bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimation of the Time-Varying Effective Reproductive Number of COVID-19 Based on Multivariate Time Series of Severe Health Outcomes
Authors: Young Benjamin R , Ho Faith , Lin Yun , Lau Eric H Y , Cowling Benjamin J , Wu Peng , Tsang Tim K
Published: October 2023

The time-varying effective reproduction number (Rt at time t) measures the transmissibility of SARS-CoV-2 and is conventionally based on daily case counts, which may suffer from time-varying ascertainment. We analyzed Rt estimates from case counts and severe COVID-19 (intensive care unit admissions, severe or critical cases, and mortality) across 2022 in Hong Kong's fifth and sixth waves of infection. Within the fifth wave, the severe disease–based Rt (3.5) was significantly higher than the case-based Rt (2.4) but not in the sixth wave. During periods with fluctuating underreporting, data based on severe diseases may provide more reliable Rt estimates.
β-Lactams plus doxycycline versus azithromycin for treatment of severe community-acquired pneumonia in critically ill patients
Authors: Greco Kinney Alexandra , Kovacic Scherrer Nicole , Sarkar Sauradeep , Jain Pranav , Wen Sijin , Hadique Sarah
Published: October 2023

Objectives

Community-acquired pneumonia (CAP) is a significant source of hospital admissions and mortality. Atypical organisms are implicated in up to 40% of cases of CAP diagnoses. We studied the difference in outcomes of severe CAP patients treated with doxycycline versus azithromycin in addition to β-lactam therapy.

Patients and methods

This was a prospective observational cohort study from March 2020 to July 2022 in a medical ICU (MICU) of an academic quaternary medical center. Adults ≥18 years admitted to the MICU receiving doxycycline or azithromycin in addition to β-lactam therapy for the treatment of CAP were included for analysis. The primary outcomes were in-hospital and 30 day mortality. Secondary outcomes were ICU and hospital length-of-stay, 30 day readmission, days of mechanical ventilation, escalation and duration of antibiotics, adverse effects such as Clostridioides difficile infection and QTc prolongation.

Results

Sixty-three patients were in the azithromycin group and eighty-six patients in the doxycycline group. Both groups had similar APACHE IV and CURB-65 scores. The mean Charlson Comorbidity Index score was higher for the doxycycline group compared with the azithromycin group (P = 0.04). There was no statistically significant difference in in-hospital and 30 day mortality between the groups (P = 0.53, P = 0.57). There were no significant differences in any of the secondary outcomes.

Conclusions

MICU patients with severe CAP who received doxycycline versus azithromycin in addition to β-lactam treatment showed no significant differences in outcomes. These data offer support for inclusion of doxycycline as an alternative regimen in current IDSA recommendations.
Chemical composition of horse hooves with functional qualities for competing barefoot
Authors: Spörndly-Nees Ellinor , Jansson Anna , Pökelmann Mette , Pickova Jana , Ringmark Sara
Published: October 2023

Barefoot racing is a common practice within the harness racing industry, but not all horses have hooves of sufficient quality to race sustainably without shoes. There is currently no objective approach available to assess whether a horse’s hooves are suitable for barefoot racing, raising animal welfare issues if trainers misjudge the functional qualities of hooves. This study compared chemical composition of the hoof wall and fatty acid (FA) composition of the digital cushion in a group of horses that had raced barefoot often (RB) and a group of horses that could not race barefoot and therefore raced with shoes (RS). Trimmings from the hind hoof wall were collected from the lateral quarters in one sub-cohort postmortem and in another sub-cohort of live horses and analyzed for macro- and microelements, nitrogen, dry matter (DM), and total and free amino acid content. For the postmortem horses, samples of the digital cushion were also collected and analyzed for total and free FAs. RB horses had lower concentrations of copper in the hoof wall (17.5 ± 3.9 vs. 32.8 ± 4.7 mg/kg DM, P = 0.02) than RS horses. RB horses also tended (P < 0.1) to have higher concentrations of nitrogen (164.2 ± 0.2 vs. 163.5 ± 0.3 g/kg DM) and sulfur (22.9 ± 0.2 vs. 22.3 ± 0.3 g/kg DM). RB horses had higher hoof wall concentrations of arginine (10.51 ± 0.05 vs. 10.34 ± 0.06 g/100 g DM, P = 0.03) and showed a trend (P < 0.1) for higher hoof wall concentrations of cysteine (6.14 ± 0.10 vs. 5.82 ± 0.13 g/100 g DM) and proline (4.62 ± 0.05 vs. 4.49 ± 0.06 g/100 g DM). There were no differences between the groups for any other element or amino acid analyzed. There were also no differences between the two groups in terms of FA composition of the digital cushion. These results indicate that chemical composition, especially with respect to copper, arginine, nitrogen, sulfur, cysteine, and proline, may be important for the functional qualities of the hoof capsule and the ability to race barefoot without wearing the hoof down. However, chemical analysis of hoof wall tissue and of the fat content of the digital cushion does not seem to be a definitive method for distinguishing horses that have hooves suitable for barefoot racing from those that do not.
Fragmentation and dynamics of dense gas structures in the proximity of massive young stellar object W42-MME
Authors: Bhadari N K , Dewangan L K , Pirogov L E , Pazukhin A G , Zinchenko I I , Maity A K , Sharma Saurabh
Published: October 2023

