bluuebunny/crossref_metadata_2025 huggingface dataset:
Spike-based computational primitives to reproduce neural dynamics in the parietal cortex during motor preparation
Authors: Parrilla L , Filippini M , Zendrikov D , Fattori P , Indiveri G
Published: October 2024

Biologically plausible spiking neural network models of sensory cortices can be instrumental in understanding and validating their principles of computation. Models based on Cortical Computational Primitives (CCPs), such as Hebbian plasticity and Winner-Take-All (WTA) networks, have already been successful in this approach. However, the specific nature and roles of CCPs in sensorimotor cortices during cognitive tasks are yet to be fully deciphered. The evolution of motor intention in the Posterior Parietal Cortex (PPC) before arm-reaching movements is a well-suited cognitive process to assess the effectiveness of different CCPs. To this end, we propose a biologically plausible model composed of heterogeneous spiking neurons which implements and combines multiple CCPs, such as multi-timescale learning and soft WTA modules. By training the model to replicate the dynamics of in-vivo recordings from non-human primates, we show how it is effective in generating meaningful representations from unbalanced input data, and in faithfully reproducing the transition from motor planning to action selection. Our findings elucidate the importance of distributing spike-based plasticity across multi-timescales, and provide an explanation for the role of different CCPs in models of frontoparietal cortical networks for performing multisensory integration to efficiently inform action execution.
Endosomal actin branching, fission, and receptor recycling require FCHSD2 recruitment by MICAL-L1
Authors: Frisby Devin , Murakonda Ajay B. , Ashraf Bazella , Dhawan Kanika , Almeida-Souza Leonardo , Naslavsky Naava , Caplan Steve
Published: October 2024

Endosome fission is required for the release of carrier vesicles and the recycling of receptors to the plasma membrane. Early events in endosome budding and fission rely on actin branching to constrict the endosomal membrane, ultimately leading to nucleotide hydrolysis and enzymatic fission. However, our current understanding of this process is limited, particularly regarding the coordination between the early and late steps of endosomal fission. Here we have identified a novel interaction between the endosomal scaffolding protein, MICAL-L1, and the human homologue of the Drosophila Nervous Wreck (Nwk) protein, FCH and double SH3 domains protein 2 (FCHSD2). We demonstrate that MICAL-L1 recruits FCHSD2 to the endosomal membrane, where it is required for ARP2/3-mediated generation of branched actin, endosome fission and receptor recycling to the plasma membrane. Because MICAL-L1 first recruits FCHSD2 to the endosomal membrane, and is subsequently responsible for recruitment of the ATPase and fission protein EHD1 to endosomes, our findings support a model in which MICAL-L1 orchestrates endosomal fission by connecting between the early actin-driven and subsequent nucleotide hydrolysis steps of the process.
Number of lymph nodes retrieved in patients with locally advanced rectal cancer after total neoadjuvant therapy: post-hoc analysis from the STELLAR trial
Authors: Zhang Yueyang , Tang Yuan , Ma Huiying , Su Hao , Xu Zheng , Gao Changyuan , Zhou Haitao , Jin Jing
Published: October 2024

Background

The current gold standard for extraperitoneal locally advanced rectal cancer is total neoadjuvant therapy (TNT) followed by total mesorectal excision. This research explored the number of lymph nodes in patients with locally advanced rectal cancer after TNT and its correlation with survival.

Materials and Methods

This is a post-hoc analysis based on the STELLAR trial, including patients with locally advanced rectal cancer from 16 tertiary centres who were randomized for short-term radiotherapy followed by chemotherapy (TNT group) or long-term concurrent chemotherapy group followed by total mesorectal excision between 2015 and 2018. This lymph node-related analysis is based on the TNT group. Subgroups were differentiated based on the lymph node harvest (below the median number: limited lymphadenectomy group, and greater than/equal to the median number: extended lymphadenectomy group). The primary outcomes were overall survival and disease-free survival (DFS). Correlations with clinical/pathological variables, lymphadenectomy categories and use of adjuvant chemotherapy were explored.

Results

Among the 451 patients enrolled in the STELLAR trial, 227 patients (50.3%) were assigned to the TNT group, including 29.5% females. The median number of lymph nodes retrieved in the TNT group was 11.0. Patients in the limited lymphadenectomy subgroup exhibited worse overall survival than those with extended lymphadenectomy (HR 2.95 (95% c.i. 1.47 to 5.92), P = 0.001). The overall survival was similar in the ypN0-limited and ypN1-extended subgroups (HR 0.38 (95% c.i. 0.11 to 1.30), P = 0.109). Adjuvant chemotherapy was associated with better overall survival and DFS than no adjuvant chemotherapy overall (P < 0.001) and in the limited lymphadenectomy subgroup (P < 0.001). However, there was no significant difference in overall survival or DFS with or without adjuvant chemotherapy in the extended lymphadenectomy subgroup (P = 0.887 and P = 0.192, respectively).

Conclusion

In the STELLAR trial, the median number of lymph nodes harvested was 11. In patients with limited lymphadenectomy, the use of adjuvant therapy after TNT was beneficial and correlated with better prognosis compared with patients who did not receive adjuvant chemotherapy.
Spontaneous space closure after extraction of permanent first molars in children and adolescents: a systematic review and meta-analysis
Authors: Hamza Blend , Papageorgiou Spyridon N , Patcas Raphael , Schätzle Marc
Published: October 2024

Background

Extraction of the permanent first molars is sometimes necessitated in children and adolescents due to deep carious lesions or developmental defects.

