimar con datos transversales del Reino Unido la probabilidad para diferentes cohortes de nacimiento de alcanzar determinados umbrales de antigüedad. Se constata que la proporción de trabajadores del Reino Unido que ocuparon puestos por 30 años o más en la era fordista fue baja, con variaciones entre los grupos sociodemográficos. La prevalencia de los empleos de larga duración (20 años o más) disminuyó entre los hombres nacidos entre 1947 y 1966, en parte por la menor estabilidad laboral durante la juventud.
PAICS is related to glioma grade and can promote glioma growth and migration
Authors: Du Baoshun , Zhang Zheying , Di Wenyu , Xu Wenzhong , Yang Lei , Zhang Shitao , He Guoyang , Yang Rui , Wang Maode 
Published: June 2021

AbstractGlioma is a common malignant tumour of the brain. In this study, we aimed to investigate diagnostic biomarkers and its role in glioma. Weighted gene co‐expression network analysis (WGCNA) and Cytoscape software were used to screen the marker genes in glioma. RT‐qPCR and Western blotting methods were performed to determine the expression of PAICS, ERCC1 and XPA genes in glioma tissues. Expression level of PAICS in different grades of glioma was examined by immunohistochemistry. CCK8 and Colony formation assays were used to detect cell proliferation. Cell adhesion assay was used to detect adhesion ability. Wound healing and transwell tests were used to detect cell migration ability. Flow cytometry was used to detect cell cycle and apoptosis. According to the predicted co‐expression network, we identified the hub gene PAICS. Furthermore, we observed that PAICS expression level was up‐regulated in glioma tissues compared with normal tissues, and the expression level was correlated with the grade of glioma. Moreover, we found PAICS can promote glioma cells proliferation and migration in vitro. Flow cytometry results showed that si‐PAICS cells were stalled at the G1 phase compared with the si‐NC cells and knocking down PAICS expression can increase apoptotic rate. PAICS can regulate the mRNA and protein levels of nucleotide excision repair pathway core genes ERCC1 and XPA. l‐aspartic acid can affect the expression of PAICS and then inhibit glioma cell proliferation. Our results indicated that PAICS can promote glioma proliferation and migration. PAICS may act as a potential diagnostic marker and a therapeutic target for glioma.