We present an analysis of the dense gas structures in the immediate surroundings of the massive young stellar object (MYSO) W42-MME, using the high-resolution (0″.31 × 0″.25) Atacama Large Millimetre/submillimetre Array dust continuum and molecular line data. We performed a dendrogram analysis of H13CO+ (4–3) line data to study multiscale structures and their spatio–kinematic properties, and analysed the fragmentation and dynamics of dense structures down to ∼2000 au scale. Our results reveal 19 dense gas structures, out of which 12 are leaves and 7 are branches in dendrogram terminology. These structures exhibit transonic–supersonic gas motions (1$\lt \mathcal {M}\lt 5$) with overvirial states (αvir ≥ 2). The non-thermal velocity dispersion–size relation (σnt–L) of dendrogram structures shows a weak negative correlation, while the velocity dispersion across the sky ($\delta \mathit {V_{\rm lsr}}$) correlates positively with structure size (L). Velocity structure function (S2(l)1/2) analysis of H13CO+ data reveals strong power-law dependences with lag (l) up to a scale length of ≲6000 au. The mass–size (M–R) relation of dendrogram structures shows a positive correlation with power-law index of 1.73 ± 0.23, and the leaf L17 hosting W42-MME meets the mass–size conditions for massive star formation. Blue asymmetry is observed in the H12CO+ (4–3) line profiles of most of the leaves, indicating infall. Overall, our results observationally support the hierarchical and chaotic collapse scenario in the proximity of the MYSO W42-MME.
Type-A quasi-periodic oscillation in the black hole transient MAXI J1348−630
Authors: Zhang Liang , Méndez Mariano , García Federico , Zhang Yuexin , Ma Ruican , Altamirano Diego , Yang Zi-Xu , Ma Xiang , Tao Lian , Huang Yue , Jia Shumei , Zhang Shuang-Nan , Qu Jinlu , Song Liming , Zhang Shu
Published: October 2023

We present a detailed analysis of the spectral and timing characteristics of a 7-Hz type-A quasi-periodic oscillation (QPO) detected in NICER observations of the black hole X-ray binary MAXI J1348−630 during its high-soft state. The QPO is broad and weak, with an integrated fractional rms amplitude of 0.9 per cent in the 0.5–10 keV band. Thanks to the large effective area of NICER, combined with the high flux of the source and a relatively long accumulative exposure time, we construct the first rms and phase-lag spectra for a type-A QPO. Our analysis reveals that the fractional rms amplitude of the QPO increases with energy from below 1 per cent at 1 keV to ∼3 per cent at 6 keV. The shape of the QPO spectrum is similar to that of the Comptonized component, suggesting that the Comptonized region is driving the variability. The phase lags at the QPO frequency are always soft taking the lowest energy as reference. By jointly fitting the time-averaged spectrum of the source and the rms and phase-lag spectra of the QPO with the time-dependent Comptonization model vkompthdk, we find that the radiative properties of the type-A QPO can be explained by a vertically extended Comptonized region with a size of ∼2300 km.
Extreme photometric and polarimetric variability of blazar S4 0954+65 at its maximum optical and γ-ray brightness levels
Authors: Raiteri C M , Villata M , Carnerero M I , Savchenko S S , Kurtanidze S O , Vlasyuk V V , Marchini A , Matsumoto K , Lorey C , Joner M D , Gazeas K , Carosati D , Mirzaqulov D O , Acosta Pulido J A , Agudo I , Bachev R , Benítez E , Borman G A , Calcidese P , Chen W P , Damljanovic G , Ehgamberdiev S A , Elsässer D , Feige M , Frasca A , Gaur H , Grishina T S , Gupta A C , Hiriart D , Holland M , Horst B , Ibryamov S , Ivanidze R Z , Jensen J , Jithesh V , Jovanovic M D , Kiehlmann S , Kimeridze G N , Kishore S , Kopatskaya E N , Kurtanidze O M , Larionova E G , Lin H C , Mannheim K , Marinelli C , Moreira Reyes J , Morozova D A , Nikolashvili M G , Reinhart D , Romanov F D , Semkov E , Seufert J , Shishkina E V , Sigua L A , Skalidis R , Spiridonova O I , Stojanovic M , Strigachev A , Troitskaya Y V , Troitskiy I S , Tsai A , Vasilyev A A , Vince O , Vrontaki K , Wani K , Watts D , Zhovtan A V
Published: October 2023

In 2022 the BL Lac object S4 0954+65 underwent a major variability phase, reaching its historical maximum brightness in the optical and γ-ray bands. We present optical photometric and polarimetric data acquired by the Whole Earth Blazar Telescope (WEBT) Collaboration from 2022 April 6 to July 6. Many episodes of unprecedented fast variability were detected, implying an upper limit to the size of the emitting region as low as $10^{-4}$ parsec. The WEBT data show rapid variability in both the degree and angle of polarization. We analyse different models to explain the polarization behaviour in the framework of a twisting jet model, which assumes that the long-term trend of the flux is produced by variations in the emitting region viewing angle. All the models can reproduce the average trend of the polarization degree, and can account for its general anticorrelation with the flux, but the dispersion of the data requires the presence of intrinsic mechanisms, such as turbulence, shocks, or magnetic reconnection. The WEBT optical data are compared to γ-ray data from the Fermi satellite. These are analysed with both fixed and adaptive binning procedures. We show that the strong correlation between optical and γ-ray data without measurable delay assumes different slopes in faint and high brightness states, and this is compatible with a scenario where in faint states we mainly see the imprint of the geometrical effects, while in bright states the synchrotron self-Compton process dominates.
Envelope ejection and the transition to homologous expansion in common-envelope events
Authors: Valsan Vinaya , Borges Sarah V , Prust Logan , Chang Philip
Published: October 2023

