bluuebunny/crossref_metadata_2025 huggingface dataset:
Revealing H2O dissociation in WASP-76 b through combined high- and low-resolution transmission spectroscopy
Authors: Gandhi Siddharth , Landman Rico , Snellen Ignas , Welbanks Luis , Madhusudhan Nikku , Brogi Matteo
Published: April 2024

Numerous chemical constraints have been possible for exoplanetary atmospheres thanks to high-resolution spectroscopy (HRS) from ground-based facilities as well as low-resolution spectroscopy (LRS) from space. These two techniques have complementary strengths, and hence combined HRS and LRS analyses have the potential for more accurate abundance constraints and increased sensitivity to trace species. In this work, we retrieve the atmosphere of the ultra-hot Jupiter WASP-76 b, using high-resolution CARMENES/CAHA (Calar Alto high-Resolution search for M dwarfs with Exoearths with Near-infrared and optical Échelle Spectrographs) and low-resolution Hubble Space Telescope’s (HST) Wide Field Camera 3 (WFC3) and Spitzer observations of the primary eclipse. As such, hot planets are expected to have a substantial fraction of H2O dissociated, we conduct retrievals including both H2O and OH. We explore two retrieval models, one with self-consistent treatment of H2O dissociation and another where H2O and OH are vertically homogeneous. Both models constrain H2O and OH, with H2O primarily detected by LRS and OH through HRS, highlighting the strengths of each technique and demonstrating the need for combined retrievals to fully constrain chemical compositions. We see only a slight preference for the H2O-dissociation model given that the photospheric constraints for both are very similar, indicating $\log (\mathrm{OH/H_2O}) = 0.7^{+0.3}_{-0.3}$ at 1.5 mbar, showing that the majority of the H2O in the photosphere is dissociated. However, the bulk O/H and C/O ratios inferred from the models differs significantly, and highlights the challenge of constraining bulk compositions from photospheric abundances with strong vertical chemical gradients. Further observations with JWST and ground-based facilities may help shed more light on these processes.
hayate: photometric redshift estimation by hybridizing machine learning with template fitting
Authors: Tanigawa Shingo , Glazebrook K , Jacobs C , Labbe I , Qin A K
Published: April 2024

Machine learning photo-z methods, trained directly on spectroscopic redshifts, provide a viable alternative to traditional template-fitting methods but may not generalize well on new data that deviates from that in the training set. In this work, we present a Hybrid Algorithm for WI(Y)de-range photo-z estimation with Artificial neural networks and TEmplate fitting (hayate), a novel photo-z method that combines template fitting and data-driven approaches and whose training loss is optimized in terms of both redshift point estimates and probability distributions. We produce artificial training data from low-redshift galaxy spectral energy distributions (SEDs) at z < 1.3, artificially redshifted up to z = 5. We test the model on data from the ZFOURGE surveys, demonstrating that hayate can function as a reliable emulator of eazy for the broad redshift range beyond the region of sufficient spectroscopic completeness. The network achieves precise photo-z estimations with smaller errors (σNMAD) than eazy in the initial low-z region (z < 1.3), while being comparable even in the high-z extrapolated regime (1.3 < z < 5). Meanwhile, it provides more robust photo-z estimations than eazy with the lower outlier rate ($\eta _{0.2}\lesssim 1~{{\ \rm per\ cent}}$) but runs ∼100 times faster than the original template-fitting method. We also demonstrate hayate offers more reliable redshift probability density functions, showing a flatter distribution of Probability Integral Transform scores than eazy. The performance is further improved using transfer learning with spec-z samples. We expect that future large surveys will benefit from our novel methodology applicable to observations over a wide redshift range.
Biochemical and structural characterization of Fapy•dG replication by Human DNA polymerase β
Authors: Gao Shijun , Oden Peyton N , Ryan Benjamin J , Yang Haozhe , Freudenthal Bret D , Greenberg Marc M
Published: April 2024

N6-(2-deoxy-α,β-d-erythro-pentofuranosyl)-2,6-diamino-4-hydroxy-5-formamido-pyrimidine (Fapy•dG) is formed from a common intermediate and in comparable amounts to the well-studied mutagenic DNA lesion 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-OxodGuo). Fapy•dG preferentially gives rise to G → T transversions and G → A transitions. However, the molecular basis by which Fapy•dG is processed by DNA polymerases during this mutagenic process remains poorly understood. To address this we investigated how DNA polymerase β (Pol β), a model mammalian polymerase, bypasses a templating Fapy•dG, inserts Fapy•dGTP, and extends from Fapy•dG at the primer terminus. When Fapy•dG is present in the template, Pol β incorporates TMP less efficiently than either dCMP or dAMP. Kinetic analysis revealed that Fapy•dGTP is a poor substrate but is incorporated ∼3-times more efficiently opposite dA than dC. Extension from Fapy•dG at the 3′-terminus of a nascent primer is inefficient due to the primer terminus being poorly positioned for catalysis. Together these data indicate that mutagenic bypass of Fapy•dG is likely to be the source of the mutagenic effects of the lesion and not Fapy•dGTP. These experiments increase our understanding of the promutagenic effects of Fapy•dG.
Sex differences in chronic kidney disease–related complications and mortality across levels of glomerular filtration rate
Authors: Lombardi Gianmarco , Ferraro Pietro Manuel , De Tomi Elisa , Bargagli Matteo , Spasiano Andrea , Gambaro Giovanni
Published: April 2024

Background

Chronic kidney disease (CKD) is a growing global health concern. Recent research has indicated sex disparities in CKD-related complications, yet the impact of sex differences on critical kidney function levels that trigger these complications and mortality remains inadequately documented.

