bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural insights into the antifungal drug target guanosine monophosphate synthase from Aspergillus fumigatus
Authors: Nguyen Stephanie , Jovcevski Blagojce , Pukala Tara L. , Bruning John B. 
Published: January 2022

Purine biosynthesis is a fundamental cellular process that sustains life by maintaining the intracellular pool of purines for DNA/RNA synthesis and signal transduction. As an integral determinant of fungal survival and virulence, the enzymes in this metabolic pathway have been pursued as potential antifungal targets. Guanosine monophosphate (GMP) synthase has been identified as an attractive target as it is essential for virulence in the clinically prominent fungal pathogens Aspergillus fumigatus, Candida albicans and Cryptococcus neoformans. However, a lack of structural information on GMP synthase has hindered drug-design efforts. Here, the first structure of a GMP synthase of fungal origin, that from A. fumigatus (at 2.3 Å resolution), is presented. Structural analysis of GMP synthase shows a distinct absence of the D1 dimerization domain that is present in the human homologue. Interestingly, A. fumigatus GMP synthase adopts a dimeric state, as determined by native mass spectrometry and gel-filtration chromatography, in contrast to the monomeric human homologue. Analysis of the substrate-binding pockets of A. fumigatus GMP synthase reveals key differences in the ATP- and XMP-binding sites that can be exploited for species-specific inhibitor drug design. Furthermore, the inhibitory activities of the glutamine analogues acivicin (IC50 = 16.6 ± 2.4 µM) and 6-diazo-5-oxo-L-norleucine (IC50 = 29.6 ± 5.6 µM) against A. fumigatus GMP synthase are demonstrated. Together, these data provide crucial structural information required for specifically targeting A. fumigatus GMP synthase for future antifungal drug-discovery endeavours.
Effects of climate‐driven hydrological changes in the reproduction of Amazonian floodplain fishes
Authors: Röpke Cristhiana , Pires Tiago H. S. , Zuchi Nágila , Zuanon Jansen , Amadio Sidinéia 
Published: January 2022

Abstract

Abnormal hydroclimatic years in the Amazon have been increasingly frequent in the last two decades, creating more prolonged droughts and severe floods. These events are expected to impact organismal phenology, including seasonal reproduction of fish. Droughts are also expected to increase fish mortality and vulnerability to fishing. However, empirical evidence on the impact of these novel conditions on fish reproduction and demography is still limited.

Here, we evaluate how changes in hydrological conditions and fishing affected reproduction and demographic parameters for the 16 most common floodplain fish species in the central Amazon. We used water level data collected for 113 years together with a 19‐year dataset of fish biology, sampled monthly from a floodplain lake at the confluence of Amazon and Negro rivers.

We observed a lower proportion of ripe females after long, drier low‐water and abrupt rising‐water seasons. For many species, we detected a progressive reduction in the female’s size at sexual maturity, the average size of the ripe females and in the abundance of larger adult females. These effects were observed for both fished and non‐fished species, suggesting that the effect of the recent hydroclimatic events might be affecting most fish species. However, fished species showed a steeper decline in the average body size of ripe females, suggesting that size reduction is a combined effect of drought severity and fishing pressure.

Policy implications. Our results for the proportion of females in reproduction mediated by hydrological conditions and temporal changes of demographic and life‐history parameters suggest that drought events can reduce the resilience of fish populations in the central Amazon. The increasing frequency of droughts and rapid changes in fish reproductive parameters highlight the need for conservation policies to consider the impact of droughts in addition to fisheries and habitat degradation. Our results should be taken as an early warning regarding the conservation and sustainable use of Amazon aquatic biodiversity. Conserving fish diversity and fish stocks will require substantial ecosystem management in a large portion of the Amazon floodplains and a greater enforcement of fisheries management regulations in years of predicted drought.
Recent developments in cold plasma‐based enzyme activity (browning, cell wall degradation, and antioxidant) in fruits and vegetables
Authors: Punia Bangar Sneh , Trif Monica , Ozogul Fatih , Kumar Manoj , Chaudhary Vandana , Vukic Milan , Tomar Maharishi , Changan Sushil 
Published: January 2022