Objective

To estimate the prevalence of spontaneous space closure after extraction of permanent first molars and identify factors associated with it.

Search methods

Unrestricted searches in five databases for human studies until February 2024.

Selection criteria

Longitudinal before-and-after (cohort) human studies assessing eruption of the permanent second molars and spontaneous space closure after extraction of the permanent first molar.

Data collection and analysis

Study selection, data extraction, and risk of bias assessment were performed in duplicate. Random-effects meta-analyses of average spontaneous space closure prevalences and odds ratios (OR) with their 95% confidence intervals (CI) were performed, followed by meta-regression/sensitivity/reporting biases’ analyses and evaluation of our confidence in effect estimates.

Results

Sixteen reports pertaining to 15 studies (1 prospective /14 retrospective) were included covering 1159 patients (ages 5.5–15.0 years [mean 10.0 years]; 45% male on average) and 2310 permanent second molars. The prevalence of spontaneous space closure was higher in the maxilla (nine studies; 85.3%; 95% CI = 73.7%–92.3%) than the mandible (11 studies; 48.1%; 95% CI = 34.5%–62.0%) to a significant extent (nine studies; OR = 7.77; 95% CI = 4.99–12.11; P < 0.001). For both maxillary/mandibular second molars, Demirjian category E was associated with increased space closure odds than earlier/later stages (P < 0.05). Spontaneous space closure in the mandible was seen more often for patients ages 8–10 years (compared with older patients; three studies; OR = 3.32; 95% CI = 1.73–6.36; P < 0.001) and when the mandibular permanent third molar was present (four studies; OR = 2.28; 95% CI = 1.67–3.09; P = 0.003). Additional analyses failed to find any significant modifying factors.

Limitations

The quality of evidence was very low in all instances due to the inclusion of retrospective studies with methodological issues.

Conclusions

Existing evidence indicates that spontaneous space closure in children and adolescents after extraction of the permanent first molar is seen more often in the maxilla than the mandible. Extraction of the permanent first molar at the Demirjian stage E of the second molar and presence of the lower permanent third molar is associated with increased odds of space closure, but uncertainty persists, due to methodological issues of existing studies.

Registration

PROSPERO (CRD42023395371).
A Lullian divertissement for King William III at Kensington in 1698
Authors: Thorp Jennifer
Published: October 2024

On 13 May 1698, according to the London press, ‘there was fine Dancing at Kensington, where his Majesty was present, as also his Excellency the French Ambassador’. The ‘Dancing’ referred to was a vocal and danced entertainment called (with many allusions to the beauties of Kensington Palace) Le Palais des Plaisirs, and probably staged at the behest of the new French ambassador, Camille d’Hostun, comte de Tallard, as part of the series of delicate negotiations in London following the signing of the Peace of Ryswick the previous year. The French libretto of the Kensington divertissement indicates that it was created out of extracts from scenes in earlier French court entertainments and operas, their music by Lully and words by Molière, Benserade and Quinault. The vocal music and dances for each of the five entrées were performed by members of the Paris Opéra and the London theatres, with choreography devised by Anthony L’Abbé, newly arrived in London from the Paris Opéra.
Young people’s perspectives on policies to create healthier food environments in England
Authors: Rinaldi Chiara , McGill Elizabeth , Petticrew Mark , Knai Cecile , Egan Matt
Published: October 2024

Food environments are important determinants of healthy diets among young people. This study explored young people’s perspectives on their food environment, their recommendations to policymakers and views on youth engagement in policy processes. There is limited research on young people’s perspectives on their involvement in developing food environment policies. Youth engagement in policymaking processes can lead to greater policy integrity and inclusivity. Four focus group discussions were conducted with 39 young people (12–21 years) from a town in North West England and a metropolitan area in the English Midlands. Participants were recruited through youth organizations. Data were analysed using inductive thematic analysis. Young people reported concerns about the density of fast food outlets in their local area, the unaffordability of healthier food, and fast food advertisement. These issues were not believed to be prioritized in local and national policymaking. Accordingly, policy recommendations were mainly for structural food environment policies, including restrictions on fast food outlet density and incentives for menu reformulation. Young people did not feel involved in local decisions about the food environment. They expressed a need for more meaningful engagement beyond consultation. Young people have repeatedly shown to have a deep understanding of the social, commercial and political factors that influence diet and health. It is essential that policymakers aiming to improve young people’s diets take their unique views and concerns into account to create effective policies that resonate with young people.
Treatment of degenerated mitral bioprosthesis using inovare alpha rapid deployment balloon-expandable prosthesis—a minimally invasive approach
Authors: Corso Ricardo Barros , Nascimento dos Santos Marcus Vinicius , Kalil da Silva Pina Glauco , Carlos Ferreira Leal João
Published: October 2024

This case report describes an 82-year-old woman with severe mitral bioprosthesis stenosis and NYHA II–III heart failure, EuroScore II of 22.54% and STS Score of 13.7%. She received innovative treatment with transatrial mitral valve-in-valve implantation of a rapid deployment balloon-expandable prosthesis via video-assisted right lateral mini-thoracotomy, with myocardial protection through ventricular fibrillation. The patient was discharged and, under cardiology follow-up, achieved NYHA I class with no angina.
Role of vitamin E on bovine skeletal-muscle-derived cells from Korean native cattle under heat treatment
Authors: Kim Bo-Mi , Jin Xue-Cheng , Lee Jun-Hee , Peng Dong-Qiao , Kim Won-Seob , Lee Hong-Gu
Published: October 2024