Methods

We investigated sex-specific disparities in CKD-related complications and mortality according to estimated glomerular filtration rate (eGFR) levels. We analyzed National Health and Nutrition Examination Survey (NHANES) data spanning from 1999 to 2018, including adult participants with an eGFR of 15–150 mL/min/1.73 m2. The outcomes were CKD-related complications [hypertension, anaemia, cardiovascular (CV) diseases, acidosis, hyperphosphatemia, hyperparathyroidism] and all-cause and cause-specific mortality (CV mortality and non-CV mortality). Sex-stratified multivariable logistic and Cox regression models yielded odds ratios and hazard ratios for the relationship between eGFR categories and outcomes. Sex-stratified natural splines were used to explore the relationship between continuous eGFR and outcomes and identified eGFR thresholds of statistical significance.

Results

The study included 49 558 participants (50.3% women, 49.7% men). Multivariable logistic regression demonstrated a significant eGFR association with all CKD-related complications, exhibiting a linear trend across eGFR categories. Modelling eGFR as a natural spline revealed varied significance thresholds between sexes for anaemia and hyperparathyroidism. Additionally, the eGFR–hyperphosphatemia association was more pronounced in men. We observed substantial but not statistically significant differences between men and women in the thresholds of statistical significance for CV (significance appeared at a higher eGFR in men) and non-CV mortality (significance appeared at a higher eGFR in women).

Conclusions

Research shows sex disparities in most CKD-related complications. Men develop anaemia and hyperparathyroidism earlier; women show a steeper anaemia increase. Men have higher CV mortality risk. As eGFR decreased, men faced a higher risk of CV mortality at a higher eGFR threshold than women.
2-Step Scores with optional nephropathology for the prediction of adverse outcomes for brain-dead donor kidneys in Eurotransplant
Authors: Ernst Angela , Regele Heinz , Chatzikyrkou Christos , Dendooven Amélie , Turkevi-Nagy Sándor , Tieken Ineke , Oberbauer Rainer , Reindl-Schwaighofer Roman , Abramowicz Daniel , Hellemans Rachel , Massart Annick , Ljubanovic Danica Galesic , Senjug Petar , Maksimovic Bojana , Aßfalg Volker , Neretljak Ivan , Schleicher Christina , Clahsen-van Groningen Marian , Kojc Nika , Ellis Carla L , Kurschat Christine E , Lukomski Leandra , Stippel Dirk , Ströhlein Michael , Scurt Florian G , Roelofs Joris J , Kers Jesper , Harth Ana , Jungck Christian , Eccher Albino , Prütz Isabel , Hellmich Martin , Vasuri Francesco , Malvi Deborah , Arns Wolfgang , Becker Jan U
Published: April 2024

Background

The decision to accept or discard the increasingly rare and marginal brain-dead donor kidneys in Eurotransplant (ET) countries has to be made without solid evidence. Thus, we developed and validated flexible clinicopathological scores called 2-Step Scores for the prognosis of delayed graft function (DGF) and 1-year death-censored transplant loss (1y-tl) reflecting the current practice of six ET countries including Croatia and Belgium.

Methods

The training set was n = 620 for DGF and n = 711 for 1y-tl, with validation sets n = 158 and n = 162, respectively. In Step 1, stepwise logistic regression models including only clinical predictors were used to estimate the risks. In Step 2, risk estimates were updated for statistically relevant intermediate risk percentiles with nephropathology.

Results

Step 1 revealed an increased risk of DGF with increased cold ischaemia time (CIT), donor and recipient body mass index, dialysis vintage, number of HLA-DR mismatches or recipient cytomegalovirus immunoglobulin G positivity. On the training and validation set, c-statistics were 0.672 and 0.704, respectively. At a range between 18% and 36%, accuracy of DGF-prognostication improved with nephropathology including number of glomeruli and Banff cv (updated overall c-statistics of 0.696 and 0.701, respectively). Risk of 1y-tl increased in recipients with CIT, sum of HLA-A, -B, -DR mismatches, and donor age. On training and validation sets, c-statistics were 0.700 and 0.769, respectively. Accuracy of 1y-tl prediction improved (c-statistics = 0.706 and 0.765) with Banff ct. Overall, calibration was good on the training, but moderate on the validation set; discrimination was at least as good as established scores when applied to the validation set.

Conclusion

Our flexible 2-Step Scores with optional inclusion of time-consuming and often unavailable nephropathology should yield good results for clinical practice in ET, and may be superior to established scores. Our scores are adaptable to donation after cardiac death and perfusion pump use.
Arabidopsis class A S-acyl transferases modify the pollen receptors LIP1 and PRK1 to regulate pollen tube guidance
Authors: Xiang Xiaojiao , Wan Zhi-Yuan , Zhang Shuzhan , Feng Qiang-Nan , Li Shan-Wei , Yin Gui-Min , Zhi Jing-Yu , Liang Xin , Ma Ting , Li Sha , Zhang Yan
Published: April 2024

