bluuebunny/crossref_metadata_2025_split huggingface dataset:
From sink to source: changing climate and disturbance regimes could tip the 21st century carbon balance of an unmanaged mountain forest landscape
Authors: Albrich Katharina , Seidl Rupert , Rammer Werner , Thom Dominik 
Published: June 2022

Abstract
Forests are one of the most important components of the global carbon cycle. Consequently, forest protection as a nature-based climate solution has garnered increasing interest. Protected areas instated to safeguard biodiversity provide an opportunity to maximize carbon storage in situ, with important co-benefits between conservation and climate change mitigation. However, changing climate and disturbance regimes put this carbon storage function at risk. Here we investigated carbon sequestration and storage in a protected landscape in the German Alps (Berchtesgaden National Park) throughout the 21st century. We simulated the impacts of climate change as well as increasing wind and bark beetle disturbances on cumulative Net Ecosystem Production using a process-based forest landscape model. Considering a wide range of potential changes in wind frequency and speed under a variety of climate change scenarios, we addressed the question under which future conditions the landscape will turn from a carbon sink to a carbon source. While the landscape was a net carbon sink at the end of the simulation in 76 per cent of the simulation runs, increasing disturbances and climate change greatly reduced its carbon sink capacity. Under RCP2.6, the landscape remained a robust carbon sink even under elevated disturbance (probability of turning from sink to source between 0 per cent and 25 per cent). In contrast, carbon release was likely under RCP8.5 even with little change in the disturbance regime (probability: 30 per cent to 95 per cent). Productive areas in lower elevations that currently have the highest carbon density on the landscape were contributing most strongly to a reduction of the carbon sink strength. Our study reveals that the effect of protected areas acting as nature-based climate solutions might be overestimated if the risks from changing climate and disturbance regimes are neglected. We therefore call for a more explicit consideration of future forest dynamics in the discussion of the potential role of forests in climate change mitigation.
Altering enhancer–promoter linear distance impacts promoter competition in cis and in trans
Authors: Bateman Jack R , Johnson Justine E 
Published: June 2022

Abstract
In Drosophila, pairing of maternal and paternal homologs can permit trans-interactions between enhancers on one homolog and promoters on another, an example of a phenomenon called transvection. When chromosomes are paired, promoters in cis and in trans to an enhancer can compete for the enhancer’s activity, but the parameters that govern this competition are as yet poorly understood. To assess how the linear spacing between an enhancer and promoter can influence promoter competition in Drosophila, we employed transgenic constructs wherein the eye-specific enhancer GMR is placed at varying distances from a heterologous hsp70 promoter driving a fluorescent reporter. While GMR activates the reporter to a high degree when the enhancer and promoter are spaced by a few hundred base pairs, activation is strongly attenuated when the enhancer is moved 3 kb away. By examining transcription of endogenous genes near the point of transgene insertion, we show that linear spacing of 3 kb between GMR and the hsp70 promoter results in elevated transcription of neighboring promoters, suggesting a loss of specificity between the enhancer and its intended transgenic target promoter. Furthermore, increasing spacing between GMR and hsp70 by just 100 bp can enhance transvection, resulting in increased activation of a promoter on a paired homolog at the expense of a promoter in cis to the enhancer. Finally, cis-/trans-promoter competition assays in which one promoter carries mutations to key core promoter elements show that GMR will skew its activity toward a wild-type promoter, suggesting that an enhancer is in a balanced competition between its potential target promoters in cis and in trans.
ST6Gal1 in plasma is dispensable for IgG sialylation
Authors: Oswald Douglas M , Lehoux Sylvain D , Zhou Julie Y , Glendenning Leandre M , Cummings Richard D , Cobb Brian A 
Published: June 2022

