bluuebunny/crossref_metadata_2025 huggingface dataset:
Severity of Brugada syndrome disease manifestation and risk of new-onset depression or anxiety: a Danish nationwide study
Authors: Jespersen Camilla H B , Krøll Johanna , Bhardwaj Priya , Winkel Bo Gregers , Jacobsen Peter Karl , Jøns Christian , Haarbo Jens , Kristensen Jens , Johansen Jens Brock , Philbert Berit T , Riahi Sam , Torp-Pedersen Christian , Køber Lars , Tfelt-Hansen Jacob , Weeke Peter E
Published: May 2023

Aims

Reduced psychological health is associated with adverse patient outcomes and higher mortality. We aimed to examine if a Brugada syndrome (BrS) diagnosis and symptomatic disease presentation were associated with an increased risk of new-onset depression or anxiety and all-cause mortality.

Methods and results

All Danish patients diagnosed with BrS (2006–2018) with no history of psychiatric disease and available for ≥6 months follow-up were identified using nationwide registries and followed for up to 5 years after diagnosis. The development of clinical depression or anxiety was evaluated using the prescription of medication and diagnosis codes. Factors associated with developing new-onset depression or anxiety were determined using a multivariate Cox proportional hazards regression model. Disease manifestation was categorized as symptomatic (aborted cardiac arrest, ventricular tachycardia, or syncope) or asymptomatic/unspecified at diagnosis. A total of 223 patients with BrS and no history of psychiatric disease were identified (72.6% male, median age at diagnosis 46 years, 45.3% symptomatic). Of these, 15.7% (35/223) developed new-onset depression or anxiety after BrS diagnosis (median follow-up 5.0 years). A greater proportion of symptomatic patients developed new-onset depression or anxiety compared with asymptomatic patients [21/101 (20.8%) and 14/122 (11.5%), respectively, P = 0.08]. Symptomatic disease presentation (HR 3.43, 1.46–8.05) and older age (lower vs. upper tertile: HR 4.41, 1.42–13.63) were significantly associated with new-onset depression or anxiety. All-cause mortality in this group of patients treated according to guidelines was low (n = 4, 1.8%); however, 3/4 developed depression or anxiety before death.

Conclusion

Approximately, one-sixth of patients with BrS developed new-onset depression or anxiety following a diagnosis of BrS. Symptomatic BrS disease manifestation was significantly associated with new-onset depression or anxiety.
The evolutionary demise of a social interaction: experimentally induced loss of traits involved in the supply and demand of care
Authors: Bladon Eleanor K , Pascoal Sonia , Bird Nancy , Mashoodh Rahia , Kilner Rebecca M
Published: May 2023

Phenotypic plasticity enables animals to adjust their behavior flexibly to their social environment—sometimes through the expression of adaptive traits that have not been exhibited for several generations. We investigated how long social adaptations can usefully persist when they are not routinely expressed, by using experimental evolution to document the loss of social traits associated with the supply and demand of parental care. We allowed populations of burying beetles Nicrophorus vespilloides to evolve in two different social environments for 48 generations in the lab. In “Full Care” populations, traits associated with the supply and demand of parental care were expressed at every generation, whereas in “No Care” populations we prevented expression of these traits experimentally. We then revived trait expression in the No Care populations at generations 24, 43, and 48 by allowing parents to supply post-hatching care and compared these social traits with those expressed by the Full Care populations. We found that offspring demands for care and male provision of care in the No Care populations were lost sooner than female provision of care. We suggest that this reflects differences in the strength of selection for the expression of alternative traits in offspring, males and females, which can enhance fitness when post-hatching care is disrupted.
Structural and functional diversity of bacterial cyclic nucleotide perception by CRP proteins
Authors: Krol Elizaveta , Werel Laura , Essen Lars Oliver , Becker Anke
Published: May 2023

Cyclic AMP (cAMP) is a ubiquitous second messenger synthesized by most living organisms. In bacteria, it plays highly diverse roles in metabolism, host colonization, motility, and many other processes important for optimal fitness. The main route of cAMP perception is through transcription factors from the diverse and versatile CRP–FNR protein superfamily. Since the discovery of the very first CRP protein CAP in Escherichia coli more than four decades ago, its homologs have been characterized in both closely related and distant bacterial species. The cAMP-mediated gene activation for carbon catabolism by a CRP protein in the absence of glucose seems to be restricted to E. coli and its close relatives. In other phyla, the regulatory targets are more diverse. In addition to cAMP, cGMP has recently been identified as a ligand of certain CRP proteins. In a CRP dimer, each of the two cyclic nucleotide molecules makes contacts with both protein subunits and effectuates a conformational change that favors DNA binding. Here, we summarize the current knowledge on structural and physiological aspects of E. coli CAP compared with other cAMP- and cGMP-activated transcription factors, and point to emerging trends in metabolic regulation related to lysine modification and membrane association of CRP proteins.
Agents, audiences and peers: why international organizations diversify their legitimation discourse
Authors: Lenz Tobias , Schmidtke Henning
Published: May 2023

In the face of public contestation, international organizations (IOs) invoke norms in their public communication to enhance relevant audiences' legitimacy beliefs. This article offers the first comprehensive analysis of what we term normative diversity in IOs' discursive legitimation by drawing on a novel dataset on norm-based justifications in more than 32,000 paragraphs of text published by 28 regional IOs between 1980 and 2019. We show that IOs vary strikingly in this respect: whereas some IOs invoke a narrow set of norms, often focused on economic welfare and functional capability, others engage a wide variety that includes security, national sovereignty, democracy or human rights. To explain this variance, we specify and test an explanatory framework that emphasizes IO audiences, agents and peer organizations as distinct origins. Our statistical analysis reveals that IOs diversify their discursive legitimation to 1) address heterogeneous audiences, 2) reconcile competing beliefs amongst agents themselves, and 3) integrate the legitimation of peer IOs. These findings indicate that IOs respond to the growing complexity of international cooperation in their discursive legitimation and may raise policy-makers' awareness of the difficulties in contemporary legitimation efforts.
The politics of legitimation in combined sanction regimes: the case of Venezuela
Authors: Palestini Stefano
Published: May 2023

