bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extralysosomal cathepsin B in central nervous system: Mechanisms and therapeutic implications
Authors: Ni Junjun , Lan Fei , Xu Yan , Nakanishi Hiroshi , Li Xue 
Published: April 2022

AbstractCathepsin B (CatB) is a typical cysteine lysosomal protease involved in a variety of physiologic and pathological processes. It is expressed in most cell types and is primarily localized within subcellular endosomal and lysosomal compartments. Emerging scientific evidence indicates that lysosomal leaked CatB is involved in mitochondrial stress, inflammasome activation, and nuclear senescence, but without the acidic environment. CatB is also secreted as a myokine, which is involved in muscle‐brain cross talk and neuronal dendritic remodeling. Lysosomal‐leaked and cellular‐secreted CatB functions are dependent on its enzymatic activity at a neutral pH. In the present review, we summarize the available experimental evidence that mechanistically links extralysosomal CatB to physiological and pathological functions in central nervous system, and their potential for use in therapeutic approaches.
The role of non‐discrimination in a world of discriminatory preferential trade agreements
Authors: Saggi Kamal , Wong Woan Foong , Yildiz Halis Murat 
Published: April 2022

AbstractIn a three‐country model of endogenous trade agreements, we study the implications of the most‐favoured‐nation (MFN) clause when countries are free to form discriminatory preferential trade agreements (PTAs). Under current rules of the World Trade Organization (WTO), although non‐member countries face discrimination at the hands of PTA members, they themselves are obligated to abide by MFN and treat PTA members in a non‐discriminatory fashion. The non‐discrimination constraint of MFN reduces the potency of a country's optimal tariffs and therefore its incentive for unilaterally opting out of trade liberalization. Thus, MFN can act as a catalyst for trade liberalization. However, when PTAs take the form of customs unions, the efficiency case for MFN as well as its pro‐liberalization effect is weaker because one country finds itself deliberately excluded by the other two as opposed to staying out voluntarily.
The Effect of Social Presence on Mentalizing Behavior
Authors: Morgan Emma J. , Carroll Daniel J. , Chow Constance K. C. , Freeth Megan 
Published: April 2022

AbstractOur behavior is frequently influenced by those around us. However, the majority of social cognition research is conducted using socially isolated paradigms, without the presence of real people (i.e., without a “social presence”). The current study aimed to test the influence of social presence upon a measure of mentalizing behavior in adults. Study 1 used a first‐order theory of mind task; and study 2 used a second‐order theory of mind task. Both studies included two conditions: live, where the task protagonists were physically present acting out the task, or recorded, where the same task protagonists demonstrated the task in a video recording. In both experiments, participants were affected by the social presence and demonstrated significantly different patterns of behavior in response to the presence of real people. This study, therefore, highlights the critical importance of understanding the effect of a social presence in mentalizing research, and suggests that the inclusion of a social presence needs to be given strong consideration across social cognition paradigms.
A Computational Model of Context‐Dependent Encodings During Category Learning
Authors: Carvalho Paulo F. , Goldstone Robert L. 
Published: April 2022

AbstractAlthough current exemplar models of category learning are flexible and can capture how different features are emphasized for different categories, they still lack the flexibility to adapt to local changes in category learning, such as the effect of different sequences of study. In this paper, we introduce a new model of category learning, the Sequential Attention Theory Model (SAT‐M), in which the encoding of each presented item is influenced not only by its category assignment (global context) as in other exemplar models, but also by how its properties relate to the properties of temporally neighboring items (local context). By fitting SAT‐M to data from experiments comparing category learning with different sequences of trials (interleaved vs. blocked), we demonstrate that SAT‐M captures the effect of local context and predicts when interleaved or blocked training will result in better testing performance across three different studies. Comparatively, ALCOVE, SUSTAIN, and a version of SAT‐M without locally adaptive encoding provided poor fits to the results. Moreover, we evaluated the direct prediction of the model that different sequences of training change what learners encode and determined that the best‐fit encoding parameter values match learners’ looking times during training.
Bioequivalence of two oral formulations of tebipenem pivoxil hydrobromide in healthy subjects
Authors: Gupta Vipul K. , Patel Gina , Gasink Leanne , Bajraktari Floni , Lei Yang , Jain Akash , Srivastava Praveen , Talley Angela K. 
Published: April 2022