Protein S-acylation catalyzed by protein S-acyl transferases (PATs) is a reversible lipid modification regulating protein targeting, stability, and interaction profiles. PATs are encoded by large gene families in plants, and many proteins including receptor-like cytoplasmic kinases (RLCKs) and receptor-like kinases (RLKs) are subject to S-acylation. However, few PATs have been assigned substrates, and few S-acylated proteins have known upstream enzymes. We report that Arabidopsis (Arabidopsis thaliana) class A PATs redundantly mediate pollen tube guidance and participate in the S-acylation of POLLEN RECEPTOR KINASE1 (PRK1) and LOST IN POLLEN TUBE GUIDANCE1 (LIP1), a critical RLK or RLCK for pollen tube guidance, respectively. PAT1, PAT2, PAT3, PAT4, and PAT8, collectively named PENTAPAT for simplicity, are enriched in pollen and show similar subcellular distribution. Functional loss of PENTAPAT reduces seed set due to male gametophytic defects. Specifically, pentapat pollen tubes are compromised in directional growth. We determine that PRK1 and LIP1 interact with PENTAPAT, and their S-acylation is reduced in pentapat pollen. The plasma membrane (PM) association of LIP1 is reduced in pentapat pollen, whereas point mutations reducing PRK1 S-acylation affect its affinity with its interacting proteins. Our results suggest a key role of S-acylation in pollen tube guidance through modulating PM receptor complexes.
BRZ-INSENSITIVE-LONG HYPOCOTYL8 inhibits kinase-mediated phosphorylation to regulate brassinosteroid signaling
Authors: Chagan Zhana , Nakata Genki , Suzuki Shin , Yamagami Ayumi , Tachibana Ryo , Surina Surina , Fujioka Shozo , Matsui Minami , Kushiro Tetsuo , Miyakawa Takuya , Asami Tadao , Nakano Takeshi
Published: April 2024

Glycogen synthase kinase 3 (GSK3) is an evolutionarily conserved serine/threonine protein kinase in eukaryotes. In plants, the GSK3-like kinase BRASSINOSTEROID-INSENSITIVE 2 (BIN2) functions as a central signaling node through which hormonal and environmental signals are integrated to regulate plant development and stress adaptation. BIN2 plays a major regulatory role in brassinosteroid (BR) signaling and is critical for phosphorylating/inactivating BRASSINAZOLE-RESISTANT 1 (BZR1), also known as BRZ-INSENSITIVE-LONG HYPOCOTYL 1 (BIL1), a master transcription factor of BR signaling, but the detailed regulatory mechanism of BIN2 action has not been fully revealed. In this study, we identified BIL8 as a positive regulator of BR signaling and plant growth in Arabidopsis (Arabidopsis thaliana). Genetic and biochemical analyses showed that BIL8 is downstream of the BR receptor BRASSINOSTEROID-INSENSITIVE 1 (BRI1) and promotes the dephosphorylation of BIL1/BZR1. BIL8 interacts with and inhibits the activity of the BIN2 kinase, leading to the accumulation of dephosphorylated BIL1/BZR1. BIL8 suppresses the cytoplasmic localization of BIL1/BZR1, which is induced via BIN2-mediated phosphorylation. Our study reveals a regulatory factor, BIL8, that positively regulates BR signaling by inhibiting BIN2 activity.
RNA splicing modulates the postharvest physiological deterioration of cassava storage root
Authors: Gu Jinbao , Ma Xiaowen , Ma Qiuxiang , Xia Zhiqiang , Lin Yan , Yuan Jianbo , Li Yang , Li Cong , Chen Yanhang , Wang Wenquan , Zhang Peng , Wang Zhen-Yu
Published: April 2024

Rapid postharvest physiological deterioration (PPD) of cassava (Manihot esculenta Crantz) storage roots is a major constraint that limits the potential of this plant as a food and industrial crop. Extensive studies have been performed to explore the regulatory mechanisms underlying the PPD processes in cassava to understand their molecular and physiological responses. However, the exceptional functional versatility of alternative splicing (AS) remains to be explored during the PPD process in cassava. Here, we identified several aberrantly spliced genes during the early PPD stage. An in-depth analysis of AS revealed that the abscisic acid (ABA) biosynthesis pathway might serve as an additional molecular layer in attenuating the onset of PPD. Exogenous ABA application alleviated PPD symptoms through maintaining ROS generation and scavenging. Interestingly, the intron retention transcript of MeABA1 (ABA DEFICIENT 1) was highly correlated with PPD symptoms in cassava storage roots. RNA yeast 3-hybrid and RNA immunoprecipitation (RIP) assays showed that the serine/arginine-rich protein MeSCL33 (SC35-like splicing factor 33) binds to the precursor mRNA of MeABA1. Importantly, overexpressing MeSCL33 in cassava conferred improved PPD resistance by manipulating the AS and expression levels of MeABA1 and then modulating the endogenous ABA levels in cassava storage roots. Our results uncovered the pivotal role of the ABA biosynthesis pathway and RNA splicing in regulating cassava PPD resistance and proposed the essential roles of MeSCL33 for conferring PPD resistance, broadening our understanding of SR proteins in cassava development and stress responses.
Jasmonate mimic modulates cell elongation by regulating antagonistic bHLH transcription factors via brassinosteroid signaling
Authors: Wang Xing , Ren Zhaobin , Xie Shipeng , Li Zhaohu , Zhou Yuyi , Duan Liusheng
Published: April 2024