Regional international organizations (RIOs) and states are increasingly sanctioning governments, firms and individuals they consider to have violated international norms. How do different RIOs legitimize the decision to impose (or not impose) sanctions? And how do they react to the legitimation strategies of other RIOs and states? This article addresses these questions by analysing the legitimation strategies of the United States and four RIOs involved in the combined sanction regimes against Venezuela between 2014 and 2019: the Organization of American States, the Union of South American Nations, the Common Market of the South and the European Union. Refining the environment-based perspective on legitimation, the article proposes that combined sanction regimes work as environments that shape the legitimation strategies of senders not only by providing templates to emulate but also by triggering processes of differentiation. The article shows how Latin American RIOs adapted their legitimation strategies dynamically in reaction to changes in the strategies of Washington and Brussels. This process, however, was not unidirectional. When Latin American RIOs managed to articulate coherent strategies, they forced Washington and Brussels to recalibrate their own positions and engage in discursive legitimation processes as well.
Mercosur at 30: political ideologies and (de)legitimation strategies
Authors: Hoffmann Andrea Ribeiro
Published: May 2023

Mercosur celebrated its 30th anniversary in 2021 in a situation of severe stress, in which the idea of rolling it back from a customs union towards a free trade area was discussed in polarized terms, raising the question about its legitimacy. This article analyses the legitimation strategies pursued by Mercosur member states' presidents and regional bureaucrats to build, maintain, defend and enhance the belief among relevant audiences that the regional organization is legitimate. It focuses on three critical moments in which Mercosur was the object of public debate, namely, the Brazilian currency devaluation in 1999, the accession of Venezuela in 2012, and the current proposal of ‘flexibilization’, and, drawing on secondary literature and qualitative content analysis, argues that the origins of Mercosur agents' discursive legitimation strategies are their political ideologies. Given the strong role of presidents and lack of stronger regional institutions and leadership, Mercosur is left hostage to domestic electoral cycles and vulnerableto undemocratic trends of governments in power.
Two-sided legitimation strategies: informal groups at the World Trade Organization
Authors: Viola Lora Anne
Published: May 2023

Who engages in legitimation strategies in global governance and why and how do they do it? This article studies the legitimation strategies and legitimacy-generating capacity of low-authority institutions, specifically informal groups within formal international organizations (IOs). It argues that informal groups seek legitimation and they can also be a source of legitimation for formal IOs. In doing so, the article makes three contributions to recent legitimation literature: 1) contra recent arguments, it shows why not only high-authority, but also low-authority institutions have special incentives to engage in legitimation; 2) it expands our understanding of the reasons why institutions engage in legitimation, showing why authority-deficits can motivate legitimation; 3) it studies legitimation strategies to show when they are likely to be audience- or agent-driven. A case-study of informal groups at the World Trade Organization yields three policy implications. First, developing countries could invest greater resources in legitimizing informal groups in order to boost their representation and voice opportunities within IOs. Second, formal IOs can increase their own legitimacy by supporting informal groups that enhance the representation of marginalized members. Third, however, to the extent that these strategies deflect pressure for formal rule changes, increasing investments in informal groups may be a long-term liability for developing countries.
Supply chain pricing strategies for advance selling with a deposit
Authors: Lyu Qi , Wu Shuang , Li Bo , Zhang Yawen
Published: May 2023

Accepted by: Konstantinos Nikolopoulos

This research studies the pricing strategy of a supply chain with a manufacturer and a retailer. We analyze the customers’ purchase behaviour in advance selling with deposit by using utility theory and obtain the pricing decision of the supply chain by using the Stackelberg model. We find that when consumers are not sensitive to the distribution lead time, the retailer’s advance selling strategy could Pareto improve the whole supply chain. Better informed consumers and moderate advance selling distribution lead time information could expand the retailer’s pre-sale possibilities by enlarging the feasible range of advance selling.
Hepatitis B e Antigen-Negative Single Hepatocyte Analysis Shows Transcriptional Silencing and Slow Decay of Infected Cells With Treatment
Authors: Thio Chloe L , Taddese Maraake , Saad Yasmeen , Zambo Kristina , Ribeiro Ruy M , Grudda Tanner , Sulkowski Mark S , Sterling Richard K , Zhang Yang , Young Eric D , Hwang Hyon S , Balagopal Ashwin
Published: May 2023

Background

Nucleos(t)ide analogues (NUCs) rarely cure chronic hepatitis B (CHB) because they do not eliminate covalently closed circular deoxyribonucleic acid, the stable replication template. In hepatitis B e antigen (HBeAg)-positive CHB during NUCs, HBV-infected cells decline slowly and are transcriptionally silenced. Whether these occur in HBeAg-negative CHB is unknown.

Methods

Using paired liver biopsies separated by 2.7–3.7 years in 4 males with HIV and HBeAg-negative CHB at both biopsies and 1 male with HIV who underwent HBeAg seroconversion between biopsies, we quantified amounts of viral nucleic acids in hundreds of individual hepatocytes.