AbstractTebipenem pivoxil hydrobromide (TBP‐PI‐HBr) is a novel oral carbapenem prodrug of tebipenem (TBP), the active moiety, currently in development for treating serious bacterial infections. This study assessed the bioequivalence (BE) of the clinical trial and registration tablet formulations of TBP‐PI‐HBr and evaluated the effect of food on the pharmacokinetics (PKs) of tebipenem. This was a single center, open‐label, randomized, single‐dose, three‐sequence, four‐period crossover, BE, and food‐effect study. Subjects received single 600 mg oral doses of TBP‐PI‐HBr as the reference clinical trial tablet (treatment A) and test registration tablet (treatment B) formulations in alternating sequence while fasting, and then the test formulation under fed conditions. Whole blood samples were collected predose and at specified intervals up to 24 h postdose to evaluate TBP PK parameters. Safety and tolerability were monitored. Thirty‐six healthy, adult subjects were enrolled and completed the study. The criteria for BE were met for the TBP‐PI‐HBr test (registration tablet) and reference (clinical trial tablet) formulations as the 90% confidence intervals for the geometric mean ratios for TBP area under the curve (AUC)0‐t, AUC0‐inf, and maximum plasma concentration (Cmax) fell within the established 80% to 125% BE limits. Dosing with food had no meaningful effect on TBP PK parameters. Five (14%) subjects reported adverse events (AEs) of mild severity. No deaths, serious AEs, or discontinuations due to AEs were reported, and no clinically relevant electrocardiograms, vital signs, or safety laboratory findings were observed. The study results demonstrate the BE of oral TBP‐PI‐HBr registration and clinical trial tablet formulations and indicate that TBP‐PI‐HBr can be administered without regard to meals.
What areas of everyday functioning are affected by theory of mind deficits in recent‐onset schizophrenia spectrum disorders?
Authors: Achim Amélie M. , Thibaudeau Élisabeth , Huot Andréanne , Cellard Caroline , Roy Marc‐André 
Published: April 2022

AbstractAimFunctional recovery is now a recognized treatment goal for schizophrenia. It is therefore important to better understand the cognitive and psychological factors that influence functioning. Theory of mind (ToM) deficits are common in schizophrenia and have been linked to greater impairments in functioning. The current study aimed to identify which specific areas of functioning are linked to ToM in a group of 54 patients with a recent‐onset of a schizophrenia spectrum disorder.MethodsToM was assessed with the Combined Stories Test (COST). Several areas of functioning were rated based on an extensive semi‐structured interviews.ResultsAmong the different areas of functioning that were examined, ToM showed a significant, positive relationship with ratings for productive activities (e.g. work or school) as well as with collaboration to psychiatric care.ConclusionThese results suggest that ToM can impair functioning especially in situations in which patients need to collaborate with others, including the interactions with the clinical team.
Chinese childbearing decision‐making in mainland China in the post‐one‐child‐policy era
Authors: Su‐Russell Chang , Sanner Caroline 
Published: April 2022

AbstractIn 2016, China enacted its two‐child policy, further lifted to a three‐child policy in 2021, in response to low birth rates and imbalanced sex ratios resulting from the almost 40‐year one‐child policy. Despite this, China's birthrate is at a historic low as fewer parents are having children. Now more than ever, inductive explorations are needed to understand what motivates Chinese parents to have first and second children in the post‐one‐child policy era, particularly explorations that situate individual decision‐making within the larger social context. Individual and relational choices occur in larger sociopolitical contexts. Understanding these “personal” actions involves considering how micro and macro processes inform each other. In this study, we elicited qualitative responses from Chinese mothers (N = 117) with two children in early childhood (firstborn ≤8 years old) from Liao Ning province. Most mothers were well educated, employed, and married to children's fathers. Using inductive thematic analysis procedures, we coded qualitative responses about the factors that motivated mothers to have first and second children. Our data revealed that (a) mothers expressed different reasons for having firstborns compared to secondborns, and (b) decision‐making occurred against a backdrop of interacting micro‐level and macro‐level influences (e.g., cultural norms, national policy changes). In particular, mothers described the decision to have secondborns as more deliberative than with firstborns, considering long‐term benefits siblinghood and shared demands of elderly caregiving. If efforts to stimulate the national birthrate are likely to succeed, policymakers should consider micro‐level as well as macro‐level factors that shape mothers' childbearing decision‐making.
Resilient biotic response to long‐term climate change in the Adriatic Sea
Authors: Scarponi Daniele , Nawrot Rafał , Azzarone Michele , Pellegrini Claudio , Gamberi Fabiano , Trincardi Fabio , Kowalewski Michał 
Published: April 2022