AbstractAccording to the Food and Agriculture Organization of United Nations reports, approximately half of the total harvested fruits and vegetables vanish before they reach the end consumer due to their perishable nature. Enzymatic browning is one of the most common problems faced by fruit and vegetable processing. The perishability of fruits and vegetables is contributed by the various browning enzymes (polyphenol oxidase, peroxidase, and phenylalanine ammonia‐lyase) and ripening or cell wall degrading enzyme (pectin methyl‐esterase). In contrast, antioxidant enzymes (superoxide dismutase and catalase) assist in reversing the damage caused by reactive oxygen species or free radicals. The cold plasma technique has emerged as a novel, economic, and environmentally friendly approach that reduces the expression of ripening and browning enzymes while increasing the activity of antioxidant enzymes; microorganisms are significantly inhibited, therefore improving the shelf life of fruits and vegetables. This review narrates the mechanism and principle involved in the use of cold plasma technique as a nonthermal agent and its application in impeding the activity of browning and ripening enzymes and increasing the expression of antioxidant enzymes for improving the shelf life and quality of fresh fruits and vegetables and preventing spoilage and pathogenic germs from growing. An overview of hurdles and sustainability advantages of cold plasma technology is presented.
MCycDB: A curated database for comprehensively profiling methane cycling processes of environmental microbiomes
Authors: Qian Lu , Yu Xiaoli , Zhou Jiayin , Gu Hang , Ding Jijuan , Peng Yisheng , He Qiang , Tian Yun , Liu Jihua , Wang Shanquan , Wang Cheng , Shu Longfei , Yan Qingyun , He Jianguo , Liu Guangli , Tu Qichao , He Zhili 
Published: January 2022

AbstractMethane is a critical greenhouse gas with significant impacts on environmental and global change. However, CH4 cycling processes and coupling mechanisms with the biogeochemical cycling of carbon, nitrogen, sulfur and metals in the environment remain elusive. To fill such knowledge gaps, we constructed a manually curated methane cycling database (MCycDB) for comprehensive and accurate analysis of methane cycling microbial communities. MCycDB contains 298 methane cycling gene families covering 10 methane metabolism pathways with 610,208 representative sequences, and associated reference sequences from the NCBI RefSeq database with 48 phyla and 2,197 genera, and five phyla and 100 genera for bacteria and archaea, respectively. Also, homologous groups from public orthology databases were identified and included in MCycDB to reduce false positive assignments. We applied MCycDB to profile methane cycling gene families and associated taxonomic groups from various environments. Gene families involved in methanogenesis were abundant in hot spring sediment and less abundant in freshwater, whereas the ones involved in aerobic oxidation of methane were abundant in permafrost and peatland. This study demonstrates that MCycDB is a useful tool for studying microbially‐driven methane cycling processes with high specificity, coverage and accuracy.
Effects of acute and repeated administration of the selective M4 PAM VU0152099 on cocaine versus food choice in male rats
Authors: Thomsen Morgane , Crittenden Jill R. , Lindsley Craig W. , Graybiel Ann M. 
Published: January 2022

AbstractLigands that stimulate muscarinic acetylcholine receptors 1 and 4 (M1, M4) have shown promising effects as putative pharmacotherapy for cocaine use disorder in rodent assays. We have previously shown reductions in cocaine effects with acute M4 stimulation, as well as long‐lasting, delayed reductions in cocaine taking and cocaine seeking with combined M1/M4 receptor stimulation or with M1 stimulation alone. M4 stimulation opposes dopaminergic signalling acutely, but direct dopamine receptor antagonists have proved unhelpful in managing cocaine use disorder because they lose efficacy with long‐term administration. It is therefore critical to determine whether M4 approaches themselves can remain effective with repeated or chronic dosing. We assessed the effects of repeated administration of the M4 positive allosteric modulator (PAM) VU0152099 in rats trained to choose between intravenous cocaine and a liquid food reinforcer to obtain quantitative measurement of whether M4 stimulation could produce delayed and lasting reduction in cocaine taking. VU0152099 produced progressively augmenting suppression of cocaine choice and cocaine intake, but produced neither rebound nor lasting effects after treatment ended. To compare and contrast effects of M1 versus M4 stimulation, we tested whether the M4 PAM VU0152100 suppressed cocaine self‐administration in mice lacking CalDAG‐GEFI signalling factor, required for M1‐mediated suppression of cocaine self‐administration. CalDAG‐GEFI ablation had no effect on M4‐mediated suppression of cocaine self‐administration. These findings support the potential usefulness of M4 PAMs as pharmacotherapy to manage cocaine use disorder, alone or in combination with M1‐selective ligands, and show that M1 and M4 stimulation modulate cocaine‐taking behaviour by distinct mechanisms.
Impact of thiopurine discontinuation at anti‐tumour necrosis factor initiation in inflammatory bowel disease treatment: a nationwide Danish cohort study
Authors: Thomsen Sandra Bohn , Ungaro Ryan C. , Allin Kristine H. , Elmahdi Rahma , Poulsen Gry , Andersson Mikael , Colombel Jean‐Frederic , Jess Tine 
Published: January 2022