Abstract
The glycosylation of immunoglobulin G (IgG) has attracted increased attention due to the impact of N-glycan modifications at N297 on IgG function, acting primarily through modulation of Fc domain conformation and Fcγ receptor-binding affinities and signaling. However, the mechanisms regulating IgG glycosylation and especially α2,6-sialylation of its N-glycan remain poorly understood. We observed previously that IgG is normally sialylated in mice with B cells lacking the sialyltransferase ST6Gal1. This supported the hypothesis that IgG may be sialylated outside of B cells, perhaps through the action of hepatocyte-released plasma ST6Gal1. Here, we demonstrate that this model is incorrect. Animals lacking hepatocyte expressed ST6Gal1 retain normal IgG α2,6-sialylation despite the lack of detectable ST6Gal1 in plasma. Moreover, we confirmed that B cells were not a redundant source of IgG sialylation. Thus, while α2,6-sialylation is lacking in IgG from mice with germline ablation of ST6Gal1, IgG α2,6-sialylation is normal in mice lacking ST6Gal1 in either hepatocytes or B cells. These results indicate that IgG α2,6-sialylation arises after release from a B cell but is not dependent on plasma-localized ST6Gal1 activity.
Appendix and Ulcerative Colitis: a Key to Explaining the Pathogenesis and Directing Novel Therapies?
Authors: Arjomand Fard Nazanin , Armstrong Heather , Perry Troy , Wine Eytan 
Published: June 2022

Abstract
The vermiform appendix is generally considered a redundant organ, but recent evidence suggests that the appendix could contribute to the pathogenesis of inflammatory bowel diseases, in particular ulcerative colitis (UC), and may even have a therapeutic role; however, mechanisms of the appendix involvement remain unclear. Here, we highlight current evidence on the link between the appendix and UC and consider plausible therapeutic implications. A literature search was conducted using PubMed and PubMed Central from inception to Nov 2021 using the terms “Appendix”, “UC”, “Appendix & UC,” “Appendectomy”, and “Peri-appendicular patch,” including only articles published in English. Reference lists from the selected studies were manually searched and reviewed to gather additional related reports. Inflammation around the appendix (“peri-appendicular patch”) has been frequently observed in UC patients without other cecal involvement, and this inflammation can even precede the onset of UC. Epidemiologic studies propose that appendectomy reduces the risk of developing UC or even the risk of flare after UC is diagnosed, although this remains controversial. We reviewed studies showing altered host-microbe interactions in the appendix in UC, which suggest that the appendix could act as a priming site for disease via alterations in the immune response and changes in microbiota carried distally to the colon. In summary, recent literature suggests a possible role for microbes and immune cells within the appendix; however, the role of the appendix in the pathogenesis of UC remains unclear. Further research could clarify the therapeutic potential related to this organ.
MiRNA-Based Therapies for the Treatment of Inflammatory Bowel Disease: What Are We Still Missing?
Authors: Innocenti Tommaso , Bigagli Elisabetta , Lynch Erica Nicola , Galli Andrea , Dragoni Gabriele 
Published: June 2022

Abstract
Micro-RNAs (miRNAs) are noncoding RNAs usually 24-30 nucleotides long that play a central role in epigenetic mechanisms of inflammatory diseases and cancers. Recently, several studies have assessed the involvement of miRNAs in the pathogenesis of inflammatory bowel disease (IBD) and colitis-associated neoplasia. Particularly, it has been shown that many members of miRNAs family are involved in the pathways of inflammation and fibrogenesis of IBD; therefore, their use as inflammatory and fibrosis biomarkers has been postulated. In light of these results, the role of miRNAs in IBD therapy has been proposed and is currently under investigation with many in vitro and in vivo studies, murine models, and a phase 2a trial. The accumulating data have pushed miRNA-based therapy closer to clinical practice, although many open questions remain.
With this systematic review, we discuss the current knowledge about the therapeutic effects of miRNAs mimicking and inhibition, and we explore the new potential targets of miRNA family for the treatment of inflammation and fibrosis in IBD.
Behavioural responses of wild anadromous Arctic char experimentally infested in situ with salmon lice
Authors: Strøm John Fredrik , Bjørn Pål Arne , Bygdnes Eirik Emil , Kristiansen Lars , Skjold Bjørnar , Bøhn Thomas 
Published: June 2022

