bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinician’s Guide to Using Ozanimod for the Treatment of Ulcerative Colitis
Authors: Sands Bruce E , Schreiber Stefan , Blumenstein Irina , Chiorean Michael V , Ungaro Ryan C , Rubin David T
Published: July 2023

The emergence of advanced therapies [eg, biologics, Janus kinase inhibitors] over the past few decades has revolutionised the treatment of ulcerative colitis. However, the limitations of these therapies leave an unmet need for safer and more effective or convenient treatment options. There is growing interest in the development of novel oral small molecule therapies for the treatment of ulcerative colitis. Ozanimod is an oral small molecule therapy that is approved in the USA, the European Union, and other countries as the first sphingosine 1-phosphate receptor modulator for the treatment of moderately to severely active ulcerative colitis in adults. This review provides guidance for ozanimod use for the treatment of ulcerative colitis, based on the prescribing information, clinical trial and real-world data, and the authors’ clinical experiences. This guidance outlines patient characteristics to consider when deciding if ozanimod treatment is suitable and describes how to educate patients on risks and best practices. It also details the nature and frequency of monitoring during treatment, which should be adapted to the individual patient based on pre-existing risk factors and events that possibly occur during treatment. This review also provides insights into the patient characteristics and clinical scenarios best suited for ozanimod treatment, based on its efficacy, safety profile, and risks compared with other therapies.
Discontinuation of Anti-Tumour Necrosis Factor Therapy in Patients with Perianal Fistulizing Crohn’s Disease: Individual Participant Data Meta-Analysis of 309 Patients from 12 Studies
Authors: ten Bokkel Huinink Sebastiaan , Thomassen Doranne , Steyerberg Ewout W , Pauwels Renske W M , Casanova Maria J , Bouguen Guillaume , Mak Joyce W Y , Molnár Tamas , Lobo Alan J , Seidelin Jacob B , Amiot Aurelien , D’Haens Geert , Rivière Pauline , Guidi Luisa , Bor Renata , Lin Wei-Chen , Peyrin-Biroulet Laurent , Gisbert Javier P , Janneke van der Woude C , de Vries Annemarie C
Published: July 2023

Background

The risk of relapse after anti-tumour necrosis factor [TNF] therapy discontinuation in Crohn’s disease patients with perianal fistulas [pCD] is unclear. We aimed to assess this risk.

Methods

A systematic literature search was conducted to identify cohort studies on the incidence of relapse following anti-TNF discontinuation in pCD patients. Individual participant data were requested from the original study cohorts. Inclusion criteria were age ≥16 years, pCD as a (co)indication for start of anti-TNF therapy, more than three doses, and remission of luminal and pCD at anti-TNF discontinuation. The primary outcome was the cumulative incidence of CD relapse using Kaplan–Meier estimates. Secondary outcomes included response to re-treatment and risk factors associated with relapse as assessed by Cox regression analysis.

Results

In total, 309 patients from 12 studies in ten countries were included. The median duration of anti-TNF treatment was 14 months [interquartile range 5.8–32.5]. Most patients were treated for pCD without active luminal disease [89%], received first-line anti-TNF therapy [87%], and continued immunomodulatory therapy following anti-TNF discontinuation [78%]. The overall cumulative incidence of relapse was 36% (95% confidence interval [CI] 25–48%) and 42% [95% CI 32–53%] at 1 and 2 years after anti-TNF discontinuation, respectively. Risk factors for relapse included smoking (hazard ratio [HR] 1.5 [1.0, 2.1]) and history of proctitis (HR 1.7 [1.1, 2.5]). The overall re-treatment response rate was 82%.

Conclusions

This individual participant data meta-analysis, on predominantly patients with pCD without active luminal disease and first-line anti-TNF therapy, shows that over half of patients remain in remission 2 years after anti-TNF discontinuation. Therefore, anti-TNF discontinuation may be considered in this subgroup.
Faecal Microbiota Transplantation [FMT] in the Treatment of Chronic Refractory Pouchitis: A Systematic Review and Meta-analysis
Authors: Zaman Shafquat , Akingboye Akinfemi , Mohamedahmed Ali Yasen Y , Peterknecht Elizabeth , Bhattacharya Pratik , El-Asrag Mohammed E , Iqbal Tariq H , Quraishi Mohammed Nabil , Beggs Andrew D
Published: July 2023

Background

The aim of this systematic review and meta-analysis is to assess the efficacy and safety of faecal microbiota transplantation [FMT] in the treatment of chronic pouchitis.

Methods

A PRISMA-compliant systematic review and meta-analysis was conducted using the following databases and clinical trial registers: Medline, Embase, Scopus, Cochrane Database of Systematic Reviews [CENTRAL], clinical trials.gov, ScienceDirect, and VHL [virtual health library]. The primary outcome was clinical response/remission in patients treated with FMT. Secondary outcomes included safety profile, quality of life, and changes in the gut microbiome.

Results

Seven observational cohort studies/case series and two randomised, controlled trials with a total of 103 patients were included. The route, preparation, and quantity of FMT administered varied among the included studies. Clinical response rate of 42.6% with a remission rate of 29.8% was estimated in our cohort following FMT therapy. Minor, self-limiting, adverse events were reported, and the treatment was well tolerated with good short- and long-term safety profiles. Successful FMT engraftment in recipients varied and, on average, microbial richness and diversity was lower in patients with pouchitis. In some instances, shifts with specific changes towards abundance of species, suggestive of a ‘healthier’ pouch microbiota, were observed following treatment with FMT.

