bluuebunny/crossref_metadata_2025 huggingface dataset:
Perturbative analysis of low-frequency instabilities in high-field ST40 experiments
Authors: Duarte V.N. , Gorelenkov N.N. , Kaye S.M. , Bonofiglo P.J. , Podestà M. , Bland J. , Buxton P. , Gryaznevich M. , Romanelli M. , Sertoli M.
Published: January 2023

Linear and nonlinear perturbative analyses of low-frequency instabilities are presented for ST40 spherical torus high field plasmas, with simultaneous neutral beam heating due to two tangential sources at 25 keV and 55 keV. Initial plasma profiles on which the TRANSP and NUBEAM codes were based were obtained using an integrated analysis of several diagnostics including line-of-sight integrated and volume average measurements, as well as limited profile information from a charge-exchange-recombination spectrometer. Magnetohydrodynamics (MHD) analysis using the NOVA/NOVA-K codes suggests that the modes in the experiments are core-localized n = 1 eigenmodes with mixed acoustic and electromagnetic Alfvénic polarization. The global transport combined with the perturbative mode analysis indicates that there is greater tendency for bursty chirping response as the level of background micro-turbulence decreases in time and those predictions are shown to be consistent with the experimental data. This finding is interpreted in terms of the suppression of coherent phase-space structures that support chirping when the resonant fast ion dynamics is dominated by frequent stochastic, orbit-decorrelating events.
A high-resolution clock phase shifter circuitry for ALTIROC
Authors: Huang X. , de La Taille C. , Gong D. , Liu C. , Liu T. , Morenas M. , Seguin-Moreau N. , Ye J. , Zhang L.
Published: January 2023

A high-resolution clock phase shifter is implemented to adjust the phase of multiple clocks at 40 MHz, 80 MHz, or 640 MHz in the ALTIROC chip. The phase shifter has a coarse-phase shifter and a fine-phase shifter to achieve a step size of 97.7 ps and an adjustable range of 25 ns. The fine delay unit is based on a Delay Locked Loop (DLL) operating at 640 MHz. The phase shifter is fabricated in a 130 nm CMOS process. The area of the phase shifter is 725 µm × 248 µm. The Differential Non-Linearity (DNL) and the Integral Non-Linearity (INL) are ±0.6 LSB and ±0.75 LSB, respectively. The jitter from −25 °C to 20 °C is less than 15.5 ps (RMS), including the contributions from the FPGA clock source and the PLL. The power consumption is 11.2 mW.
The Airy2 process and the 3D Ising model
Authors: Ferrari Patrik L , Shlosman Senya
Published: January 2023

The Ferrari–Spohn diffusion process arises as limit process for the 2D Ising model as well as random walks with area penalty. Motivated by the 3D Ising model, we consider M such diffusions conditioned not to intersect. We show that the top process converges to the Airy2 process as

M
→
∞

. We then explain the relation with the 3D Ising model and present some conjectures about it.
Fully solution-processed carbon nanotubes thin film transistors and PMOS inverters on glass substrate
Authors: Singh Subhash
Published: January 2023

We report fully solution-processed thin film transistors and PMOS inverters fabricated on glass substrates using single-walled carbon nanotubes (SWCNTs) as active semiconducting material. All the electrodes (gate, source, and drain) were inkjet-printed using silver (Ag) as conductive ink. Spin coated poly-4-vinylphenol dielectric was optimized in terms of thickness and heating conditions for solution-processed SWCNTs thin film transistors to achieve a mobility equal to 0.81 cm2 V−1s−1. We will show that, hole traps at the dielectric-semiconductor interface are responsible for the hysteresis in the transfer curve, and controlled by the different sweep rate of the gate field. Drain-current transients under different bias conditions were studied and the increase in current occurs due to slow polarizations of residual dipolar groups in the dielectric. The adopted technology has been exploited to fabricate a PMOS inverter and studied for high gain and noise margin values at the supply voltage, V
DD = −40 V.
What’s not trending on Weibo: China’s missing climate change discourse
Authors: Liu Chuxuan , Wallace Jeremy Lee
Published: January 2023

Given the central role of People’s Republic of China (PRC) in the global climate crisis, discussion and analysis of Chinese actions and pledges on decarbonization abound. However, less examined are the popular ‘demand’ side of climate change politics inside of China. Our article explores a new set of data to gauge public discourse in China related to climate change by looking at trending topics on the prominent social media platform, Sina Weibo. In over 348,000 trending topics on Weibo from June 2017 to February 2021, we find only 336 unique topics, that is 0.12%, related to climate change. Even in the rare occasions when climate-related topics start trending, we find a general lack of substantive engagement in Weibo posts.
Extreme pressure properties of garlic oil: comparative investigations with PAO4 base oil and PAO/garlic oil blend
Authors: Bashir Shahnaz , Khan M Jebran , Wani M F , Saleem S Shahid , John Mir Mohsin , Ashraf Qazi Junaid , Nissar Tabin
Published: January 2023