Lodging restricts growth, development, and yield formation in maize (Zea mays L.). Shorter internode length is beneficial for lodging tolerance. However, although brassinosteroids (BRs) and jasmonic acid (JA) are known to antagonistically regulate internode growth, the underlying molecular mechanism is still unclear. In this study, application of the JA mimic coronatine (COR) inhibited basal internode elongation at the jointing stage and repressed expression of the cell wall-related gene XYLOGLUCAN ENDOTRANSGLUCOSYLASE/HYDROLASE 1 (ZmXTH1), whose overexpression in maize plants promoted internode elongation. We demonstrated that the basic helix–loop–helix (bHLH) transcription factor ZmbHLH154 directly binds to the ZmXTH1 promoter and induces its expression, whereas the bHLH transcription factor ILI1 BINDING BHLH 1 (ZmIBH1) inhibits this transcriptional activation by forming a heterodimer with ZmbHLH154. Overexpressing ZmbHLH154 led to longer internodes, whereas zmbhlh154 mutants had shorter internodes than the wild type. The core JA-dependent transcription factors ZmMYC2-4 and ZmMYC2-6 interacted with BRASSINAZOLE RESISTANT 1 (ZmBZR1), a key factor in BR signaling, and these interactions eliminated the inhibitory effect of ZmBZR1 on its downstream gene ZmIBH1. Collectively, these results reveal a signaling module in which JA regulates a bHLH network by attenuating BR signaling to inhibit ZmXTH1 expression, thereby regulating cell elongation in maize.
Validating the “Genuine Pipeline” to Limit Social Desirability Bias in Survey Estimates of Voter Turnout
Authors: DeBell Matthew , Hillygus D Sunshine , Shaw Daron R , Valentino Nicholas A
Published: April 2024

It is well documented that survey overreporting of voter turnout due to social desirability bias threatens inference about political behavior. This paper reports four studies that contained question wording experiments to test questions designed to minimize that bias using a “pipeline” approach. The “pipeline” informs survey participants that researchers can perform vote validation to verify turnout self-reports. This approach reduced self-reported turnout by 5.7 points in the 2020 American National Election Study, which represents a majority of the estimated overreporting bias. It reduced reported turnout by 4 points in two nonprobability samples. No effect was found in a third nonprobability study with Amazon Mechanical Turk workers. Validated vote data also confirm that the pipeline approach reduced overreporting. We tested heterogeneous effects for sophistication and several other variables, but results were inconclusive. The pipeline approach reduces overreporting of voter turnout and produces more accurate estimates of voters’ characteristics.
Public Reactions to Communication of Uncertainty: How Long-Term Benefits Can Outweigh Short-Term Costs
Authors: Stedtnitz Christine , Szewach Paula , Johns Robert
Published: April 2024

Uncertainty is a fact of political life but not a fact of political communication. Elites are prone to make confident predictions and downplay uncertainty about future outcomes, presumably fearing that the acknowledgement of uncertainty would undermine public confidence in their predictions and the evidence they are based on. But this calculation might both exaggerate the costs and downplay the potential benefits of reporting uncertainty. On costs, the evidence from previous studies is mixed; on benefits, previous research has neglected the possibility that, by acknowledging that outcomes may be worse than expected, those communicating uncertainty will dampen public reactions to the bad news. Here, based on a two-stage online survey experiment (N = 2,165) from December 2020 about COVID-19 vaccines, we find results suggesting that governments are well advised to communicate uncertainty. The costs at Stage 1 were low: reporting a confidence interval around the safety and effectiveness of a hypothetical COVID-19 vaccine did not undermine belief in the statistics or intentions to take the vaccine. And there were indeed benefits at Stage 2: when outcomes turned out to be worse than expected but within that confidence interval, confidence in the vaccine was partly insulated from negative effects.
Defending aesthetic internalism: Liking, loving, and wholeheartedness
Authors: Harold James
Published: April 2024

Aesthetic internalism claims a link between judgement and motivation: aesthetic judgements bring with them motivations to act in characteristic ways. Critics object that there is a difference between merely liking something and judging it to be aesthetically good, and that it is our likings, not our aesthetic judgements, that motivate us. This paper develops a version of aesthetic internalism that can respond to this criticism. Wholehearted aesthetic judgements are characterized by stability, attention, and motivation. Making such judgements is an important part of a good life, and so at least some aesthetic judgements are motivating. So we have reason to think that this version of aesthetic internalism is true. This paper defends wholehearted aesthetic internalism against objections, and assesses an argument from aesthetic internalism to aesthetic non-cognitivism. While wholehearted aesthetic internalism can only offer qualified support to non-cognitivism, it nonetheless offers a number of fruitful avenues for further work.
The diagnosis and management of systemic autoimmune rheumatic disease-related interstitial lung disease: British Society for Rheumatology guideline scope
Authors: Hannah Jennifer , Rodziewicz Mia , Mehta Puja , Heenan Kerri-Marie , Ball Elizabeth , Barratt Shaney , Carty Sara , Conway Richard , Cotton Caroline V , Cox Sarah , Crawshaw Anjali , Dawson Julie , Desai Sujal , Fahim Ahmed , Fielding Carol , Garton Mark , George Peter M , Gunawardena Harsha , Kelly Clive , Khan Fasihul , Koduri Gouri , Morris Helen , Naqvi Marium , Perry Elizabeth , Riddell Claire , Sieiro Santos Cristiana , Spencer Lisa G , Chaudhuri Nazia , Nisar Muhammad K
Published: April 2024

