bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of HBV and HCV transmission in multi-transfused Thalassemia patients of Azad Jammu and Kashmir, Pakistan
Authors: Mahmood Majid , Aslam Marum , Zaman Nasib , Parvaiz Fahed , Muhammad Ali , Irshad Nausheen , Pervez KAamir , Ahmad Khawaja Shafique
Published: January 2022

Background

Thalassemia patients need regular blood transfusion which saves their lives but increases the risk of acquiring viral infections like hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV).

Objective(s)

This study aimed to screen out the HCV and HBV infections in Thalassemia patients receiving regular blood in three centers of Azad Jammu and Kashmir (AJK), Pakistan.

Materials and Methods

It was a cross sectional, multicenter study involving 224 Thalassemia patients. The study was carried out from August 2019 to January 2020 in Thalassemia centers of Sheikh Khalifa Bin Zaid hospital Rawalakot, District Headquarters hospital (DHQ) Palandari, and Combined Military Hospital (CMH) Muzaffarabad, AJK. A total of 224 patients were screened out for HCV and HBV. Indirect ELISA was carried out to detect anti HCV antibodies while direct ELISA was carried out to detect the HBsAg from all the samples using commercially available ELISA kits.

Results

Overall, 12 patients (5.36%) were found to be positive for HBV while 63 (28.1%) were positive for HCV. HBV positive patients included 7 (5.69%) males and 5 (4.95%) females while HCV positive patients included 26 (41.27%) males and 37 (58.73%) female patients. Both the viruses were more common among elder patients as compared to younger patients.

Conclusion

Prevalence of HCV is very high and that of HBV is moderately high among Thalassemia patients of AJK.
Impaired alpha and beta modulation in response to social stimuli in children with autism spectrum disorder
Authors: Cantonas Lucia-Manuela , Seeber Martin , Mancini Valentina , Bochet Aurélie , Kojovic Nada , Rihs Tonia A. , Schaer Marie
Published: January 2022

Background

Early preferential attention to biological motion is a fundamental mechanism priming the development of sophisticated skills to detect and react to social stimuli. Children diagnosed with autism spectrum disorders (ASD) demonstrate reduced visual orientation towards biological motion, however, the underlying neurobiological mechanisms are unknown.

Methods

We measured the neural oscillations in children with ASD (n=34, mean age 3.43 years) and age and gender matched typically developing children (TD, n=27) while watching videos of social biological (BM) and geometrical motion (GM). Their visual interest in BM stimuli was measured with eye-tracking techniques. Neural oscillations were measured as amplitude modulation of the frequency bands with the electroencephalogram and calculated as the power ratio between BM and GM conditions using scalp and brain source reconstruction analyses.

Results

We observed a reduced visual exploration of the BM stimuli along with (1) unchanged sensorimotor mu rhythm and (2) altered cortical alpha and beta power ratio in widespread right prefrontal areas associated with default mode and fronto-parietal networks in young children with ASD as compared to their TD peers. Furthermore, we measured significant correlations between prefrontal and posterior cingulate regions of the default mode network with the developmental quotient in both the ASD and TD groups.

Conclusion

We observed abnormal alpha and beta modulation of the fronto-parietal and default mode networks along with altered visual exploration of the social biological motion. These deficits represent core impairments of the disorder and may be informative in developing future behavioural and neuroregulation interventions, such as neurofeedback.
LPS-TLR4 pathway exaggerates alcohol-induced acute-on-chronic liver failure via provoking NETs formation
Authors: Liu Yang , Chen Shuo , Wang Jiazhong , Yu Shuo , Zhang Xin , Li Yiming , Cao Gang
Published: January 2022