This study aims at exploring the improvement in extreme pressure (EP) properties with addition of natural Garlic oil as EP additive. Comparative investigations were conducted on PAO4 base oil, Natural Garlic oil (NGO) and PAO4 + 1 wt% NGO (Natural Garlic Oil) for evaluating the extreme pressure properties. The EP tests were conducted on a four ball tester according to ASTM D 2783. The results revealed that NGO possesses significantly good extreme pressure properties having a weld load of 3087N and load wear index of 513N. The results also revealed that NGO could significantly improve the weld load and load wear index of PAO4 base oil. After adding 1 wt% garlic oil to PAO4 the load wear index increased by 62.51% and weld load increased by 25%. This study proposes garlic oil as a replacement to the use of nano-particles as EP additives and aims to eliminate the disadvantages that are prominent with nano-particles without comprising the performance.
On the stable Harbourne conjecture for ideals defining space monomial curves
Authors: Fukumuro Kosuke , Irie Yuki
Published: January 2023

For the ideal

p

\mathfrak {p}

in

k
[
x
,
y
,
z
]

k[x, y, z]

defining a space monomial curve, we show that

p

(
2
n
−
1
)

⊆

m

p

n

\mathfrak {p}^{(2 n - 1)} \subseteq \mathfrak {m} \mathfrak {p}^{n}

for some positive integer

n
n

, where

m

\mathfrak {m}

is the maximal ideal

(
x
,
y
,
z
)

(x, y, z)

. Moreover, the smallest such

n
n

is determined. It turns out that there is a counterexample to a claim due to Grifo, Huneke, and Mukundan, which states that

p

(
3
)

⊆

m

p

2

\mathfrak {p}^{(3)} \subseteq \mathfrak {m} \mathfrak {p}^2

if

k
k

is a field of characteristic not

3
3

; however, the stable Harbourne conjecture holds for space monomial curves as they claimed.
AFTGAN: prediction of multi-type PPI based on attention free transformer and graph attention network
Authors: Kang Yanlei , Elofsson Arne , Jiang Yunliang , Huang Weihong , Yu Minzhe , Li Zhong
Published: January 2023

Motivation

Protein–protein interaction (PPI) networks and transcriptional regulatory networks are critical in regulating cells and their signaling. A thorough understanding of PPIs can provide more insights into cellular physiology at normal and disease states. Although numerous methods have been proposed to predict PPIs, it is still challenging for interaction prediction between unknown proteins. In this study, a novel neural network named AFTGAN was constructed to predict multi-type PPIs. Regarding feature input, ESM-1b embedding containing much biological information for proteins was added as a protein sequence feature besides amino acid co-occurrence similarity and one-hot coding. An ensemble network was also constructed based on a transformer encoder containing an AFT module (performing the weight operation on vital protein sequence feature information) and graph attention network (extracting the relational features of protein pairs) for the part of the network framework.

Results

The experimental results showed that the Micro-F1 of the AFTGAN based on three partitioning schemes (BFS, DFS and the random mode) on the SHS27K and SHS148K datasets was 0.685, 0.711 and 0.867, as well as 0.745, 0.819 and 0.920, respectively, all higher than that of other popular methods. In addition, the experimental comparisons confirmed the performance superiority of the proposed model for predicting PPIs of unknown proteins on the STRING dataset.

Availability and implementation

The source code is publicly available at https://github.com/1075793472/AFTGAN.

Supplementary information

Supplementary data are available at Bioinformatics online.
BLTSA: pseudotime prediction for single cells by branched local tangent space alignment
Authors: Li Limin , Zhao Yameng , Li Huiran , Zhang Shuqin
Published: January 2023

Motivation

The development of single-cell RNA sequencing (scRNA-seq) technology makes it possible to study the cellular dynamic processes such as cell cycle and cell differentiation. Due to the difficulties in generating genuine time-series scRNA-seq data, it is of great importance to computationally infer the pseudotime of the cells along differentiation trajectory based on their gene expression patterns. The existing pseudotime prediction methods often suffer from the high level noise of single-cell data, thus it is still necessary to study the single-cell trajectory inference methods.

Results

In this study, we propose a branched local tangent space alignment (BLTSA) method to infer single-cell pseudotime for multi-furcation trajectories. By assuming that single cells are sampled from a low-dimensional self-intersecting manifold, BLTSA first identifies the tip and branching cells in the trajectory based on cells’ local Euclidean neighborhoods. Local coordinates within the tangent spaces are then determined by each cell’s local neighborhood after clustering all the cells to different branches iteratively. The global coordinates for all the single cells are finally obtained by aligning the local coordinates based on the tangent spaces. We evaluate the performance of BLTSA on four simulation datasets and five real datasets. The experimental results show that BLTSA has obvious advantages over other comparison methods.

Availability and implementation

R codes are available at https://github.com/LiminLi-xjtu/BLTSA.

Supplementary information

Supplementary data are available at Bioinformatics online.
Immunological Efficacy of Pneumococcal Vaccination Including the 13-Valent Pneumococcal Conjugate Vaccine in Adult Patients With Sickle Cell Disease: Results of the Randomized DREVAC Controlled Trial
Authors: Melica Giovanna , Bartolucci Pablo , Audureau Etienne , Le Corvoisier Philippe , Habibi Anoosha , Gellen Justine , Selmane Dalia , Michel Marc , Lacabaratz Christine , Levy Yves
Published: January 2023

Background

Patients with sickle cell disease (SCD) are at high risk for invasive pneumococcal diseases. The immunological efficacy of 13-valent conjugate pneumococcal vaccine (PCV13) followed by a 23-valent polysaccharide vaccine (PPSV23) is poorly documented in adults with SCD.

