bluuebunny/crossref_metadata_2025_split huggingface dataset:
First‐in‐human study with ACT‐1014‐6470, a novel oral complement factor 5a receptor 1 (C5aR1) antagonist, supported by pharmacokinetic predictions from animals to patients
Authors: Anliker‐Ort Marion , Dingemanse Jasper , Hsin Chih‐hsuan , Richard Muriel , Huehn Eva , Sabattini Giancarlo , van de Wetering Jeroen , Kornberger Rüdiger , van den Anker John , Kaufmann Priska 
Published: May 2022

AbstractAberrantly controlled activation of the complement system contributes to inflammatory diseases. Safety, tolerability, and pharmacokinetics of single‐ascending doses of ACT‐1014‐6470, a novel orally available complement factor 5a receptor 1 antagonist, were assessed in a randomized, double‐blind, placebo‐controlled Phase 1 study. Six ACT‐1014‐6470 doses (0.5–200 mg) were selected after predictions from a Complex Dedrick plot. In each group, ACT‐1014‐6470 or matching placebo was administered to six and two healthy male individuals under fed conditions, respectively, including a cross‐over part with 10 mg administered also under fasted conditions. Pharmacokinetic blood sampling and safety assessments (adverse events, clinical laboratory, vital signs, 12‐lead electrocardiogram, and QT telemetry) were performed. ACT‐1014‐6470 was absorbed with a time to maximum plasma concentration (tmax) of 3 h across dose levels and eliminated with a terminal half‐life of 30–46 h at doses ≥ 2.5 mg. Exposure increased approximately dose proportionally. Under fed compared to fasted conditions, ACT‐1014‐6470 exposure was 2.2‐fold higher and tmax delayed by 1.5 h. Pharmacokinetic modelling predicted that twice‐daily oral administration is warranted in a subsequent multiple‐dose study. No clinically relevant findings were observed in safety assessments. ACT‐1014‐6470 was well tolerated at all doses and could provide a novel therapy with more patient‐friendly administration route compared to biologicals.
Educational achievement and bullying: The mediating role of psychological difficulties
Authors: Murphy Daráine , Leonard Sophie J. , Taylor Laura K. , Santos Flavia H. 
Published: May 2022

AbstractBackgroundBullying has a profound and enduring impact on academic achievement. However, there is a lack of clarity surrounding the specific mechanisms of this relationship.AimsThis study examined the link between bullying at age 9 and Numeracy/Literacy achievement at age 15 to determine if this relationship is partially or fully explained by psychological difficulties at age 13.SampleSecondary data analysis was completed on waves 1, 2 and 3 of child cohort (Cohort’98) of the Growing Up in Ireland (GUI) study, respectively, at 9 years (N = 8568), 13 years (N = 7527) and 15 years of age (N = 6216).ResultsLongitudinal path mediation model was conducted with bullying at age 9 as the predictor, total (emotional and behavioural) difficulties at age 13 as the mediator and Numeracy/Literacy scores at age 15 as outcomes revealing significant indirect effects of bullying on achievement, via psychological difficulties.ConclusionsWe discuss the impact of bullying on the student's psychological well‐being, the relationship between bullying and academic attainment and how this may be tackled to avoid consequences throughout education and later in life.Educational Impact and ImplicationsThis study emphasizes the need for schools to address the emotional and behavioural difficulties occurring as a result of bullying in order to improve the overall educational experience of a child. Existing interventions can be built upon by focusing on the continuous remediation of such psychological difficulties.
Flexibility in valenced reinforcement learning computations across development
Authors: Nussenbaum Kate , Velez Juan A. , Washington Bradli T. , Hamling Hannah E. , Hartley Catherine A. 
Published: May 2022

AbstractOptimal integration of positive and negative outcomes during learning varies depending on an environment's reward statistics. The present study investigated the extent to which children, adolescents, and adults (N = 142 8–25 year‐olds, 55% female, 42% White, 31% Asian, 17% mixed race, and 8% Black; data collected in 2021) adapt their weighting of better‐than‐expected and worse‐than‐expected outcomes when learning from reinforcement. Participants made choices across two contexts: one in which weighting positive outcomes more heavily than negative outcomes led to better performance, and one in which the reverse was true. Reinforcement learning modeling revealed that across age, participants shifted their valence biases in accordance with environmental structure. Exploratory analyses revealed strengthening of context‐dependent flexibility with increasing age.
Bidirectional associations between nightly sleep and daily happiness and negative mood in adolescents
Authors: Kouros Chrystyna D. , Keller Peggy S. , Martín‐Piñón Olivia , El‐Sheikh Mona 
Published: May 2022