Results

In the 4 persistently HBeAg-negative participants, HBV-infected hepatocytes ranged from 6.2% to 17.7% (biopsy 1) and significantly declined in 3 of 4 by biopsy 2. In the HBeAg seroconverter, the proportion was 97.4% (biopsy 1) and declined to 81.9% at biopsy 2 (P < .05). We extrapolated that HBV eradication with NUCs would take >100 years. At biopsy 1 in the persistently HBeAg-negative participants, 23%–56.8% of infected hepatocytes were transcriptionally inactive—higher than we observed in HBeAg-positive CHB—and significantly declined in 1 of 4 at biopsy 2.

Conclusions

In HBeAg-negative CHB on NUCs, the negligible decline in infected hepatocytes is similar to HBeAg-positive CHB, supporting the need for more potent therapeutics to achieve functional cure.
Antimicrobial-Resistant Nontyphoidal Salmonella Infection Following International Travel—United States, 2018–2019
Authors: Ford Laura , Shah Hazel J , Eikmeier Dana , Hanna Samir , Chen Jessica , Tagg Kaitlin A , Langley Gayle , Payne Daniel C , Plumb Ian D
Published: May 2023

Background

Antimicrobial resistance in nontyphoidal Salmonella (NTS) can limit treatment options. We assessed the contribution of international travel to antimicrobial-resistant NTS infections.

Methods

We describe NTS infections that were reported to the Foodborne Diseases Active Surveillance Network during 2018–2019 and screened for genetic resistance determinants, including those conferring decreased susceptibility to first-line agents (ciprofloxacin, ceftriaxone, or azithromycin). We used multivariable logistic regression to assess the association between resistance and international travel during the 7 days before illness began. We estimated the contribution of international travel to resistance using population-attributable fractions, and we examined reported antimicrobial use.

Results

Among 9301 NTS infections, 1159 (12%) occurred after recent international travel. Predicted resistance to first-line antimicrobials was more likely following travel; the adjusted odds ratio varied by travel region and was highest after travel to Asia (adjusted odds ratio, 7.2 [95% confidence interval, 5.5–9.5]). Overall, 19% (95% confidence interval, 17%–22%) of predicted resistance to first-line antimicrobials was attributable to international travel. More travelers than nontravelers receiving ciprofloxacin or other fluoroquinolones had isolates with predicted resistance to fluoroquinolones (29% vs 9%, respectively; P < .01).

Conclusions

International travel is a substantial risk factor for antimicrobial-resistant NTS infections. Understanding risks of resistant infection could help target prevention efforts.
Measurement of Dietary Fiber: Which AOAC Official Method of AnalysisSM to Use
Authors: McCleary Barry V
Published: May 2023

A broad range of AOAC Official Methods of AnalysisSM (OMA) have been developed and approved for the measurement of dietary fiber (DF) and DF components since the adoption of the Prosky method (OMA 985.29). OMA 985.29 and other OMA were developed to support the Trowell definition of DF. However, these methods do not measure DF as defined by the “new,” physiologically relevant, Codex Alimentarius definition. Methodology to support the Codex definition has been developed and updated in recent years. In this article, the relevance of each OMA in supporting the Codex definition of DF is described and suggestions are presented on the most appropriate method, together with proposals for changes in title and application statements for the “historic” OMA methods.
Intralipid as a matrix additive for evaluating hyperlipidemic postmortem blood
Authors: Elenstål Emily , Green Henrik , Kronstrand Robert , Elmsjö Albert
Published: May 2023

Postmortem whole blood samples can differ greatly in quality where hyperlipemia is a frequent variable that can influence the results of analytical methods. The aim of this study was to investigate the influence of lipemia on postmortem analysis as well as demonstrate the usage of Intralipid in comparison to pooled postmortem lipids as matrix additives for meaningful evaluation and validation of hyperlipidemic postmortem samples. Hyperlipidemic blood samples were simulated by adding different concentrations of Intralipid or pooled authentic postmortem lipids to bovine whole blood. The hyperlipidemic blood samples were spiked with 14 benzodiazepines and five sedative and antianxiety drugs (alprazolam, clonazepam, 7-aminoclonazepam, diazepam, flunitrazepam, 7-aminoflunitrazepam, hydroxyzine, lorazepam, midazolam, nitrazepam, 7-aminonitrazepam, nordazepam, oxazepam, propiomazine, dihydropropiomazine, temazepam, triazolam, zolpidem and zopiclone). Samples were prepared with liquid-liquid extraction followed by ultra-high performance liquid chromatography–mass spectrometry. The effects of lipemia on the recovery of analytes and internal standards (ISs) were evaluated to determine the effect of, and any differences between, the two additives. Lipemia was found to cause major interference when quantifying the analytes. For most analytes, the ISs could compensate for analyte losses. However, the most hydrophilic analytes (7-amino metabolites), together with the most lipophilic analytes (propiomazine and dihydropropiomazine), were greatly affected by lipemia (<50% recovery), and the IS could not compensate for analyte losses. In general, lower analyte recoveries were observed for samples with Intralipid as a lipemic additive in comparison to those containing pooled postmortem lipids. Both Intralipid and pooled postmortem lipids showed marked effects on the analytical results. Intralipid gave a good indication of the effects of lipemia and could be a useful tool for making a meaningful evaluation of hyperlipidemic postmortem samples during the method development and validation.
Assessment, Complications, and Surveillance of Breast Implants: Making Sense of 2022 FDA Breast Implant Guidance
Authors: Le-Petross Huong T , Scoggins Marion E , Clemens Mark W
Published: May 2023