Methods

This was a randomized open-labeled phase 2 study of the immunogenicity of PCV13 at week 0, followed by PPSV23 at week 4, compared with PPSV23 alone at week 4 in adult patients with SCD. The proportion of responders (4-fold increase in serotype-specific immunoglobulin [Ig] G antibodies) to ≥10 shared serotypes was assessed at week 8. Secondary end points were (1) geometric mean titers, (2) responders to 0–1, 2–5, 6–9, or 10–12 serotypes, (3) pneumococcal opsonophagocytic activity, and (4) response durability at weeks 24 and 96.

Results

In total, 128 patients were randomized in the PCV13/PPSV23 (n = 63) or PPSV23-alone groups (n = 65). At week 8, 24.56% and 8.20% of patients from the PCV13/PPSV23 and PPSV23 groups, respectively, reached the primary end point (P = .02). These numbers were 36.2% and 8.7% for opsonophagocytic activity responders (P = .002). A combined PCV13/PPSV23 strategy improved the breadth of responses to 0–1, 2–5, 6–9, or 10–12 serotypes with 15.8%, 35%, 24.6%, and 24.6% versus 52.5%, 31%, 8%, and 8% in the PPSV23 group. At week 96, geometric mean titers were significantly higher in the PCV13/PPSV23 than in the PPSV23-alone group for 5 serotypes (4, 14, 19A, 19F, 23F).

Conclusions

A PCV13/PPSV23 regimen improved the breadth and magnitude of antibody responses against a large range of pneumococcal serotypes in adults with SCD. The sustainability of the immune response requires recall strategies.

Clinical Trial Registration: NCT02274415
Incremental diagnostic value of post-exercise lung congestion in heart failure with preserved ejection fraction
Authors: Kagami Kazuki , Obokata Masaru , Harada Tomonari , Sorimachi Hidemi , Yuasa Naoki , Saito Yuki , Kato Toshimitsu , Wada Naoki , Adachi Takeshi , Ishii Hideki
Published: January 2023

Aims

Lung ultrasound (LUS) may unmask occult heart failure with preserved ejection fraction (HFpEF) by demonstrating an increase in extravascular lung water (EVLW) during exercise. Here, we sought to examine the dynamic changes in ultrasound B-lines during exercise to identify the optimal timeframe for HFpEF diagnosis.

Methods and results

Patients with HFpEF (n = 134) and those without HF (controls, n = 121) underwent a combination of exercise stress echocardiography and LUS with simultaneous expired gas analysis to identify exercise EVLW. Exercise EVLW was defined by B-lines that were newly developed or increased during exercise. The E/e′ ratio peaked during maximal exercise and immediately decreased during the recovery period in patients with HFpEF. Exercise EVLW was most prominent during the recovery period in patients with HFpEF, while its prevalence did not increase from peak exercise to the recovery period in controls. Exercise EVLW was associated with a higher E/e′ ratio and pulmonary artery pressure, lower right ventricular systolic function, and elevated minute ventilation to carbon dioxide production (VE vs. VCO2) slope during peak exercise. Increases in B-lines from rest to the recovery period provided an incremental diagnostic value to identify HFpEF over the H2FPEF score and resting left atrial reservoir strain.

Conclusion

Exercise EVLW was most prominent early during the recovery period; this may be the optimal timeframe for imaging ultrasound B-lines. Exercise stress echocardiography with assessments of recovery EVLW may enhance the diagnosis of HFpEF.
Corsair rotational bougie technique for facilitating balloon passage through a total occlusion lesion: a case report of balloon pulmonary angioplasty
Authors: Tamura Hiroto , Taniguchi Yu , Hosokawa Shinobu , Kishi Koichi
Published: January 2023

Case summary

A 77-year-old man presented with dyspnoea and was diagnosed with chronic thromboembolic pulmonary hypertension. Balloon pulmonary angioplasty was attempted; however, the balloons could not be advanced to the total occlusion lesion in the right A3 segment. The obstruction was overcome using a microcatheter Corsair (AsahiKASEI). This technique may be useful in managing a total occlusion lesion.
Non-continuous mobile electrocardiogram monitoring for post-transcatheter aortic valve replacement delayed conduction disorders put to the test
Authors: De Lucia Raffaele , Giannini Cristina , Parollo Matteo , Barletta Valentina , Costa Giulia , Giannotti Santoro Mario , Primerano Chiara , Angelillis Marco , De Carlo Marco , Zucchelli Giulio , Bongiorni Maria Grazia , Petronio Anna Sonia
Published: January 2023

Aims

Permanent pacemaker implantation (PPM-I) remains nowadays the most important drawback of transcatheter aortic valve replacement (TAVR) procedure and the optimal strategy of delayed conduction disturbances (CDs) in these patients is unclear. The study aimed to validate an ambulatory electrocardiogram (ECG) monitoring through a 30 s spot ambulatory digital mobile ECG (AeECG), by using KardiaMobile-6L device in a 30-day period after TAVR procedure.

Methods and results

Between March 2021 and February 2022, we consecutively enrolled all patients undergoing TAVR procedure, except pacemaker (PM) carriers. At discharge, all patients were provided of a KardiaMobile-6L device and a spot digital ECG (eECG) recording 1 month schedule. Clinical and follow-up data were collected, and eECG schedule compliance and recording quality were explored. Among 151 patients without pre-existing PM, 23 were excluded for pre-discharge PPM-I, 18 failed the KardiaMobile-6L training phase, and 10 refused the device. Delayed CDs with a Class I/IIa indication for PPM-I occurred in eight patients (median 6 days). Delayed PPM-I vs. non-delayed PPM-I patients were more likely to have longer PR and QRS intervals at discharge. PR interval at discharge was the only independent predictor for delayed PPM-I at multivariate analysis. The overall eECG schedule compliance was 96.5%. None clinical adverse events CDs related were documented using this new AeECG monitoring modality.