Conclusion

The evidence for FMT in the treatment of chronic pouchitis is sparse, which limits any recommendations being made for its use in clinical practice. Current evidence from low-quality studies suggests a variable clinical response and remission rate, but the treatment is well tolerated, with a good safety profile. This review emphasises the need for rationally designed, well-powered, randomised, placebo-controlled trials to understand the efficacy of FMT for the treatment of pouchitis.
It is never too LATE: a new look at local average treatment effects with or without defiers
Authors: Dahl Christian M , Huber Martin , Mellace Giovanni
Published: July 2023

In heterogeneous treatment effect models with endogeneity, identification of the local average treatment effect (LATE) typically relies on the availability of an exogenous instrument monotonically related to treatment participation. First, we demonstrate that a strictly weaker local monotonicity condition—invoked for specific potential outcome values rather than globally—identifies the LATEs on compliers and defiers. Second, we show that our identification results apply to subsets of compliers and defiers when imposing an even weaker local compliers-defiers assumption that allows for both types at any potential outcome value. We propose estimators that are potentially more efficient than two-stage least squares (2SLS) in finite samples, even in cases where 2SLS is consistent. Finally, we provide an empirical application to estimating returns to education using the quarter of birth instrument.
Long-term effects of primary hyperparathyroidism and parathyroidectomy on kidney function
Authors: Zhu Catherine Y , Zhou Hui X , Tseng Chi-Hong , Fackelmayer Oliver J , Haigh Philip I , Adams Annette L , Yeh Michael W
Published: July 2023

Importance

Limited evidence supports kidney dysfunction as an indication for parathyroidectomy in asymptomatic primary hyperparathyroidism (PHPT).

Objective

To investigate the natural history of kidney function in PHPT and whether parathyroidectomy alters renal outcomes.

Design

Matched control study.

Setting

A vertically integrated health care system serving 4.6 million patients in Southern California.

Participants

6058 subjects with PHPT and 16 388 matched controls, studied from 2000 to 2016.

Exposures

Biochemically confirmed PHPT with varying serum calcium levels.

Main outcomes

Estimated glomerular filtration rate (eGFR) trajectories were compared over 10 years, with cases subdivided by severity of hypercalcemia: serum calcium 2.62-2.74 mmol/L (10.5-11 mg/dL), 2.75-2.87 (11.1-11.5), 2.88-2.99 (11.6-12), and >2.99 (>12). Interrupted time series analysis was conducted among propensity-score-matched PHPT patients with and without parathyroidectomy to compare eGFR trajectories postoperatively.

Results

Modest rates of eGFR decline were observed in PHPT patients with serum calcium 2.62-2.74 mmol/L (−1.0 mL/min/1.73 m2/year) and 2.75-2.87 mmol/L (−1.1 mL/min/1.73 m2/year), comprising 56% and 28% of cases, respectively. Compared with the control rate of −1.0 mL/min/1.73 m2/year, accelerated rates of eGFR decline were observed in patients with serum calcium 2.88-2.99 mmol/L (−1.5 mL/min/1.73 m2/year, P < .001) and >2.99 mmol/L (−2.1 mL/min/1.73 m2/year, P < .001), comprising 9% and 7% of cases, respectively. In the propensity score–matched population, patients with serum calcium >2.87 mmol/L exhibited mitigation of eGFR decline after parathyroidectomy (−2.0 [95% CI: −2.6 to −1.5] to −0.9 [95% CI: −1.5 to 0.4] mL/min/1.73 m2/year).

Conclusions and relevance

Compared with matched controls, accelerated eGFR decline was observed in the minority of PHPT patients with serum calcium >2.87 mmol/L (11.5 mg/dL). Parathyroidectomy was associated with mitigation of eGFR decline in patients with serum calcium >2.87 mmol/L.
Building Bridges or Breaking Bonds? The Belt and Road Initiative and Foreign Aid Competition
Authors: Vadlamannati Krishna Chaitanya , Brazys Samuel , Dukalskis Alexander , Li Yuanxin
Published: July 2023

China’s renewed prominence is the most important development in international relations in the 21st century. Despite longstanding rhetoric of its own “peaceful rise”, China is increasingly viewed as a long-term strategic competitor, especially in the United States. Foreign aid is one arena where this competition may be playing out. While Western foreign aid principles have emphasized coordination and harmonization, the rise of China as a development partner has raised the specter of a return to competitive foreign aid practices. Most notably, China's Belt and Road Initiative (BRI), has received a wary reception by those who view it primarily as a geostrategic effort, but our knowledge of responses to the BRI is often anecdotal and fragmentary. To remedy this, we test if the BRI is inducing a competitive foreign aid response by evaluating if countries involved in this initiative are more likely to receive US support for loan packages from the major, Western, multilateral development banks (MDBs). Using an instrumental variable approach, covering 7,850 project/loan packages in 10 MDBs from 162 countries during 2013–2018 period, we find that the United States was more likely to vote for MDB packages to countries that have signed on to the BRI, but predominantly when the actual amount of Chinese aid flowing to those countries is still low, suggesting the United States is competing for “hedging” countries.
Development of a cervical cancer prevention text-messaging program for women living with HIV
Authors: Ciceron Annie Coriolan , Berg Carla J , Clausen Michelle , Jeon Min Jeong , Abroms Lorien C , Le Daisy
Published: July 2023