As more information about the potential risks and complications related to breast implants has become available, the United States Food and Drug Administration (FDA) has responded by implementing changes to improve patient education, recalling certain devices and updating the recommendations for screening for silicone implant rupture. In addition to staying up-to-date with FDA actions and guidance, radiologists need to maintain awareness about the types of implants they may see, breast reconstruction techniques including the use of acellular dermal matrix, and the multimodality imaging of implants and their complications. Radiologists should also be familiar with some key differences between the updated FDA guidelines for implant screening and the imaging recommendations from the American College of Radiology Appropriateness Criteria. The addition of US as an acceptable screening exam for silicone implant rupture by the FDA is one of the most notable changes that has potentially significant implications.
Automated Detection of Anatomical Landmarks During Colonoscopy Using a Deep Learning Model
Authors: Taghiakbari Mahsa , Hamidi Ghalehjegh Sina , Jehanno Emmanuel , Berthier Tess , di Jorio Lisa , Ghadakzadeh Saber , Barkun Alan , Takla Mark , Bouin Mickael , Deslandres Eric , Bouchard Simon , Sidani Sacha , Bengio Yoshua , von Renteln Daniel
Published: May 2023

Background and aims

Identification and photo-documentation of the ileocecal valve (ICV) and appendiceal orifice (AO) confirm completeness of colonoscopy examinations. We aimed to develop and test a deep convolutional neural network (DCNN) model that can automatically identify ICV and AO, and differentiate these landmarks from normal mucosa and colorectal polyps.

Methods

We prospectively collected annotated full-length colonoscopy videos of 318 patients undergoing outpatient colonoscopies. We created three nonoverlapping training, validation, and test data sets with 25,444 unaltered frames extracted from the colonoscopy videos showing four landmarks/image classes (AO, ICV, normal mucosa, and polyps). A DCNN classification model was developed, validated, and tested in separate data sets of images containing the four different landmarks.

Results

After training and validation, the DCNN model could identify both AO and ICV in 18 out of 21 patients (85.7%). The accuracy of the model for differentiating AO from normal mucosa, and ICV from normal mucosa were 86.4% (95% CI 84.1% to 88.5%), and 86.4% (95% CI 84.1% to 88.6%), respectively. Furthermore, the accuracy of the model for differentiating polyps from normal mucosa was 88.6% (95% CI 86.6% to 90.3%).

Conclusion

This model offers a novel tool to assist endoscopists with automated identification of AO and ICV during colonoscopy. The model can reliably distinguish these anatomical landmarks from normal mucosa and colorectal polyps. It can be implemented into automated colonoscopy report generation, photo-documentation, and quality auditing solutions to improve colonoscopy reporting quality.
Variations in amino acids caused by drought stress mediate the predisposition of Carya cathayensis to Botryosphaeria canker disease
Authors: Wang Yongjun , Wu Wenbin , Zhang Liqin , Jiang Hong , Mei Li
Published: May 2023

Abiotic stresses can affect the outcome of plant–pathogen interactions, mostly by predisposing the host plant to infection; however, the crosstalk between pathogens and plants related to such predisposition remains unclear. Here, we investigated the predisposition of Carya cathayensis to infection by the fungal pathogen Botryosphaeria dothidea (Bd) caused by drought in the host plant. High levels of drought stress resulted in a significant increase in plant susceptibility to Bd. Drought significantly induced the accumulation of H2O2 and the free amino acids Pro, Leu, and Ile, and in the phloem tissues of plants, and decreased the content of non-structural carbohydrates. In vitro assays showed that Bd was sensitive to H2O2; however, Pro played a protective role against exogenous H2O2. Leu, Ile, and Pro induced asexual reproduction of Bd. Our results provide the first analysis of how drought predisposes C. cathayensis to Botrysphaeria canker via amino acid accumulation in the host plant, and we propose a model that integrates the plant–pathogen interactions involved.
MIGHTEE-H i: the first MeerKAT H i mass function from an untargeted interferometric survey
Authors: Ponomareva Anastasia A , Jarvis Matt J , Pan Hengxing , Maddox Natasha , Jones Michael G , Frank Bradley S , Rajohnson Sambatriniaina H A , Mulaudzi Wanga , Meyer Martin , Adams Elizabeth A K , Baes Maarten , Hess Kelley M , Kurapati Sushma , Prandoni Isabella , Sinigaglia Francesco , Spekkens Kristine , Tudorache Madalina , Heywood Ian , Collier Jordan D , Sekhar Srikrishna
Published: May 2023

We present the first measurement of the H i mass function (HIMF) using data from MeerKAT, based on 276 direct detections from the MeerKAT International GigaHertz Tiered Extragalactic Exploration (MIGHTEE) Survey Early Science data covering a period of approximately a billion years (0 ≤ $z$ ≤ 0.084). This is the first HIMF measured using interferometric data over non-group or cluster field, i.e. a deep blank field. We constrain the parameters of the Schechter function that describes the HIMF with two different methods: $1/V_{\rm max}$ and modified maximum likelihood (MML). We find a low-mass slope $\alpha =-1.29^{+0.37}_{-0.26}$ , ‘knee’ mass $\log _{10}(M_{*}/{\rm {\rm M}_{\odot }}) = 10.07^{+0.24}_{-0.24}$ and normalization $\log _{10}(\phi _{*}/\rm Mpc^{-3})=-2.34^{+0.32}_{-0.36}$ (H0 = 67.4 km s−1 Mpc−1) for $1/V_{\rm max}$ , and $\alpha =-1.44^{+0.13}_{-0.10}$ , ‘knee’ mass $\log _{10}(M_{*}/{\rm {\rm M}_{\odot }}) = 10.22^{+0.10}_{-0.13}$ and normalization $\log _{10}(\phi _{*}/\rm Mpc^{-3})=-2.52^{+0.19}_{-0.14}$ for MML. When using $1/V_{\rm max}$ we find both the low-mass slope and ‘knee’ mass to be consistent within 1σ with previous studies based on single-dish surveys. The cosmological mass density of H i is found to be slightly larger than previously reported: $\Omega _{\rm H\,{\small I}}=5.46^{+0.94}_{-0.99} \times 10^{-4}\,h^{-1}_{67.4}$ from $1/V_{\rm max}$ and $\Omega _{\rm H\,{\small I}}=6.31^{+0.31}_{-0.31} \times 10^{-4}\,h^{-1}_{67.4}$ from MML but consistent within the uncertainties. We find no evidence for evolution of the HIMF over the last billion years.
Epigenetic profiling reveals a strong association between lack of 5-ALA fluorescence and EGFR amplification in IDH-wildtype glioblastoma
Authors: Drexler Richard , Sauvigny Thomas , Schüller Ulrich , Eckhardt Alicia , Maire Cecile L , Khatri Robin , Hausmann Fabian , Hänzelmann Sonja , Huber Tobias B , Bonn Stefan , Bode Helena , Lamszus Katrin , Westphal Manfred , Dührsen Lasse , Ricklefs Franz L
Published: May 2023