AbstractThis study examined bidirectional associations between daily happiness and negative mood and subjective and objective sleep measures. Participants were 311 adolescents (Mage = 17.37 years; 51.8% female; 59.2% White/European American, 38.6% Black/African American, 1% Hispanic/Latinx American, 1.4% multi‐racial; 19.3% below poverty line) observed over a 7‐day period (2017–2018) using sleep diaries and actigraphy. Daily negative mood was related to greater subjective sleep/wake problems, and happiness was related to lower subjective sleep/wake problems. Conversely, shorter self‐reported sleep duration was related to higher negative mood the next day. For actigraphy measures, daily negative mood was related to greater sleep duration and efficiency, whereas happiness was related to lower sleep efficiency. Differences in associations based on subjective versus objective sleep measures are discussed.
A review of the evidence for Mohs micrographic surgery. Part 2: basal cell carcinoma
Authors: Brown Alistair C. , Brindley Luke , Hunt William T. N. , Earp Eleanor M. , Veitch David , Mortimer Neil J. , Salmon Paul J. M. , Wernham Aaron 
Published: May 2022

SummaryMohs micrographic surgery (MMS) is considered the gold-standard treatment for basal cell carcinoma (BCC) particularly for sites with a high-risk of incomplete excision such as the central face, for tumours with an aggressive growth pattern and consequent unpredictable subclinical extension and for recurrent tumours. However, the process is more time-consuming than for standard excision (SE), and the magnitude of benefit is uncertain. This article aims to provide a more complete picture of current evidence, including a review of cosmetic outcomes, tissue-sparing ability and cost-effectiveness of MMS. Although robust evidence is lacking, there is a large volume of observational data supporting a low recurrence rate after MMS. The risk of incomplete excision and higher recurrence rate of standard excision favours the use of MMS at high-risk sites. There is some low-certainty evidence that MMS results in a smaller defect size compared with SE, and that incomplete excision with SE results in larger defects. Larger defects may affect cosmetic outcome but there is no direct evidence that MMS improves cosmetic outcome compared with SE. There is conflicting evidence regarding the cost of MMS compared with SE, as some studies consider MMS less expensive than SE and others consider it more expensive, which may reflect the healthcare setting. A multicentre 10-year randomized controlled trial comparing MMS and SE in the treatment of high-risk BCC would be desirable, but is unlikely to be feasible or ethical. Collection of robust registry data capturing both MMS and SE outcomes would provide additional long-term outcomes.
Intravenous immunoglobulin in the management and outcome of Stiff‐Person syndrome: A systematic review
Authors: Aryal Roshan , Shrestha Suraj , Homagain Sushan , Tiwari Sansar Babu , Ojha Rajeev 
Published: May 2022

AbstractBackgroundStiff Person Syndrome (SPS), a rare immune‐mediated neuromuscular disorder, is characterized by rigidity, stiffness, and intermittent spasms of axial and extremity muscles. Various immunotherapies including intravenous immunoglobulin (IVIG) have been used for this autoimmune condition. Here we aim to review the role of IVIG in the treatment of SPS along with its outcome.MethodsA systematic literature search of PubMed and Embase was conducted to identify the relevant published articles against the predefined criteria using suitable keywords combinations till September 20, 2021. Data were extracted to produce descriptive information of SPS patients on demographics, diagnostics, treatment with IVIG, and outcome.ResultsTwelve studies with 216 patients were included in the review and 63.89% of them had classical SPS. Glutamic acid decarboxylase (GAD) autoantibodies were present in 72.68% of the patients and 57.89% in whom electromyography (EMG) was performed had continuous motor activity. IVIG therapy was given to 95 patients in different regimens in various studies and varying scoring systems were used to assess the outcome, and 83.16% showed some form of improvement, 14.74% showed no improvement, while 2.10% worsened. None of the included studies mentioned an adverse effect of IVIG in the patients.ConclusionIVIG may benefit patients with SPS along with other medications. Owing to the rarity of the disease and insufficient studies on the assessment of immunotherapy in SPS, longitudinal studies with a sizable number of patients are required to clarify clinical course, treatment, and outcome in SPS with the use of IVIG.
Content validity of a psychological e‐health program of self‐control and motivation for adults with excess weight
Authors: Candelaria Martínez Maribel , Franco‐Paredes Karina , Díaz‐Reséndiz Felipe J. , Camacho‐Ruiz Esteban Jaime 
Published: May 2022

