bluuebunny/crossref_metadata_2025 huggingface dataset:
FOXP3 snatches transcription factors depending on the context
Authors: Schmidleithner Lisa , Stüve Philipp , Feuerer Markus
Published: July 2024

FOXP3 hijacks DNA-binding proteins to regulate gene expression. In this issue of JEM, He et al. (https://doi.org/10.1084/jem.20232068) propose a dynamic model in which FOXP3 associates with DNA-binding proteins to regulate Treg cell function in response to environmental cues.
Instabilities and self–organization in spatiotemporal epidemic dynamics driven by nonlinearity and noise
Authors: Singh Aman Kumar , Ramakrishnan Subramanian , Kumar Manish
Published: July 2024

Theoretical analysis of epidemic dynamics has attracted significant attention in the aftermath of the COVID–19 pandemic. In this article, we study dynamic instabilities in a spatiotemporal compartmental epidemic model represented by a stochastic system of coupled partial differential equations (SPDE). Saturation effects in infection spread–anchored in physical considerations–lead to strong nonlinearities in the SPDE. Our goal is to study the onset of dynamic, Turing–type instabilities, and the concomitant emergence of steady–state patterns under the interplay between three critical model parameters–the saturation parameter, the noise intensity, and the transmission rate. Employing a second–order perturbation analysis to investigate stability, we uncover both diffusion–driven and noise–induced instabilities and corresponding self–organized distinct patterns of infection spread in the steady state. We also analyze the effects of the saturation parameter and the transmission rate on the instabilities and the pattern formation. In summary, our results indicate that the nuanced interplay between the three parameters considered has a profound effect on the emergence of dynamical instabilities and therefore on pattern formation in the steady state. Moreover, due to the central role played by the Turing phenomenon in pattern formation in a variety of biological dynamic systems, the results are expected to have broader significance beyond epidemic dynamics.
Tradeoffs in the design of RNA thermometers
Authors: Gola Krishan Kumar , Patel Abhilash , Sen Shaunak
Published: July 2024

The synthesis of RNA thermometers is aimed at achieving temperature responses with desired thresholds and sensitivities. Although previous works have generated thermometers with a variety of thresholds and sensitivities as well as guidelines for design, possible constraints in the achievable thresholds and sensitivities remain unclear. We addressed this issue using a two-state model and its variants, as well as melt profiles generated from thermodynamic computations. In the two-state model, we found that the threshold was inversely proportional to the sensitivity, in the case of a fixed energy difference between the two states. Notably, this constraint could persist in variations of the two-state model with sequentially unfolding states and branched parallel pathways. Furthermore, the melt profiles generated from a library of thermometers exhibited a similar constraint. These results should inform the design of RNA thermometers as well as other responses that are mediated in a similar fashion.
Spatial integration for firm and load-following wind generation
Authors: López Prol Javier , deLlano-Paz Fernando , Calvo-Silvosa Anxo , Pfenninger Stefan , Staffell Iain
Published: July 2024

Wind power has considerable potential to decarbonise electricity systems due to its low cost and wide availability. However, its variability is one factor limiting uptake. We propose a simple analytical framework to optimise the distribution of wind capacity across regions to achieve a maximally firm or load-following profile. We develop a novel dataset of simulated hourly wind capacity factors (CFs) with bias correction for 111 Chinese provinces, European countries and US states spanning ten years (∼10 million observations). This flexible framework allows for near-optimal analysis, integration of demand, and consideration of additional decision criteria without additional modelling. We find that spatial integration of wind resources optimising the distribution of capacities provides significant benefits in terms of higher CF or lower residual load and lower variability at sub-, quasi- and inter-continental levels. We employ the concept of firmness as achieving a reliable and certain generation profile and show that, in the best case, the intercontinental interconnection between China, Europe and the US could restrict wind CFs to within the range of 15%–40% for 99% of the time. Smaller configurations corresponding to existing electricity markets also provide more certain and reliable generation profiles than isolated individual regions.
The topological Atiyah–Segal map
Authors: Ramras Daniel
Published: July 2024

Associated to each finite dimensional linear representation of a group

G
G

, there is a vector bundle over the classifying space

B
G

BG

. This construction was studied extensively for compact groups by Atiyah and Segal. We introduce a homotopy theoretical framework for studying the Atiyah–Segal construction in the context of infinite discrete groups, taking into account the topology of representation spaces.