Abstract
Salmon lice can impact the marine behaviour, growth, and survival of salmonids, but little is known about their effects on Arctic char. We present behavioural responses from the first dose-response experiment with wild anadromous Arctic char (n = 50) infested in situ with salmon lice (0.0–1.2 lice g−1 fish) in an area with low natural infestations. Infested fish spent less time at sea (mean ± SD = 22 ± 6 d) than non-infested fish (mean ±SD = 33 ± 5 d), and a significant dose response was evident, with even very low louse burdens (&lt;0.05 lice g−1 fish) reducing the marine feeding time. Furthermore, a negative correlation was present between time spent close to their native watercourse and parasite burden, suggesting that salmon lice influence the marine habitat use of Arctic char. No impact of salmon lice was evident on the return probability, i.e. marine survival. However, the presence of louse-induced mortality cannot be excluded as the modest sample size was only sufficient to detect extreme effects. Reduced marine feeding time and altered marine habitat use will likely have substantial negative effects on growth and fitness, suggesting that impacts of salmon lice must be considered in the conservation of anadromous Arctic char.
User Interface Evaluation of Design Alternatives of the Emotion-Libras—An Emotional Self-Report Instrument for Sign Language Users
Authors: Prietch Soraia Silva , Paim Polianna dos Santos , Miranda Flabiéli , Nogueira Camila Soncini , Leite Vanuza 
Published: June 2022

Abstract
For researchers interested in analyzing participants’ self-reflection about their emotional experience during user studies, having an instrument designed for a specific target user can be seen to show empathy for providing socio-cultural elements that involved parties feel a connection with. In user studies, communication mediation between sign language users and non-signers may include a bias; therefore, direct communication between the involved parties is welcome to reduce this risk and expand sign language users’ autonomy. This paper presents the Emotion-Libras, a self-report instrument to collect emotional responses of sign language users after interacting with technology and report findings from a user study. We conducted a focus group with five sign language users to collect their perceptions regarding the three design alternatives of the instrument. As a result, participants selected the best-fitted design interface of the instrument and also found room for improvement in video quality, language choice, written labels and user control.
Creating a framework to align antimicrobial resistance (AMR) research with the global guidance: a viewpoint
Authors: Mitchell Jessica , O’Neill Alex J , King Rebecca 
Published: June 2022

Abstract
We describe here an initial analysis of national and international guidance documents on antimicrobial resistance (AMR) to propose a framework to align AMR research activities with global guidance. The framework provides a summary roadmap for core activities in AMR research and highlights the need for interdisciplinary and One Health collaboration. This analysis also revealed limitations in the current guidance, including a lack of explicit mention of some research activities highly relevant to AMR and a dearth of concrete objectives; consequently, an over-reliance on global guidance could be funnelling research efforts down a generic trajectory without regard to contextual factors. We suggest this framework be used by academics and policymakers to align AMR research and guidance. However, we recommend that deeper exploration be undertaken to fully contextualize the development of meaningful questions based on current knowledge, methodologies and gap analyses.
Fast and Sensitive Method for the Determination of 17 Designer Benzodiazepines in Hair by Liquid Chromatography–Tandem Mass Spectrometry
Authors: DeFreitas Laura , Fonseca Pego Ana Miguel , Kronstrand Robert , Lendoiro Elena , de Castro-Ríos Ana , Concheiro Marta 
Published: June 2022