Cervical cancer screening and human papillomavirus (HPV) vaccination are critical for those immunocompromised due to human immunodeficiency virus (HIV). Health education programs, including text messaging, can effectively improve knowledge of cervical cancer and recommended screening. This paper describes the data-driven development of a 4-week text-messaging intervention to improve HPV and cervical cancer knowledge among women living with HIV (WLH). This study reports data from surveys (n = 81; January 2020 to September 2021) and focus group discussions (FGDs, n = 39; April–June 2020) conducted among WLH in the DC area. While most WLH revealed that their usual sources of health information were through in-person group sessions, they pointed out that these were impractical options due to the coronavirus 2019 pandemic. They noted that a text-messaging intervention was feasible and acceptable. FGD participants’ responses structured around the Protection Motivation Theory constructs informed the text-messaging library, covering topics such as (I) understanding of cervical cancer and HPV, (II) cervical cancer prevention and (III) HPV self-sampling. The utilization of low-cost and easily accessible health education interventions, such as mobile-based text messaging, can effectively increase knowledge and awareness of cervical cancer in populations that have been historically difficult to access and during times when health services are disrupted such as during a global pandemic or public health emergency.
Comparisons between young adult waterpipe smokers and nonsmokers’ reactions to pictorial health warning labels in Lebanon: a randomized crossover experimental study
Authors: Jebai R , Asfar T , Nakkash R , Chehab S , Schmidt M , Wu W , Bursac Z , Maziak W
Published: July 2023

This study compares the impact of pictorial health warning labels (HWLs) and their placements on waterpipe parts (device, tobacco and charcoal packages) on health communication outcomes between waterpipe smokers and nonsmokers in Lebanon. An online randomized crossover experimental study was conducted among young adults (n = 403, August 2021) who observed three conditions of HWLs: pictorial HWLs on the tobacco package, pictorial HWLs on all waterpipe’s parts and text-only HWL on the tobacco package in random order. Participants completed post-exposure assessments of health communication outcomes after each image. Using linear mixed models, we examined the differences in the effect of HWL conditions on several outcomes (i.e. warning reactions) between waterpipe smokers and nonsmokers, controlling for confounders (i.e. age, sex). Nonsmokers reported greater attention (β = 0.54 [95% confidence interval: 0.25–0.82]), cognitive elaboration (0.31 [0.05–0.58]) and social interaction (0.41 [0.18–0.65]) for pictorial HWLs on the tobacco packages than text-only compared with smokers. Pictorial HWLs on three parts versus one part elicited higher cognitive reactions and perceived message effectiveness in nonsmokers compared with waterpipe smokers. These findings provide valuable information for policymakers about the potential of implementing HWLs specific to waterpipes to prevent their use among young adults and limit tobacco-related morbidity and mortality in Lebanon.
Serum and Urine Metabolomic Profiling of Newly Diagnosed Treatment-Naïve Inflammatory Bowel Disease Patients
Authors: Aldars-García Laila , Gil-Redondo Rubén , Embade Nieves , Riestra Sabino , Rivero Montserrat , Gutiérrez Ana , Rodríguez-Lago Iago , Fernández-Salazar Luis , Ceballos Daniel , Manuel Benítez José , Aguas Mariam , Baston-Rey Iria , Bermejo Fernando , José Casanova María , Lorente Rufo , Ber Yolanda , Ginard Daniel , Esteve María , de Francisco Ruth , García María José , Francés Rubén , Rodríguez Pescador Ainhoa , Velayos Benito , del Río Elena Guerra , Marín Pedrosa Sandra , Minguez Sabater Alejandro , Barreiro-de Acosta Manuel , Algaba Alicia , Verdejo Gil Cristina , Rivas Olga , Royo Vanesa , Aceituno Montserrat , Garre Ana , Baldán-Martín Montserrat , Ramírez Cristina , Sanz-García Ancor , Lozano Juan J , Sidorova Julia , Millet Oscar , Bernardo David , Gisbert Javier P , Chaparro María
Published: July 2023

Background and Aims

Inflammatory bowel disease (IBD) is a prevalent chronic noncurable disease associated with profound metabolic changes. The discovery of novel molecular indicators for unraveling IBD etiopathogenesis and the diagnosis and prognosis of IBD is therefore pivotal. We sought to determine the distinctive metabolic signatures from the different IBD subgroups before treatment initiation.

Methods

Serum and urine samples from newly diagnosed treatment-naïve IBD patients and age and sex-matched healthy control (HC) individuals were investigated using proton nuclear magnetic resonance spectroscopy. Metabolic differences were identified based on univariate and multivariate statistical analyses.

Results

A total of 137 Crohn’s disease patients, 202 ulcerative colitis patients, and 338 HC individuals were included. In the IBD cohort, several distinguishable metabolites were detected within each subgroup comparison. Most of the differences revealed alterations in energy and amino acid metabolism in IBD patients, with an increased demand of the body for energy mainly through the ketone bodies. As compared with HC individuals, differences in metabolites were more marked and numerous in Crohn’s disease than in ulcerative colitis patients, and in serum than in urine. In addition, clustering analysis revealed 3 distinct patient profiles with notable differences among them based on the analysis of their clinical, anthropometric, and metabolomic variables. However, relevant phenotypical differences were not found among these 3 clusters.