We explain how this framework relates to the Novikov conjecture, and we consider applications to spaces of flat connections on the over the 3-dimensional Heisenberg manifold and families of flat bundles over classifying spaces of groups satisfying Kazhdan’s property (T).
Stratification of 𝑆𝑈(𝑟)-character varieties of twisted Hopf links
Authors: González-Prieto Ángel , Logares Marina , Martínez Javier , Muñoz Vicente
Published: July 2024

We describe the geometry of the character variety of representations of the fundamental group of the complement of a Hopf link with

n
n

twists, namely

Γ

n

=
⟨
x
,
y

|

[

x
n

,
y
]
=
1
⟩

{\Gamma }_{n}=\langle x,y \,| \, [x^n,y]=1 \rangle

into the group

S
U
(
r
)

SU(r)

. For arbitrary rank, we provide geometric descriptions of the loci of irreducible and totally reducible representations. In the case

r
=
2

r = 2

, we provide a complete geometric description of the character variety, proving that this

S
U
(
2
)

SU(2)

-character variety is a deformation retract of the larger

S
L
(
2
,

C

)

SL(2,\mathbb {C})

-character variety, as conjectured by Florentino and Lawton. In the case

r
=
3

r = 3

, we also describe different strata of the

S
U
(
3
)

SU(3)

-character variety according to the semi-simple type of the representation.
Other Contemporary Influential Voices
Authors: Panagariya Arvind
Published: July 2024

Nehru’s vision found near unanimous support from the relevant constituencies. Even the rare dissenting voices did not question the core strategy of primacy to heavy industries. At Nehru’s instance, his close associate and a self-taught statistician, P. C. Mahalanobis, prepared the Draft Plan-frame of the second plan, which was extensively discussed and endorsed by a panel of twenty-one leading economists of India, including V. K. R. V. Rao, D. R. Gadgil, K. N. Raj, A. K. Das Gupta, Vakil, and D. T. Lakdawala. Only Shenoy submitted a dissent note questioning the wisdom of the large deficit financing. All foreign economists invited by the government supported the Plan-frame. Milton Friedman, independently sent by the US government, provided a trenchant critique that proved prophetic later but had no salience at the time. Some dissenting voices in the parliament notwithstanding, politicians overwhelmingly endorsed Nehru’s vision, while leading businessmen had already given it a nod through their 1945 Bombay Plan.
Implementation
Authors: Panagariya Arvind
Published: July 2024

Sector-specific production targets by the five-year plans, public-sector production, and licensing-guided private-sector production implemented the industrial policy. Bureaucracy was inevitably the key player in exercising each of these instruments. Without clear priorities at the product level, planners had no choice but to resort to ad hoc decision-making in setting production targets. Translation of these targets into enterprise-level investment allocations, a task left entirely to bureaucrats, was even more arbitrary. The growing industrial base, which increased the number of license applications, and the adoption of strict foreign-exchange control in 1957, led to a progressive slowdown of the decision-making process. The 1960s saw committee after committee appointed to recommend corrective action to speed up decision-making with little actual improvement felt by businesses. Concerns with high prices and super-normal profits also led to the adoption of price and distribution controls on products such as steel and cement, expanding bureaucratic decision-making.
A Liberal Import Regime
Authors: Panagariya Arvind
Published: July 2024

Until early 1920, the British government followed a free trade policy. The door to protection opened in the 1920s, but it remained temporary and modest. It was during the Second World War that the balance of payments difficulties faced by the British led them to adopt Empire-wide exchange control, reinforced by strict import. The war years brought to India import licensing with a full-scale control regime consisting of essentiality and indigenous nonavailability of imports as preconditions. The idea of open general licensing also had its birth during this era. The end of the war witnessed considerable support for liberal import policy. As a member of the sterling area, India remained subject to British exchange control. Nevertheless, India liberalized imports through the expansion of open general licensing and issuing licenses liberally. This was particularly true of the import regime from 1951–52 to 1956–57. This liberalism came to an end in 1957 with a balance-of-payments crisis.
Growth, Industrialization, and Poverty
Authors: Panagariya Arvind
Published: July 2024

This chapter critically examines the economic outcomes during the Nehru era. It argues that the heavy-industry-centered industrialization created a dual economy consisting of a small, highly capital-intensive industrial enclave and a vast swath of unorganized sectors. The bulk of the workforce remained outside the former and was therefore denied the fruits of growth. Poverty saw almost no decline. Simultaneously, the strategy failed to take advantage of the country’s large workforce. Employed in the cottage and small industries, which were denied access to capital, it experienced little growth or skill upgradation. With the heavy industry absorbing a large proportion of scarce resources, education and health were neglected. Within education, the needs of the heavy industry required the creation of engineering and management institutions, which undermined the progress in primary education.
An Afterthought
Authors: Panagariya Arvind
Published: July 2024