Backgrounds: Intrahepatic infiltration of neutrophils is a character of alcoholic acute-on-chronic liver failure (AACLF) and neutrophil extracellular traps (NETs) are an important strategy for neutrophils to fix and kill invading microorganisms. Intestinal bacteria and the gut-liver axis have been thought to play a key role in many liver diseases also including AACLF. However, whether NETs appear in AACLF and play a role in AACLF is still unsure. Methods: WT, NE KO, and TLR4 KO mice were used to build the AACLF model, and the intestinal bacteria were eliminated at the same time and LPS was given. Then the formation of NETs and AACLF related markers were detected. Results: The serum MPO-DNA and LPS concentration was increased in AACLF patients and a correlation was revealed between these two indexes. More intrahepatic NETs formed in AACLF mice by testing MPO-DNA, Cit H3, and NE. These markers decreased with gut detergent and restored markers with gut detergent plus LPS supplement. While NETs formation failed to change with gut microbiome or combine LPS supplement in TLR4 KO mice. As we tested AACLF related characters, liver injury, intrahepatic fat deposition, inflammation, and fibrosis alleviated with depletion of NE. These related marks were also attenuated with gut sterilization by antibiotics and recovered with combined treatment with antibiotics plus LPS. But the liver injury, intrahepatic fat, fibro deposition, and liver inflammation-related markers did show a significant difference in TLR4 KO mice when they received the same treatment. Conclusion: Intestinal-derived LPS promotes NETs formation in AACLF through the TLR4 pathway and further accelerates the AACLF process by NETs.
Orphan nuclear receptors Err2 and 3 promote a feature-specific terminal differentiation program underlying gamma motor neuron function and proprioceptive movement control
Authors: Khan Mudassar N. , Cherukuri Pitchaiah , Negro Francesco , Rajput Ashish , Fabrowski Piotr , Bansal Vikas , Lancelin Camille , Lee Tsung-I , Bian Yehan , Mayer William P. , Akay Turgay , Müller Daniel , Bonn Stefan , Farina Dario , Marquardt Till
Published: January 2022

Motor neurons are commonly thought of as mere relays between the central nervous system and the movement apparatus, yet, in mammals about one-third of them function exclusively as regulators of muscle proprioception. How these gamma motor neurons acquire properties to function differently from the muscle force-producing alpha motor neurons remains unclear. Here, we found that upon selective loss of the orphan nuclear receptors Err2 and Err3 (Err2/3) in mice, gamma motor neurons acquire characteristic structural (e.g. synaptic wiring), but not functional (e.g. physiological firing rates) properties necessary for regulating muscle proprioception, thus disrupting gait and precision movements in vivo. Moreover, Err2/3 operate via transcriptional activation of neural activity modulators, one of which (Kcna10) promoted gamma motor neuron functional properties. Our work identifies a long-sought mechanism specifying gamma motor neuron properties necessary for proprioceptive movement control, which implies a ‘feature-specific’ terminal differentiation program implementing neuron subtype-specific functional but not structural properties.

The transcription factors Err2 and 3 promote functional properties in a subset of motor neurons necessary for executing precise movements.
Ecosystem gross primary productivity after autumn snowfall and melt events in a mountain meadow
Authors: Stoy P. C. , Khan A. M. , Van Dorsten K. , Sauer P. , Weaver T. , Brookshire E. N. J.
Published: January 2022

Vegetation productivity is increasing across much of the U.S. Northern Great Plains but is decreasing in some nearby Northern Rocky Mountain grasslands due to increases in aridity. Mountain grasslands support critical ecosystem services that are under threat from ongoing land use and climate changes, and it is important to understand their function across all changing seasons. Observing the full range of montane ecosystem productivity is challenging because site access is often difficult during the “shoulder seasons” in spring and autumn if the snowpack is not fully developed or degrading. It is unclear if decreases to montane grassland productivity from drying autumns can be offset in part by late-season green-ups after precipitation events. These include the snowfall/snowmelt periods that often characterize the summer-to-winter transition in the Northern Rockies. Here, we quantify the ecosystem carbon uptake that occurs after snowfall and melt in climatological autumn (September, October, and November) in a montane grassland in Montana, USA using a combination of eddy covariance, phenological camera, and remote sensing analyses. Carbon dioxide flux follows a diurnal pattern after autumn snowmelt events despite overall ecosystem losses of C, suggesting that post-snowmelt photosynthesis helps dampen C loss during autumn and provides fresh photosynthate to support ecosystem functioning. Light-saturated photosynthesis after two snow events was not different than before snowfall (∼6 µmol CO2m-2s-1in 2016 and ∼2.5 µmol CO2m-2s-1in 2017); observations are consistent with the notion that canopy photosynthesis is resistant, rather than resilient, to the first snow disturbances. MODIS observations also suggest that post-snowfall increases in NDVI can occur but do not happen every year, such that late-season photosynthesis is not a reliable source of fresh photosynthate. These late-season carbon uptake events likely play a small role in the annual ecosystem carbon balance but may be disproportionately important for organisms faced with dwindling late-season forage and regrowth in spring. Future efforts should seek to understand the community and ecosystem consequences of vegetation functioning during autumn as part of an expanded effort to understand phenological changes during this under-studied and changing time of year.
Cell size homeostasis under the circadian regulation of cell division in cyanobacteria
Authors: Kitaguchi Yuta , Tei Hajime , Uriu Koichiro
Published: January 2022