We conduct a long-time-scale ($5000\,$ d) 3D simulation of a common-envelope event with a $2\, {\rm M}_{\odot }$ red giant and a $1\, {\rm M}_{\odot }$ main-sequence companion, using the moving-mesh hydrodynamic solver manga. Starting with an orbital radius of $52\, \mathrm{ R}_{\odot }$, our binary shrinks to an orbital radius of $5\, \mathrm{ R}_{\odot }$ in $200\,$ d. We show that over a time-scale of about $1500\,$ d, the envelope is completely ejected, while 80 per cent is ejected in about $400\,$ d. The complete ejection of the envelope is solely powered by the orbital energy of the binary, without the need for late-time reheating from recombination or jets. Motivated by recent theoretical and observational results, we also find that the envelope enters a phase of homologous expansion about $550\, \rm d$ after the start of our simulation. We also run a simplified 1D model to show that heating from the central binary in the envelope at late times does not influence the ejection. This homologous expansion of the envelope would likely simplify calculations of the observational implications such as light curves.
Exceptional Early Jurassic fossils with leathery eggs shed light on dinosaur reproductive biology
Authors: Han Fenglu , Yu Yilun , Zhang Shukang , Zeng Rong , Wang Xinjin , Cai Huiyang , Wu Tianzhuang , Wen Yingfeng , Cai Sifu , Li Chun , Wu Rui , Zhao Qi , Xu Xing
Published: October 2023

Our understanding of pre-Cretaceous dinosaur reproduction is hindered by a scarcity of evidence within fossil records. Here we report three adult skeletons and five clutches of embryo-containing eggs of a new sauropodomorph from the Lower Jurassic of southwestern China, displaying several significant reproductive features that are either unknown or unlike other early-diverging sauropodomorphs, such as relatively large eggs with a relatively thick calcareous shell formed by prominent mammillary cones, synchronous hatching and a transitional prehatching posture between the crocodilians and living birds. Most significantly, these Early Jurassic fossils provide strong evidence for the earliest known leathery eggs. Our comprehensive quantitative analyses demonstrate that the first dinosaur eggs were probably leathery, elliptical and relatively small, but with relatively long eggshell units, and that along the line to living birds, the most significant change in reptilian egg morphology occurred early in theropod evolution rather than near the origin of Aves.
Eggplant transcription factor SmMYB5 integrates jasmonate and light signaling during anthocyanin biosynthesis
Authors: Li Shaohang , Dong Yanxiao , Li Dalu , Shi Suli , Zhao Na , Liao Jielei , Liu Yang , Chen Huoying
Published: October 2023

Low light conditions severely suppress anthocyanin synthesis in fruit skins, leading to compromised fruit quality in eggplant (Solanum melongena L.) production. In this study, we found that exogenous methyl-jasmonate (MeJA) application can effectively rescue the poor coloration of the eggplant pericarp under low light conditions. However, the regulatory relationship between jasmonate and light signaling for regulating anthocyanin synthesis remains unclear. Here, we identified a JA response factor, SmMYB5, as an anthocyanin positive regulator by applying RNA-sequencing and characterization of transgenic plants. Firstly, we resolved that SmMYB5 can interact with TRANSPARENT TESTA8 (SmTT8), an anthocyanin-promoted BASIC HELIX-LOOP-HELIX (bHLH) transcription factor, to form the SmMYB5–SmTT8 complex and activate CHALCONE SYNTHASE (SmCHS), FLAVANONE-3-HYDROXYLASE (SmF3H), and ANTHOCYANIN SYNTHASE (SmANS) promoters by direct binding. Secondly, we revealed that JA signaling repressors JASMONATE ZIM DOMAIN5 (SmJAZ5) and SmJAZ10 can interfere with the stability and transcriptional activity of SmMYB5–SmTT8 by interacting with SmMYB5. JA can partially rescue the transcriptional activation of SmF3H and SmANS promoters by inducing SmJAZ5/10 degradation. Thirdly, we demonstrated that the protein abundance of SmMYB5 is regulated by light. CONSTITUTIVELY PHOTOMORPHOGENIC1 (SmCOP1) interacts with SmMYB5 to trigger SmMYB5 degradation via the 26S proteasome pathway. Finally, we delineated a light-dependent JA-SmMYB5 signaling pathway that promotes anthocyanin synthesis in eggplant fruit skins. These results provide insights into the mechanism of the integration of JA and light signals in regulating secondary metabolite synthesis in plants.
IbMYB73 targets abscisic acid-responsive IbGER5 to regulate root growth and stress tolerance in sweet potato
Authors: Wang Zhen , Li Xu , Gao Xiao-ru , Dai Zhuo-ru , Peng Kui , Jia Li-cong , Wu Yin-kui , Liu Qing-chang , Zhai Hong , Gao Shao-pei , Zhao Ning , He Shao-zhen , Zhang Huan
Published: October 2023