Our study aimed to evaluate the dualistic effect of heat stress on muscle differentiation at different temperatures, and whether vitamin E, a powerful antioxidant, could offset any negative effects, using bovine skeletal-muscle-derived cells (BSMCs) with myogenic properties. The BSMCs were extracted from the skeletal muscle of 30-mo-old Korean native cattle and subjected to myogenic differentiation under 3 heat exposure conditions: 37 °C (control; CON), 39 °C (mild heat stress; MHS), and 41 °C (severe heat stress; SHS) for 24 h with or without vitamin E treatment (NE or VE). After 24 h treatments, the cells were returned to 37 °C incubators and differentiated until day 6. On day 1, because of the heat exposure, the gene expression of MYOG was the highest in MHS (P = 0.047), suggesting a promotive effect of mild heat stress on myogenic differentiation, while on day 6, compared with CON and MHS, MYOD (P = 0.013) and MYOG (P = 0.029) were the lowest in SHS. Vitamin E treatment also lowered MYOG (P = 0.097), regardless of heat exposure. On day 1, HSPB1 (P = 0.001) and HSP70 (P < 0.001) were the highest in SHS, and an interaction between heat exposure and vitamin E treatment was found on day 6 (P < 0.027). BCL-2 was also the highest on day 1 in SHS (P = 0.05), and an interaction of heat exposure and vitamin E treatment was found on day 1 on BAX expression (P = 0.038). For antioxidant genes, SOD1 (P = 0.002) and GPX1 (P < 0.001) were affected by heat exposure, with the highest levels being observed in SHS, and on day 6, GPX1 was still the highest in SHS (P = 0.027). The fusion index was also affected by heat exposure, showing a decrease in SHS and an increase in MHS compared with CON (P < 0.001). Significant effects were noted from heat exposure (P < 0.001), vitamin E treatment (P < 0.001), and the interaction of heat exposure and vitamin E treatment (P = 0.002) on the protein content. Taken together, our findings provide evidence that vitamin E could ameliorate the harmful effects of heat exposure by modulating heat shock proteins and apoptosis regulators, improving the protein synthesis of BSMCs during myogenic differentiation. These results suggest that vitamin E supplementation could potentially protect muscle development in beef cattle under summer heat stress.
A multispecies bacterial-based direct-fed microbial alleviates Salmonella invasion and supports in vitro epithelial integrity
Authors: Gresse Raphaele , Cappellozza Bruno I , Capern Lena C , Knudsen Tine T M , Copani Giuseppe
Published: October 2024

Managing bacterial infections is of great importance in livestock production, particularly those caused by Salmonella enterica serovars Typhimurium or Dublin, which can impact both animal health and performance, as well as human food safety. Direct-fed microbials (DFM) can support gastrointestinal function and alleviate the potential negative effects of bacterial infections. In the present study, the capacity of a multispecies bacterial-based DFM containing Ligilactobacillus (formerly Lactobacillus) animalis 506, Propionibacterium freudenreichii 507, Bacillus licheniformis 809, and B. subtilis 597 to reduce S. Typhimurium ATCC14028 invasion was investigated using a co-incubation model with the HT29-MTX-E12 cell line (experiment 1). Next, a possible antagonistic effect of the DFM against S. Dublin ATCC 41286 was evaluated using an in vitro agar well diffusion method following a co-incubation of 48 h (experiment 2). At last, a series of experiments were performed to evaluate how different doses (6.25 × 106, 2.50 × 107, or 1.00 × 108 CFU/well) of the DFM would support the integrity of intestinal epithelial cells challenged or not with S. Typhimurium ATCC14028 or hydrogen peroxide under a transepithelial electrical resistance (TEER) assay with Caco-2 cells (experiments 3 and 4). In experiment 1, BDP significantly (P < 0.001) reduced by 90.8% the invasion of S. Typhimurium into HT29-MTX-E12 cells, whereas viability of the potentially harmful bacteria was reduced by 21.0% (P < 0.0001). In experiment 2, the antagonistic properties of BDP towards S. Dublin were confirmed by the detection of a clear inhibition zone (size = 8.6 mm). Lastly, without challenge, the lowest dose of the DFM (6.25 × 106 CFU) provided the greatest support to the cells (treatment × hour; P < 0.0001). However, when the cells were challenged with S. Typhimurium, all doses alleviated the loss of integrity caused by the pathogen (treatment × hour; P < 0.0001). In cells challenged with hydrogen peroxide, the greater dose (1.00 × 108 CFU) supported the cells for a longer period of time (treatment × hour; P < 0.0001). These in vitro findings set the stage for exploring the potential benefits of using a novel DFM as a promising tool and strategy to mitigate S. enterica infections in ruminants and improve animal health, food safety, and public health. Further, in vivo confirmation needs to be developed to validate these preliminary in vitro results.
Influence of flake density and starch retrogradation on in vitro gas production kinetics, digestibility, and ruminal fermentation characteristics of steam-flaked corn
Authors: Trotta Ronald J , Kreikemeier Kelly K , Harmon David L
Published: October 2024