SummaryBackgroundEscalation to anti‐tumour necrosis factor (anti‐TNF) in inflammatory bowel disease (IBD) patients on thiopurine is a common clinical scenario. However, the impact of discontinuing thiopurine at escalation is unclear.AimTo assess the impact of discontinuing versus continuing thiopurine therapy at anti‐TNF initiation.MethodsWe used the Danish registries to establish a national cohort of patients with IBD on thiopurine therapy prior to initiating anti‐TNF from 2003 to 2018. We compared patients discontinuing thiopurine therapy within 90 days of anti‐TNF initiation to those continuing. Our primary outcome was a composite of any new oral corticosteroid use, IBD‐related hospitalization, surgery or death. We used Cox regression models to calculate adjusted hazard ratios (aHR) and 95% confidence intervals (CI).ResultsOf the 10,352 anti‐TNF exposed patients, 2,630 (1590 Crohn's disease (CD) and 1040 ulcerative colitis (UC)) received thiopurines prior to anti‐TNF. After anti‐TNF initiation, 979 patients discontinued thiopurines. Discontinuing thiopurines within 90 days of anti‐TNF initiation, increased the risk of the primary outcome (aHR: 1.22; 95% CI: 1.10‐1.36), particularly for IBD‐related hospitalization (aHR: 1.14; 95% CI: 1.00‐1.31) and oral corticosteroid use (aHR: 1.27; 95% CI: 1.13‐1.44). This increased risk of the primary outcome was seen in both CD (aHR: 1.17; 95% CI 1.02‐1.34) and UC (aHR: 1.32; 95% CI: 1.12‐1.55).ConclusionsIn a nationwide cohort study of IBD patients, we observed that discontinuing thiopurines after anti‐TNF initiation was associated with an increased risk of adverse outcomes, in particular an increase in hospitalizations. Further interventional studies exploring this common clinical scenario are required.
Influencing medication taking behaviors using automated two‐way digital communication: A narrative synthesis systematic review informed by the Behavior Change Wheel
Authors: Donovan Gemma , Hall Nicola , Ling Jonathan , Smith Felicity , Wilkes Scott 
Published: January 2022

PurposeAround half of prescribed medications for long‐term conditions are not taken as directed. Automated two‐way digital communication, such as text messaging and interactive voice response technology, could deliver interventions to improve medication adherence, and subsequently health. However, exploration of how such interventions may improve medication adherence is limited. This review aimed to explore how automated two‐way digital communication can improve medication taking with or without using non‐digital intervention components, such as phone calls with healthcare professionals.MethodsA theory‐informed narrative synthesis systematic review. Several databases were searched including CINAHL, Embase, Medline, and Web of Science using key words relating to ‘medication adherence’ and digital communication technologies. The Behavior Change Technique (BCT) coding using the BCT Taxonomy V1 and the Behavior Change Wheel were used to identify BCTs delivered within the included interventions.ResultsA total of 3,018 records were screened with 43 study reports included in the review. Four medication‐taking behaviors: taking medication, obtaining medication, self‐testing, and asking for support were identified as targets for behavior change within the included interventions. Most BCTs within the digital communication component aimed to increase motivation for medication adherence, with non‐digital intervention components included to address other medication taking barriers, such as physical and psychological capability.ConclusionAutomated two‐way digital communication can detect barriers to medication adherence by monitoring performance of the taking medication behavior. Monitoring outcomes from taking medication may increase reflective motivation to take medicines. Addressing physical opportunity to taking medication by facilitating the behavior obtaining medication may also increase adherence.
An in‐school social norms approach intervention for reducing unhealthy snacking behaviours amongst 11–12‐year‐olds
Authors: Calvert Sian M. , Dempsey Robert C. , Povey Rachel , Clark‐Carter David 
Published: January 2022