Conclusion

A strategy of 30 s spot AeECG is safe and efficacious in delayed CDs monitoring after TAVR procedure with a very high eECG schedule level of compliance.
Altered phenotypes due to genetic interaction between the mouse phosphoinositide biosynthesis genes Fig4 and Pip4k2c
Authors: Cao Xu , Lenk Guy M , Meisler Miriam H
Published: January 2023

Loss-of-function mutations of FIG4 are responsible for neurological disorders in human and mouse that result from reduced abundance of the signaling lipid PI(3,5)P2. In contrast, loss-of-function mutations of the phosphoinositide kinase PIP4K2C result in elevated abundance of PI(3,5)P2. These opposing effects on PI(3,5)P2 suggested that we might be able to compensate for deficiency of FIG4 by reducing expression of PIP4K2C. To test this hypothesis in a whole animal model, we generated triallelic mice with genotype Fig 4−/−, Pip4k2c+/−; these mice are null for Fig 4 and haploinsufficient for Pip4k2c. The neonatal lethality of Fig 4 null mice in the C57BL/6J strain background was rescued by reduced expression of Pip4k2c. The lysosome enlargement characteristic of Fig 4 null cells was also reduced by heterozygous loss of Pip4k2c. The data demonstrate interaction between these two genes, and suggest that inhibition of the kinase PIPK4C2 could be a target for treatment of FIG4 deficiency disorders such as Charcot-Marie-Tooth Type 4J and Yunis-Varón Syndrome.
scShapes: a statistical framework for identifying distribution shapes in single-cell RNA-sequencing data
Authors: Dharmaratne Malindrie , Kulkarni Ameya S , Taherian Fard Atefeh , Mar Jessica C
Published: January 2023

Background

Single-cell RNA sequencing (scRNA-seq) methods have been advantageous for quantifying cell-to-cell variation by profiling the transcriptomes of individual cells. For scRNA-seq data, variability in gene expression reflects the degree of variation in gene expression from one cell to another. Analyses that focus on cell–cell variability therefore are useful for going beyond changes based on average expression and, instead, identifying genes with homogeneous expression versus those that vary widely from cell to cell.

Results

We present a novel statistical framework, scShapes, for identifying differential distributions in single-cell RNA-sequencing data using generalized linear models. Most approaches for differential gene expression detect shifts in the mean value. However, as single-cell data are driven by overdispersion and dropouts, moving beyond means and using distributions that can handle excess zeros is critical. scShapes quantifies gene-specific cell-to-cell variability by testing for differences in the expression distribution while flexibly adjusting for covariates if required. We demonstrate that scShapes identifies subtle variations that are independent of altered mean expression and detects biologically relevant genes that were not discovered through standard approaches.

Conclusions

This analysis also draws attention to genes that switch distribution shapes from a unimodal distribution to a zero-inflated distribution and raises open questions about the plausible biological mechanisms that may give rise to this, such as transcriptional bursting. Overall, the results from scShapes help to expand our understanding of the role that gene expression plays in the transcriptional regulation of a specific perturbation or cellular phenotype. Our framework scShapes is incorporated into a Bioconductor R package (https://www.bioconductor.org/packages/release/bioc/html/scShapes.html).
Glacial isostatic adjustment in the northern adriatic region: estimates of the contribution from the Alpine ice sheet
Authors: Linsalata Fernando , Melini Daniele , Spada Giorgio
Published: January 2023

The present-day sea-level variations and vertical movements in the northern Adriatic Sea and in the highly vulnerable Venetian Lagoon result from a number of simultaneously operating contributions. These include Glacial Isostatic Adjustment (GIA), the global, long-term process arising from interactions between the cryosphere, the solid Earth and the oceans in response to the melting of continental ice sheets. Although the GIA contribution in northern Adriatic Sea has been the subject of various investigations so far, significant uncertainties still exist, especially related to the extent and chronology of the Würm Alpine ice sheet and to the rheological profile of the mantle. Here, taking advantage of the recent publication of updated deglaciation chronologies for the far field late-Pleistocene ice sheets and for the near-field alpine ice complex, we produce up-to-date estimates of the present-day rates of GIA-induced relative sea-level variations and vertical displacements in the Venetian Lagoon and in the northern Adriatic Sea, which are compared with GNSS and tide-gauge observations. From high-resolution numerical simulations, we find that GIA is responsible for a complex pattern of geodetic signals across the Po plain and the northern Adriatic Sea. The modeled GIA rates are of the order of fractions of mm yr−1, generally small – but not negligible – compared to the signals observed at local tide gauges and at GNSS sites in the Po plain and facing the Venetian Lagoon. Our results indicate that, while GIA represents a relatively small component among those responsible for present-day land movements and relative sea-level variations in the northern Adriatic Sea, its contribution needs to be taken into account for a correct interpretation of the observed geodetic variations.
In-utero exposure to antibiotics and risk of colorectal cancer in a prospective cohort of 18 000 adult offspring
Authors: Murphy Caitlin C , Cirillo Piera M , Krigbaum Nickilou Y , Singal Amit G , Jones Dean P , Zaki Timothy , Cohn Barbara A
Published: January 2023

Background

Incidence rates of colorectal cancer (CRC) are increasing among younger adults and in mid-life, implicating exposures in early life as risk factors. We examined the association between in-utero exposure to antibiotics and risk of CRC in adult offspring.