Root development influences plant responses to environmental conditions, and well-developed rooting enhances plant survival under abiotic stress. However, the molecular and genetic mechanisms underlying root development and abiotic stress tolerance in plants remain unclear. In this study, we identified the MYB transcription factor-encoding gene IbMYB73 by cDNA-amplified fragment length polymorphism and RNA-seq analyses. IbMYB73 expression was greatly suppressed under abiotic stress in the roots of the salt-tolerant sweet potato (Ipomoea batatas) line ND98, and its promoter activity in roots was significantly reduced by abscisic acid (ABA), NaCl, and mannitol treatments. Overexpression of IbMYB73 significantly inhibited adventitious root growth and abiotic stress tolerance, whereas IbMYB73-RNAi plants displayed the opposite pattern. IbMYB73 influenced the transcription of genes involved in the ABA pathway. Furthermore, IbMYB73 formed homodimers and activated the transcription of ABA-responsive protein IbGER5 by binding to an MYB binding sites I motif in its promoter. IbGER5 overexpression significantly inhibited adventitious root growth and abiotic stress tolerance concomitantly with a reduction in ABA content, while IbGER5-RNAi plants showed the opposite effect. Collectively, our results demonstrated that the IbMYB73-IbGER5 module regulates ABA-dependent adventitious root growth and abiotic stress tolerance in sweet potato, which provides candidate genes for the development of elite crop varieties with well-developed root-mediated abiotic stress tolerance.
Measuring Policy Diffusion in Federal Systems: The Case of Legalizing Cannabis in Canada under Time Constraints
Authors: Brie Evelyne , Huo Cynthia , Alcantara Christopher
Published: October 2023

Existing studies of policy diffusion rely on quantitative or qualitative methods depending on the number of cases and the policy at hand. Studies of diffusion in Canada, for instance, almost exclusively use qualitative techniques due to the limited number of subnational units. In this article, we explore whether machine learning techniques can complement qualitative approaches in these contexts. In 2015, the Canadian federal government decided to impose the legalization of cannabis and gave the provinces and territories a short time frame to develop and implement legislation. Previous qualitative research on this case found that within-province policy development was more salient than interprovincial diffusion. Using a plagiarism detection software, we find limited evidence of exact matches between provincial legislation, but a cosine score approach reveals significant similarities across provinces. These results suggest that computational and qualitative techniques together should be used where possible to identify and analyze policy diffusion in certain contexts.
Aldehyde Dehydrogenase 2 Preserves Mitochondrial Function in the Ischemic Heart: A Redox-dependent Mechanism for AMPK Activation by Thioredoxin-1
Authors: Zhu Yi , He Ya-Jun , Yu Yuan , Xu Dan , Yuan Shi-Ying , Yan Hong
Published: October 2023

Aldehyde dehydrogenase 2 (ALDH2) protects the ischemic heart by activating adenosine 5′-monophosphate-activated protein kinase (AMPK) signaling. However, the molecular mechanisms linking ALDH2 and AMPK signaling are not fully understood. This study aimed to explore the potential mechanisms linking ALDH2 and AMPK in myocardial ischemic injury. An ischemic model was established by ligating the left anterior descending coronary artery in rats. The overexpression or knockdown of ALDH2 in H9c2 cells treated with oxygen–glucose deprivation was obtained through lentivirus infection. Transferase-mediated dUTP nick-end labeling was used to evaluate apoptosis in an ischemic rat model and oxygen–glucose deprivation cells. ALDH2 activity, mitochondrial oxidative stress markers, adenosine triphosphate, respiratory control ratio, and cell viability in H9c2 cells were evaluated using a biological kit and 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide. Protein expression of ALDH2, 4-hydroxynonenal, thioredoxin-1 (Trx-1), and AMPK–proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) signaling pathway was detected through Western blotting. ALDH2 activation reduced ischemic-induced myocardial infarct size and apoptosis. ALDH2 protected mitochondrial function by enhancing mitochondrial respiratory control ratio and adenosine triphosphate production, alleviated mitochondrial oxidative stress, and suppressed myocardial apoptosis. Moreover, ALDH2 attenuated ischemia-induced oxidative stress and maintained Trx-1 levels by reducing 4-hydroxynonenal, thereby promoting AMPK–PGC-1α signaling activation. Inhibiting Trx-1 or AMPK abolished the cardioprotective effect of ALDH2 on ischemia. ALDH2 alleviates myocardial injury through increased mitochondrial biogenesis and reduced oxidative stress, and these effects were achieved through Trx1-mediating AMPK–PGC1-α signaling activation.
Racial and Ethnic Disparities in Veno-Venous Extracorporeal Membrane Oxygenation Mortality for Patients With Severe COVID-19
Authors: Kopanczyk Rafal , Lisco Steven J. , Pearl Ronald , Demiralp Gozde , Naik Bhiken I. , Mazzeffi Michael A.
Published: October 2023

Racial/ethnic disparities in mortality were observed during the coronavirus disease-2019 pandemic, but investigations examining the association between race/ethnicity and mortality during extracorporeal membrane oxygenation (ECMO) are limited. We performed a retrospective observational cohort study using the 2020 national inpatient sample. Multivariable logistic regression was used to estimate the odds of mortality in patients of difference race/ethnicity while controlling for confounders. There was a significant association between race/ethnicity and in-hospital mortality (p < 0.001). Hispanic patients had significantly higher in-hospital mortality compared with White patients (odds ratio [OR] = 1.39, 95% confidence interval [CI] = 1.16–1.67, p < 0.001). Black patients and patients of other races did not have significantly higher in-hospital mortality compared with White patients (OR = 0.82, 95% CI = 0.66–1.02, p = 0.07 and OR = 1.20, 95% CI = 0.92–1.57, p = 0.18). Other variables that had a significant association with mortality included age, insurance type, Charlson comorbidity index, all patient-refined severity of illness, and receipt of care in a low-volume ECMO center (all p < 0.001). Further studies are needed to understand causes of disparities in ECMO mortality.
Experiences of fear of recurrence in patients with sarcoma
Authors: Vindrola-Padros Cecilia , Fern Lorna A. , Gerrand Craig , Hulbert-Williams Nicholas J. , Lawal Maria , Storey Lesley , Wells Mary , Windsor Rachael , Woodford Julie , Taylor Rachel M.
Published: October 2023

Background:

Fear of cancer recurrence (FCR) is often described as the most distressing consequence of cancer and has a negative impact on quality of life. There have been few investigations into the FCR in patients with sarcomas. We sought to explore the patient's FCR after a sarcoma diagnosis to determine when these fears were presented and the strategies patients used to address these fears.