Conclusions

This study highlights the molecular alterations present within the different subgroups of newly diagnosed treatment-naïve IBD patients. The metabolomic profile of these patients may provide further understanding of pathogenic mechanisms of IBD subgroups. Serum metabotype seemed to be especially sensitive to the onset of IBD.
Empirical issues concerning studies of firm entry
Authors: Coad Alex , Kato Masatoshi , Srhoj Stjepan
Published: July 2023

We discuss that entry can be considered from various levels of analysis: entrepreneur-level, firm-level, and also at higher levels of aggregation, such as the industry-level and country-level. We also formulate a list of six challenges for econometric studies of firm entry, highlighting the data sources, typical empirical setups, potential sources of bias, and appropriate econometric techniques. While progress can be made with sophisticated econometric estimators, a pressing need for entry studies concerns detailed data on the gestation process, entry modes, and the value of resource endowments and knowledge endowments.
Justice Now and Later: How Measures Taken to Address Wrongdoings during Armed Conflict Affect Postconflict Justice
Authors: Binningsbø Helga Malmin , Drange Bård , Loyle Cyanne E
Published: July 2023

ABSTRACT∞

Transitional justice has become a default response when rebuilding postconflict societies. Indeed, to reconcile and move forward, it is argued that societies need to confront the violence of the past. But what factors influence when and how past violence will be addressed? We argue that judicial and quasi-judicial processes initiated while armed conflict is ongoing have a substantial impact on the judicial policies pursued once conflict has ended. Through an analysis of during- and postconflict justice in Colombia since 2000, we demonstrate that a history of addressing human rights violations makes it more likely that transitional justice will be adopted given three mechanisms: policy precedent, institutional repertories and public expectations. We analyse this relationship through global patterns of during- and postconflict justice since 1946. Our findings confirm the expectation that justice polices pursued (or not pursued) during conflict are a strong factor in understanding how the past will be addressed post conflict.
The Epistemic Violence of Transitional Justice: A View from Sri Lanka
Authors: Grewal Kiran Kaur
Published: July 2023

In this article I explore the failures of transitional justice in post-war Sri Lanka. For most commentators this is simply explained in terms of a lack of political will. However, I argue that beyond this transitional justice in Sri Lanka is a story of epistemic violence. This is a result of its over-reliance on abstract, universalist liberal democratic theory that fails to properly grasp the historical, cultural and socio-political specificity not just of the locations where transitional justice is proposed but of the conceptual foundation of transitional justice itself. As a result, transitional justice simultaneously discounts colonial legacies while reproducing colonial categories. In the case of Sri Lanka this has resulted in a failure to fully understand and address the root causes of conflict and an inability to see and draw upon resources for reconciliation, reparation and redress.
Memory Activism as Advocacy for Transitional Justice: Memory Laws, Mass Graves and Impunity in Spain
Authors: Hepworth Andrea
Published: July 2023

ABSTRACT∞

Transitional justice in Spain is still an ongoing process. This article examines the impact of memory laws and the rise of the radical right on transitional justice measures and the historical memory movement in Spain. It contends that the continued application of the 46/1977 Amnesty Law and the campaigning by radical right party Vox to repeal memory laws left a legal vacuum that precipitated interventions by memory activist groups. It is argued that these protest actions are a form of advocacy for participatory transitional justice. The article first focuses on Andalusia’s 2017 memory law and the rise of Vox in the region. Subsequently, it examines the effect of the state’s Democratic Memory Law (2022) on memory and justice measures and argues that both bottom-up approaches by civil society organizations and top-down measures by state actors are essential to transform Spain into a society anchored in the five pillars of transitional justice.
Superior Boosting of Neutralizing Titers Against Omicron SARS-CoV-2 Variants by Heterologous SCB-2019 Vaccine vs a Homologous Booster in CoronaVac-Primed Adults
Authors: Roa Camilo C , de Los Reyes Mari Rose A , Plennevaux Eric , Smolenov Igor , Hu Branda , Gao Faith , Ilagan Hannalyn , Ambrosino Donna , Siber George , Clemens Ralf
Published: July 2023

Background

We compared homologous and heterologous boosting in adults in the Philippines primed with 2 or 3 doses of CoronaVac, with recombinant protein vaccine, SCB-2019.

Methods

CoronaVac-immunized adults (18–72 years) received a homologous or heterologous full or half dose SCB-2019 booster. We assessed all neutralizing antibody (NAb) responses against prototype SARS-CoV-2 after 15 days and NAb against SARS-CoV-2 Delta and Omicron variants in subsets (30‒50 per arm). Participants recorded adverse events.

Results

In 2-dose CoronaVac-primed adults prototype NAb geometric mean titers (GMT) were 203 IU/mL (95% confidence interval [CI], 182–227) and 939 IU/mL (95% CI, 841–1049) after CoronaVac and SCB-2019 boosters; the GMT ratio (4.63; 95% CI, 3.95–5.41) met predefined noninferiority and post-hoc superiority criteria. After 3-dose CoronaVac-priming prototype NAb GMTs were 279 IU/mL (95% CI, 240–325), 1044 IU/mL (95% CI, 898–1213), and 668 IU/mL (95% CI, 520–829) following CoronaVac, full and half-dose SCB-2019 boosters, respectively. NAb GMT ratios against Delta and Omicron comparing SCB-2019 with CoronaVac were all greater than 2. Mild to moderate reactogenicity was evenly balanced between groups. No vaccine-related serious adverse events were reported.