Methods

The Child Health and Development Studies is a prospective cohort of women receiving prenatal care between 1959 and 1966 in Oakland, California, with deliveries through June 1967. Diagnosed conditions and all prescribed medications were abstracted from mothers’ medical records beginning 6 months prior to pregnancy through delivery. We identified mothers who received antibiotics in pregnancy, including penicillins, tetracyclines, short-acting sulfonamides and long-acting sulfonamides. Diagnoses of CRC in adult (age ≥18 years) offspring were ascertained through 2021 by linkage with the California Cancer Registry. Cox proportional models were used to estimate adjusted hazard ratios (aHR), with follow-up accrued from birth through cancer diagnosis, death or last contact.

Results

Of 18 751 liveborn offspring, about 15% (n = 2635) were exposed in utero to antibiotics: 5.4% (n = 1016) to tetracyclines, 4.9% (n = 918) to penicillins, 4.2% (n = 785) to short-acting sulfonamides and 1.5% (n = 273) to long-acting sulfonamides. Compared with offspring not exposed, associations between in-utero exposure and CRC in adult offspring were: aHR 1.03 (95% CI 0.32, 3.31) for tetracyclines; aHR 1.12 (95% CI 0.35, 3.58) for penicillins; aHR 0.83 (95% CI 0.20, 3.42) for short-acting sulfonamides; and aHR 4.40 (95% CI 1.63, 11.88) for long-acting sulfonamides.

Conclusion

Our findings support an association between in-utero exposure to long-acting sulfonamides and CRC in adulthood.
Lessons From a House on Fire—From Smallpox to Polio
Authors: Maldonado Yvonne A
Published: January 2023

Global burden of disease morbidity and mortality has shifted dramatically in the last 30 years from infectious to non-communicable diseases, leading to major improvements in global child survival and enhanced life expectancy for all age groups. Vaccination efforts worldwide have been key to this achievement, but with a reduction in vaccine preventable diseases, anti-vaccine sentiments have concurrently increased. Eradication of smallpox in 1977 is a testament to vaccination impacts on human health. Despite this historic success, recent increases in infectious disease outbreaks, such as polio and measles, especially among poorly vaccinated populations, have underscored the risks of resurgence of diseases once thought eliminated in the United States and elsewhere. Engaging governments, community leaders, and the public will be critical to continuing the advancement of global health through elimination of vaccine preventable diseases.
Comparison of the relative efficacy of β-lactam/β-lactamase inhibitors and carbapenems in the treatment of complicated urinary tract infections caused by ceftriaxone-non-susceptible Enterobacterales: a multicentre retrospective observational cohort study
Authors: Chen Liang , Hua Jie , Hong Shu-Jie , Yuan Chen-Yang , Jing Ruo-Chen , Luo Xuan-Yu , Xue Hao-Wen , Yue Yue , He Xiao-Pu
Published: January 2023

Background

Treating complicated urinary tract infections (cUTIs) caused by ESBL-producing Enterobacterales represents a significant clinical challenge. The present study was thus developed to explore the relative efficacy of β-lactam/β-lactamase inhibitors (BLBLIs) and carbapenems for the treatment of hospitalized patients suffering from cUTIs caused by BLBLI-susceptible ceftriaxone-non-susceptible Enterobacterales.

Methods

Data from 557 patients from four Chinese teaching hospitals diagnosed with cUTIs caused by ceftriaxone-non-susceptible Enterobacterales from January 2017 to May 2022 were retrospectively assessed.

Result

The 30 day rate of treatment failure, defined by unresolved symptoms or mortality, was 10.4% (58/557). Independent predictors of 30 day treatment failure included immunocompromised status, bacteraemia, septic shock, lack of infection source control and appropriate empirical treatment. When data were controlled for potential confounding variables, BLBLI treatment exhibited a comparable risk of 14 day (OR 1.61, 95% CI 0.86–3.00, P = 0.133) and 30 day treatment failure (OR 1.45, 95% CI 0.66–3.15, P = 0.354) relative to carbapenem treatment for the overall cohort of patients. In contrast, BLBLI treatment in immunocompromised patients was associated with an elevated risk of both 14 day (OR 3.18, 95% CI 1.43–7.10, P = 0.005) and 30 day treatment failure (OR 3.06, 95% CI 1.07–8.80, P = 0.038) relative to carbapenem treatment.

Conclusions

These results suggested that carbapenem treatment may be superior to BLBLI treatment for immunocompromised patients suffering from cUTIs caused by ceftriaxone-non-susceptible Enterobacterales species. However, these results will need to be validated in appropriately constructed randomized controlled trials to ensure appropriate patient treatment.
Partnering with patients and families living with chronic conditions to coproduce diagnostic safety through OurDX: a previsit online engagement tool
Authors: Bell Sigall K , Dong Zhiyong J , Desroches Catherine M , Hart Nicholas , Liu Stephen , Mahon Brianna , Ngo Long H , Thomas Eric J , Bourgeois Fabienne
Published: January 2023

Objective

Patients and families are key partners in diagnosis, but methods to routinely engage them in diagnostic safety are lacking. Policy mandating patient access to electronic health information presents new opportunities. We tested a new online tool (“OurDX”) that was codesigned with patients and families, to determine the types and frequencies of potential safety issues identified by patients/families with chronic health conditions and whether their contributions were integrated into the visit note.