Methods:

This was a secondary analysis of qualitative semi-structured interview data from patients with sarcoma, as part of a study to develop a patient-reported outcome measure. This study included 121 patients from across the United Kingdom aged 13–82 years. Telephone and face-to-face interviews focused on the experiences of living with and beyond a sarcoma diagnosis, based on the domains of quality of life (physical, emotional, and social well-being). A secondary analysis was performed using the Common-Sense Model.

Results:

The following four key themes were identified: triggers for FCR (symptoms and events), discussion of FCR, consequences of FCR (negative impact on quality of life), and strategies used to deal with FCR.

Conclusion:

Patients with sarcoma reported a FCR at different stages of treatment and how these fears played a role in their daily lives. Despite these experiences, the identification and management of FCR have not been reported as a core component of routine clinical practice.
Effect of Early Physical Therapy on Children of School Age With Hematological Cancer: A Quasi-Randomized Controlled Pilot Study
Authors: Sonoda Yuma , Tobita Ryo , Ikeda Yuhachi , Taga Takashi
Published: October 2023

Purpose:

Although physical therapy (PT) positively impacts exercise capacity and health-related quality of life (HRQOL) in children with hematological cancers, the optimal time for intervention is unknown. We compared the effects of PT administered before and after initial cancer treatment on the exercise capacity and HRQOL of children with hematological cancer.

Methods:

The participants were allocated to early (before initiating treatment) and late PT (after initiating treatment) groups. We evaluated exercise capacity using the 6-min walking distance (6MWD) test and HRQOL using the Pediatric Quality of Life Inventory.

Results:

Thirteen school children (7-13 years) were included. The early PT cohort had significant improvements in Pediatric Quality of Life Inventory but not 6MWD scores from admission to the completion of initial treatment; however, both scores reduced significantly in the late PT cohort.

Conclusions:

Early rather than late PT during hospitalization might prevent reduced exercise capacity and improve HRQOL in children with hematological cancers.
Safety and Efficacy of a Third Dose of the BNT162b2 Vaccine in Liver-Transplanted and Healthy Adolescents
Authors: Sintusek Palittiya , Buranapraditkun Supranee , Khunsri Siriporn , Thongmee Thanunrat , Vichaiwattana Preeyaporn , Polsawat Warunee , Poovorawan Yong
Published: October 2023

Objectives:

According to our previous study, the 2-dose-BNT162b2 vaccination is less effective against the Omicron variant. This study aimed to assess the safety and efficacy of a 3-dose-BNT162b2 vaccination in liver-transplanted (LT) and healthy adolescents.

Methods:

LT and healthy adolescents who met the inclusion criteria received a third dose of the BNT162b2 vaccine (30 µg). Antireceptor-binding domain immunoglobulin and T-cell-specific responses to severe acute respiratory syndrome coronavirus 2 spike peptides were assessed 3 months before the third dose (Visit −1) and 0 (Visit 0), 1 (Visit 1), and 2 months (Visit 2) after the third dose. Antinucleocapsid immunoglobulin and neutralizing antibodies were assessed at Visits 0 and 1. Adverse events (AEs) were monitored.

Results:

Eleven LT and 14 healthy adolescents aged 14.64 (13.2, 15.7) years (44.2% male) had antireceptor-binding domain immunoglobulin geometric mean titers of 1412.47 (95% confidence interval [CI], 948.18–2041.11) and 1235.79 (95% CI, 901.07–1705.73) U/mL at Visit −1 but increased to 38 587.76 (95% CI, 24 628.03–60 460.18) and 29 222.38 (95% CI, 16 291.72–52 401.03) U/mL (P < 0.05) at Visit 1, respectively. This was consistent with neutralizing antibodies (42.29% and 95.37% vs 44.65% and 91.68%, P < 0.001) and interferon-γ-secreting cells in LT and healthy adolescents at Visit 0 versus Visit 1, respectively. For serious AEs, an LT girl with autoimmune overlap syndrome died 5 months postvaccination from acute liver failure.

Conclusions:

In both LT and healthy adolescents, humoral and cellular immune responses were high after the 3-dose-BNT162b2 vaccination. However, serious AEs were suspected in LT adolescents with autoimmune diseases.
The next frontier: cytomegalovirus antiviral stewardship programs in solid organ transplant
Authors: Kleiboeker Hanna L. , Saddler Christopher M. , Jorgenson Margaret R.
Published: October 2023

Purpose of review

Cytomegalovirus (CMV) is a driver of negative patient and allograft outcomes after solid organ transplantation (SOT) and new tools are needed to circumvent these outcomes. We will review key elements of CMV antiviral stewardship in SOT, discuss the available evidence for CMV antiviral stewardship programs and feature areas for expansion in the current landscape of CMV management.

Recent findings

CMV remains a common complication after SOT. While consensus guidelines provide recommendations for the prevention and treatment of CMV, a one-size-fits-all approach is not necessarily appropriate for all unique patients and posttransplant courses, types of SOT recipients and transplant centers. Additionally, consensus guidelines have not been updated since the approval of two new antiviral therapies for the treatment of CMV after SOT or emerging evidence for the incorporation of immune functional assays into clinical practice.