Abstract
In recent years, identification and analysis of designer benzodiazepines have become a challenge in forensic toxicology. These substances are analogs of the classic benzodiazepines, but their pharmacology is not well known, and many of them have been associated with overdoses and deaths. As a result, there has been a surge in efforts to develop analytical methods to determine these compounds in different biological samples. Our aim was to develop and validate a fast, sensitive and specific method for determining 17 designer benzodiazepines (adinazolam, clobazam, clonazolam, delorazepam, deschloroetizolam, diclazepam, etizolam, flualprazolam, flubromazepam, flubromazolam, flunitrazolam, N-desmethylclobazam, nifoxipam, nitrazolam, meclonazepam, pyrazolam and zolazepam) in hair by liquid chromatography–tandem mass spectrometry (LC–MS-MS). Hair samples were decontaminated and pulverized, and a 20 mg aliquot was incubated in methanol in an ultrasound bath (1 h, 25°C). The supernatant was evaporated and reconstituted in 200 µL of mobile phase, and the extracts were filtered (nano-filter vials) before injection into LC–MS-MS. All analytes were eluted from the chromatographic column in 8 min, and two multiple-reaction monitoring (MRM) transitions were used to identify each compound. The limits of quantification were 5 or 25 pg/mg depending on the analyte, and the calibration functions were linear to 200 pg/mg. Imprecision was &lt;19.2% (n = 15), and bias was from −13.7 to 18.3% (n = 15). All the analytes yielded high extraction efficiencies &gt;70% and displayed ion suppression between −62.8% and −23.9% (n = 10). The method was applied to 19 authentic cases. Five samples were positive for flualprazolam (&lt;LOQ—&gt; 200 pg/mg) and/or etizolam (47.4–88.5 pg/mg). In conclusion, the present validated method has proven to be fast, sensitive, specific and capable of determining 17 designer benzodiazepines in hair using LC–MS-MS.
The Benefits of Early Detection: Evidence From Modern International Mammography Service Screening Programs
Authors: Eby Peter R , Ghate Sujata , Hooley Regina 
Published: June 2022

Abstract
Research from randomized controlled trials initiated up to 60 years ago consistently confirms that regular screening with mammography significantly reduces breast cancer mortality. Despite this success, there is ongoing debate regarding the efficacy of screening, which is confounded by technologic advances and concerns about cost, overdiagnosis, overtreatment, and equitable care of diverse patient populations. More recent screening research, designed to quell the debates, derives data from variable study designs, each with unique strengths and weaknesses. This article reviews observational population-based screening research that has followed the early initial long-term randomized controlled trials that are no longer practical or ethical to perform. The advantages and disadvantages of observational data and study design are outlined, including the three subtypes of population-based observational studies: cohort/case-control, trend, and incidence-based mortality/staging. The most recent research, typically performed in countries that administer screening mammography to women through centralized health service programs and directly track patient-specific outcomes and detection data, is summarized. These data are essential to understand and inform construction of effective new databases that facilitate continuous assessment of optimal screening techniques in the current era of rapidly developing medical technology, combined with a focus on health care that is both personal and equitable.
Post-COVID-19 modular building review on problem-seeking framework: function, form, economy, and time
Authors: Hwang Kyung-Eun , Kim Inhan 
Published: June 2022

AbstractModular building is an innovative and sustainable construction method and a notable architectural, engineering, and construction trend. Owing to the new constructability and sustainability, significant research efforts have been focused on the engineering aspects of modular building. Since the global outbreak of the COVID-19 pandemic, space utilization has changed radically, and a rethinking of modular building design has become essential. However, current literature lacks a comprehensive understanding of occupants’ newly developed requirements and the relevant changes associated with engineering developments. Therefore, this study aims to review the current status of residential modular building design and construction, define its problems, and identify the key factors necessary for modular design and construction during the post-COVID-19 period from the perspective of architectural design. A total of 220 articles were selected from the Scopus database, out of which 94 papers were selected for a systematic review. The findings indicate that the present academic research primarily focuses on the technical aspects of optimizing architecture and on modularized plans to facilitate cost-effective factory production. Modular residential design has rarely considered people and cultural factors. Therefore, the authors derived 15 problems by adapting four architectural programming frameworks; function, form, economy, and time. The identified problems are mapped for future development with 11 problem-solving proposals. The proposed method contributes to developing new insights into COVID-19’s impacts on dwelling environments and can help introduce modular residential design responses that enhance the quality of life by creating better residentials in the post-pandemic.
Early Detection and Identification of Parasitoid Wasps Trichogramma Westwood (Hymenoptera: Trichogrammatidae) in Their Host Eggs Using Polymerase Chain Reaction–Restriction Fragment Length Polymorphism
Authors: Yan Zhi-Chao , Hua Hai-Qing , Qi Guang-Yuan , Li Yuan-Xi 
Published: June 2022