AbstractPreserving adaptive capacities of coastal ecosystems, which are currently facing the ongoing climate warming and a multitude of other anthropogenic impacts, requires an understanding of long‐term biotic dynamics in the context of major environmental shifts prior to human disturbances. We quantified responses of nearshore mollusk assemblages to long‐term climate and sea‐level changes using 223 samples (~71,300 specimens) retrieved from latest Quaternary sediment cores of the Adriatic coastal systems. These cores provide a rare chance to study coastal systems that existed during glacial lowstands. The fossil mollusk record indicates that nearshore assemblages of the penultimate interglacial (Late Pleistocene) shifted in their faunal composition during the subsequent ice age, and then reassembled again with the return of interglacial climate in the Holocene. These shifts point to a climate‐driven habitat filtering modulated by dispersal processes. The resilient, rather than persistent or stochastic, response of the mollusk assemblages to long‐term environmental changes over at least 125 thousand years highlights the historically unprecedented nature of the ongoing anthropogenic stressors (e.g., pollution, eutrophication, bottom trawling, and invasive species) that are currently shifting coastal regions into novel system states far outside the range of natural variability archived in the fossil record.
Iron deficiency anemia and bleeding management in pediatric patients with Bernard‐Soulier syndrome and Glanzmann Thrombasthenia: A single‐institution analysis
Authors: Lee Annika , Maier Cheryl L. , Batsuli Glaivy 
Published: April 2022

AbstractIntroductionFrequent and severe bleeding events (SBE) in patients with inherited qualitative platelet disorders Bernard‐Soulier Syndrome (BSS) and Glanzmann Thrombasthenia (GT) can lead to secondary iron deficiency anemia (IDA). SBE are primarily treated with platelet transfusions or recombinant activated factor VII (rFVIIa) infusions. The impact of IDA on bleeding management and disease outcomes is understudied.AimTo evaluate bleeding management, outcomes, and any association with IDA in pediatric patients with BSS and GT.MethodsRetrospective chart‐review of pediatric patients with BSS or GT followed at a single hemophilia treatment center between 2007 and 2019.ResultsWe identified 14 patients with BSS (n = 2) or GT (n = 12). Patients received rFVIIa (7%), platelet transfusions (7%), or a combination of both (57%) for SBE. Eleven patients (79%) had IDA requiring oral and/or intravenous iron replacement and 50% required red blood cell transfusions. Due to recurrent SBE and refractory IDA, three patients (21%) received rFVIIa prophylaxis at 90 μg/kilogram 2‐3 times/week for ≥15 months. Patients initiated on rFVIIa prophylaxis had a median baseline hemoglobin of 9.8 g/dL (min‐max: 8.0–10.7 g/dL) compared to 11.7 g/dL (8.4–13.8 g/dL) for patients treated on‐demand. Following initiation of rFVIIa prophylaxis, median hemoglobin and ferritin increased by 1.3 g/dL (0.7–2.5 g/dL) and 14.6 ng/mL (0.2–42.9 ng/mL), respectively, and bleeding rates were reduced by 7–78%.ConclusionIDA is a known complication of recurrent bleeding events in individuals with inherited bleeding disorders. Routine monitoring for IDA may help improve bleeding management and reduce bleed burden in BSS/GT.
A study of Italian young adults’ transnational mobility to Australia: The reproduction of unequal trajectories in the host society
Authors: Giardiello Mauro , Cuervo Hernan , Capobianco Rosa 
Published: April 2022