A central theme in this volume is that post-Nehru, India was on a deterministic path with no prospect of change of course until 1991. Externally, the change had to wait for the fall of the Soviet Union and the rise of the Chinese economy. Internally, a change could not have come without an economic crisis. Is there, then, a scenario in which the course of Indian economic history could have been different? This chapter develops the argument that such a possibility could materialize only if the age profiles of Nehru and Sardar Vallabh Bhai Patel had been switched. In that case, Nehru would have departed the scene in December 1950, while Patel would have succeeded him and remained in office until May 1964. A plausible case can be made that he would have kept socialism at bay and adopted an economic policy framework reliant principally on private enterprise.
Warring Peaces
Authors: Antony Alexander K , Thompson William R
Published: July 2024

This chapter focuses on the key concepts revolving around peace. It explains that the transition process of industrialization influenced democratization, border settlements, economic modernization, and trade interdependence. The type of peace designated often gives some clue as to what the main causal force is that is thought to be bringing about peace. The chapter explains that the main influences of peace, such as nuclear weapons and democratic dyads, are promoted as most directly responsible for influencing the perception of the costs of war or the benefits of peace. It mentions how industrialization resulted in a decrease in the probability of warfare between industrial states.
The Main Contenders
Authors: Antony Alexander K , Thompson William R
Published: July 2024

This chapter looks into some of the factors affecting peace. It cites the difficulty of ignoring the possibility that univariate explanations cannot fully account for the pattern of peace within the international system. Theorizing and measuring conflict processes at the dyadic level provide little insight into the webs of interaction that produce conflict in certain geographic clusters and cooperation in others. The chapter explains the prominence of the impact of democracy and economic interdependence theories on conflict likelihoods, which also mentions the claims that economic interdependence fosters peace. It then provides an overview of the differences and distinctions between democratic peace, capitalist peace, and territorial peace.
Heterogeneity in the effect of type 2 diabetes on dementia incidence in a diverse cohort of Asian American and non-Latino White older adults
Authors: Hayes-Larson Eleanor , Zhou Yixuan , Wu Yingyan , Mobley Taylor M , Gee Gilbert C , Brookmeyer Ron , Whitmer Rachel A , Gilsanz Paola , Kanaya Alka M , Mayeda Elizabeth Rose
Published: July 2024

Dementia incidence is lower among Asian Americans than among Whites, despite higher prevalence of type 2 diabetes, a well-known dementia risk factor. Determinants of dementia, including type 2 diabetes, have rarely been studied in Asian Americans. We followed 4846 Chinese, 4129 Filipino, 2784 Japanese, 820 South Asian, and 123 360 non-Latino White members of a California-based integrated health-care delivery system from 2002 to 2020. We estimated dementia incidence rates by race/ethnicity and type 2 diabetes status, and we fitted Cox proportional hazards and Aalen additive hazards models for the effect of type 2 diabetes (assessed 5 years before baseline) on age of dementia diagnosis, controlling for sex/gender, educational attainment, nativity, height, race/ethnicity, and a race/ethnicity × diabetes interaction. Type 2 diabetes was associated with higher dementia incidence in Whites (hazard ratio [HR] = 1.46; 95% CI, 1.40-1.52). Compared with Whites, the estimated effect of diabetes was larger in South Asians (HR = 2.26; 95% CI, 1.48-3.44), slightly smaller in Chinese (HR = 1.32; 95% CI, 1.08-1.62) and Filipino (HR = 1.31; 95% CI, 1.08-1.60) individuals, and similar in Japanese individuals (HR = 1.44; 95% CI, 1.15-1.81). Heterogeneity in this association across Asian subgroups may be related to type 2 diabetes severity. Understanding this heterogeneity may inform prevention strategies to prevent dementia for all racial and ethnic groups.
Patient Experience in a Remote Patient Monitoring Program for Hypertension: A Qualitative Study
Authors: Chu Fion , Stark Allison , Telzak Andrew , Rikin Sharon
Published: July 2024

BACKGROUND

Remote patient monitoring (RPM), which includes out-of-office blood pressure (BP) measurement, coupled with interventions including telehealth and team-based care, is recommended for hypertension (HTN) management. We aimed to assess participant experience with RPM for HTN (RPM-HTN) to understand barriers and facilitators to implementing RPM-HTN in a primary care population where health disparities and social inequities are prevalent.