Abstract
Parasitoid wasps are invaluable agents in pest biological control. Early detection and identification of parasitoid immatures are vital in characterizing parasitoid–host interactions and for evaluating parasitism rates accurately in the field. Trichogramma is the most widely used parasitoid wasp, and several studies have been performed for its molecular identification. However, those studies were mainly focused on Trichogramma adults and rarely on immatures. Here, we report a method to detect and identify Trichogramma larvae in their host eggs. We designed a pair of Trichogramma-specific primers that amplified Trichogramma mtCOI sequences from Corcyra cephalonica (Stainton) eggs parasitized by any of eight Trichogramma species tested but not from nonparasitized eggs of four lepidopteran hosts. This PCR method reliably detected Trichogramma immatures in parasitized eggs as early as 1 h after parasitism. We further developed an RFLP (restriction fragment length polymorphism) assay using restriction enzymes SspI and VspI to differentiate eight Trichogramma species at their immature stage. Overall, we developed a sensitive and reliable PCR–RFLP method to detect and identify immature-stage Trichogramma in their lepidopteran hosts. This method shows promise for conveniently identifying Trichogramma in insectaries and accurately evaluating parasitism rates in the field.
Indirect Co-Perpetration and the Control Theory
Authors: Osten Philipp 
Published: June 2022

Abstract
In the case law of the International Criminal Court (ICC), the notion of indirect co-perpetration, based on the control theory, has been applied extensively. The Ntaganda appellate ruling has shown that this concept of attributing liability to persons in a position of leadership remains contested and thus requires further clarification and refinement. To this end, this article provides a comparative view on the related jurisprudence of the ICC from a Japanese perspective, which has not been reflected in the international debate on modes of liability so far. Even though the control theory has only been adopted partially in domestic law in Japan, many Japanese scholars have conveyed generally affirmative assessments of this ICC jurisprudence. In addition, the approaches that Japanese criminal law has to offer on attributing responsibility to remote masterminds behind crimes are also presented in this article. The predominating notion in Japanese case law, ‘collusive co-perpetration’ — for the most part unnoticed (or underexplored) outside of Japan — exemplifies that it is practically viable (and theoretically construable) to incorporate combined vertical and horizontal attribution mechanisms into a normative model of co-perpetration — without necessarily resorting to the notion of control over an organization.
Identifying Risk Factors and Their Premia: A Study on Electricity Prices
Authors: Wei Wei , Lunde Asger 
Published: June 2022

Abstract
Risk premia are difficult to identify in nonstorable commodities such as electricity. In this article, we propose a modified Fama–French regression framework and show that when the spot prices do not follow a martingale—a common assumption in the electricity market—model specifications play an important role in detecting time-varying risk premia in the futures market. With this insight, we propose a multi-factor model that captures important dynamics in electricity prices and an estimation method based on particle Markov chain Monte Carlo to separate risk factors in energy prices. Using spot and futures data in the Germany/Austria electricity market, we demonstrate that our proposed model surpasses alternative models that ignore some of risk factors in forecasting spot prices and in detecting time-varying risk premia. Based on our proposed model, we separately identify risk premia carried by individual risk factors and document large variations in the premia of each factor.
Anatomy of a Sovereign Debt Crisis: Machine Learning, Real-Time Macro Fundamentals, and CDS Spreads
Authors: Balduzzi Pierluigi , Savona Roberto , Alessi Lucia 
Published: June 2022

AbstractWe employ a Least Absolute Shrinkage and Selection Operator (LASSO)-based extension of the Fama–MacBeth procedure to characterize the time-varying dependence of sovereign Credit Default Swap (CDS) spreads on macro indicators during the samples 2009–2013 and 2013–2020. While CDS spreads are mainly reflective of fundamentals, this relationship varies substantially over time, leading to price variation that appears unrelated to fundamentals. The estimated LASSO coefficients are used to endogenously identify macro-sensitivity “regimes” of variation, consistently with a multiple-equilibrium view of the sovereign debt markets.