ObjectivesAdolescents tend to overestimate the extent of peers’ unhealthy snacking consumption and such misperceptions have been associated with increased personal unhealthy snacking. This study aims to test whether a Social Norms Approach (SNA) intervention which challenges these misperceptions of peers’ unhealthy snacking will have a positive effect on students’ personal unhealthy snacking behaviours, related attitudes, and behavioural intentions.DesignA quasi‐experimental study tested the effectiveness of an in‐school SNA intervention (n = 163) compared to a control condition (n = 95) among 11–12‐year‐old students.MethodBoth conditions received healthy eating information, while students in the SNA intervention received additional normative feedback (outlining the discrepancies between perceived and actual unhealthy snacking of the majority based on baseline data) delivered through an interactive poster‐making session. Students completed self‐reported measures of personal unhealthy snacking, related‐attitudes, behavioural intentions, and normative perceptions (descriptive and injunctive) at baseline, post‐intervention, and at a 3‐month follow‐up.ResultsStudents who received SNA feedback were significantly less likely to overestimate peers’ unhealthy snacking attitudes post‐intervention (F(1,232) = 16.405, p < .001), and at 3‐month follow‐up consumed fewer unhealthy snacks (F(1,232) = 6.133, p = .014) and had less positive attitudes towards unhealthy snacking (F(1,198) = 8.779, p = .003). The changes in personal snacking attitudes at 3‐month follow‐up were mediated by changes in normative misperceptions about peers’ unhealthy snacking attitudes post‐intervention, which indicated that the reductions in normative misperceptions following SNA messages mediated the effect of the intervention.ConclusionThe results indicate that in‐school SNA interventions which challenge normative misperceptions constitute a promising strategy for reducing unhealthy snacking in young adolescents.
Long noncoding RNA EIF1AX‐AS1 promotes endometrial cancer cell apoptosis by affecting EIF1AX mRNA stabilization
Authors: Lv Chengyu , Sun Jiandong , Ye Yuhong , Lin Zihang , Li Hua , Liu Yue , Mo Kaien , Xu Weiwei , Hu Weitao , Draz Eman , Wang Shie 
Published: January 2022

AbstractLong noncoding RNAs (lncRNAs) have been found to play an important role in the occurrence and development of endometrial carcinoma (EC). Here, using RNA sequencing analysis, we systemically screened and identified the lncRNA eukaryotic translation initiation factor 1A, X‐linked (EIF1AX)‐AS1, which is aberrantly downregulated in clinical EC tissues and closely correlated with tumor type. EIF1AX‐AS1 markedly inhibited EC cell proliferation and promoted apoptosis in vitro and in vivo. Mechanistically, EIF1AX‐AS1 interacts with EIF1AX mRNA and poly C binding protein 1 (PCBP1), which promote EIF1AX mRNA degradation. Intriguingly, by interacting with internal ribosome entry site‐related protein Y‐box binding protein 1 (YBX‐1), EIF1AX promotes c‐Myc translation through the internal ribosome entry site pathway. c‐Myc promotes EIF1AX transcription and thus forms a feed‐forward loop to regulate EC cell proliferation. Taken together, these data reveal new insights into the biology driving EC proliferation and highlights the potential of lncRNAs as biomarkers for prognosis and future therapeutic targets for cancer.
BRAF V600K vs. BRAF V600E: a comparison of clinical and dermoscopic characteristics and response to immunotherapies and targeted therapies
Authors: Zengarini Corrado , Mussi Martina , Veronesi Giulia , Alessandrini Aurora , Lambertini Martina , Dika Emi 
Published: January 2022