Conclusions

Full or half dose SCB-2019 boosters were well tolerated with superior immunogenicity than homologous CoronaVac, particularly against newly emerged variants.

Clinical Trials Registration. NCT05188677.
The multifaceted genusAcinetobacter: from infection to bioremediation
Authors: Dahal Ujwal , Paul Karan , Gupta Shelly
Published: July 2023

Acinetobacter is a vast bacterial genus comprising of numerous species with variable characteristics. The enigma associated with clinical strains that have been implicated in many nosocomial outbreaks has prompted the need for continuous research on pathogens like Acinetobacter baumannii and members of the ACB complex. However, numerous species of Acinetobacter genus possess diverse metabolic capabilities and have the potential for a plethora of industrial and environment-based applications. Therefore, a comprehensive review on the entire genus, including many under-represented topics, would contribute extensive information to the scientific community indulged in Acinetobacter research. The current review is a unique compilation that attempts to provide the latest update on the genus covering its clinical as well as ecological aspects. Moreover, it is the first study of its kind that focuses on the entire genus and elaborates on the phylogenetic relationships, pathogenesis, and virulence mechanisms, followed by emerging biotechnological applications with future directions.
Seeing things the same way: perspectives and lessons learned from research-design collaborations
Authors: Mangal Sabrina , Berger Lauren , Bruzzese Jean-Marie , de la Cruz Alexandra , Lor Maichou , Naqvi Imama A , Solis de Ovando Eugenio , Spiegel-Gotsch Nicole , Stonbraker Samantha , Arcia Adriana
Published: July 2023

Information visualizations are increasingly being developed by informatics researchers to communicate health information to lay audiences. For high-quality results, it is advisable to collaborate with creative professionals such as graphic designers, illustrators, or user interface/user experience designers. However, such collaborations are often a novel experience for both parties, each of which may be unfamiliar with the needs and processes of the other. We have coalesced our experiences from both the research and design perspectives to offer practical guidance in hopes of promoting the success of future collaborations. We offer suggestions for determining design needs, communicating with design professionals, and carrying out the design process. We assert that successful collaborations are predicated on careful and intentional planning at the outset of a project, a thorough understanding of each party’s scope expertise, clear communication, and ample time for the design process to unfold.
Targeted messaging to improve the adoption of clinical decision support for prescription drug monitoring program use
Authors: Sommers Stuart , Tolle Heather , Napier Cheryl , Hoppe Jason
Published: July 2023

Clinical decision support (CDS) can prevent medical errors and improve patient outcomes. Electronic health record (EHR)-based CDS, designed to facilitate prescription drug monitoring program (PDMP) review, has reduced inappropriate opioid prescribing. However, the pooled effectiveness of CDS has exhibited substantial heterogeneity and current literature does not adequately detail why certain CDS are more successful than others. Clinicians regularly override CDS, limiting its impact. No studies recommend how to help nonadopters recognize and recover from CDS misuse. We hypothesized that a targeted educational intervention would improve CDS adoption and effectiveness for nonadopters. Over 10 months, we identified 478 providers consistently overriding CDS (nonadopters) and sent each up to 3 educational message(s) via email or EHR-based chat. One hundred sixty-one (34%) nonadopters stopped consistently overriding CDS and started reviewing the PDMP after contact. We concluded that targeted messaging is a low-resource way to disseminate CDS education and improve CDS adoption and best practice delivery.
Replacement of dietary fish meal by fermented soybean meal improves growth, energy metabolism, and innate immune response in Penaeus vannamei Boone, 1931 (Decapoda: Dendrobranchiata: Penaeidae)
Authors: Lin Yu-Ru , Hu Yeh-Fang , Chu Yu-Ting , Chen Yin-Yu , Chang Jui-Jen , Chen Shing-Wen , Nan Fan-Hua
Published: July 2023

Fishmeal (FM) is considered a preferred source of protein for aquatic feed due to its good palatability and digestibility, a balanced amino acid profile, and a low level of anti-nutritional factors (ANFs). Shortage of FM supply and increases in price, however, are major challenges faced by feed producers and aquaculture farmers. Fermented soybean meal (FSBM) has been proposed to partially replace FM because of its high nutritional value and low cost. The optimal FSBM concentration for substituting FM and effects of FSBM substitution on growth performance, energy metabolism, and immune response nevertheless remain unclear. We evaluated the effects of shrimp diets containing FSBM at 0% (FM), 25% (FSBM25), 50% (FSBM50), 75% (FSBM75), and 100% (FSBM100) on the shrimp Penaeus vannameiBoone, 1931. FSBM50 led to a significantly higher weight gain (postlarvae 1927.36 ± 46.64%, young juveniles 237.00 ± 8.25%, and juveniles 153.96 ± 2.18%) than the other experimental and control diets in different stages of the shrimp. The FM group consumed less oxygen than the experimental diet groups. FSBM75 and FSBM100 led to a significantly higher ammonia-N excretion than FM, FSBM25, and FBSM50. All experimental diet groups exhibited a significantly higher O:N ratio (8.3 ± 0.8–9.4 ± 1.7) than the FM group (7.1 ± 0.2). Shrimp fed with FSBM25- and FSBM50-containing diets exhibited an increased total hemocyte count, and FSBM25, FBSM50, and FSBM100 led to a significantly higher superoxide anion production than FSBM75 and FM. FSBM substitution in shrimp diets resulted in a significantly higher phagocytic activity than the FM diet, suggesting that FSBM substitution improves the cell-mediated immune response in shrimps. In challenge trials with white spot syndrome virus (WSSV), all experimental diets led to a higher survival rate than the FM diet, and in Vibrio parahaemolyticus challenge trials, FSBM50 led to a higher survival rate than the other experimental and control diets, indicating that FSBM substitution in shrimp diets could improve the defense capacity of shrimps against WSSV and V. parahaemolyticus.
The great recession and the public sector in rural America
Authors: Rodden Jonathan
Published: July 2023