Previous research has demonstrated that decreasing starch availability of steam-flaked corn by increasing flake density or increasing the degree of starch retrogradation influences in vitro gas production kinetics. However, it is unclear if increasing flake density or the degree of starch retrogradation influences end-products of in vitro ruminal fermentation (methane, volatile fatty acids, ammonia). The objective of this experiment was to evaluate the effects of increasing flake density and the degree of starch retrogradation on in vitro gas production kinetics, digestibility, and ruminal fermentation characteristics of steam-flaked corn. Three ruminally cannulated steers were fed a high-concentrate diet and sampled for ruminal digesta for an in vitro fermentation experiment with a 5 × 2 factorial arrangement of treatments. Steam-flaked corn was produced to flake densities of 257, 296, 335, 373, and 412 g/L by adjusting the rolls of a steam-flaker. Samples were stored for 3 d at either 23 °C to produce fresh steam-flaked corn or at 55 °C in heat-sealed foil bags to produce retrograded steam-flaked corn. In vitro fermentation vessels were incubated for 24 h and then assessed for fermentation parameters including dry matter digestibility, volatile fatty acid concentrations, and total gas and methane production. Increasing the degree of starch retrogradation decreased (P < 0.01) the rate of gas production across all flake densities of steam-flaked corn but did not decrease the extent of gas production. In vitro methane production, dry matter digestibility, and microbial biomass concentration were not influenced by increasing flake density or starch retrogradation. Increasing the degree of starch retrogradation decreased (P = 0.03) the molar propionate proportion and increased (P < 0.06) the molar proportions of butyrate, isobutyrate, and isovalerate and the acetate:propionate ratio. Enzymatic starch availability of steam-flaked corn was positively correlated with mean propionate proportion (r2 = 0.93) and negatively correlated with the mean butyrate proportion (r2 = 0.89). Results from the current study demonstrate that increasing the degree of starch retrogradation of steam-flaked corn decreased the rate of in vitro gas production and altered volatile fatty acid profiles in the ruminal fermentation media.
Erasing the ‘Victim’ from the ‘Victim–Perpetrator’
Authors: Festa Vasiliki Zoi
Published: October 2024

Dominic Ongwen — child soldier turned warlord — was tried, convicted and sentenced by Trial Chamber IX of the International Criminal Court (ICC). Using the theoretical vehicle of expressivism, this article aims to look beyond the straightforward, normative consequences of his adjudication, identifying the Trial Judgment’s — and hence, the ICC’s — implicit, didactic/symbolic messages around his controversial victim–perpetrator duality. To achieve this goal, the article deploys the methods of empirical, discourse, and legal/doctrinal analysis, which examine the Judgment’s relevant legal, contextual and linguistic choices around the depiction of Ongwen’s two portraits — that of the victim and that of the perpetrator. Through the juxtaposition of the two portraits, defined by the absence of victimhood and the overpresence of perpetratorhood, the researcher extracts the Judgment’s expressive imprint, including the preservation of the victim–perpetrator dichotomy, the non-elucidation of the child soldiering phenomenon, the problematic deductions on the role and liability of child soldiers, as well as the defendant’s over-stigmatization. In light of the above, the article assesses the messages’ adherence to the aspirations and principles of expressivism.
Neutrophil plasticity in liver diseases
Authors: Teo Jia Ming Nickolas , Chen Weixin , Ling Guang Sheng
Published: October 2024

The liver has critical digestive, metabolic, and immunosurveillance roles, which get disrupted during liver diseases such as viral hepatitis, fatty liver disease, and hepatocellular carcinoma. While previous research on the pathological development of these diseases has focused on liver-resident immune populations, such as Kupffer cells, infiltrating immune cells responding to pathogens and disease also play crucial roles. Neutrophils are one such key population contributing to hepatic inflammation and disease progression. Belonging to the initial waves of immune response to threats, neutrophils suppress bacterial and viral spread during acute infections and have homeostasis-restoring functions, whereas during chronic insults, they display their plastic nature by responding to the inflammatory environment and develop new phenotypes alongside longer life spans. This review summarizes the diversity in neutrophil function and subpopulations present at steady state, during liver disease, and during liver cancer.
CRISPR/Cas9 editing of two adenine phosphoribosyl transferase coding genes reveals the functional specialization of adenine salvage proteins in common bean
Authors: López Cristina Mª , Alseekh Saleh , Martínez Rivas Félix J , Fernie Alisdair R , Prieto Pilar , Alamillo Josefa M
Published: October 2024

Adenine metabolism is important for common bean (Phaseolus vulgaris L.) productivity since this legume uses ureides derived from the oxidation of purine nucleotides as its primary nitrogen storage molecules. Purine nucleotides are produced from de novo synthesis or through salvage pathways. Adenine phosphoribosyl transferase (APRT) is the enzyme dedicated to adenine nucleobase salvage for nucleotide synthesis, but it can also convert active cytokinin bases into their inactive nucleotide forms. In common bean, APRT is encoded by four genes. Gene expression analysis, biochemical properties, and subcellular location indicated functional differences among the common bean APRT isoforms. CRISPR/Cas9 targeted down-regulation of two of the four PvAPRTs followed by metabolomic and physiological analyses of targeted hairy roots revealed that, although the two proteins have redundant functions, PvAPRT1 mostly participated in the salvage of adenine, whereas PvAPRT5 was the predominant form in the regulation of cytokinin homeostasis and stress responses with a high impact in root and nodule growth.
Aintree Catheter Versus Gum Elastic Bougie for Airway Exchange Using the i-Gel Supraglottic Device: A Cadaver Study
Authors: Jin Lee , Perdue Matthew J , Sandoval Clifford , Walker Jerimiah D , Mitchell Christopher
Published: October 2024

Introduction

Airway compromise is the third leading cause of preventable death on the battlefield. Most combat medics carry supraglottic airway (SGA) devices for airway management. However, exchanging an SGA device for a definitive airway can be challenging, especially in austere environments. This study aims to compare the Aintree intubation catheter (AIC) to the gum elastic bougie (GEB) as adjuncts for performing airway device exchange with the i-gel SGA device in place.