Interstitial lung disease (ILD) is a significant complication of many systemic autoimmune rheumatic diseases (SARDs), although the clinical presentation, severity and outlook may vary widely between individuals. Despite the prevalence, there are no specific guidelines addressing the issue of screening, diagnosis and management of ILD across this diverse group. Guidelines from the ACR and EULAR are expected, but there is a need for UK-specific guidelines that consider the framework of the UK National Health Service, local licensing and funding strategies. This article outlines the intended scope for the British Society for Rheumatology guideline on the diagnosis and management of SARD-ILD developed by the guideline working group. It specifically identifies the SARDs for consideration, alongside the overarching principles for which systematic review will be conducted. Expert consensus will be produced based on the most up-to-date available evidence for inclusion within the final guideline. Key issues to be addressed include recommendations for screening of ILD, identifying the methodology and frequency of monitoring and pharmacological and non-pharmacological management. The guideline will be developed according to methods and processes outlined in Creating Clinical Guidelines: British Society for Rheumatology Protocol version 5.1.
Tapping into Talent: Coupling Education and Innovation Policies for Economic Growth
Authors: Akcigit Ufuk , Pearce Jeremy , Prato Marta
Published: April 2024

How do innovation and education policy affect individual career choices and aggregate productivity? This paper analyses the effect of R&D subsidies and higher education policy on productivity growth through the supply of innovative talent. We put scarce talent, higher education attainment, and career choice at the centre of a new endogenous growth framework with individual-level heterogeneity in talent, financial resources, and preferences. We link the model to micro-level data from Denmark on the backgrounds of who obtains a PhD and becomes an inventor and the outcomes of a set of policy interventions. We find that R&D subsidies can be strengthened when combined with higher education subsidies, which enable talented but poor youth to pursue a career in research. Education and innovation policies not only alleviate different frictions, but also impact innovation at different time horizons. Education policy is more effective in societies with higher income inequality.
Prognostic factors for colchicine prophylaxis-related adverse events when initiating allopurinol for gout: retrospective cohort study
Authors: Bajpai Ram , Partington Richard , Muller Sara , Forrester Harry , Mallen Christian D , Clarson Lorna , Padmanabhan Nishita , Whittle Rebecca , Roddy Edward
Published: April 2024

Objectives

Colchicine is commonly used to prevent flares when starting urate-lowering therapy for gout. Patients with gout are frequently concurrently prescribed other medications (such as statins) that may interact with colchicine, increasing the risk of adverse events. The aim of this study was to describe potential prognostic factors for adverse events in patients prescribed colchicine when initiating allopurinol.

Methods

We conducted a retrospective cohort study in linked UK Clinical Practice Research Datalink and Hospital Episode Statistics datasets. Adults initiating allopurinol for gout with colchicine (1 April 1997 to 30 November 2016) were included. Potential prognostic factors were defined, and the likelihood of adverse events, including diarrhoea, nausea or vomiting, myocardial infarction, neuropathy, myalgia, myopathy, rhabdomyolysis and bone marrow suppression, were estimated.

Results

From 1 April 1997 to 30 November 2016, 13 945 people with gout initiated allopurinol with colchicine prophylaxis [mean age 63.9 (s.d. 14.7) years, 78.2% male]. One-quarter (26%, 95% CI 25%, 27%) were prescribed one or more potentially interacting medicines, most commonly statins (21%, 95% CI 20%, 22%). Statins were not associated with increased adverse events, although other drugs were associated with some adverse outcomes. Diarrhoea and myocardial infarction were associated with more comorbidities and more severe chronic kidney disease.

Conclusion

People were given colchicine prophylaxis despite commonly having preexisting prescriptions for medications with potential to interact with colchicine. Adverse events were more common in people who had more comorbidities and certain potentially interacting medications. Our findings will provide much-needed information about prognostic factors for colchicine-related adverse events that can inform treatment decisions about prophylaxis when initiating allopurinol.
Initial public offerings and the local economy: evidence of crowding out
Authors: Cornaggia Jess , Gustafson Matthew , Kotter Jason , Pisciotta Kevin
Published: April 2024

We test the effect of going public on economic growth in the areas surrounding initial public offering (IPO) firms. We compare the effects of IPO filers that complete their IPOs with those that do not, using post-filing stock market fluctuations as an instrument for IPO completion. We show that IPOs that are large relative to the size of their counties lead to a 1.1 percentage point relative reduction in annual county-level establishment growth, with similar effects for employment and population growth. There are no corresponding effects for relatively small IPOs. These negative effects appear to be driven by a crowding out of local sector peers, but the crowding out also disrupts local agglomerations and slows down growth among other businesses that rely on local demand. Overall, our results indicate that macroeconomic gains from IPOs trade off against disruptions in local agglomeration economies where public firms originate.
Parameter grouping and co-estimation in physiologically based kinetic models using genetic algorithms
Authors: Tsiros Periklis , Minadakis Vasileios , Li Dingsheng , Sarimveis Haralambos
Published: April 2024