Why did rural areas recover from the great recession much more slowly than metropolitan areas? Due to declining tax revenues and intergovernmental aid, employment in the American local government sector fell substantially after the great recession. Cuts to local public employment were especially large, long-lasting and consequential in rural areas, which have become relatively dependent on public-sector employment and intergovernmental transfers. The public sector is relatively inconsequential in urban America, but in many rural places, a decade after the great recession, the public sector was the slowest category of employment to recover and the leading source of long-term job losses.
Heterogeneity of Signaling Complex Nanostructure in T Cells Activated Via the T Cell Antigen Receptor
Authors: Barr Valarie A , Piao Juan , Balagopalan Lakshmi , McIntire Katherine M , Schoenberg Frederic P , Samelson Lawrence E
Published: July 2023

Activation of the T cell antigen receptor (TCR) is a key step in initiating the adaptive immune response. Single-molecule localization techniques have been used to investigate the arrangement of proteins within the signaling complexes formed around activated TCRs, but a clear picture of nanoscale organization in stimulated T cells has not emerged. Here, we have improved the examination of T cell nanostructure by visualizing individual molecules of six different proteins in a single sample of activated Jurkat T cells using the multiplexed antibody-size limited direct stochastic optical reconstruction microscopy (madSTORM) technique. We formally define irregularly shaped regions of interest, compare areas where signaling complexes are concentrated with other areas, and improve the statistical analyses of the locations of molecules. We show that nanoscale organization of proteins is mainly confined to the areas with dense concentrations of TCR-based signaling complexes. However, randomly distributed molecules are also found in some areas containing concentrated signaling complexes. These results are consistent with the view that the proteins within signaling complexes are connected by numerous weak interactions, leading to flexible, dynamic, and mutable structures which produce large variations in the nanostructure found in activated T cells.
Clinical characteristics and outcomes of pancreatic fungal infection in patients with necrotizing pancreatitis
Authors: Chesdachai Supavit , Yetmar Zachary A , Lahr Brian D , Vege Santhi Swaroop , Vergidis Paschalis
Published: July 2023

Pancreatic fungal infection (PFI) in patients with necrotizing pancreatitis can lead to significant morbidity and mortality. The incidence of PFI has increased during the past decade. Our study aimed to provide contemporary observations on the clinical characteristics and outcomes of PFI in comparison to pancreatic bacterial infection and necrotizing pancreatitis without infection. We conducted a retrospective study of patients with necrotizing pancreatitis (acute necrotic collection or walled-off necrosis), who underwent pancreatic intervention (necrosectomy and/or drainage) and had tissue/fluid culture between 2005 and 2021. We excluded patients with pancreatic procedures prior to hospitalization. Multivariable logistic and Cox regression models were fitted for in-hospital and 1-year survival outcomes. A total of 225 patients with necrotizing pancreatitis were included. Pancreatic fluid and/or tissue was obtained from endoscopic necrosectomy and/or drainage (76.0%), CT-guided percutaneous aspiration (20.9%), or surgical necrosectomy (3.1%). Nearly half of the patients had PFI with or without concomitant bacterial infection (48.0%), while the remaining patients had either bacterial infection alone (31.1%) or no infection (20.9%). In multivariable analysis to assess the risk of PFI or bacterial infection alone, only previous pancreatitis was associated with an increased odds of PFI vs. no infection (OR 4.07, 95% CI 1.13-14.69, p = .032). Multivariable regression analyses revealed no significant differences in in-hospital outcomes or one-year survival between the 3 groups. Pancreatic fungal infection occurred in nearly half of necrotizing pancreatitis. Contrary to many of the previous reports, there was no significant difference in important clinical outcomes between the PFI group and each of the other two groups.
Opacities of singly and doubly ionized neodymium and uranium for kilonova emission modeling
Authors: Flörs A , Silva R F , Deprince J , Carvajal Gallego H , Leck G , Shingles L J , Martínez-Pinedo G , Sampaio J M , Amaro P , Marques J P , Goriely S , Quinet P , Palmeri P , Godefroid M
Published: July 2023