SummaryExcess weight requires multidisciplinary treatment, including psychology in face‐to‐face and e‐health interventions. The need to analyse interventions' content validity has become evident. The objective is to assess content validity of a psychological e‐health program of self‐control and motivation for adults with excess weight. Six health professionals (a nutritionist, a personal trainer, physician and three psychologists) evaluated the content validity of the program. The results showed that the item‐level content validity index (I‐CVI) was 1 (the maximum value) for 11 of the 22 activities that comprise the program. This index fluctuated between 0.83 and 0.85 for the other activities, and the scale‐level content validity index was greater than 0.90 for the four modules. In terms of relevance, effectiveness and appropriateness, 90%, 65% and 60% of the activities, respectively, obtained the maximum possible I‐CVI, while the index was acceptable for the remainder of the activities. This is the first study about content validity of a psychological program for adults with excess weight in Mexico and it supported that the content program was suitable, and it may be used as a part of multidisciplinary treatments. This study also highlights the importance of involving an expert review in the development of intervention programs. This intervention program may be useful in the context of a multidisciplinary intervention; however, it is important to conduct studies to evaluate its efficacy.
Assessing the differences in muscle stiffness measured with shear wave elastography and myotonometer during the menstrual cycle in young women
Authors: Khowailed Iman Akef , Lee Youngjin , Lee Haneul 
Published: May 2022

AbstractThis study assessed the differences in muscle stiffness of the medial gastrocnemius (MG) and tibialis anterior (TA) muscles at rest and contraction during ovulation and follicular phase (menstruation) in women with regular menstrual cycle. Thirty‐four young healthy women (mean age 21.3 ± 1.3 years) with regular menstrual cycles participated in this study. Stiffness of the TA and MG muscles at rest and voluntary contraction during ovulation and follicular phase in young women were measured using shear‐wave elastography (SWE) and the handheld myotonometer MyotonPRO. The absolute stiffness difference between resting and contraction was expressed as the stiffness increase rate (SIR). The stiffness of the MG and TA at the resting position was not significantly different between the two phases of the menstrual cycle (p > 0.05). A significantly greater stiffness of both muscles measured using MyotonPRO in the follicular phase than during ovulation was found (p < 0.05), while stiffness measured by SWE showed a difference only in the TA muscle during contraction (p < 0.05). In addition, there were no significant differences in the SIR of both muscles between the two phases (p > 0.05). The results of our study showed a significantly greater stiffness of the MG and TA muscles at the follicular phase than at ovulation during contraction only. As muscle stiffness affects the risk of injury owing to reduced stability during sports activities, these changes in mechanical properties during the menstrual cycle should be noted, and training strategies should be used in female athletes.
The role of T‐tubes and abdominal drains on short‐term outcomes in liver transplantation – A systematic review of the literature and expert panel recommendations
Authors: Kalisvaart Marit , de Jonge Jeroen , Abt Peter , Orloff Susan , Muiesan Paolo , Florman Sander , Spiro Michael , Raptis Dimitri Aristotle , Eghtesad Bijan ,   ERAS4OLT.org working group
Published: May 2022