Background

5-aminolevulinic acid (5-ALA) fluorescence-guided resection increases the percentage of complete CNS tumor resections and improves the progression-free survival of IDH-wildtype glioblastoma patients. A small subset of IDH-wildtype glioblastoma shows no 5-ALA fluorescence. An explanation for these cases is missing. In this study, we used DNA methylation profiling to further characterize non-fluorescent glioblastomas.

Methods

Patients with newly diagnosed and recurrent IDH-wildtype glioblastoma that underwent surgery were analyzed. The intensity of intraoperative 5-ALA fluorescence was categorized as non-visible or visible. DNA was extracted from tumors and genome-wide DNA methylation patterns were analyzed using Illumina EPIC (850k) arrays. Furthermore, 5-ALA intensity was measured by flow cytometry on human gliomasphere lines (BT112 and BT145).

Results

Of 74 included patients, 12 (16.2%) patients had a non-fluorescent glioblastoma, which were compared to 62 glioblastomas with 5-ALA fluorescence. Clinical characteristics were equally distributed between both groups. We did not find significant differences between DNA methylation subclasses and 5-ALA fluorescence (P = .24). The distribution of cells of the tumor microenvironment was not significantly different between the non-fluorescent and fluorescent tumors. Copy number variations in EGFR and simultaneous EGFRvIII expression were strongly associated with 5-ALA fluorescence since all non-fluorescent glioblastomas were EGFR-amplified (P < .01). This finding was also demonstrated in recurrent tumors. Similarly, EGFR-amplified glioblastoma cell lines showed no 5-ALA fluorescence after 24 h of incubation.

Conclusions

Our study demonstrates an association between non-fluorescent IDH-wildtype glioblastomas and EGFR gene amplification which should be taken into consideration for recurrent surgery and future studies investigating EGFR-amplified gliomas.
Utility of Urine Cultures During Febrile Neutropenia Workup in Hematopoietic Stem Cell Transplantation Recipients Without Urinary Symptoms
Authors: Tran Mya , Palmer Shannon , Moore Dominic T , Bartelt Luther , Friedland Anne , Grgic Tatjana , Lachiewicz Anne , Ptachcinski Jon , Sena Arlene , Trepte Morgan , van Duin David , Andermann Tessa M , Shaw Ryan
Published: May 2023

The utility of obtaining screening urine cultures for febrile neutropenia (FN) during hematopoietic stem cell transplant (HCT) is unknown. In 667 adult HCT patients with FN, only 40 (6%) were found with bacteriuria. Antibiotics were modified in 3 patients (0.4%) based on urine cultures and none developed urinary-associated infectious complications.
Predicting the 25th and 26th solar cycles using the long short-term memory method
Authors: Liu Xiaohuan , Zeng Shuguang , Deng Linhua , Zeng Xiangyun , Zheng Sheng
Published: May 2023

Solar activities directly or indirectly affect space missions, geophysical environment, space climate, and human activities. We used the long short-term memory (LSTM) deep learning method to predict the amplitude and peak time of solar cycles (SCs) 25 and 26 by using the monthly relative sunspot number data taken from the National Astronomical Observatory of Japan (NAOJ). The dataset is divided into eight schemes of two to nine slices for training, showing that the five-slice LSTM model with root mean square error of 11.38 is the optimal model. According to the prediction, SC 25 will be about 21$\%$ stronger than SC 24, with a peak of 135.2 occurring in 2024 April. SC 26 will be similar to SC 25 and reach its peak of 135.0 in 2035 January. Our analysis results indicate that the sunspot data from NAOJ is highly credible and comparable.
Formation of a Stable PSI–PSII Megacomplex in Rice That Conducts Energy Spillover
Authors: Kim Eunchul , Yokono Makio , Tsugane Kazuo , Ishii Asako , Noda Chiyo , Minagawa Jun
Published: May 2023

In green plants, photosystem I (PSI) and photosystem II (PSII) bind to their respective light-harvesting complexes (LHCI and LHCII) to form the PSI−LHCI supercomplex and the PSII−LHCII supercomplex, respectively. These supercomplexes further form megacomplexes, like PSI−PSII and PSII−PSII in Arabidopsis (Arabidopsis thaliana) and spinach to modulate their light-harvesting properties, but not in the green alga Chlamydomonas reinhardtii. Here, we fractionated and characterized the stable rice PSI−PSII megacomplex. The delayed fluorescence from PSI (lifetime ∼25 ns) indicated energy transfer capabilities between the two photosystems (energy spillover) in the rice PSI−PSII megacomplex. Fluorescence lifetime analysis revealed that the slow PSII to PSI energy transfer component was more dominant in the rice PSI−PSII supercomplexes than in Arabidopsis ones, suggesting that PSI and PSII in rice form a megacomplex not directly but through LHCII molecule(s), which was further confirmed by the negatively stained electron microscopy analysis. Our results suggest species diversity in the formation and stability of photosystem megacomplexes, and the stable PSI–PSII supercomplex in rice may reflect its structural adaptation.
In vivo noninvasive mitochondrial redox assessment of the optic nerve head to predict disease
Authors: Cakir Bertan , Tomita Yohei , Yagi Hitomi , Romfh Padraic , Allen William , Ko Minji , Chen Peili , Fu Zhongjie , Vakhshoori Daryoosh , Smith Lois E H
Published: May 2023