From the models provided in recent literature, CMV antiviral stewardship programs have demonstrated efficacy by increasing successful treatment of viremia, optimizing and reducing unnecessary use of (val)ganciclovir for both prophylaxis and treatment, and preventing development of ganciclovir-resistant CMV infections. These models highlight the multidisciplinary approach required of CMV antiviral stewardship programs to provide standardization of management, including incorporation of new therapies and diagnostic tools.

CMV antiviral stewardship programs represent a promising avenue to considerably improve the management of CMV after SOT. Future studies are needed to evaluate a potential positive impact on graft outcomes and patient survival.
Sonographic Evaluation of the Lateral Femoral Cutaneous Nerve
Authors: Lee Susan C. , Ko Lydia , Gornbein Chase , Nwawka Ogonna Kenechi
Published: October 2023

The location of the lateral femoral cutaneous nerve (LFCN) makes it susceptible to injury with trauma, external compression, and iatrogenic injury. The objectives of this study were to report the single-institution efficacy of LFCN visualization on ultrasound (US), define the clinical characteristics of patients with LFCN palsy, and describe sonographic appearances of LFCN abnormalities by pictorial review. A retrospective chart review of LFCN cases evaluated using US at a single institution was performed, documenting rate of visibility on US, mode of nerve injury, and US imaging findings. Nerve visibility rates on US were correlated with magnetic resonance imaging (MRI) when both modalities were used. Imaging findings were confirmed with clinical/surgical history and follow-up. Retrospective review found that 170 patients underwent US for LFCN evaluation in the last 10 years. Injury was associated with surgical intervention in 56% of cases, and perineural scarring was the most common pathology described using US. Lateral femoral cutaneous nerve was visible on US in 97% of cases; MRI visualized LFCN in 60%. Chart review showed US as an effective tool in evaluating LFCN pathology, with a higher visualization rate than MRI. Through pictorial review, the array of LFCN pathology sonographically detectable is demonstrated.
Assessing Kidney Transplantation Using ECMO-Supported Donors Within a KDPI-Based Allocation System
Authors: Altshuler Peter J. , Pace Devon J. , Preston William A. , Vincent Sage A. , Shah Ashesh P. , Glorioso Jaime M. , Maley Warren R. , Frank Adam M. , Ramirez Carlo B. , West Sharon , Hasz Richard , Bodzin Adam S.
Published: October 2023

Background.

Organ donors supported by extracorporeal membrane oxygenation (ECMO) have historically been considered high-risk and are judiciously utilized. This study examines transplant outcomes using renal allografts from donors supported on ECMO for nondonation purposes.

Methods.

Retrospective review of the Gift of Life (Pennsylvania, New Jersey, Delaware) organ procurement organization database, cross-referenced to the Organ Procurement and Transplantation Network database, assessed kidney transplants using donors supported on venoarterial (VA) and venovenous (VV) ECMO for nondonation purposes. Transplants using VA- and VV-ECMO donors were compared with Kidney Donor Profile Index (KDPI)-stratified non-ECMO donors. Regression modeling of the entire ECMO and non-ECMO populations assessed ECMO as predictive of graft survival. Additional regression of the ECMO population alone assessed for donor features associated with graft survival.

Results.

Seventy-eight ECMO donors yielded 128 kidney transplants (VA: 80, VV: 48). Comparing outcomes using these donors to kidney transplants using organs from KDPI-stratified non-ECMO donors, VA- and VV-ECMO donor grafts conferred similar rates of delayed graft function and posttransplant renal function to KDPI-matched non-ECMO counterparts. VA-ECMO kidneys demonstrated superior graft survival compared with the lowest-quality (KDPI 86%–100%) non-ECMO kidneys and similar graft survival to KDPI <85% non-ECMO kidneys. VV-ECMO showed inferior graft survival to all but the lowest-quality (KDPI 86%–100%) non-ECMO kidneys. VV-ECMO, but not VA-ECMO, was associated with increased risk of graft loss on multivariable regression (hazard ratios—VA: 1.02, VV: 2.18). Higher KDPI, advanced age, increased body mass index, hypertension, and diabetes were identified as high-risk features of ECMO donors.

Conclusions.

Kidney transplantation using appropriately selected ECMO donors can safely expand the donor pool. Ongoing studies are necessary to determine best practice patterns using kidneys from these donors.
Reproductive biology of the mudskippersBoleophthalmus boddartiandPeriophthalmus novemradiatusin the Indian Sundarbans
Authors: Ray Ishita , Himberg Benjamin E. , Sengupta Sanghita , Homechaudhuri Sumit
Published: October 2023