Materials and Methods

This randomized crossover cadaver study of 48 participants examined the success rate of two endotracheal introducers (AIC and GEB) when performing a blind airway exchange with an i-gel in place. Study participants were combat medics (MOS 68W), physician assistant students, physician assistant staff, emergency medicine (EM) physician residents, and emergency medicine attending physicians attending classes at the installation Medical Simulations Training Center. Each participant performed up to three attempts using both endotracheal tube introducers on the same cadaver. The primary outcome was successful airway exchange rate with each device, and the secondary outcome was time to successful airway exchange.

Results

Although the AIC had a slightly higher success rate of 33% compared to the GEB success rate of 30%, this result was not statistically significant, P = .56. Similarly, participants completed successful airway exchanges with the AIC faster, with a mean time of 86.5 seconds (95% CI: 71.2 to 101.9) versus 101.2 seconds (95% CI: 85.5 to 116.9) with the GEB. However, this result was also not statistically significant, P = 0.18.

Conclusions

This study demonstrates no significant difference in success rate and time to completion of successful iterations of airway exchanges between the two devices. Although the AIC performed slightly better overall, these results are not statistically significant. Additionally, blind exchange intubations appear to be of high risk with minimal success, so we recommend against this technique in routine practice.
Clinical Characteristics and Risk Factors for Cryptococcal Meningitis in Diverse Patient Populations in New York City
Authors: Sardar Zomer , Kim Carla Y , Thakur Kiran T
Published: October 2024

Background

Cryptococcal meningitis (CM) is responsible for 15%–20% of human immunodeficiency virus (HIV)–associated mortalities. CM prevalence has also increased in other immunocompromised populations of transplant recipients, patients with cancer, and individuals on immunomodulatory medication.

Methods

This retrospective review included 51 definitive patients with CM hospitalized at a tertiary academic medical center in New York City between 2010 and 2023. We assessed clinical features and outcomes of CM, with additional analysis of factors related to antiretroviral therapy (ART) adherence in HIV-infected cases and immunomodulatory medication history of HIV-negative cases.

Results

The cohort had a mean (standard deviation) age of 47.1 ± 15.1 years, and was predominantly male (37, 72.5%). Of 32 patients with HIV, 3 (9.4%) were newly diagnosed with HIV at the time of CM hospitalization, 5 (15.6%) had recurrent CM, and 2 (6.3%) had a CM relapse. The majority (30, 93.8%) of patients with HIV were ART nonadherent. Of 19 HIV-negative patients, 8 (42.1%) were solid-organ transplant recipients, 5 (26.3%) had autoimmune conditions of sarcoidosis or systemic lupus erythematosus, and 3 (15.8%) had chronic lymphocytic leukemia. Six (11.8%) patients died during hospitalization, 4 of whom had HIV.

Conclusions

The burden of CM in people with HIV and immunocompromised patients continues even in settings with accessible standard antifungal treatment though interventions of increased ART adherence for those with HIV and antifungal prophylaxis may improve morbidity and mortality.
Identifying Gaps in the International Consensus Case Definitions for Invasive Aspergillosis: A Review of Clinical Cases Not Meeting These Definitions
Authors: Tio Shio Yen , Chen Sharon C A , Heath Christopher H , Pradhan Alyssa , Morris Arthur J , Korman Tony M , Morrissey C Orla , Halliday Catriona L , Kidd Sarah , Spelman Timothy , Brell Nadiya , McMullan Brendan , Clark Julia E , Mitsakos Katerina , Hardiman Robyn P , Williams Phoebe C M , Campbell Anita J , Beardsley Justin , Van Hal Sebastiaan , Yong Michelle K , Worth Leon J , Slavin Monica A
Published: October 2024

Background

International consensus definitions for invasive aspergillosis (IA) in research are rigorous, yet clinically significant cases are often excluded from clinical studies for not meeting proven/probable IA case definitions. To better understand reasons for the failure to meet criteria for proven/probable infection, we herein review 47 such cases for their clinical and microbiological characteristics and outcomes.

Methods

Data on 47 cases that did not meet consensus IA definitions but were deemed significant were derived from a retrospective, observational, multicenter survey of 382 presumed IA cases across Australasia, of which findings of 221 proven/probable infections were recently published. The clinical, microbiological, and radiologic characteristics of these cases were analyzed. Mortality outcomes were compared with those of 221 proven/probable cases.