Bacterial cells maintain their characteristic cell size over many generations. Several rodshaped bacteria, such as Escherichia coli and the cyanobacteria Synechococcus elongatus, divide after adding a constant length to their length at birth. Through this division control known as the adder mechanism, perturbation in cell length due to physiological fluctuation decays over generations at a rate of 2−1 per cell division. However, previous experiments have shown that the circadian clock in cyanobacteria reduces cell division frequency at a specific time of day under constant light. This circadian gating should modulate the division control by the adder mechanism, but its significance remains unknown. Here we address how the circadian gating affects cell length, doubling time, and cell length stability in cyanobacteria by using mathematical models. We show that a cell subject to circadian gating grows for a long time, and gives birth to elongated daughter cells. These elongated daughter cells grow faster than the previous generation, as elongation speed is proportional to cell length and divide in a short time before the next gating. Hence, the distributions of doubling time and cell length become bimodal, as observed in experimental data. Interestingly, the average doubling time over the population of cells is independent of gating because the extension of doubling time by gating is compensated by its reduction in the subsequent generation. On the other hand, average cell length is increased by gating, suggesting that the circadian clock controls cell length. We then show that the decay rate of perturbation in cell length depends on the ratio of delay in division by the gating τG to the average doubling time τ0 as 2τG/τ0−1. We estimated τG ≈ 2.5, τ0 ≈ 13.6 hours, and τG/τ0 ≈ 0.18 from experimental data, indicating that a long doubling time in cyanobacteria maintains the decay rate similar to that of the adder mechanism. Thus, our analysis suggests that the acquisition of the circadian clock during evolution did not impose a constraint on cell size homeostasis in cyanobacteria.
Adverse events following COVISHIELD (ChAdOx1nCoV-19) vaccination among health care workers in Sri Lanka; a multi-centre cross sectional survey
Authors: Manilgama Suranga Ravinda , Hettiarachchi Nirosha Madhuwanthi , Jayasinghe I Kumudini , De Silva Shamila T , Jayalath Thilak , Wanigaratne Thushari , Rathnayake Bandusiri P , Suganthan Navaneethakrishnan , Sudarshan P , Pathirage Manoji , Rajaratnam Nalayini , Senaratne Ganaka , Rajapaksha Vishaka , Wickramasinghe Asanga , Ranaweera S P A L , Thilakarathna Arjuna H M , Kulaweera M Thilini D
Published: January 2022

Introduction

A community vaccination programme is the best approach to combat the COVID-19 pandemic. Post-vaccine surveillance is important to identify adverse events (AE) following COVID -19 vaccination in the population.

Methods

A multicentre cross-sectional survey was conducted in six provinces to estimate the prevalence of AE following the first dose of COVISHIELD (ChAdOx1nCoV-19) among all categories of health care workers (HCWs). A self-administered questionnaire was used to gather demographic data and AE.

Results

Of 5140 participants 67.8% were females. The mean (SD) age was 40.69 (±9.85) years. At least one comorbidity was reported in 15.4%. At least one AE was reported in 86.6% and 49.3% had local AE. Fever (67.2%), headaches (57.3%), body aches (54.4%), chills (51.2%), fatigue (37.5%) and arthralgia (36%) were the most reported systemic AE. The majority of AE lasted less than 24 hours. Pain and redness at the site were the most reported local AE. Mean duration of onset of fever and pain at injection site from the time of the vaccination was 6.65 and 9.67 hours respectively.

When participants were divided into two groups by mean age (≤40 and >40 years) and parameters were compared, most systemic (fever, nausea, fatigue, itching) and all local AE were significantly more prevalent in the ≤40 age group.

Two percent had reactions within the first 20 minutes. Anaphylaxis developed in 12 participants. Past history of anaphylaxis, drug or food allergy were reported in 0.6%, 2.8% and 6.7% respectively. However, previous history of allergy was not significantly related to immediate reactions or anaphylaxis following vaccination. Despite having minor AE, 71.1% attended routine work while 0.2% required hospitalisation.

Conclusions

While 86.6% reported minor AE, only a few serious AE were reported. Overall, the first dose of the vaccine was well-tolerated by HCWs.
Genomic context sensitivity of insulator function
Authors: Ribeiro-dos-Santos André M. , Hogan Megan S. , Luther Raven D. , Brosh Ran , Maurano Matthew T.
Published: January 2022