Reproductive biology of mudskippersBoleophthalmus boddartiandPeriophthalmus novemradiatusare investigated along the mudflats of the Indian Sundarbans. We investigated a total of 794 sampes for both male and femaleBoleophthalmus boddartiandPeriophthalmus novemradiatusfish species to explore properties such as the size-at-50% maturity, fecundity, spawning, gona-dosomatic and hepatosomatic indices along with the characterization of the macroscopic and histological attributes of the female gonads. Our work reports for the first time the weight-length relationships for these fish species in the Sundarbans region depicting a negative allometric growth pattern. The size-at-50% maturity which is often a crucial parameter for stock and reserve management is found for the female and maleBoleophthalmus boddartias 10.2 cm and 9.9 cm respectively, whereas, for thePeriophthalmus novemradiatus, the same were 4.0 cm and 4.4 cm, respectively. Fully matured femaleBoleophthalmus boddartiwere found to be multiple spawners in comparison toPeriophthalmus novemradiatuswith monthly variation of Le Cren’s relative condition ≤1, indicating good physiological conditions of the fish. The relationships between batch fecundity (F), body weight (i.e., BW, gm) and total length (i.e., TL, cm) were Log10F = 1.12 Log10BW + 2.41 and Log10F = 1.93 Log10TL + 1.82, respectively forBoleoph-thalmus boddartiand for thePeriophthalmus novemradiatus, it was Log10F = 2.15 Log10BW + 2.57 and Log10F = 5.43 Log10TL - 0.81. The reproductive parameters estimated in this study are important information for studying population dynamics and stock assessments of these mudskippers in the Indian Sundarbans and will contribute to the management, conservation and prediction of environmental changes as these mudskippers are often studied as bio-indicators for climate-change effects.
A neural mechanism for learning from delayed postingestive feedback
Authors: Zimmerman Christopher A , Bolkan Scott S , Pan-Vazquez Alejandro , Wu Bichan , Keppler Emma F , Meares-Garcia Jordan B , Guthman Eartha Mae , Fetcho Robert N , McMannon Brenna , Lee Junuk , Hoag Austin T , Lynch Laura A , Janarthanan Sanjeev R , López Luna Juan F , Bondy Adrian G , Falkner Annegret L , Wang Samuel S-H , Witten Ilana B
Published: October 2023

Animals learn the value of foods based on their postingestive effects and thereby develop aversions to foods that are toxic and preferences to those that are nutritious. However, it remains unclear how the brain is able to assign credit to flavors experienced during a meal with postingestive feedback signals that can arise after a substantial delay. Here, we reveal an unexpected role for postingestive reactivation of neural flavor representations in this temporal credit assignment process. To begin, we leverage the fact that mice learn to associate novel, but not familiar, flavors with delayed gastric malaise signals to investigate how the brain represents flavors that support aversive postingestive learning. Surveying cellular resolution brainwide activation patterns reveals that a network of amygdala regions is unique in being preferentially activated by novel flavors across every stage of the learning process: the initial meal, delayed malaise, and memory retrieval. By combining high-density recordings in the amygdala with optogenetic stimulation of genetically defined hindbrain malaise cells, we find that postingestive malaise signals potently and specifically reactivate amygdalar novel flavor representations from a recent meal. The degree of malaise-driven reactivation of individual neurons predicts strengthening of flavor responses upon memory retrieval, leading to stabilization of the population-level representation of the recently consumed flavor. In contrast, meals without postingestive consequences degrade neural flavor representations as flavors become familiar and safe. Thus, our findings demonstrate that interoceptive reactivation of amygdalar flavor representations provides a neural mechanism to resolve the temporal credit assignment problem inherent to postingestive learning.
Analysis of the effect of the scorpion toxin AaH-II on action potential generation in the axon initial segment
Authors: Abbas Fatima , Blömer Laila Ananda , Millet Hugo , Montnach Jérôme , De Waard Michel , Canepari Marco
Published: October 2023

The toxin AaH-II, from the scorpionAndroctonus australis Hectorvenom, is a 64 amino acid peptide that targets voltage-gated Na+channels (VGNCs) and slows their inactivation. While at macroscopic cellular level AaH-II prolongs the action potential (AP), a functional analysis of the effect of the toxin in the axon initial segment (AIS), where VGNCs are highly expressed, was never performed so far. Here, we report an original analysis of the effect of AaH-II on the AP generation in the AIS of neocortical layer-5 pyramidal neurons from mouse brain slices. After determining that AaH-II does not discriminate between Nav1.2 and Nav1.6, i.e. between the two VGNC isoforms expressed in this neuron, we established that 7 nM was the smallest toxin concentration producing a minimal detectable deformation of the somatic AP after local delivery of the toxin. Using membrane potential imaging, we found that, at this minimal concentration, AaH-II substantially widened the AP in the AIS. Using ultrafast Na+imaging, we found that local application of 7 nM AaH-II caused a large increase in the slower component of the Na+influx in the AIS. Finally, using ultrafast Ca2+imaging, we observed that 7 nM AaH-II produces a spurious slow Ca2+influx via Ca2+-permeable VGNCs. Molecules targeting VGNCs, including peptides, are proposed as potential therapeutic tools. Thus, the present analysis in the AIS can be considered a general proof-of-principle on how high-resolution imaging techniques can disclose drug effects that cannot be observed when tested at the macroscopic level.
KINNTREX: A Neural Network Unveils Protein Mechanism from Time Resolved X-ray Crystallography
Authors: Biener Gabriel , Malla Tek Narsingh , Schwander Peter , Schmidt Marius
Published: October 2023

Here, a machine learning method based on a kinetically informed neural network (NN) is introduced. The proposed method is designed to analyze a time series of difference electron density (DED) maps from a time-resolved X-ray crystallographic experiment. The method is named KINNTREX (Kinetics Inspired NN for Time-Resolved X-ray Crystallography). To validate KINNTREX, multiple realistic scenarios were simulated with increasing level of complexity. For the simulations, time-resolved X-ray data was generated that mimic data collected from the photocycle of the photoactive yellow protein (PYP).