Results

Of 47 cases studied, 15 lacked classical host factors; 22 exhibited only a single positive Aspergillus polymerase chain reaction result; 7 lacked typical IA radiologic findings on chest computed tomography; and 3 had borderline galactomannan optical density indices (<1.0 but ≥0.5) in bronchoalveolar lavage fluid. The median age of patients was 61 years (IQR, 52–68); 34 were male (72%). Seven patients (15%) required intensive care admission. All patients had lung as the primary site of infection. Antifungal treatment was initiated in 42 patients (89%). All-cause 90-day mortality was 33%, similar to the 30% mortality in the comparative cohort (n = 221).

Conclusions

Our findings highlight the limitations of current consensus definitions for IA. Notably, the mortality of patients not meeting these definitions was similar to that of patients with proven/probable IA. Further studies, especially of patients with a single positive Aspergillus polymerase chain reaction result and those without host factors, are needed to determine if future consensus definitions may benefit from modifications.
Prospective Evaluation of Routine Statewide Integration of Molecular Epidemiology and Contact Tracing to Disrupt Human Immunodeficiency Virus Transmission
Authors: Kantor Rami , Steingrimsson Jon , Fulton John , Novitsky Vladimir , Howison Mark , Gillani Fizza , Bhattarai Lila , MacAskill Meghan , Hague Joel , Guang August , Khanna Aditya , Dunn Casey , Hogan Joseph , Bertrand Thomas , Bandy Utpala
Published: October 2024

Background

Human immunodeficiency virus (HIV) remains a global challenge and novel measures for transmission disruption are needed. Contact tracing is limited by reluctance or inability of newly diagnosed individuals to name at-risk contacts. Molecular cluster analysis is mostly used for outbreak investigations, and its role in routine public health activities remains uncertain.

Methods

We conducted a 2-year prospective statewide study in Rhode Island to evaluate integration of HIV cluster analyses into routine contact tracing, by attempting to reinterview all new diagnoses who clustered, notifying them of clustering, and evaluating benefits of this strategy. Clustering was compared between a phylogenetic ensemble versus distance-based HIV-TRACE.

Results

Of 100 new diagnoses during 2021–2022, 52 individuals clustered, of whom only 31% were reinterviewed. Reinterviewing did not improve contact tracing beyond initial interviews, and the study was stopped early for futility. Clustering concordance within the phylogenetic ensemble was high (88%–89%), but lower (74%) for HIV-TRACE. Despite hypothesis rejection, we established a public health–academic partnership, developed a bioinformatics pipeline enabling near real-time cluster analysis, and identified gaps and unique opportunities for intervention.

Conclusions

Attempting to reinterview all statewide new HIV diagnoses in molecular clusters showed no evidence of improving contact tracing. However, a strong academic–public health partnership enabled near real-time, longitudinal integration of molecular cluster analysis into routine public health activities, and identified barriers and opportunities tailoring data-driven approaches to unique individual and community characteristics, guiding future work on optimal use of molecular epidemiology to disrupt HIV transmission.
MASTER OT J030227.28+191754.5: An unprecedentedly energetic dwarf nova outburst
Authors: Tampo Yusuke , Kato Taichi , Isogai Keisuke , Kimura Mariko , Kojiguchi Naoto , Nogami Daisaku , Ito Junpei , Shibata Masaaki , Yamanaka Masayuki , Taguchi Kenta , Maehara Hiroyuki , Itoh Hiroshi , Matsumoto Katsura , Nakagawa Momoka , Nishida Yukitaka , Dvorak Shawn , Murata Katsuhiro L , Hosokawa Ryohei , Imai Yuri , Ito Naohiro , Niwano Masafumi , Sato Shota , Noto Ryotaro , Yamaguchi Ryodai , Schramm Malte , Oasa Yumiko , Kanai Takahiro , Sasaki Yu , Tordai Tamás , Vanmunster Tonny , Kiyota Seiichiro , Katysheva Nataly , Shugarov Sergey Yu , Zubareva Alexandra M , Antipin Sergei , Ikonnikova Natalia , Belinski Alexandr , Dubovsky Pavol A , Medulka Tomáš , Takahashi Jun , Takayama Masaki , Ohshima Tomohito , Saito Tomoki , Tozuka Miyako , Sako Shigeyuki , Tanaka Masaomi , Tominaga Nozomu , Horiuchi Takashi , Hanayama Hidekazu , Reichart Daniel E , Kouprianov Vladimir V , Davidson Jr James W , Caton Daniel B , Romanov Filipp D , Lane David J , Hambsch Franz-Josef , Narita Norio , Fukui Akihiko , Ikoma Masahiro , Tamura Motohide , Kawabata Koji S , Nakaoka Tatsuya , Imazawa Ryo
Published: October 2024