SummaryBackgroundA number of mutations related to malignant melanoma (MM) have been identified, and of the mutated genes, BRAF has been found to be altered in &gt; 50% of cases. Most of these have been BRAF V600E mutations, whereas the incidence of BRAF V600K may vary from 10% to 30%. Little is known about the clinical prognostic correlations of BRAF V600K MMs. We evaluated the clinical and dermoscopic features, incidence, therapy response and outcomes in the medium to long term.AimTo compare the clinical and dermoscopic characteristics, the response to systemic therapies and the prognosis among MMs with BRAF V600E and BRAF V600K mutations.MethodsWe retrieved the data of patients tested in our centre for MM from 2012 to 2015, including clinical features, dermoscopic pictures, clinical history and tumour mutations. Only patients with BRAF V600E and BRAF V600K mutations were included. Any MMs positive for BRAF V600K mutation were collected, and the number of V600K cases and their features were used to extract the same number of patients with BRAF V600E from our database using a matching method. The clinical and dermoscopic presentation, therapy response and disease progression of the two groups were then evaluated.ResultsIn total, 132 cases of BRAF V600E-mutated MMs were identified, and then randomized with a propensity-score method to match the 10 retrieved cases of BRAF V600K mutation. Both groups had a nodular appearance to the tumours and an advanced disease stage, and no significant differences in dermoscopic features were highlighted. During the follow-up period, four patients with BRAF V600K died of disease-specific causes. Moreover, we found a higher frequency of metastasis, a faster disease progression and more rapid mortality in patients with BRAF V600K.ConclusionDespite the small size of this study, the results show similar clinical and dermoscopic characteristics between V600E and V600K mutations, but compared with BRAF V600E MMs, BRAF V600K MMs seem to be less responsive to therapy and have a worse prognosis.
Understanding the social worker–family relationship through self‐determination theory: A realist synthesis of Signs of Safety
Authors: Caffrey Louise , Browne Freda 
Published: January 2022

AbstractSigns of Safety (SofS) is a popular framework for child protection social work practice, used in more than 200 jurisdictions worldwide. Although workers tend to find SofS tools easy to use, skilled application of the approach is challenging, and research has found that SofS is often not implemented as intended. This study aimed to deepen and inform the explanation (initial theory) of what key SofS tools and processes are expected to achieve in the family–worker interaction and why. A realist synthesis was used, involving a realist review of literature and focus groups with 22 international SofS experts. Using self‐determination theory, we detail how SofS can be conceptualized as aiming to support families to experience ‘autonomous’ rather than ‘controlled’ motivation by supporting basic human needs for ‘autonomy’ (feeling a sense of volition), ‘competence’ (feeling effective) and ‘relatedness’ (feeling cared for). This explanation can be used for training and evaluation purposes to better explain and test how SofS expects to engage families in the child protection process. More broadly, we suggest that self‐determination theory may contribute a mechanistic explanation of effective social work practice more generally and that this hypothesis should be empirically investigated.
Exploring migrant mothers' experiences of alienation in association with parenting: A scoping review
Authors: Yang Taoran , Featherston Rebecca , Shlonsky Aron 
Published: January 2022

AbstractAlienation describes an individual's sense of separation between themselves and various objects, such as other people, their community or society. Alienation is mediated by a wide range of psychological and social factors, and most people likely experience it in some form across their lifespan. Previous research suggests that migrants may be at an increased risk of experiencing alienation due to the challenges associated with adapting to a new environment. When migrants become parents in their adopted culture, this has the potential to exacerbate experiences of alienation because parenting introduces further life changes. This scoping review identifies and describes qualitative research studies that explored migrant mothers' feelings/experiences of alienation associated with parenting. It also identifies different conceptualizations of alienation reported in these studies. All methods for the literature search strategy, study screening and selection and data extraction were determined a priori. Eight studies were included from 1250 publications identified by the literature search. Alienation was a subtheme of each of the included studies, rather than a primary focus. Three conceptualizations of alienation were reported by migrant mothers across these studies, including isolation, normlessness and powerlessness. The reported findings suggest that these migrant mothers from diverse backgrounds did experience alienation, and their experiences of alienation were associated with parenting challenges. Given none of the studies comprehensively examined alienation, more work that explicitly explores associations between alienation and parenting is needed.