KINNTREX only requires the number of intermediates and approximate relaxation times (both obtained from a singular valued decomposition) and does not require an assumption of a candidate mechanism. It successfully predicts a consistent chemical kinetic mechanism, together with difference electron density maps of the intermediates that appear during the reaction. These features make KINNTREX attractive for tackling a wide range of biomolecular questions. In addition, the versatility of KINNTREX can inspire more NN-based applications to time-resolved data from biological macromolecules obtained by other methods.
Pleiotropy alleviates the fitness costs associated with resource allocation trade-offs in immune signaling networks
Authors: Martin Reese , Tate Ann.T.
Published: October 2023

Many genes and signaling pathways within plant and animal taxa drive the expression of multiple organismal traits. This form of genetic pleiotropy instigates trade-offs among life-history traits if a mutation in the pleiotropic gene improves the fitness contribution of one trait at the expense of another. Whether or not pleiotropy gives rise to conflict among traits, however, likely depends on the resource costs and timing of trait deployment during organismal development. To investigate factors that could influence the evolutionary maintenance of pleiotropy in gene networks, we developed an agent-based model of co-evolution between parasites and hosts. Hosts comprise signaling networks that must faithfully complete a developmental program while also defending against parasites, and trait signaling networks could be independent or share a pleiotropic component as they evolved to improve host fitness. We found that hosts with independent developmental and immune networks were significantly more fit than hosts with pleiotropic networks when traits were deployed asynchronously during development. When host genotypes directly competed against each other, however, pleiotropic hosts were victorious regardless of trait synchrony because the pleiotropic networks were more robust to parasite manipulation, potentially explaining the abundance of pleiotropy in immune systems despite its contribution to life history trade-offs.
Above- and below-ground links mediated by arboreal ants and host tree modify soil aggregation scaling, infiltration, and chemistry
Authors: Medina Nicholas , Schmitt Lauren , Perfecto Ivette , Vandermeer John
Published: October 2023

Soils are increasingly recognized as complex systems, emphasizing a need to study unique properties such as long-tailed scaling laws and the role of indirect interactions among arboreal above- and below-ground soil invertebrates. However, few studies consider the above-below-ground connections mediated by invertebrates’ activity and behavior compared to mediated by tree physiology. Given previous work showing that arboreal ants can compete and affect ground foragers as well as alter foraging behavior on different host trees, it is plausible that persistent above-ground ant nesting could extend to affect soil properties including structure and chemistry, mediated by ground ant exclusion. This study analyzes soil aggregation, water infiltration, and macro-chemical data associated with longer-term (5+ year) ant nesting in a rustic tropical agroforest. Results show that, 1) ant nesting maintained scaling law exponents or fractal dimensions of soil aggregate size distributions, and was significantly associated with relatively larger micro-aggregate diameters and log-normal variance in macro-aggregate size distributions, suggesting more consistent (less variable) underlying aggregation processes similar to host tree species effects; 2) areas in the vicinity of trees with no dominant ant nests had three-times faster water infiltration than in the vicinity of trees with dominant ant nests; and 3) a tendency toward changes in soil carbon and nitrogen stocks by one-quarter depending on host tree. These patterns are consistent with expected effects of ground ant suppression by an aggressive keystone arboreal ant, and are supported by previous studies reporting positive ground ant nest effects on soil chemistry and documenting ground ant foraging as a source of soil aggregate fragmentation. This study presents new ecological processes affecting ecosystem-scale functions, and suggests that future research on indirect interaction cascades would be beneficial to advance fundamental understanding of whole-ecosystem processes.
Cell autonomous role of leucine-rich repeat kinase in protection of dopaminergic neuron survival
Authors: Kang Jongkyun , Huang Guodong , Ma Long , Tong Youren , Shahapal Anu , Chen Phoenix , Shen Jie
Published: October 2023

Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common genetic cause of Parkinson’s disease (PD), which is the leading neurodegenerative movement disorder characterized by the progressive loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). However, whether LRRK2 mutations cause PD and degeneration of DA neuronsviaa toxic gain-of-function or a loss-of-function mechanism is unresolved and has pivotal implications for LRRK2-based PD therapies. In this study, we investigate whether LRRK2 and its functional homologue LRRK1 play an essential, intrinsic role in DA neuron survival through the development of DA neuron-specificLRRKconditional double knockout (cDKO) mice. We first generated and characterized floxedLRRK1andLRRK2mice and then confirmed that germline deletions of the floxedLRRK1andLRRK2alleles result in null mutations, as evidenced by the absence ofLRRK1andLRRK2mRNA and protein in the respective homozygous deleted mutant mice. We further examined the specificity of Cre-mediated recombination driven by thedopamine transporter-Cre(DAT-Cre) knockin (KI) allele using a GFP reporter line and confirmed thatDAT-Cre-mediated recombination is restricted to DA neurons in the SNpc. Crossing these validated floxedLRRK1andLRRK2mice withDAT-CreKI mice, we then generated DA neuron-restrictedLRRKcDKO mice and further showed that levels of LRRK1 and LRRK2 are reduced in dissected ventral midbrains ofLRRKcDKO mice. While DA neuron-restrictedLRRKcDKO mice of both sexes exhibit normal mortality and body weight, they develop age-dependent loss of DA neurons in the SNpc, as demonstrated by the progressive reduction of DA neurons in the SNpc ofLRRKcDKO mice at the ages of 20 and 24 months but the unaffected number of DA neurons at the age of 15 months. Moreover, DA neurodegeneration is accompanied with increases of apoptosis and elevated microgliosis in the SNpc as well as decreases of DA terminals in the striatum, and is preceded by impaired motor coordination. Taken together, these findings provide the unequivocal evidence for the importance of LRRK in DA neurons and raise the possibility that LRRK2 mutations may impair its protection of DA neurons, leading to DA neurodegeneration in PD.