METHODS

This is a qualitative implementation study of participants’ experiences with an RPM-HTN program for primary care patients with uncontrolled HTN at an academic health system. We recruited participants with high and low levels of engagement (≥16 or <16 days of transmitted BP readings per month). Semi-structured interviews were conducted, and descriptive statistics and rapid qualitative analysis were used to identify factors affecting the implementation of RPM-HTN, specifically adoption, acceptability, appropriateness, and feasibility.

RESULTS

Multiple themes emerged from interviews with 14 participants. A doctor’s recommendation and wanting help with BP management were facilitators for engagement, while work conflicts and forgetfulness were barriers to engagement. Participants enjoyed the format and content of nurse and clinical pharmacist phone calls and forming a relationship with the team; expressed improved understanding of HTN and BP management; and appreciated the convenience of remote monitoring.

CONCLUSIONS

Participants found RPM-HTN acceptable and appropriate, highlighting the team-based and out-of-office approach to care. This study provides actionable targets to overcome feasibility barriers to implementation. In order to increase engagement, RPM policies and procedures should take into account barriers including the quantity of required BP measurements and mechanisms of telehealth communication.
Machine learning of cellular metabolic rewiring
Authors: Xavier Joao B
Published: July 2024

Metabolic rewiring allows cells to adapt their metabolism in response to evolving environmental conditions. Traditional metabolomics techniques, whether targeted or untargeted, often struggle to interpret these adaptive shifts. Here, we introduce MetaboLiteLearner, a lightweight machine learning framework that harnesses the detailed fragmentation patterns from electron ionization (EI) collected in scan mode during gas chromatography/mass spectrometry to predict changes in the metabolite composition of metabolically adapted cells. When tested on breast cancer cells with different preferences to metastasize to specific organs, MetaboLiteLearner predicted the impact of metabolic rewiring on metabolites withheld from the training dataset using only the EI spectra, without metabolite identification or pre-existing knowledge of metabolic networks. Despite its simplicity, the model learned captured shared and unique metabolomic shifts between brain- and lung-homing metastatic lineages, suggesting cellular adaptations associated with metastasis to specific organs. Integrating machine learning and metabolomics paves the way for new insights into complex cellular adaptations.
Visible-light activation of a Ru(II) complex catalyst via a carbazole-modified donor–acceptor ligand for CO2 reduction
Authors: Nakada Akinobu , Tomiura Yuya , Suzuki Hajime , Tomita Osamu , Abe Ryu
Published: July 2024

Visible-light activation of photocatalysts is crucial for effectively utilizing solar energy in molecular conversions. This study demonstrates that modifying the bipyridine ligand with carbazole enables visible-light activation of a Ru(II) carbonyl complex catalyst, which was originally developed as an electrocatalyst for CO2 reduction but is inactive as a photocatalyst on its own. The present study opens avenues for individually designing light-absorbing ligands and catalytic functions within one mononuclear complex.
Flexible porous coordination polymer with multiple configurations for guest recognition and switchable CO2 sorption properties
Authors: Wang Ping , Otake Ken-ichi , Hiraide Shotaro , Kubota Yoshiki , Kawaguchi Shogo , Kitagawa Susumu
Published: July 2024

Realizing multiple metastable configurations in a single porous coordination polymer has long been pursued to achieve switchable functionality. In this study, we reported multiple configurations in one porous coordination polymer material via the design of the adjustable intraframework π–π stacking moieties. We demonstrated that the porous coordination polymer can accommodate three different open pore phases depending on the type of solvent. Furthermore, this porous coordination polymer exhibits three distinct closed pore phases depending on the activation approaches, demonstrating different CO2 sorption properties.
IPOD2: an irrecoverable and verifiable deletion scheme for outsourced data
Authors: Zhang Xiaolei , Chen Zhaoyu , Zhang Xin , Shen Qingni , Wu Zhonghai
Published: July 2024