The specificity of interactions between genomic regulatory elements and potential target genes is influenced by the binding of insulator proteins such as CTCF, which can act as potent enhancer blockers when interposed between an enhancer and a promoter in a reporter assay. But not all CTCF sites genome-wide function as insulator elements, depending on cellular and genomic context. To dissect the influence of genomic context on enhancer blocker activity, we integrated reporter constructs with promoter-only, promoter and enhancer, and enhancer blocker configurations at hundreds of thousands of genomic sites using the Sleeping Beauty transposase. Deconvolution of reporter activity by genomic position reveals distinct expression patterns subject to genomic context, including a compartment of enhancer blocker reporter integrations with robust expression. The high density of integration sites permits quantitative delineation of characteristic genomic context sensitivity profiles and their decomposition into sensitivity to both local and distant DNase I hypersensitive sites. Furthermore, using a single-cell expression approach to test the effect of integrated reporters for differential expression of nearby endogenous genes reveals that CTCF insulator elements do not completely abrogate reporter effects on endogenous gene expression. Collectively, our results lend new insight into genomic regulatory compartmentalization and its influence on the determinants of promoter–enhancer specificity.
1-Allyl-4-hydroxy-2,2-dioxo-N-(4-methoxyphenyl)-1H-2λ6,1-benzothiazine-3-carboxamide: polymorphic transition due to grinding with the loss of the biological activity
Authors: Shishkina Svitlana V. , Shaposhnyk Anna M. , Baumer Vyacheslav N. , Voloshchuk Natali I. , Bondarenko Pavlo S. , Ukrainets Igor V.
Published: January 2022

A study of two polymorphic forms of 1-allyl-4-hydroxy-2,2-dioxo-N-(4-methoxyphenyl)-1-2λ6,1-benzothiazine-3-carboxamide (a structural analogue of piroxicam) has revealed some regularities in the crystal structure formation due to different evaporation rates from the tested solvents. The monoclinic polymorph crystallized from ethyl acetate is formed due to a large number of very weak C—H...O and C—H...π interactions as well as one strong stacking interaction. The triclinic polymorph crystallized from N,N-dimethylformamide is formed due to a small number of weak specific interactions and a maximal number of strong stacking interactions. The stacked dimer is a complex building unit in both polymorphic structures. Further analysis showed that the monoclinic structure is layered while the triclinic one is columnar. The two polymorphic structures also differ in their biological activity (antidiuretic and analgesic). The monoclinic polymorph possesses very high biological activity while the triclinic polymorph is almost inactive. The polymorphic transition of the biologically active metastable monoclinic structure into the inactive stable triclinic one within four weeks of grinding is caused by orientational factors rather than conformational ones and is accompanied by a change in the redistribution of interaction energies in the crystal from anisotropic to more isotropic. Thus, a slow polymorphic transition after grinding results in a loss of the biological activity.
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

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

According 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

Methane 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

Ligands 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

Background

Escalation 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.

Aim

To assess the impact of discontinuing versus continuing thiopurine therapy at anti‐TNF initiation.

Methods

We 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).

Results

Of 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).

Conclusions

In 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

Purpose

Around 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.

Methods

A 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.

Results

A 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.

Conclusion

Automated 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

Objectives

Adolescents 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.

Design

A 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.

Method

Both 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.

Results

Students 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.

Conclusion

The results indicate that in‐school SNA interventions which challenge normative misperceptions constitute a promising strategy for reducing unhealthy snacking in young adolescents.
Distance‐based logistic model for cross‐classified categorical data
Authors: Vera José Fernando
Published: January 2022

Logistic regression models are a powerful research tool for the analysis of cross‐classified data in which a categorical response variable is involved. In a logistic model, the effect of a covariate refers to odds, and the simple relationship between the coefficients and the odds ratio often makes these the parameters of interest due to their easy interpretation. In this article we present a distance‐based logistic model that allows a simple graphical interpretation of the association coefficients using the odds ratio in a contingency table. Two configurations are estimated, one for the rows and one for the columns, as the categories of a polytomous predictor and a nominal response variable respectively, such that the local odds ratio and the distances between the predictor and response categories are inversely related. The associations in terms of the odds ratios, or the ratios of the odds to their geometric means, are interpreted through distances for the most common coding schemes of the predictor variable, and the relationship between the distances related to different codings is investigated in its full dimension. The performance of the estimation procedure is analysed with a Monte Carlo experiment. The interpretation of the model and its performance, as well as its comparison with a two‐step procedure involving first a logistic regression and then unfolding, is illustrated using real data sets.
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

Long 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

Background

A number of mutations related to malignant melanoma (MM) have been identified, and of the mutated genes, BRAF has been found to be altered in > 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.

Aim

To compare the clinical and dermoscopic characteristics, the response to systemic therapies and the prognosis among MMs with BRAF V600E and BRAF V600K mutations.

Methods

We 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.

Results

In 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.