Physiologically based kinetic (PBK) models are widely used in pharmacology and toxicology for predicting the internal disposition of substances upon exposure, voluntarily or not. Due to their complexity, a large number of model parameters need to be estimated, either through in silico tools, in vitro experiments, or by fitting the model to in vivo data. In the latter case, fitting complex structural models on in vivo data can result in overparameterization and produce unrealistic parameter estimates. To address these issues, we propose a novel parameter grouping approach, which reduces the parametric space by co-estimating groups of parameters across compartments. Grouping of parameters is performed using genetic algorithms and is fully automated, based on a novel goodness-of-fit metric. To illustrate the practical application of the proposed methodology, two case studies were conducted. The first case study demonstrates the development of a new PBK model, while the second focuses on model refinement. In the first case study, a PBK model was developed to elucidate the biodistribution of titanium dioxide (TiO2) nanoparticles in rats following intravenous injection. A variety of parameter estimation schemes were employed. Comparative analysis based on goodness-of-fit metrics demonstrated that the proposed methodology yields models that outperform standard estimation approaches, while utilizing a reduced number of parameters. In the second case study, an existing PBK model for perfluorooctanoic acid (PFOA) in rats was extended to incorporate additional tissues, providing a more comprehensive portrayal of PFOA biodistribution. Both models were validated through independent in vivo studies to ensure their reliability.
People with painful knee osteoarthritis hold negative implicit attitudes towards activity
Authors: Pulling Brian W. , Braithwaite Felicity A. , Mignone Joanne , Butler David S. , Caneiro J.P. , Lipp Ottmar V. , Stanton Tasha R.
Published: April 2024

Negative attitudes/beliefs surrounding osteoarthritis, pain, and activity contribute to reduced physical activity in people with knee osteoarthritis (KOA). These attitudes/beliefs are assessed using self-report questionnaires, relying on information one is consciously aware of and willing to disclose. Automatic (ie, implicit) assessment of attitudes does not rely on conscious reflection and may identify features unique from self-report. We developed an implicit association test that explored associations between images of a person moving/twisting their knee (activity) or sitting/standing (rest), and perceived threat (safe vs dangerous). We hypothesised that people with KOA would have greater implicit threat–activity associations (vs pain-free and non-knee pain controls), with implicit attitudes only weakly correlating with self-reported measures (pain knowledge, osteoarthritis/pain/activity beliefs, fear of movement). Participants (n = 558) completed an online survey: 223 had painful KOA (n = 157 female, 64.5 ± 8.9 years); 207 were pain free (n = 157 female, 49.3 ± 15.3 years); and 99 had non-KOA lower limb pain (n = 74 female, 47.5 ± 15.04 years). An implicit association between “danger” and “activity” was present in those with and without limb pain (KOA: 0.36, 95% CI 0.28-0.44; pain free: 0.13, 95% CI 0.04-0.22; non-KOA lower limb pain 0.11, 95% CI −0.03 to 0.24) but was significantly greater in the KOA group than in the pain free (P < 0.001) and non-KOA lower limb pain (P = 0.004) groups. Correlations between implicit and self-reported measures were nonsignificant or weak (rho = −0.29 to 0.19, P < 0.001 to P = 0.767). People with painful KOA hold heightened implicit threat–activity associations, capturing information unique to that from self-report questionnaires. Evaluating links between implicit threat–activity associations and real-world behaviour, including physical activity levels, is warranted.
Re-188 lipiodol in hepatocellular carcinoma with portal vein thrombosis: a pilot study using novel chelating agent N-DEDC and its comparison with (A)HDD
Authors: Datta Gupta Shreya Shalimar , Shamim Shamim A. , Gamanagatti Shivanand , Gupta Priyanka , Khan Maroof A. , Mallia Madhav B. , Chirayil Viju , Dash Ashutosh , Bal Chandrasekhar
Published: April 2024

Objective

Hepatocellular carcinoma (HCC) with portal vein thrombosis (PVT) have limited therapeutic options, Re-188 lipiodol transarterial therapy being one of them. We aimed to assess the safety and efficacy of Re-188 lipiodol exclusively in HCC with PVT as well as to compare two chelating agents for the synthesis of Re-188 lipiodol: novel bis-(diethyldithiocarbamato) nitrido (N-DEDC) with existing acetylated 4-hexadecyl 1-2,9,9-tetramethyl-4,7-diaza-1,10-decanethiol [(A)HDD].

Methods

Patients with radiological diagnosis of HCC with PVT having Eastern Cooperative Oncology Group (ECOG) performance status ≤2 and Child Pugh score (PS) A or B were recruited. Patients received an empirical dose of transarterial Re-188 lipiodol, labelled with (A)HDD or N-DEDC. Radiological response on MRI (modified response evaluation criteria in solid tumors), biochemical response with serum alpha fetoprotein and clinical response with ECOG PS was assessed at three months and survival was estimated at the end of the study.

Results

Fifteen therapies were performed in 14 patients with a median age of 62 years (range: 41–70 years). Eight therapies were with Re-188 (A)HDD lipiodol and seven with Re-188 N-DEDC lipiodol. Overall mean injected dose was 2.6 ± 0.37 GBq. Radiological objective response rate was 31% and disease control rate was 85%. Mean overall survival was 14.21 months and mean progression free survival was 10.23 months. Percentage survival assessed at 3, 6 and 9 months was 93%, 64% and 57%, respectively. Safety parameters, response and survival outcome were comparable for (A)HDD and N-DEDC groups.