Methods

Patients/families at 2 US healthcare sites were invited to contribute, through an online previsit survey: (1) visit priorities, (2) recent medical history/symptoms, and (3) potential diagnostic concerns. Two physicians reviewed patient-reported diagnostic concerns to verify and categorize diagnostic safety opportunities (DSOs). We conducted a chart review to determine whether patient contributions were integrated into the note. We used descriptive statistics to report implementation outcomes, verification of DSOs, and chart review findings.

Results

Participants completed OurDX reports in 7075 of 18 129 (39%) eligible pediatric subspecialty visits (site 1), and 460 of 706 (65%) eligible adult primary care visits (site 2). Among patients reporting diagnostic concerns, 63% were verified as probable DSOs. In total, probable DSOs were identified by 7.5% of pediatric and adult patients/families with underlying health conditions, respectively. The most common types of DSOs were patients/families not feeling heard; problems/delays with tests or referrals; and problems/delays with explanation or next steps. In chart review, most clinician notes included all or some patient/family priorities and patient-reported histories.

Conclusions

OurDX can help engage patients and families living with chronic health conditions in diagnosis. Participating patients/families identified DSOs and most of their OurDX contributions were included in the visit note.
Development of a Dispersive Liquid–Liquid Microextraction for Synthetic Cathinones in Biological Fluids Based on Principles of Green Analytical Toxicology
Authors: Fabris André Luis , Lanaro Rafael , Costa Jose Luiz , Yonamine Mauricio
Published: January 2023

The present work describes a practical application of Green Analytical Toxicology (GAT) during the development of an eco-friendly dispersive liquid–liquid microextraction (DLLME) avoiding the use of highly toxic chlorinated solvents that are commonly used in this type of the technique. The purpose was to further consolidate GAT guidelines during method development. Thus, a full method optimization using a multivariate statistical approach and validation were performed. To that end, synthetic cathinones (SCs), one of the major classes of new psychoactive substances, were the target analytes due to their relevance and chemical diversity. Furthermore, whole blood and urine samples were the matrices of choice due to their clinical relevance. The sample preparation step prior to DLLME consisted of protein precipitation of whole blood samples, while urine specimens were centrifuged and diluted with ultrapure water. Then, borate buffer, sodium chloride and ethyl acetate:acetonitrile were added and vortexed. Finally, vials were centrifuged and the organic layer was transferred to autosampler vials, evaporated to dryness and resuspended with mobile phase prior to injection into the ultra-high performance liquid chromatography–tandem mass spectrometry system. Once optimized, the proposed DLLME was fully validated: 0.2 and 1 ng/mL as the limit of detection and 1 and 10 ng/mL as the limit of quantitation for urine and blood samples, respectively. The linear range was established as 1–100 and 10–1,000 ng/mL for urine and blood samples, respectively (r2 > 0.99), while the bias and precision were within acceptable limits (≥80%). The matrix effect was of 1.9–260.2% and −12.3–139.6%; while the recovery was of 27.4–60.0% and 13.0–55.2%; the process efficiency ranged from 45.0% to 192.0% and 17.9% to 58.4% for whole blood and urine, respectively. Finally, the method was applied to real case samples as proof of applicability. Thus, a simple, cheap and fast eco-friendly technique to analyze SCs in two biological specimens was described.
Model-based clustering for multidimensional social networks
Authors: D’Angelo Silvia , Alfò Marco , Fop Michael
Published: January 2023

Social network data are relational data recorded among a group of actors, interacting in different contexts. Often, the same set of actors can be characterised by multiple social relations, captured by a multidimensional network. A common situation is that of colleagues working in the same institution, whose social interactions can be defined on professional and personal levels. In addition, individuals in a network tend to interact more frequently with similar others, naturally creating communities. Latent space models for network data are useful to recover clustering of the actors, as they allow to represent similarities between them by their positions and relative distances in an interpretable low-dimensional social space. We propose the infinite mixture latent position cluster model for multidimensional network data, which enables model-based clustering of actors interacting across multiple social dimensions. The model is based on a Bayesian non-parametric framework that allows to perform automatic inference on the clustering allocations, the number of clusters, and the latent social space. The method is tested on extensive simulated data experiments. It is also employed to investigate the presence of communities in two multidimensional workplace social networks recording relations of different types among colleagues.
Revealing the Milky Way’s most recent major merger with a Gaia EDR3 catalogue of machine-learned line-of-sight velocities
Authors: Dropulic Adriana , Liu Hongwan , Ostdiek Bryan , Lisanti Mariangela
Published: January 2023

Machine learning can play a powerful role in inferring missing line-of-sight velocities from astrometry in surveys such as Gaia. In this paper, we apply a neural network to Gaia Early Data Release 3 (EDR3) and obtain line-of-sight velocities and associated uncertainties for ∼92 million stars. The network, which takes as input a star’s parallax, angular coordinates, and proper motions, is trained and validated on ∼6.4 million stars in Gaia with complete phase-space information. The network’s uncertainty on its velocity prediction is a key aspect of its design; by properly convolving these uncertainties with the inferred velocities, we obtain accurate stellar kinematic distributions. As a first science application, we use the new network-completed catalogue to identify candidate stars that belong to the Milky Way’s most recent major merger, Gaia-Sausage-Enceladus (GSE). We present the kinematic, energy, angular momentum, and spatial distributions of the ∼450 000 GSE candidates in this sample, and also study the chemical abundances of those with cross matches to GALAH and APOGEE. The network’s predictive power will only continue to improve with future Gaia data releases as the training set of stars with complete phase-space information grows. This work provides a first demonstration of how to use machine learning to exploit high-dimensional correlations on data to infer line-of-sight velocities, and offers a template for how to train, validate, and apply such a neural network when complete observational data is not available.
The active weak-line T Tauri star LkCa 4 observed with SPIRou and TESS
Authors: Finociety B , Donati J-F , Grankin K , Bouvier J , Alencar S , Ménard F , Ray T P , Kóspál Á , consortium the S L S
Published: January 2023