AbstractBackgroundThis systematic review and expert panel recommendation aims to answer the question regarding the routine use of T‐tubes or abdominal drains to better manage complications and thereby improve outcomes after liver transplantation.MethodsSystematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel to assess the potential risks and benefits of T‐tubes and intra‐abdominal drainage in liver transplantation (CRD42021243036).ResultsOf the 2996 screened records, 33 studies were included in the systematic review, of which 29 (six RCTs) assessed the use of T‐tubes and four regarding surgical drains. Although some studies reported less strictures when using a T‐tube, there was a trend toward more biliary complications with T‐tubes, mainly related to biliary leakage. Due to the small number of studies, there was a paucity of evidence on the effect of abdominal drains with no clear benefit for or against the use of drainage. However, one study investigating the open vs. closed circuit drains found a significantly higher incidence of intra‐abdominal infections when open‐circuit drains were used.ConclusionsDue to the potential risk of biliary leakage and infections, the routine intraoperative insertion of T‐tubes is not recommended (Level of Evidence moderate ‐ very low; grade of recommendation strong). However, a T‐tube can be considered in cases at risk for biliary stenosis. Due to the scant evidence on abdominal drainage, no change in clinical practice in individual centers is recommended. (Level of Evidence very low; weak recommendation).
Mosaic gene expression analysis of semaphorin–plexin interactions in Caenorhabditis elegans using the IR‐LEGO single‐cell gene induction system
Authors: Suzuki Motoshi , Nukazuka Akira , Kamei Yasuhiro , Yuba Shunsuke , Oda Yoichi , Takagi Shin 
Published: May 2022

AbstractGenetic mosaic analysis is a powerful means of addressing the sites of gene action in multicellular organisms. In conventional genetic analysis, the generation of desired mosaic patterns is difficult to control due to the randomness of generating the genetic mosaic which often renders the analysis laborious and time consuming. The infrared laser–evoked gene operator (IR‐LEGO) microscope system facilitates genetic mosaic analysis by enabling gene induction in targeted single cells in a living organism. However, the level of gene induction is not controllable due to the usage of a heat‐shock promoter. Here, we applied IR‐LEGO to examine the cell–cell interactions mediated by semaphoring–plexin signaling in Caenorhabditis elegans by inducing wild‐type semaphorin/plexin in single cells within the population of mutant cells lacking the relevant proteins. We found that the cell contact–dependent termination of the extension of vulval precursor cells is elicited by the forward signaling mediated by the semaphorin receptor, PLX‐1, but not by the reverse signaling via the transmembrane semaphorin, SMP‐1. By utilizing Cre/loxP recombination coupled with the IR‐LEGO system to induce SMP‐1 at a physiological level, we found that SMP‐1 interacts with PLX‐1 only in trans upon contact between vulval precursor cells. In contrast, when overexpressed, SMP‐1 exhibits the ability to cis‐interact with PLX‐1 on a single cell. These results indicate that mosaic analysis with IR‐LEGO, especially when combined with an in vivo recombination system, efficiently complements conventional methods.
No‐take marine protected areas enhance the benefits of kelp‐forest restoration for fish but not fisheries
Authors: Hopf Jess K. , Caselle Jennifer E. , White J. Wilson 
Published: May 2022

AbstractKelp habitat restoration is gaining traction as a management action to support recovery in areas affected by severe disturbances, thereby ensuring the sustainability of ecosystem services. Knowing when and where to restore is a major question. Using a single‐species population model, we consider how restoring inside marine protected areas (MPAs) might benefit coastal fish populations and fisheries. We found that MPAs can greatly enhance the population benefits of restoration but at a small cost to fishery yields. Generally, restoring inside MPAs had a better overall gains‐loss outcome, especially if the system is under high fishing pressure or severe habitat loss. However, restoring outside became preferable when predatory fish indirectly benefit kelp habitats. In either case, successful restoration actions may be difficult to detect in time‐series data due to complex transient dynamics. We provide context for setting management goals and social expectations for the ecosystem service implications of restoration in MPAs.
A melting cryosphere constrains fish growth by synchronizing the seasonal phenology of river food webs
Authors: Bellmore J. Ryan , Fellman Jason B. , Hood Eran , Dunkle Matthew R. , Edwards Richard T. 
Published: May 2022