AbstractIn this article, we examine the mobility patterns of a group of Italian young adults migrating to Australia in the search of new education, labour and lifestyle opportunities. The article represents a contribution to the study of the link between youth mobility and unequal trajectories through the elaboration of a new conceptual framework based on the theory of epistemological fallacy that points to the growing disjuncture between the expectations of individual autonomy and the unequal distribution of resources to achieve them. This conceptual framework contributes to elucidate the paradox of mobility that drives young people between the aspiration to mobility and the reproduction of the structural factors that influence their success. We draw on data from a mixed methods research project examining the mobility of Italian young adults to Australia. Participants imagined mobility as a way of exiting insecurities and precarities in their local context to a more open and meritocratic society, but the analysis of their trajectories in the host country reflects similar patterns of stratification as experienced in the context of origin.
Predictors of influenza severity among hospitalized adults with laboratory confirmed influenza: Analysis of nine influenza seasons from the Valencia region, Spain
Authors: Derqui Nieves , Nealon Joshua , Mira‐Iglesias Ainara , Díez‐Domingo Javier , Mahé Cedric , Chaves Sandra S. 
Published: April 2022

PurposeInfluenza hospitalizations contribute substantially to healthcare disruption. We explored the impact of ageing, comorbidities and other risk factors to better understand associations with severe clinical outcomes in adults hospitalized with influenza.MethodsWe analysed multi‐season data from adults ≥18 years, hospitalized with laboratory‐confirmed influenza in Valencia, Spain. Severity was defined as intensive care unit (ICU) admission, assisted ventilation and/or death. Generalized estimating equations were used to estimate associations between risk factors and severity. Rate of hospital discharge was analysed with a cumulative incidence function.ResultsOnly 26% of influenza patients had their primary discharge diagnosis coded as influenza. Comorbidities were associated with severity among adults aged 50–79 years, with the highest odds ratio (OR) in patients with ≥3 comorbidities aged 50–64 years (OR = 6.7; 95% CI: 1.0–44.6). Morbid obesity and functional dependencies were also identified risk factors (ORs varying from 3 to 5 depending on age). The presence of increasing numbers of comorbidities was associated with prolonged hospital stay.ConclusionsInfluenza clinical outcomes are aggravated by the presence of comorbidities and ageing. Increased awareness of influenza among hospitalized patients could prompt clinical and public health interventions to reduce associated burden.
Quality of life in neurofibromatosis 1: development and validation of a tool dedicated to cutaneous neurofibromas in adults
Authors: Fertitta L. , Bergqvist C. , Armand M.L. , Moryousef S. , Ferkal S. , Jannic A. , Ravaud P. , Tran V.T. , Ezzedine K. , Wolkenstein P. 
Published: April 2022

AbstractBackgroundCutaneous neurofibromas (cNF), present in 95% of individuals with neurofibromatosis 1 (NF1), are considered as one of the greatest medical burden because of physical disfigurement. No specific score evaluates their impact on quality of life (QoL).ObjectiveTo develop a specific score assessing cNF‐related QoL.MethodsThrough a multidisciplinary workshop including 10 patients, 3 expert‐in‐NF1 physicians, 3 health care workers (nurses and psychologist) and 1 methodologist, the French version of the Skindex‐16 was modified by adding 3 items. The new cNF‐Skindex was validated among patients with NF1 recruited in the ComPaRe online cohort, in France (N = 284). Construct validity was assessed by comparing it with the EQ‐5D‐5L, its visual analogue scale and the MYMOP2 and by assessing its association with patients' characteristics. Reliability was assessed by a test–retest. An English version of the tool was developed using a back‐forward translation.ResultsA total of 228 individuals with NF1, with cNF answered the 19‐item questionnaire. These items fitted into 3 domains: emotions, symptoms, functioning. One was dropped during analysis because >90% responders were not concerned. The cNF‐Skindex significantly correlated with the EQ‐5D‐5L (N = 193) and MYMOP2 (N = 210) indicating good external validity: rs 0.38 (P < 0.001), and 0.58 (P < 0.001), respectively. Having >50 cNF was the only independent variable associated with the total score cNF‐Skindex (β = 15.88, 95%CI 6.96–24.81, P = 0.001), and with the 3 sub‐scores: ‘functioning’ (β = 2.65, 95%CI 0.71–4.59, P = 0.008), ‘emotions’ (β = 17.03, 95%CI 4.11–29.96, P = 0.010) and ‘symptoms’ (β = 3.90, 95%CI 1.95–5.85, P < 0.001). Test–retest reliability (N = 133) found an ICC at 0.96 demonstrating good reproducibility.ConclusionThe cNF‐Skindex demonstrated excellent psychometric properties. The global and sub‐scores were increased with higher number of cNF arguing for its use in further trials aiming to reduce their number or prevent their development. Cross‐cultural validation and evaluation of its responsiveness are the next steps.
Moderate‐to‐severe atopic dermatitis in adolescents treated with dupilumab: A multicentre Italian real‐world experience
Authors: Stingeni L. , Bianchi L. , Antonelli E. , Caroppo E.S. , Ferrucci S.M. , Ortoncelli M. , Fabbrocini G. , Nettis E. , Schena D. , Napolitano M. , Gola M. , Bonzano L. , Rossi M. , Belloni Fortina A. , Balato A. , Peris K. , Foti C. , Guarneri F. , Romanelli M. , Patruno C. , Savoia P. , Fargnoli M.C. , Russo F. , Errichetti E. , Bianchelli T. , Bianchi L. , Pellacani G. , Feliciani C. , Offidani A. , Corazza M. , Micali G. , Milanesi N. , Malara G. , Chiricozzi A. , Tramontana M. , Hansel K. ,   DADA – Dupilumab for Atopic Dermatitis of the Adolescence Study Group
Published: April 2022