We report results of a spectropolarimetric and photometric monitoring of the weak-line T Tauri star LkCa 4 within the SPIRou Legacy Survey large programme, based on data collected with SPIRou at the Canada–France–Hawaii Telescope and the TESS space probe between October 2021 and January 2022. We applied Zeeman–Doppler Imaging to our spectropolarimetric and photometric data to recover a surface brightness distribution compatible with TESS photometry, as well as the large-scale magnetic topology of the star. As expected from the difference in wavelength between near-infrared and optical data, the recovered surface brightness distribution is less contrasted than the previously published one based on ESPaDOnS data, but still features mid-latitude dark and bright spots. The large-scale magnetic field is consistent in shape and strength with the one derived previously, with a poloidal component resembling a 2.2 kG dipole and a toroidal component reaching 1.4 kG and encircling the star at the equator. Our new data confirm that the surface differential rotation of LkCa 4 is about 10 times weaker than that of the Sun, and significantly different from zero. Using our brightness reconstruction and Gaussian Process Regression, we were able to filter the radial velocity activity jitter down to a precision of 0.45 and 0.38 $\text{km}\, \text{s}^{-1}$ (from an amplitude of 6.10 $\text{km}\, \text{s}^{-1}$), respectively, yielding again no evidence for a close-in massive planet orbiting the star.
A Single Nucleotide Variant in the PPARγ-homolog Eip75B Affects Fecundity in Drosophila
Authors: Hoedjes Katja M , Kostic Hristina , Flatt Thomas , Keller Laurent
Published: January 2023

Single nucleotide polymorphisms are the most common type of genetic variation, but how these variants contribute to the adaptation of complex phenotypes is largely unknown. Experimental evolution and genome-wide association studies have demonstrated that variation in the PPARγ-homolog Eip75B has associated with longevity and life-history differences in the fruit fly Drosophila melanogaster. Using RNAi knockdown, we first demonstrate that reduced expression of Eip75B in adult flies affects lifespan, egg-laying rate, and egg volume. We then tested the effects of a naturally occurring SNP within a cis-regulatory domain of Eip75B by applying two complementary approaches: a Mendelian randomization approach using lines of the Drosophila Genetic Reference Panel, and allelic replacement using precise CRISPR/Cas9-induced genome editing. Our experiments reveal that this natural polymorphism has a significant pleiotropic effect on fecundity and egg-to-adult viability, but not on longevity or other life-history traits. Our results provide a rare functional validation at the nucleotide level and identify a natural allelic variant affecting fitness and life-history adaptation.
High rates of psychological distress, mental health diagnoses and suicide attempts in people with chronic kidney disease in Ireland
Authors: Cogley Clodagh , Bramham Jessica , Bramham Kate , Smith Aoife , Holian John , O'Riordan Aisling , Teh Jia Wei , Conlon Peter , Mac Hale Siobhan , D'Alton Paul
Published: January 2023

Background

People with chronic kidney disease (CKD) experience high levels of psychological distress, which is associated with higher mortality and adverse health outcomes. Little is known about the rates of a range of mental health difficulties or rates of suicide attempts in people with CKD.

Methods

Individuals with CKD (n = 268; age range 18–94 years, mean = 49.96 years) on haemodialysis (n = 79), peritoneal dialysis (n = 46), transplant recipients (n = 84) and who were not on renal replacement therapy (RRT; n = 59) were recruited through the Irish Kidney Association social media pages and three Irish hospitals. Participants completed surveys to gather demographics and mental health histories, the Hospital Anxiety and Depression Scale (HADS) and the 12-item Short Form Health Survey (SF-12) to measure health-related quality of life (HRQoL).

Results

A total of 23.5% of participants self-reported they had received a mental health diagnosis, with depression (14.5%) and anxiety (14.2%) being the most common, while 26.4% of participants had experienced suicidal ideation and 9.3% had attempted suicide. Using a clinical cut-off ≥8 on the HADS subscales, current levels of clinically significant anxiety and depression were 50.7% and 35.4%, respectively. Depression levels were slightly higher for those on haemodialysis compared with those with a transplant and those not on RRT. Depression, anxiety and having a mental health diagnosis were all associated with lower HRQoL.

Conclusions

People with CKD in Ireland experience high levels of psychological distress, mental health difficulties, suicidal ideation and suicide attempts. The identification of and intervention for mental health difficulties in CKD should be prioritised in clinical care.
Do Tobacco Companies Have an Incentive to Promote “Harm Reduction” Products?: The Role of Competition
Authors: Levy David T , Thirlway Frances , Sweanor David , Liber Alex , Maria Sanchez-Romero Luz , Meza Rafael , Douglas Clifford E , Michael Cummings K
Published: January 2023

Introduction

Some cigarette companies have started to talk about replacing cigarettes with less harmful alternatives, which might include nicotine vaping products (NVPs), heated tobacco products (HTPs), and oral nicotine delivery products. We consider market competition as a primary driver of whether cigarette companies follow through on their stated intentions.