Even though the electromagnetic counterpart AT2017gfo to the binary neutron star merger GW170817 is powered by the radioactive decay of r-process nuclei, only few tentative identifications of light r-process elements have been made so far. One of the major limitations for the identification of heavy nuclei is incomplete or missing atomic data. While substantial progress has been made on lanthanide atomic data over the last few years, for actinides there has been less emphasis, with the first complete set of opacity data only recently published. We perform atomic structure calculations of neodymium (Z = 60) as well as the corresponding actinide uranium (Z = 92). Using two different codes [flexible atomic code (fac) and hartree–fock-relativistic (hfr)] for the calculation of the atomic data, we investigate the accuracy of the calculated data (energy levels and electric dipole transitions) and their effect on kilonova opacities. For the fac calculations, we optimize the local central potential and the number of included configurations and use a dedicated calibration technique to improve the agreement between theoretical and available experimental atomic energy levels (AELs). For ions with vast amounts of experimental data available, the presented opacities agree quite well with previous estimations. On the other hand, the optimization and calibration method cannot be used for ions with only few available AELs. For these cases, where no experimental nor benchmarked calculations are available, a large spread in the opacities estimated from the atomic data obtained with the various atomic structure codes is observed. We find that the opacity of uranium is almost double the neodymium opacity.
A Hunting Expedition For High-Order Hierarchies
Authors: Powell Brian P , Kostov Veselin B , Tokovinin Andrei
Published: July 2023

Stellar hierarchical systems of high order containing more than three stars are rare and fascinating objects; their discovery and study highlight still unknown aspects of star formation and early evolution. We matched eclipsing binaries discovered by Transiting Exoplanet Survey Satellite with a Gaia catalogue of wide binaries and selected candidate quadruple (or higher order) systems based on excessive astrometric noise. A subset of 192 southern candidates located within 500 pc was observed by speckle interferometry, and we resolved for the first time 50 close pairs, confirming their high-order (from four to five components) multiplicity. These observations are reported, and some remarkable hierarchical systems are discussed.
The bright end of the galaxy luminosity function at z ≃ 7 from the VISTA VIDEO survey
Authors: Varadaraj R G , Bowler R A A , Jarvis M J , Adams N J , Häußler B
Published: July 2023

We have conducted a search for z ≃ 7 Lyman-break galaxies over 8.2 deg2 of near-infrared imaging from the Visible and Infrared Survey Telescope for Astronomy (VISTA) Deep Extragalactic Observations (VIDEO) survey in the XMM–Newton-Large Scale Structure (XMM-LSS) and the Extended Chandra Deep Field-South (ECDF-S) fields. Candidate galaxies were selected from a full photometric redshift analysis down to a Y + J depth of 25.3 (5σ), utilizing deep auxiliary optical and Spitzer/Infrared Array Camera (IRAC) data to remove brown dwarf and red interloper galaxy contaminants. Our final sample consists of 28 candidate galaxies at 6.5 ≤ z ≤ 7.5 with −23.5 ≤ MUV ≤ −21.6. We derive stellar masses of 9.1 ≤ log10(M⋆/M⊙) ≤ 10.9 for the sample, suggesting that these candidates represent some of the most massive galaxies known at this epoch. We measure the rest-frame ultraviolet (UV) luminosity function (LF) at z ≃ 7, confirming previous findings of a gradual decline in number density at the bright end (MUV < −22) that is well described by a double power law (DPL). We show that quasar contamination in this magnitude range is expected to be minimal, in contrast to conclusions from recent pure-parallel Hubble studies. Our results are up to a factor of 10 lower than previous determinations from optical-only ground-based studies at MUV ≲ −23. We find that the inclusion of YJHKs photometry is vital for removing brown dwarf contaminants, and z ≃ 7 samples based on red optical data alone could be highly contaminated (≳50 per cent). In comparison with other robust z > 5 samples, our results further support little evolution in the very bright end of the rest-frame UV LF from z = 5–10, potentially signalling a lack of mass quenching and/or dust obscuration in the most massive galaxies in the first Gyr.
Detectability of a phase transition in neutron star matter with third-generation gravitational wave interferometers
Authors: Mondal C , Antonelli M , Gulminelli F , Mancini M , Novak J , Oertel M
Published: July 2023

Possible strong first-order hadron-quark phase transitions in neutron star interiors leave an imprint on gravitational waves, which could be detected with planned third-generation interferometers. Given a signal from the late inspiral of a binary neutron star (BNS) coalescence, assessing the presence of such a phase transition depends on the precision that can be attained in the determination of the tidal deformability parameter, as well as on the model used to describe the hybrid star equation of state. For the latter, we employ here a phenomenological meta-modelling of the equation of state that largely spans the parameter space associated with both the low-density phase and the quark high density compatible with current constraints. We show that with a network of third-generation detectors, a single loud BNS event might be sufficient to infer the presence of a phase transition at low baryon densities with an average Bayes factor B ≈ 100, up to a luminosity distance ($\mathcal {D}_\mathrm{ L} \lesssim$ 300 Mpc).
Constraint on the minimally extended varying speed of light using time dilations in Type Ia supernovae
Authors: Lee Seokcheon
Published: July 2023