AbstractBackgroundModerate‐to‐severe atopic dermatitis (AD) in the adolescence is a high burden disease, and its treatment can be very challenging due to paucity of approved systemic drugs for this age and their side‐effects. Dupilumab was recently approved for treatment of adolescent AD.ObjectivesA multicentre, prospective, real‐world study on the effectiveness and safety of dupilumab in adolescents (aged from ≥12 to <18 years) with moderate‐to‐severe AD was conducted. The main AD clinical phenotypes were also examined.MethodsData of adolescents with moderate‐to‐severe AD treated with dupilumab at label dosage for 16 weeks were collected. Treatment outcome was assessed by EASI, NRS itch, NRS sleep loss and CDLQI scores at baseline and after 16 weeks of treatment. The clinical scores were also evaluated according to clinical phenotypes.ResultsOne hundred and thirty‐nine adolescents were enrolled in the study. Flexural eczema and head and neck eczema were the most frequent clinical phenotypes, followed by hand eczema and portrait‐like dermatitis. Coexistence of more than 1 phenotype was documented in 126/139 (88.5%) adolescents. Three patients (2.1%) contracted asymptomatic SARS‐CoV‐2 infection and 1 of the discontinued dupilumab treatment before the target treatment period. A significant improvement in EASI, NRS itch, NRS sleep loss and CDLQI was observed after 16 weeks of treatment with dupilumab. This outcome was better than that observed in clinical trials. Dupilumab resulted effective in all AD phenotypes, especially in diffuse eczema. Twenty‐eight (20.1%) patients reported adverse events, conjunctivitis and flushing being the most frequent. None of patients discontinued dupilumab due to adverse event.ConclusionsDupilumab in adolescent AD showed excellent effectiveness at week 16 with consistent improvement of all clinical scores. Moreover, dupilumab showed a good safety profile also in this COVID‐19 pandemic era.
Divergent selection on behavioural and chemical traits between reproductively isolated populations of Drosophila melanogaster
Authors: Jin Bozhou , Barbash Daniel A. , Castillo Dean M. 
Published: April 2022

AbstractSpeciation is driven by traits that can act to prevent mating between nascent lineages, including male courtship and female preference for male traits. Mating barriers involving these traits evolve quickly because there is strong selection on males and females to maximize reproductive success, and the tight co‐evolution of mating interactions can lead to rapid diversification of sexual behaviour. Populations of Drosophila melanogaster show strong asymmetrical reproductive isolation that is correlated with geographic origin. Using strains that capture natural variation in mating traits, we ask two key questions: which specific male traits are females selecting, and are these traits under divergent sexual selection? These questions have proven extremely challenging to answer, because even in closely related lineages males often differ in multiple traits related to mating behaviour. We address these questions by estimating selection gradients for male courtship and cuticular hydrocarbons for two different female genotypes. We identify specific behaviours and particular cuticular hydrocarbons that are under divergent sexual selection and could potentially contribute to premating reproductive isolation. Additionally, we report that a subset of these traits are plastic; males adjust these traits based on the identity of the female genotype they interact with. These results suggest that even when male courtship is not fixed between lineages, ongoing selection can act on traits that are important for reproductive isolation.