We present a detailed study of the MASTER OT J030227.28$+$191754.5 outburst in 2021–2022, which reached an amplitude of $10.2\:$mag and a duration of $60\:$d. The detections of (1) the double-peaked optical emission lines, and (2) the early and ordinary superhumps, established that MASTER OT J030227.28$+$191754.5 is an extremely energetic WZ Sge-type dwarf nova (DN). Based on the superhump observations, we obtained its orbital period and mass ratio as $0.05986(1)\:$d and 0.063(1), respectively. These values are within a typical range for low-mass-ratio DNe. According to the binary parameters derived based on the thermal–tidal instability model, our analyses showed that (1) the standard disk model requires an accretion rate $\simeq\!\! 10^{20}\:$g$\:$s$^{-1}$ to explain its peak optical luminosity, and (2) large mass was stored in the disk at the outburst onset. These factors cannot be explained solely by the impact of its massive ($\gtrsim\!\! 1.15\, M_{\odot }$) primary white dwarf implied by Kimura et al. (2023, ApJ, 951, 124). Instead, we propose that the probable origin of this enormously energetic DN outburst is the even lower quiescence viscosity than other WZ Sge-type DNe. This discussion is qualitatively valid for most possible binary parameter spaces unless the inclination is low enough ($\lesssim\!\! 40^\circ$) for the disk to be bright, explaining the outburst amplitude. Such low inclinations, however, would not allow detectable amplitude of early superhumps in the current thermal–tidal instability model. The optical spectra at outburst maximum showed strong emission lines of the Balmer, He i, and He ii series, the core of which is narrower than $\sim \! 800\:$km$\:$s$^{-1}$. Considering its binary parameters, a Keplerian disk cannot explain this narrow component, but the presumable origin is disk winds.
Quasi-biennial oscillation of the Ca ii K plage area
Authors: Xu Xiang , Zeng ShuGuang , Zheng Sheng , Wan Miao , Zeng XiangYun , Deng LinHua , Huang Yao
Published: October 2024

Solar quasi-biennial oscillations (QBOs) are crucial not only for comprehending the solar dynamo mechanism but also for forecasting space weather. In this present work, composite monthly Ca ii K plage area (PA) data were utilized, derived from cross-calibrated Ca ii K spectra and filtered maps collected at 38 stations from 1892 to 2023 December. The analysis, covering 14–25 solar cycles, employes synchrosqueezed wavelet transforms (SWT) to examine the periodicity of the plage area data. The following prominent results are found: (1) There are many periodic modes with different characteristics in plage area (PA) data, including the $40\:$yr periodic mode, the $22\:$yr magnetic periodic mode, the $11\:$yr Schwabe periodic mode, a medium-term periodic mode, a quasi-sexennial oscillation period mode, and the QBOs periodic modes; (2) the reconstructed solar QBOs exhibit intermittence with signs of stochasticity; (3) the Gnevyshev gap is observed in solar cycles 15–24, and triple peaks are observed in solar cycles 16, 17, and 19. There are two possible mechanisms by which the Gnevyshev gap may occur; one is as a result of the modulation of solar QBOs by the $11\:$yr Schwabe cycle, and the other is as a result of the reversal of the solar magnetic field.
Blue supergiants as a progenitor of intermediate-luminosity red transients
Authors: Moriya Takashi J , Menon Athira
Published: October 2024

The current perspective about the explosions of massive hydrogen-rich blue supergiants is that they resemble SN 1987A. These so-called peculiar Type II supernovae, however, are one of the rarest types of supernovae and may not hence be the fate of all blue supergiants. In this work, we explore other explosion scenarios for blue supergiants. We create synthetic light curves from the explosions of blue supergiant models born from binary mergers, over a range of explosion energies and $^{56}\mathrm{Ni}$ masses. We find that blue supergiant explosions may also lead to intermediate-luminosity red transients. We thus identify two categories of supernovae possible from blue supergiant explosions: those with high $^{56}\mathrm{Ni}$ masses ($\gtrsim$0.01  ${M}_\odot$) result in slow-rising, dome-shaped light curves like SN 1987A. Lower $^{56}\mathrm{Ni}$ masses result in low-luminosity, short-plateau light curves resembling some intermediate-luminosity red transients and Type II supernovae like SN 2008bp, which are possible from the explosions of compact blue supergiants and not from the far more extended red supergiants. Our results indicate that blue supergiant explosions are more diverse than SN 1987A-like events and may be hidden among different kinds of transients, explaining the possible discrepancies between the expected fraction of blue supergiants born from binary mergers and the observed fraction of SN 1987A-like supernovae.
High accuracy meets high throughput for near full-length 16S ribosomal RNA amplicon sequencing on the Nanopore platform
Authors: Lin Xuan , Waring Katherine , Ghezzi Hans , Tropini Carolina , Tyson John , Ziels Ryan M
Published: October 2024

Small subunit (SSU) ribosomal RNA (rRNA) gene amplicon sequencing is a foundational method in microbial ecology. Currently, short-read platforms are commonly employed for high-throughput applications of SSU rRNA amplicon sequencing, but at the cost of poor taxonomic classification due to limited fragment lengths. The Oxford Nanopore Technologies (ONT) platform can sequence full-length SSU rRNA genes, but its lower raw-read accuracy has so-far limited accurate taxonomic classification and de novo feature generation. Here, we present a sequencing workflow, termed ssUMI, that combines unique molecular identifier (UMI)-based error correction with newer (R10.4+) ONT chemistry and sample barcoding to enable high throughput near full-length SSU rRNA (e.g. 16S rRNA) amplicon sequencing. The ssUMI workflow generated near full-length 16S rRNA consensus sequences with 99.99% mean accuracy using a minimum subread coverage of 3×, surpassing the accuracy of Illumina short reads. The consensus sequences generated with ssUMI were used to produce error-free de novo sequence features with no false positives with two microbial community standards. In contrast, Nanopore raw reads produced erroneous de novo sequence features, indicating that UMI-based error correction is currently necessary for high-accuracy microbial profiling with R10.4+ ONT sequencing chemistries. We showcase the cost-competitive scalability of the ssUMI workflow by sequencing 87 time-series wastewater samples and 27 human gut samples, obtaining quantitative ecological insights that were missed by short-read amplicon sequencing. ssUMI, therefore, enables accurate and low-cost full-length 16S rRNA amplicon sequencing on Nanopore, improving accessibility to high-resolution microbiome science.
The fully activated open state of KCNQ1 controls the cardiac “fight-or-flight” response
Authors: Hou Panpan , Zhao Lu , Zhong Ling , Shi Jingyi , Wang Hong Zhan , Gao Junyuan , Liu Huilin , Zuckerman Joan , Cohen Ira S , Cui Jianmin
Published: October 2024