AbstractMountain watersheds often contain a mosaic of glacier‐, snow‐, and rain‐fed streams that have distinct hydrologic, temperature, and biogeochemical regimes. However, as glaciers diminish and precipitation shifts from snow to rain, the physical and chemical characteristics that make glacial or snowmelt streams distinct from rain‐fed streams will fade. Among the unforeseen consequences of this hydrologic homogenization could be the loss of unique food webs that sustain aquatic consumers. To explore the impacts of a melting cryosphere on stream food webs, we parameterized an aquatic food web model with empirical physicochemical data from glacier‐, snow‐, and rain‐fed streams in southeast Alaska and used the model to simulate the seasonal biomass dynamics of aquatic primary producers and consumers and the growth of juvenile salmon. Model results suggest that glacier‐, snow‐, and rain‐fed streams exhibit seasonal asynchronies in the timing of biofilm and aquatic invertebrate abundance. Although warmer rain‐fed streams were more productive during the summer (June through September), colder glacial and snowmelt streams provided enhanced foraging and growth opportunities throughout the remainder of the year. For juvenile salmon that can track peaks in resource abundance within river networks, the loss of meltwater streams strongly constrained modeled growth opportunities by removing spatially and temporally distinct foraging habitats within a watershed. These findings suggest that climate change induced homogenization of high latitude river networks may result in the loss of unique food web dynamics, which could diminish the capacity of watersheds to sustain mobile consumers.
Human activities have reduced plant diversity in eastern China over the last two millennia
Authors: Cao Xianyong , Tian Fang , Herzschuh Ulrike , Ni Jian , Xu Qinghai , Li Wenjia , Zhang Yanrong , Luo Mingyu , Chen Fahu 
Published: May 2022

AbstractUnderstanding the history and regional singularities of human impact on vegetation is key to developing strategies for sustainable ecosystem management. In this study, fossil and modern pollen datasets from China are employed to investigate temporal changes in pollen composition, analogue quality, and pollen diversity during the Holocene. Anthropogenic disturbance and vegetation's responses are also assessed. Results reveal that pollen assemblages from non‐forest communities fail to provide evidence of human impact for the western part of China (annual precipitation less than 400 mm and/or elevation more than 3000 m.a.s.l.), as inferred from the stable quality of modern analogues, principal components, and diversity of species and communities throughout the Holocene. For the eastern part of China, the proportion of fossil pollen spectra with good modern analogues increases from ca. 50% to ca. 80% during the last 2 millennia, indicating an enhanced intensity of anthropogenic disturbance on vegetation. This disturbance has caused the pollen spectra to become taxonomically less diverse over space (reduced abundances of arboreal taxa and increased abundances of herbaceous taxa), highlighting a reduced south–north differentiation and divergence from past vegetation between regions in the eastern part of China. We recommend that care is taken in eastern China when basing the development of ecosystem management strategies on vegetation changes in the region during the last 2000 years, since humans have significantly disturbed the vegetation during this period.
Chemical profiling of Punica granatum peels from Jordan using LC–MS/MS and study on their biological activities
Authors: Altarawneh Rakan M. , Al‐Jaafreh Ahmad M. , Qaralleh Haitham , Al‐Qaralleh Omar S. 
Published: May 2022

SummaryA paucity of local information concerning the chemical profiles and biological activities of extracts obtained from less‐studied P. granatum peel of Jordanian origin was considered in this study for the first time. Fractionation of the crude ethanol extracts was performed because of their higher phenolic and flavonoid contents compared to the water and acetone extracts. The chemical compositions of the respective samples, that is, extracts/fractions were identified by LC–MS/MS, and the elemental content of the raw materials was also analysed using atomic absorption spectrometry. Antioxidant activities of extracts and fractions were evaluated against DPPH and ABTS radical scavenging assays, and the antibacterial activities were investigated by disc diffusion method and MIC (Minimum Inhibitory Concentration). The LC–MS/MS results correlated strongly with the total phenolic and flavonoid contents, where ethanol displayed higher efficacy for extracting bioactive ingredients. Overall, a total of 19 phenolics were detected in the ethanolic peel extract of P. granatum. All of the analysed extracts showed strong antioxidant activities. Fractionation of ethanolic extracts resulted in fractions with almost similar chemical LC–MS/MS profiles, but the relative proportion of constituents was different. All fractions showed lower intensities of antioxidant capacities than crude extracts, highlighting the superiority of some components, either individually or combined, as well as their relative proportion on the biological activity of each fraction. The results of the present study emphasise the need to further explore the effect of putative interactions among plant bioactive ingredients and focus on possible interactions with drugs along with foods.