Eye diseases are diagnosed by visualizing often irreversible structural changes occurring late in disease progression, such as retinal ganglion cell loss in glaucoma. The retina and optic nerve head have high mitochondrial energy need. Early mitochondrial/energetics dysfunction may predict vulnerability to permanent structural changes. In the in vivo murine eye, we used light-based resonance Raman spectroscopy (RRS) to assess noninvasively the redox states of mitochondria and hemoglobin which reflect availability of electron donors (fuel) and acceptors (oxygen). As proof of principle, we demonstrated that the mitochondrial redox state at the optic nerve head correlates with later retinal ganglion loss after acute intraocular pressure (IOP) elevation. This technology can potentially map the metabolic health of eye tissue in vivo complementary to optical coherence tomography, defining structural changes. Early detection (and normalization) of mitochondrial dysfunction before irreversible damage could lead to prevention of permanent neural loss.
White-matter abnormalities and cognitive dysfunction are linked to astrocyte activation in sickle mice
Authors: Hazra Rimi , Pu Hongjian , Foley Lesley M , Little-Ihrig Lynda , Hitchens T Kevin , Ghosh Samit , Ofori-Acquah Solomon F , Hu Xiaoming , Novelli Enrico M
Published: May 2023

White-matter injury in sickle-cell disease (SCD) includes silent cerebral infarction diagnosed by diffusion tensor imaging (DTI), a complication associated with cognitive dysfunction in children with SCD. The link between white-matter injury and cognitive dysfunction has not been fully elucidated. The goal of this study was to define whether cerebrovascular lesions and cognitive function in SCD are linked to neuroaxonal damage and astrocyte activation in humanized Townes’ SCD mice homozygous for human sickle hemoglobin S (SS) and control mice homozygous for human normal hemoglobin A (AA). Mice underwent MRI with DTI and cognitive testing, and histology sections from their brains were stained to assess microstructural tissue damage, neuroaxonal damage, and astrocyte activation. Fractional anisotropy, showing microstructural cerebrovascular abnormalities identified by DTI in the white matter, was significantly associated with neuronal demyelination in the SS mouse brain. SS mice had reduced learning and memory function with a significantly lower discrimination index compared with AA control mice in the novel object recognition tests. Neuroaxonal damage in the SS mice was synchronously correlated with impaired neurocognitive function and activation of astrocytes. The interplay between astrocyte function and neurons may modulate cognitive performance in SCD.
The best practice for microbiome analysis using R
Authors: Wen Tao , Niu Guoqing , Chen Tong , Shen Qirong , Yuan Jun , Liu Yong-Xin
Published: May 2023

With the gradual maturity of sequencing technology, many microbiome studies have published, driving the emergence and advance of related analysis tools. R language is the widely used platform for microbiome data analysis for powerful functions. However, tens of thousands of R packages and numerous similar analysis tools have brought major challenges for many researchers to explore microbiome data. How to choose suitable, efficient, convenient, and easy-to-learn tools from the numerous R packages has become a problem for many microbiome researchers. We have organized 324 common R packages for microbiome analysis and classified them according to application categories (diversity, difference, biomarker, correlation and network, functional prediction, and others), which could help researchers quickly find relevant R packages for microbiome analysis. Furthermore, we systematically sorted the integrated R packages (phyloseq, microbiome, MicrobiomeAnalystR, Animalcules, microeco, and amplicon) for microbiome analysis, and summarized the advantages and limitations, which will help researchers choose the appropriate tools. Finally, we thoroughly reviewed the R packages for microbiome analysis, summarized most of the common analysis content in the microbiome, and formed the most suitable pipeline for microbiome analysis. This paper is accompanied by hundreds of examples with 10,000 lines codes in GitHub, which can help beginners to learn, also help analysts compare and test different tools. This paper systematically sorts the application of R in microbiome, providing an important theoretical basis and practical reference for the development of better microbiome tools in the future. All the code is available at GitHub github.com/taowenmicro/EasyMicrobiomeR.
The impact of the COVID-19 pandemic on referrals to musculoskeletal services from primary care and subsequent incidence of inflammatory rheumatic musculoskeletal disease: an observational study
Authors: Burton Claire , Bajpai Ram , Mason Kayleigh J , Bailey James , Jordan Kelvin P , Mallen Christian D , Welsh Victoria K
Published: May 2023

Objective

The aim was to describe the impact of the COVID-19 pandemic upon referral patterns and incident diagnosis of inflammatory rheumatic and musculoskeletal diseases (iRMDs).

Methods

UK primary care data were used to describe referral patterns for patients with musculoskeletal conditions. Trends in referrals to musculoskeletal services and incident diagnoses of iRMDs (specifically, RA and JIA) were described using Joinpoint Regression and comparisons made between key pandemic time periods.