The cardiac KCNQ1 + KCNE1 (IKs) channel regulates heart rhythm under both normal and stress conditions. Under stress, the β-adrenergic stimulation elevates the intracellular cyclic adenosine monophosphate (cAMP) level, leading to KCNQ1 phosphorylation by protein kinase A and increased IKs, which shortens action potentials to adapt to accelerated heart rate. An impaired response to the β-adrenergic stimulation due to KCNQ1 mutations is associated with the occurrence of a lethal congenital long QT syndrome (type 1, also known as LQT1). However, the underlying mechanism of β-adrenergic stimulation of IKs remains unclear, impeding the development of new therapeutics. Here, we find that the unique properties of KCNQ1 channel gating with two distinct open states are key to this mechanism. KCNQ1's fully activated open (AO) state is more sensitive to cAMP than its intermediate open state. By enhancing the AO state occupancy, the small molecules ML277 and C28 are found to effectively enhance the cAMP sensitivity of the KCNQ1 channel, independent of KCNE1 association. This finding of enhancing AO state occupancy leads to a potential novel strategy to rescue the response of IKs to β-adrenergic stimulation in LQT1 mutants. The success of this approach is demonstrated in cardiac myocytes and also in a high-risk LQT1 mutation. In conclusion, the present study not only uncovers the key role of the AO state in IKs channel phosphorylation, but also provides a target for antiarrhythmic strategy.
Inaccurate Borrower Information and Credit Risk: Evidence from Marketplace Loans
Authors: Pursiainen Vesa
Published: October 2024

Inaccurate borrower-provided information in marketplace loans is informative about credit risk. An inaccuracy index constructed from the consistency of loan amount with outstanding credit balance, roundness of reported income, and roundness of chosen loan amount predicts the likelihood of default, and the additional default risk is not compensated by higher interest. Inaccurate information is more prevalent in areas with lower social capital and weaker social norms. It is also lower among borrowers whose professions are considered less honest, and among borrowers with higher income uncertainty. These results suggest that inaccuracy is driven by both deliberate misreporting and genuine uncertainty. (JEL D12, D91, G23, G41)

Received: 6 April 2023; Editorial decision: 31 March 2024

Editor: Isil Erel Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
Colistin-resistant Klebsiella pneumoniae sepsis in neonates and infants: an alarming crisis in an Indian NICU
Authors: Kumar Sushil , Verma Akanksha , Singh Anita , Naranje Kirti M , Misra Richa
Published: October 2024

Emergence of multidrug-resistant strain of Klebsiella pneumoniae has led to limited number of antimicrobial options for treatment. Even though outbreaks of colistin–carbapenem-resistant K. pneumoniae (CCRKp) are evolving, reported literature is scarce. This is a retrospective case series of three infants who acquired CCRKp sepsis during an outbreak in a Level III neonatal intensive care unit (NICU) of a tertiary care centre in Northern India. Data were retrieved from medical records of patients. Three babies developed new onset clinical worsening during an outbreak of sepsis. All had respiratory comorbidities and previous antibiotic exposure prior to isolation of CCRKp sepsis from blood. The organism was sensitive to combination of ceftazidime plus avibactam and tetracyclines in two infants; in one other newborn, no sensitive antibiotic was found. Two neonates deceased due to multiorgan dysfunction. An outbreak investigation revealed one common source of sterile water used in a humidifier. The outbreak was resolved by temporarily closing the NICU, segregating the infected infants and using corrective measures such as procuring a fresh batch of sterile water bottles, disinfecting the NICU, and reinforcing the use of antiseptic techniques. The emergence of CCRKp is alarming, particularly in low- and middle-income countries and tropical regions where such outbreaks are difficult to control due to limited healthcare infrastructure. These findings highlight the urgent need for stringent antimicrobial stewardship practices, enhanced infection control, and tailored interventions in resource-limited settings. It is also to be emphasized that the main mechanism of carbapenem resistance in Kp organisms in Asia seems to be different from the West and is mainly mediated by metallo-beta-lactamases and Class D carbapenemases.
CE: Nursing Roles in Extracorporeal Membrane Oxygenation
Authors: Parrett Michelle , Yi Cassia , Weaver Brooke , Jones Meghan , Almachar Marites B. , Davidson Judy , Odish Mazen , Pollema Travis
Published: October 2024

Extracorporeal membrane oxygenation (ECMO) is a type of mechanical circulatory support that is increasingly utilized in the United States for severe respiratory and/or cardiac failure refractory to conventional therapies. It is an expensive and complex life support modality. Moreover, patients on ECMO are critically ill and require a strong multidisciplinary care team. A successful ECMO program involves a trained team consisting of physicians, perfusionists, nurses, and respiratory therapists. This article discusses the multiple roles of ECMO nurses, the various ECMO delivery care models, and the potential cost savings of an RN ECMO specialist staffing model—and introduces the novel role of the ECMO lead.