Conclusion

Transarterial Re-188 lipiodol in HCC with PVT is safe and effective in disease control as well as improving survival outcome. Additionally, cost-effective and high-yielding novel agent N-DEDC appears to be a comparable alternative to (A)HDD for the same.
Major Clinical Adverse Events of Breast Implant in the Manufacturer and User Facility Device Experience Database
Authors: Su Bing , Chen Lichuan , Zhang Bohan , Wang Hong , Zhou Jie , Du Benjun
Published: April 2024

Objective

Search the Manufacturer and User Facility Device Experience database to collect information on adverse events of breast implant. We analyzed the local complications and the breast implant illness (BII) of silicone breast implants, as well as saline breast implants separately, aim to provide a reference for women who want to breast augmentation.

Materials and Methods

The Manufacturer and User Facility Device Experience database was queried for events reports related to the breast implant between July 1, 2012, and June 30, 2022. Event year and reporting year were summarized. Patient problem was collected and analyzed to distinguish between local complications and BII.

Results

A total of 108,728 adverse events in the past 3 years were analyzed, silicone breast implants accounted for 62.1% and saline breast implants accounted for 37.9%. The most common local complication of women receiving silicone breast implants was “Capsular Contracture,” accounting for 48.73%. However, the incidence of “capsular contracture” in women who received saline breast implants was only 17.49%. The most common BII was “fatigue/weakness” in both women receiving 2 different breast implants, 17.20% in women receiving silicone breast implants and 24.71% in women receiving saline breast implants. Of note, in all the reports, there was a wide variation in the timing of reporting as compared with the timing of the adverse event.

Conclusions

Although the adverse events of breast implant cannot completely be determined from this study, we provide a reference for women who want to get breast implants, so that they can choose breast implants more carefully. In addition, a better understanding of BII may allow them to think further about whether the benefits of breast implants outweigh the risks.
HIV combined with skin infection of Nocardia brasiliensis: A rare case report
Authors: XING YUN , Li Shilu
Published: April 2024

Introduction. The HIV virus can attack and gradually damage the human immune system, causing the host to be unprotected when infected. Nocardia is a type of opportunistic pathogenic bacteria that can easily cause infections in patients with chronic wasting diseases, immune dysfunction, and the use of immunosuppressants. Nocardia can invade various tissues and parts of the body, causing corresponding clinical symptoms. There are few reports of HIV patients being infected with Brazilian Nocardia.
 
Case presentation. This article reports a case of an HIV patient with concurrent infection with Brazilian Nocardia. A patient with HIV developed a lump on the surface of their left skin without any obvious cause. Due to improper disinfection and treatment methods, the condition worsened, and they subsequently sought medical attention at our hospital. A series of laboratory related tests are conducted clinically based on the patient's medical history, symptoms, and signs. Based on the test results, a reasonable treatment plan was adopted clinically, ultimately achieving satisfactory treatment outcomes for patients.
 
Conclusion . HIV patients are prone to various types of infections, even rare bacteria, as their immune function decreases. With the popularity of new identification methods such as mass spectrometry, laboratories should pay attention to traditional staining methods and use microscopes to detect pathogens.
Exploration and characterization of a newly isolated bacterium, Enterobacter quasihormaechei strain BDIFST24001, capable of producing rhamnolipids biosurfactant for oil remediation
Authors: Jui Afsana Habib , Bhuiyan Mohammad Nazrul Islam , Bhowmik Banasree , Khatun Nazia , Chowdhury Abhijit , Bhuiyan Riyadh Hossen , Kabir Md. Alamgir , Rashid Md. Mamunur , Bhuiyan Md. Habibur Rahman , Afrin Sadia
Published: April 2024

Biosurfactants are naturally occurring compounds synthesized by microorganisms that increasingly attract attention due to both their living area and application in various industries. In this study, we explore and characterize a novel bacterium, Enterobacter quasihormaechei strain BDIFST24001, isolated for its ability to produce rhamnolipids biosurfactants, with the aim of facilitating oil remediation processes. The isolation of this bacterium was carried out using Luria-Bertani broth (LB) media from environmental samples collected from oil-contaminated sites in Dhaka city. Screening tests, including the oil spreading method and drop collapse assay, were conducted to identify potential biosurfactant-producing strains, leading to the selection of E. quasihormaechei strain BDIFST24001 based on its favorable performance. Subsequent molecular identification revealed a high similarity of the strain's 16S rRNA gene to E. quasihormaechei, which was corroborated through phylogenetic analysis. Further analysis of the biosurfactant produced by this strain indicated its rhamnolipids nature, as confirmed by FT-IR spectroscopy. The rhamnolipids exhibited promising surface-active properties, including a significant reduction in surface tension and emulsification activity, as evidenced by surface tension measurements and emulsification index assays. Optimization studies revealed that the optimal conditions for rhamnolipids production by E. quasihormaechei strain BDIFST24001 were a temperature of 37°C, pH 10.0, and salinity of 4%. The rhamnolipids produced by this strain demonstrated effective oil remediation capabilities, as observed through controlled experiments using petrol oil. The rhamnolipids effectively reduced the surface tension of the oil-water interface, facilitating the dispersion and emulsification of the oil phase in water. Overall, our findings highlight the potential of E. quasihormaechei strain BDIFST24001 as a promising candidate for biosurfactant-mediated oil spill cleanup and environmental remediation efforts.
Potent and reversible open-channel blocker of NMDA receptor derived from dizocilpine with enhanced membrane-to-channel inhibition
Authors: Misiachna Anna , Konecny Jan , Kolcheva Marharyta , Ladislav Marek , Prchal Lukas , Netolicky Jakub , Kortus Stepan , Barackova Petra , Langore Emily , Novak Martin , Hemelikova Katarina , Hermanova Zuzana , Hrochova Michaela , Pelikanova Anezka , Odvarkova Jitka , Pejchal Jaroslav , Kassa Jiri , Karasova Jana Zdarova , Korabecny Jan , Soukup Ondrej , Horak Martin
Published: April 2024