Results

The incidence of RA and JIA reduced by −13.3 and −17.4% per month, respectively, between January 2020 and April 2020, then increased by 1.9 and 3.7% per month, respectively, between April 2020 and October 2021. The incidence of all diagnosed iRMDs was stable until October 2021. Referrals decreased between February 2020 and May 2020 by −16.8% per month from 4.8 to 2.4% in patients presenting with a musculoskeletal condition. After May 2020, referrals increased significantly (16.8% per month) to 4.5% in July 2020. The time from first musculoskeletal consultation to RA diagnosis and from referral to RA diagnosis increased in the early pandemic period [rate ratio (RR) 1.11, 95% CI 1.07, 1.15 and RR 1.23, 95% CI 1.17, 1.30, respectively] and remained consistently higher in the late pandemic period (RR 1.13, 95% CI 1.11, 1.16 and RR 1.27, 95% CI 1.23, 1.32, respectively), compared with the pre-COVID-19 pandemic period.

Conclusion

Patients with underlying RA and JIA that developed during the pandemic might be yet to present or might be in the referral and/or diagnostic process. Clinicians should remain alert to this possibility, and commissioners should be aware of these findings, enabling the appropriate planning and commissioning of services.
Safety of the JAK and TNF inhibitors in rheumatoid arthritis: real world data from the Hong Kong Biologics Registry
Authors: Mok Chi Chiu , So Ho , Yim Cheuk Wan , To Chi Hung , Lao Weng Nga , Wong Stella Pui Yan , Ng Hoi Yan , Lee Jolly Man Yee , Lee Patrick Man Leung , Ying Shirley King Yee , Leung Moon Ho , Ho Carmen Tze Kwan
Published: May 2023

Objectives

To compare the incidence of major adverse cardiovascular events (MACEs), cancer and infective complications in RA patients using Janus kinase (JAKis) and TNF (TNFis) inhibitors.

Method

A retrospective analysis of data from the Hong Kong Biologics Registry 2008–2021 was performed. RA patients who had ever used JAKis or TNFis were included. The incidence of MACEs, cancer and infections were compared between the two groups, with adjustment for confounding factors.

Results

A total of 2471 courses of JAKis (n = 551) and TNFis (n = 1920) were used in 1732 RA patients (83.7% women, age 53.8 [12.5] years; follow-up 6431 patient-years). JAKi users had significantly older age, more atherosclerotic risk factors and higher frequency of past malignancies. A total of 15 and 40 MACEs developed in the JAKi and TNFi users, respectively (incidence 1.34 vs 0.75 per 100 patient-years; P = 0.22). There was no significant difference in the incidence of cancers between the two groups (0.81 [JAKi] vs 0.85 [TNFi] per 100 patient-years; P = 0.25). The adjusted hazard ratios of MACE and cancer in the JAKi users were 1.36 (95% CI: 0.62, 2.96) (P = 0.44) and 0.87 (95% CI: 0.39, 1.95) (P = 0.74), respectively. Rates of infections were significantly higher in the JAKi than TNFi users (16.3 vs 9.9 per 100 patient-years; P = 0.02), particularly herpes zoster (3.49 vs 0.94 per 100 patient-years; P < 0.001).

Conclusions

In a real-life setting, there is no increase in MACEs or cancers in users of JAKis compared with TNFis. However, the incidence of non-serious infections, including herpes zoster, was increased in users of JAKis.
Large muscle group movements during sleep in healthy people: normative values and correlation to sleep features
Authors: Ibrahim Abubaker , Ferri Raffaele , Cesari Matteo , Frauscher Birgit , Heidbreder Anna , Bergmann Melanie , Högl Birgit , Stefani Ambra
Published: May 2023

Study Objectives

To investigate the frequency and characteristics of large muscle group movements (LMMs) during sleep in healthy adults.

Methods

LMMs were scored following the International Restless Legs Syndrome Study Group criteria in 100 healthy participants aged 19–77 years. A LMM was defined as a temporally overlapping increase in EMG activity and/or the occurrence of movement artifacts in at least two channels. LMM indices and durations in total sleep time (TST), NREM and REM sleep, and association with arousals, awakenings, and/or respiratory events were calculated. Correlations of LMMs indices and durations with sleep architecture, respiratory and motor events, and subjective sleep quality were investigated.

Results

Median LMMs index in TST was 6.8/h (interquartile range (IQR), 4.5–10.8/h), median mean duration 12.4 s (IQR 10.7–14.4 s). Mean LMMs duration was longer in NREM (median 12.7 s, IQR 11.1–15.2 s) versus REM sleep (median 10.3 s, IQR 8.0–13.5s), p < 0.001. LMMs associated with awakening increased with age (p = 0.029). LMMs indices in TST were higher in men than women (p = 0.018). LMMs indices correlated positively with N1 sleep percentage (ρ = 0.49, p < 0.001), arousal index (ρ = 0.40, p = 0.002), sleep stages shift index (ρ = 0.43, p < 0.001, apnea index (ρ = 0.36, p = 0.017), and video-visible movements indices (ρ = 0.45, p < 0.001), and negatively with N3 sleep (ρ = −0.38, p= 0.004) percentage.