Aims and Methods

We focus on the behavior of cigarette companies in the United States. We compare competition in the pre- and post-2012 time periods, analyze the impact of the growth in NVPs on smoking prevalence and cigarette company profits, and examine the potential future role of competition.

Results

Since 2006, consumers have broadened their use of non-combustible nicotine delivery products (NCNDPs) to include, inter alia, NVPs, HTPs, and oral nicotine pouches. U.S. cigarette companies have acquired major stakes in each of these product categories which corresponds to a period of rapidly declining adult smoking prevalence, especially among younger adults (ages 18–24 years). The shifting dynamics of the nicotine product marketplace are also reflected in cigarette company stock prices. While cigarette companies are likely to promote HTPs and nicotine delivery products over NVPs, their incentives will be directly related to competition from independent firms, which in turn will depend on government regulation.

Conclusions

Although cigarette companies will back alternatives to combusted tobacco when threatened by competition, the prospects for their lasting conversion to NCNDPs will depend on the extent of such competition, which will be influenced by government regulation of tobacco products.

Implications

Regulations that limit competition from independent firms while also protecting cigarette company profits risk slowing or even reversing recent declines in smoking, especially among youth and young adults. Regulations that reduce the appeal and addictiveness of combusted tobacco products, such as higher cigarette taxes or a reduced nicotine standard, will encourage smokers to quit and/or switch to less harmful non-combusted forms of tobacco. The regulation of non-combustible nicotine delivery products and cigarettes should be proportionate to their relative risks, so that smokers have incentives to switch from combustibles to safer alternatives, and cigarette companies have incentives to promote safer products.
The Gynandropsis gynandra genome provides insights into whole-genome duplications and the evolution of C4 photosynthesis in Cleomaceae
Authors: Hoang Nam V , Sogbohossou E O Deedi , Xiong Wei , Simpson Conor J C , Singh Pallavi , Walden Nora , van den Bergh Erik , Becker Frank F M , Li Zheng , Zhu Xin-Guang , Brautigam Andrea , Weber Andreas P M , van Haarst Jan C , Schijlen Elio G W M , Hendre Prasad S , Van Deynze Allen , Achigan-Dako Enoch G , Hibberd Julian M , Schranz M Eric
Published: January 2023

Gynandropsis gynandra (Cleomaceae) is a cosmopolitan leafy vegetable and medicinal plant, which has also been used as a model to study C4 photosynthesis due to its evolutionary proximity to C3 Arabidopsis (Arabidopsis thaliana). Here, we present the genome sequence of G. gynandra, anchored onto 17 main pseudomolecules with a total length of 740 Mb, an N50 of 42 Mb and 30,933 well-supported gene models. The G. gynandra genome and previously released genomes of C3 relatives in the Cleomaceae and Brassicaceae make an excellent model for studying the role of genome evolution in the transition from C3 to C4 photosynthesis. Our analyses revealed that G. gynandra and its C3 relative Tarenaya hassleriana shared a whole-genome duplication event (Gg-α), then an addition of a third genome (Th-α, +1×) took place in T. hassleriana but not in G. gynandra. Analysis of syntenic copy number of C4 photosynthesis-related gene families indicates that G. gynandra generally retained more duplicated copies of these genes than C3T. hassleriana, and also that the G. gynandra C4 genes might have been under positive selection pressure. Both whole-genome and single-gene duplication were found to contribute to the expansion of the aforementioned gene families in G. gynandra. Collectively, this study enhances our understanding of the polyploidy history, gene duplication and retention, as well as their impact on the evolution of C4 photosynthesis in Cleomaceae.
Deadly acceleration in dehydration of Eucalyptus viminalis leaves coincides with high-order vein cavitation
Authors: Tonet Vanessa , Carins-Murphy Madeline , Deans Ross , Brodribb Timothy J
Published: January 2023

Xylem cavitation during drought is proposed as a major driver of canopy collapse, but the mechanistic link between hydraulic failure and leaf damage in trees is still uncertain. Here, we used the tree species manna gum (Eucalyptus viminalis) to explore the connection between xylem dysfunction and lethal desiccation in leaves. Cavitation damage to leaf xylem could theoretically trigger lethal desiccation of tissues by severing water supply under scenarios such as runaway xylem cavitation, or the local failure of terminal parts of the leaf vein network. To investigate the role of xylem failure in leaf death, we compared the timing of damage to the photosynthetic machinery (Fv/Fm decline) with changes in plant hydration and xylem cavitation during imposed water stress. The water potential at which Fv/Fm was observed to decline corresponded to the water potential marking a transition from slow to very rapid tissue dehydration. Both events also occurred simultaneously with the initiation of cavitation in leaf high-order veins (HOV, veins from the third order above) and the analytically derived point of leaf runaway hydraulic failure. The close synchrony between xylem dysfunction and the photosynthetic damage strongly points to water supply disruption as the trigger for desiccation of leaves in this hardy evergreen tree. These results indicate that runaway cavitation, possibly triggered by HOV network failure, is the tipping agent determining the vulnerability of E. viminalis leaves to damage during drought and suggest that HOV cavitation and runaway hydraulic failure may play a general role in determining canopy damage in plants.