Conclusion

Despite 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

Signs 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

Alienation 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.
Clinical characteristics of non‐small cell lung cancer patients with EGFR mutations and ALK&ROS1 fusions
Authors: Liu Qinghua , Huang Qingyan , Yu Zhikang , Wu Heming
Published: January 2022

Objective

To study the relationship between clinical characteristics and anaplastic lymphoma kinase (ALK) fusions, c‐ros oncogene 1, receptor tyrosine kinase (ROS1) gene fusions, and epidermic growth factor receptor (EGFR) mutations in non‐small cell lung cancer (NSCLC) patients to distinguish these different types.

Methods

Both ALK, ROS1 gene rearrangements and EGFR mutations testing were performed. The clinical characteristics and associated pulmonary abnormalities were investigated.

Results

Four hundred fifty‐three NSCLC patients were included for analysis. One hundred seventy (37.5%), 32 (7.1%), and 9 cases (2.0%) with EGFR mutations, ALK gene fusions, and ROS1 gene fusions were identified, respectively. The EGFR‐positive and ALK&ROS1‐positive were more common in female (χ2 = 61.934, P < 0.001 and χ2 = 28.152, P < 0.001), non‐smoking (χ2 = 59.315, P < 0.001 and χ2 = 11.080, P = 0.001), and adenocarcinoma (χ2 = 44.864, P < 0.001 and χ2 = 12.318, P = 0.002) patients; proportion of patients with emphysema was lower (χ2 = 35.494, P < 0.001 and χ2 = 15.770, P < 0.001) than the wild‐type patients. The results of logistic regression analysis indicated that female (adjusted odds ratio [OR] 1.834, 95% confidence interval [CI] 1.069–3.144, P = 0.028), non‐smoking (adjusted OR 2.504, 95% CI 1.456–4.306, P = 0.001), lung adenocarcinoma (adjusted OR 4.512, 95% CI 2.465–8.260, P < 0.001), stage III–IV (adjusted OR 2.232, 95% CI 1.066–4.676, P = 0.033), and no symptoms of emphysema (adjusted OR 2.139, 95% CI 1.221–3.747, P = 0.008) were independent variables associated with EGFR mutations. Young (adjusted OR 3.947, 95% CI 1.873–8.314, P < 0.001) and lung adenocarcinoma (adjusted OR 2.950, 95% CI 0.998–8.719, P = 0.050) were associated with ALK/ROS1 fusions.

Conclusions

EGFR mutations were more likely to occur in non‐smoking, stage III–IV, and female patients with lung adenocarcinoma, whereas ALK&ROS1 gene fusions were more likely to occur in young patients with lung adenocarcinoma. Emphysema was less common in patients with EGFR mutations.
Mepolizumab improves work productivity, activity limitation, symptoms, and rescue medication use in severe eosinophilic asthma
Authors: Albers Frank C. , Bratton Daniel J. , Gunsoy Necdet B. , Cockle Sarah M. , Alfonso‐Cristancho Rafael , Braunstahl Gert‐Jan
Published: January 2022

Patients with severe eosinophilic asthma experience daily activity limitations and reduced productivity at work. Using anonymized individual patient‐level data from two previously conducted randomized, double‐blind, placebo‐controlled studies (MENSA [GSK ID:115588/NCT01691521]; MUSCA [GSK ID:200862/NCT02281318]), we investigated the effect of mepolizumab on work productivity, activity limitation, symptoms, and rescue medication use. Patient‐reported outcomes including Work Productivity and Activity Impairment–General Health (WPAI‐GH) scores (impairment percentages, 0%–100%), global activity limitation (scale 1–4), and perceived change in activity limitation (Likert scale 1–7) since the start of the study were analyzed. WPAI‐GH scores from MENSA were analyzed post hoc for employed patients using mixed model repeated measures; global activity limitation and perceived change in activity limitation from MUSCA were analyzed by ordinal logistic regression. Mean changes from baseline in daily asthma symptom scores (scale 0–5) and rescue medication use (occasions/day) were also assessed, via a post hoc meta‐analysis of MENSA and MUSCA. At study end, WPAI‐GH scores indicative of overall work impairment, impairment while working, and activity impairment consistently improved with mepolizumab versus placebo. Overall, 76% versus 54% of patients rated their activity as “much better,” “better,” or “slightly better” since the start of the study with mepolizumab versus placebo. Mepolizumab was associated with numerically larger improvements from baseline in asthma symptoms (treatment difference 0.21–0.29 points) and rescue medication use (treatment difference −0.08 to −0.22 occasions/day) versus placebo. Our results indicate that patients with severe eosinophilic asthma may experience improved activity limitation, work productivity, symptoms, and rescue medication use with mepolizumab.