N-methyl-D-aspartate receptors (NMDARs) play a significant role in developing several central nervous system (CNS) disorders. Currently, memantine, used for treating Alzheimer’s disease, and ketamine, known for its anesthetic and antidepressant properties, are two clinically used NMDAR open-channel blockers. However, despite extensive research into NMDAR modulators, many have shown either harmful side effects or inadequate effectiveness. For instance, dizocilpine (MK-801) is recognized for its powerful psychomimetic effects due to its high-affinity and nearly irreversible inhibition of the GluN1/GluN2 NMDAR subtypes. Unlike ketamine, memantine and MK-801 also act through a unique, low-affinity “membrane-to-channel inhibition” (MCI). We aimed to develop an open-channel blocker based on MK-801 with distinct inhibitory characteristics from memantine and MK-801. Our novel compound, K2060, demonstrated effective voltage-dependent inhibition in the micromolar range at key NMDAR subtypes, GluN1/GluN2A and GluN1/GluN2B, even in the presence of Mg2+. K2060 showed reversible inhibitory dynamics and a partially trapping open-channel blocking mechanism with a significantly stronger MCI than memantine. Using hippocampal slices, 30 µM K2060 inhibited excitatory postsynaptic currents in CA1 hippocampal neurons by ∼51%, outperforming 30 µM memantine (∼21% inhibition). K2060 exhibited No Observed Adverse Effect Level (NOAEL) of 15 mg/kg upon intraperitoneal administration in mice. Administering K2060 at a 10 mg/kg dosage resulted in brain concentrations of approximately 2 µM, with peak concentrations (Tmax) achieved within 15 minutes. Finally, applying K2060 with trimedoxime and atropine in mice exposed to tabun improved treatment outcomes. These results underscore K2060’s potential as a therapeutic agent for CNS disorders linked to NMDAR dysfunction.
NSm is a critical determinant for bunyavirus transmission between vertebrate and arthropod hosts
Authors: Terhzaz Selim , Kerrigan David , Almire Floriane , Szemiel Agnieszka M , Palmarini Massimo , Kohl Alain , Shi Xiaohong , Pondeville Emilie
Published: April 2024

Bunyaviralesis a very large order including viruses infecting a variety of taxonomic groups such as arthropods, vertebrates, plants, and protozoan. Some bunyaviruses are transmitted between vertebrate hosts by blood-sucking arthropods and cause major diseases in humans and animals. It is not understood why only some bunyaviruses have evolved the capacity to be transmitted by arthropod vectors. Here we show that only vector-borne bunyaviruses express a non-structural protein, NSm, whose function has so far remained largely elusive. Using as experimental system Bunyamwera virus (BUNV) and its invertebrate host,Aedes aegypti, we show that NSm is dispensable for viral replication in mosquito cellsin vitrobut is absolutely required for successful infection in the female mosquito following a blood meal. More specifically, NSm is required for cell-to-cell spread and egress from the mosquito midgut, a known barrier to viral infection. Notably, the requirement for NSm is specific to the midgut; bypassing this barrier by experimental intrathoracic infection of the mosquito eliminates the necessity of NSm for virus spread in other tissues, including the salivary glands. Overall, we unveiled a key evolutionary process that allows the transmission of vector-borne bunyaviruses between arthropod and vertebrate hosts.
Designing quantum annealing schedules using Bayesian optimization
Authors: Finžgar Jernej Rudi , Schuetz Martin J. A. , Brubaker J. Kyle , Nishimori Hidetoshi , Katzgraber Helmut G.
Published: April 2024

We propose and analyze the use of Bayesian optimization techniques to design quantum annealing schedules with minimal user and resource requirements. We showcase our scheme with results for two paradigmatic spin models. We find that Bayesian optimization is able to identify schedules resulting in fidelities several orders of magnitude better than standard protocols for both quantum and reverse annealing, as applied to the p-spin model. We also show that our scheme can help improve the design of hybrid quantum algorithms for hard combinatorial optimization problems, such as the maximum independent set problem, and illustrate these results via experiments on a neutral-atom quantum processor available on Amazon Braket.

Published by the American Physical Society
2024
Leadership empowerment behavior and employee referrals: chain mediation of perceived challenge stress and employee experience
Authors: Li Teng , Yi Lingfeng
Published: April 2024

Purpose

Internal employees of firms are a reliable source of information for potential job seekers. However, few studies have focused on why internal employees actively recommend their firms. Based on the social exchange theory, this study aims to construct a chain mediation model using perceived challenge stress and employee experience as mediators to explore how leadership empowerment behavior affects employee referrals.

Design/methodology/approach

Bootstrap repeated sampling analysis was conducted on a sample of 307 employees collected through two-time points.

Findings

Leadership empowerment behavior is positively related to employee referrals; perceived challenge stress and employee experience mediate the effect of leadership empowerment behavior on employee referrals, respectively; in addition, perceived challenge stress and employee experience play a chain mediating role between leadership empowerment behavior and employee referrals.

Originality/value

The findings can help provide insight into the drivers of employee referrals and can effectively guide organization reputation management.