The Friedmann–Lemaître–Robertson–Walker model establishes the correlation between redshifts and distances. It has a metric expansion of space. As a result, the wavelength of photons propagating through the expanding space is stretched, creating the cosmological redshift, z. It also relates the frequency of light detected by a local observer to that emitted from a distant source. In standard cosmology (i.e. a constant speed light model), this relation is given by a factor 1/(1 + z). However, this ratio is modified in the minimally extended varying speed of light model (meVSL, c = c0ab/4) as 1/(1 + z)1 − b/4. This time dilation effect is detected as the observed rate of the time variation in the intensity of emitted radiation. The spectra of Type Ia supernovae (SNe Ia) provide a reliable way to measure the apparent aging rate of distant objects. We use data on 13 high-redshift (0.28 ≤ z ≤ 0.62) SNe Ia to obtain b = 0.198 ± 0.415 at the 1-σ confidence interval. The current data is too sparse to give meaningful constrain on the meVSL and cannot distinguish the meVSL model from the standard model.
Likelihood-Based Tests of Species Tree Hypotheses
Authors: Adams Richard , DeGiorgio Michael
Published: July 2023

Likelihood-based tests of phylogenetic trees are a foundation of modern systematics. Over the past decade, an enormous wealth and diversity of model-based approaches have been developed for phylogenetic inference of both gene trees and species trees. However, while many techniques exist for conducting formal likelihood-based tests of gene trees, such frameworks are comparatively underdeveloped and underutilized for testing species tree hypotheses. To date, widely used tests of tree topology are designed to assess the fit of classical models of molecular sequence data and individual gene trees and thus are not readily applicable to the problem of species tree inference. To address this issue, we derive several analogous likelihood-based approaches for testing topologies using modern species tree models and heuristic algorithms that use gene tree topologies as input for maximum likelihood estimation under the multispecies coalescent. For the purpose of comparing support for species trees, these tests leverage the statistical procedures of their original gene tree-based counterparts that have an extended history for testing phylogenetic hypotheses at a single locus. We discuss and demonstrate a number of applications, limitations, and important considerations of these tests using simulated and empirical phylogenomic data sets that include both bifurcating topologies and reticulate network models of species relationships. Finally, we introduce the open-source R package SpeciesTopoTestR (SpeciesTopology Tests in R) that includes a suite of functions for conducting formal likelihood-based tests of species topologies given a set of input gene tree topologies.
Proterozoic Acquisition of Archaeal Genes for Extracellular Electron Transfer: A Metabolic Adaptation of Aerobic Ammonia-Oxidizing Bacteria to Oxygen Limitation
Authors: Gulay Arda , Fournier Greg , Smets Barth F , Girguis Peter R
Published: July 2023

Many aerobic microbes can utilize alternative electron acceptors under oxygen-limited conditions. In some cases, this is mediated by extracellular electron transfer (or EET), wherein electrons are transferred to extracellular oxidants such as iron oxide and manganese oxide minerals. Here, we show that an ammonia-oxidizer previously known to be strictly aerobic, Nitrosomonas communis, may have been able to utilize a poised electrode to maintain metabolic activity in anoxic conditions. The presence and activity of multiheme cytochromes in N. communis further suggest a capacity for EET. Molecular clock analysis shows that the ancestors of β-proteobacterial ammonia oxidizers appeared after Earth's atmospheric oxygenation when the oxygen levels were >10−4pO2 (present atmospheric level [PAL]), consistent with aerobic origins. Equally important, phylogenetic reconciliations of gene and species trees show that the multiheme c-type EET proteins in Nitrosomonas and Nitrosospira lineages were likely acquired by gene transfer from γ-proteobacteria when the oxygen levels were between 0.1 and 1 pO2 (PAL). These results suggest that β-proteobacterial EET evolved during the Proterozoic when oxygen limitation was widespread, but oxidized minerals were abundant.
Structures of CTCF–DNA complexes including all 11 zinc fingers
Authors: Yang Jie , Horton John R , Liu Bin , Corces Victor G , Blumenthal Robert M , Zhang Xing , Cheng Xiaodong
Published: July 2023

The CCCTC-binding factor (CTCF) binds tens of thousands of enhancers and promoters on mammalian chromosomes by means of its 11 tandem zinc finger (ZF) DNA-binding domain. In addition to the 12–15-bp CORE sequence, some of the CTCF binding sites contain 5′ upstream and/or 3′ downstream motifs. Here, we describe two structures for overlapping portions of human CTCF, respectively, including ZF1–ZF7 and ZF3–ZF11 in complex with DNA that incorporates the CORE sequence together with either 3′ downstream or 5′ upstream motifs. Like conventional tandem ZF array proteins, ZF1–ZF7 follow the right-handed twist of the DNA, with each finger occupying and recognizing one triplet of three base pairs in the DNA major groove. ZF8 plays a unique role, acting as a spacer across the DNA minor groove and positioning ZF9–ZF11 to make cross-strand contacts with DNA. We ascribe the difference between the two subgroups of ZF1–ZF7 and ZF8–ZF11 to residues at the two positions −6 and −5 within each finger, with small residues for ZF1–ZF7 and bulkier and polar/charged residues for ZF8–ZF11. ZF8 is also uniquely rich in basic amino acids, which allows salt bridges to DNA phosphates in the minor groove. Highly specific arginine–guanine and glutamine–adenine interactions, used to recognize G:C or A:T base pairs at conventional base-interacting positions of ZFs, also apply to the cross-strand interactions adopted by ZF9–ZF11. The differences between ZF1–ZF7 and ZF8–ZF11 can be rationalized structurally and may contribute to recognition of high-affinity CTCF binding sites.