Conclusions

This is the first study providing normative data on LMMs frequency in healthy adults. LMMs are a ubiquitous phenomenon often associated with other events. Correlation with arousals and respiratory events suggests a potential clinical significance of LMMs in adults that awaits further investigation.
Predicting fecal composition, intake, and nutrient digestibility in beef cattle consuming high forage diets using near infrared spectroscopy
Authors: Peters Jenilee F , Swift Mary L , Penner Gregory B , Lardner Herbert A , McAllister Tim A , Ribeiro Gabriel O
Published: May 2023

The objective of this study was to develop near infrared spectroscopy (NIRS) calibrations to predict fecal nutrient composition, intake, and diet digestibility from beef cattle fed high forage diets. Heifers were fed 12 different forage-based diets (>95% forage dry matter basis) in 3 total collection digestibility studies, resulting in individual fecal samples and related spectra (n = 135), corresponding nutrient intake, and apparent total tract digestibility (aTTD) data. Fecal samples were also collected from steers grazing two annual and two perennial forage mixtures over two growing seasons. Samples (n = 13/paddock) were composited by paddock resulting in 30 samples from year 1, and 24 from year 2. The grazing fecal spectra (n = 54) were added to the existing fecal composition spectral library. Dried and ground fecal samples were scanned using a FOSS DS2500 scanning monochromator (FOSS, Eden Prairie, MN). Spectra were mathematically treated for detrend and scatter correction and modified partial least squares (MPLS) regression was performed. The coefficient of determination for cross validation (R2cv) and standard error of cross validation (SECV) were used to evaluate the quality of calibrations. Prediction equations were developed for fecal composition [organic matter (OM), nitrogen (N), amylase-treated ash-corrected neutral detergent fiber (aNDFom), acid detergent fiber (ADF), acid detergent lignin (ADL), undigestible NDF after 240 h of in vitro incubation (uNDF), calcium (Ca), and phosphorus (P)], digestibility [DM, OM, aNDFom, N], and intake [DM, OM, aNDFom, N, uNDF]. The calibrations for fecal OM, N, aNDFom, ADF, ADL, uNDF, Ca, P resulted in R2cv between 0.86 and 0.97 and SECV of 1.88, 0.07, 1.70, 1.10, 0.61, 2.00, 0.18, and 0.06, respectively. Equations predicting intake of DM, OM, N, aNDFom, ADL, and uNDF resulted in R2cv values between 0.59 and 0.91, SECV values of 1.12, 1.10, 0.02, 0.69, 0.06, 0.24 kg·d−1, respectively, and SECV values between 0.00 and 0.16 when expressed as % body weight (BW). Digestibility calibrations for DM, OM, aNDFom, and N resulted in R2cv ranging from 0.65 to 0.74 and SECV values from 2.20 to 2.82. We confirm the potential of NIRS to predict fecal chemical composition, digestibility, and intake of cattle fed high forage diets. Future steps include validation of the intake calibration equations for grazing cattle using forage internal marker and modelling energetics of grazing growth performance.
STAR-Caregivers Virtual Training and Follow-up: a cultural adaptation for Latino caregivers of people with dementia
Authors: Ramirez Magaly , Duran Miriana C , Penfold Robert B , Pabiniak Chester J , Hansen Kelly E , Ornelas India J
Published: May 2023

STAR-Caregivers Virtual Training and Follow-up (STAR-VTF) is an evidence-based intervention that teaches family caregivers how to manage behavioral and psychological symptoms of dementia. The study objective was to identify what adaptations to STAR-VTF are needed to improve cultural relevance for Latino caregivers. A qualitative research study was conducted that interviewed Spanish- and English-speaking caregivers of people with dementia who self-identify as Hispanic/Latino (N = 30) and healthcare and social service providers of older Latino clients and/or Latino family caregivers (N = 14). Thematic analysis methods were applied to code and analyze interview transcripts. The codebook was theory-driven, relying mainly on codes that directly represented components of the Cultural Treatment Adaptation Framework. Based on the content of the excerpts, the codes were sorted into themes that represented opportunities to culturally adapt STAR-VTF. Three themes were identified: (i) there was a need to increase awareness about dementia and decrease stigma; (ii) semantics mattered as certain words and phrases could be stigmatizing, offensive, or culturally inappropriate; and (iii) there was a need to incorporate into program materials the traditional family structure and nature of caregiving in Latino families. Based on findings, adaptations were performed on STAR-VTF that included expanding content to improve understanding of dementia, revising language that was viewed as problematic, and adding cultural examples to reflect the range of family involvement in caring for people living with dementia and multigenerational living. Findings from this qualitative research study advance understanding of the Latino caregiver experience and how to modify programs to better serve their needs.
Childhood obesity is linked to putative neuroinflammation in brain white matter, hypothalamus, and striatum
Authors: Li Zhaolong Adrian , Samara Amjad , Ray Mary Katherine , Rutlin Jerrel , Raji Cyrus A , Shimony Joshua S , Sun Peng , Song Sheng-Kwei , Hershey Tamara , Eisenstein Sarah A
Published: May 2023

Neuroinflammation is both a consequence and driver of overfeeding and weight gain in rodent obesity models. Advances in magnetic resonance imaging (MRI) enable investigations of brain microstructure that suggests neuroinflammation in human obesity. To assess the convergent validity across MRI techniques and extend previous findings, we used diffusion basis spectrum imaging (DBSI) to characterize obesity-associated alterations in brain microstructure in 601 children (age 9–11 years) from the Adolescent Brain Cognitive DevelopmentSM Study. Compared with children with normal-weight, greater DBSI restricted fraction (RF), reflecting neuroinflammation-related cellularity, was seen in widespread white matter in children with overweight and obesity. Greater DBSI-RF in hypothalamus, caudate nucleus, putamen, and, in particular, nucleus accumbens, correlated with higher baseline body mass index and related anthropometrics. Comparable findings were seen in the striatum with a previously reported restriction spectrum imaging (RSI) model. Gain in waist circumference over 1 and 2 years related, at nominal significance, to greater baseline RSI-assessed restricted diffusion in nucleus accumbens and caudate nucleus, and DBSI-RF in hypothalamus, respectively. Here we demonstrate that childhood obesity is associated with microstructural alterations in white matter, hypothalamus, and striatum. Our results also support the reproducibility, across MRI methods, of findings of obesity-related putative neuroinflammation in children.