To alleviate the burden of data storage and management, there is a growing trend of outsourcing data to the cloud that enables users to remotely manage their data flexibly. However, this shift also raises concerns regarding outsourced data deletion, as users lose physical control over their outsourced data and are unable to verify its proper eradication. To address this issue, cloud service providers are required to provide a scheme that guarantees the effective deletion of outsourced data. Existing schemes, including key management-based and overwriting-based schemes, fail to ensure both the irrecoverability of deleted data and the verifiability of the deletion process. In this paper, we propose IPOD2, an irrecoverable and verifiable deletion scheme for outsourced data. Specifically, IPOD2 utilizes the overwriting-based deletion method to implement outsourced data deletion and extends the Integrity Measurement Architecture to measure the operations in the deletion process. The measurement results are protected by the Trusted Platform Module and verifiable for users. To demonstrate the viability of IPOD2, we implement a prototype of IPOD2 on the Linux kernel 5.4.120. Experimental results show that, compared with the three existing schemes, IPOD2 has the minimum overhead in both deletion and verification processes.
Long-term outcomes in patients with Cushing's disease vs nonfunctioning pituitary adenoma after pituitary surgery: an active-comparator cohort study
Authors: Germann Sara , Wimmer Roxana , Laager Rahel , Mueller Beat , Schuetz Philipp , Kaegi-Braun Nina , Kutz Alexander
Published: July 2024

Objective

There is increasing evidence that multisystem morbidity in patients with Cushing’s disease (CD) is only partially reversible following treatment. We investigated complications from multiple organs in hospitalized patients with CD compared to patients with nonfunctioning pituitary adenoma (NFPA) after pituitary surgery.

Design

Population-based retrospective cohort study using data from the Swiss Federal Statistical Office between January 2012 and December 2021.

Methods

Through 1:5 propensity score matching, we compared hospitalized patients undergoing pituitary surgery for CD or NFPA, addressing demographic differences. The primary composite endpoint included all-cause mortality, major adverse cardiac events (ie, myocardial infarction, unstable angina, heart failure, cardiac arrest, and ischemic stroke), hospitalization for psychiatric disorders, sepsis, severe thromboembolic events, and fractures in need of hospitalization. Secondary endpoints comprised individual components of the primary endpoint and surgical reintervention due to disease persistence or recurrence.

Results

After matching, 116 patients with CD (mean age 45.4 years [SD, 14.4], 75.0% female) and 396 with NFPA (47.3 years [14.3], 69.7% female) were included and followed for a median time of 50.0 months (IQR 23.5, 82.0) after pituitary surgery. Cushing’s disease presence was associated with a higher incidence rate of the primary endpoint (40.6 vs 15.7 events per 1000 person-years, hazard ratio [HR] 2.75; 95% CI, 1.54-4.90). Cushing’s disease patients also showed increased hospitalization rates for psychiatric disorders (HR 3.27; 95% CI, 1.59-6.71) and a trend for sepsis (HR 3.15; 95% CI, .95-10.40).

Conclusions

Even after pituitary surgery, CD patients faced a higher hazard of complications, especially psychiatric hospitalizations and sepsis.
European Health Information Training Programme: a sustainable strategy for strengthening capacity in health information
Authors: Peyroteo Mariana , Maia Mélanie R , Paulo Marília Silva , Saso Miriam , Schutte Nienke , Bogaert Petronille , Habl Claudia , Lapão Luís Velez ,   Population Health Information Research Infrastructure
Published: July 2024

Background

Before the COVID-19 pandemic, a need for a uniform approach to health information (HI) knowledge in population health analysis across Europe was evident. The Population Health Information Research Infrastructure (PHIRI) emerged as a proactive initiative to strengthen European HI capacities. This article describes the achievements of PHIRI, highlighting its capacity-building activities and their contribution towards a sustainable strategy for the implementation of the European Health Data Space (EHDS).

Methods

PHIRI collaboration established a work package for skill-building activities in population health in partnership with other organizations. Activities included webinars, workshops, sessions, training schools and courses for researchers and public administration workers from Europe and beyond. The primary goal of the activities was to examine the impact of COVID-19 on European health systems at both local and national levels, including healthcare facilities and policymaking entities.

Results

Twelve activities were organized between October 2020 and the summer of 2023. In March 2023, the Spring School on Health Information was organized to share the knowledge achieved from PHIRI and other European Union-related projects. This event also validated the European Health Information Training Programme.

Conclusions

PHIRI’s findings emphasized the importance of equipping the workforce with core HI skills to improve health systems’ preparedness and resilience. Through this research, it is possible to propose a strategy for building capacity that emphasizes the importance of providing training in human-machine dynamics. This approach will contribute to the sustainable implementation of the EHDS.
Delayed treatment in breast cancer patients during the COVID-19 pandemic: a population health information research infrastructure (PHIRI) case study
Authors: Estupiñán-Romero Francisco , Royo-Sierra Santiago , González-Galindo Javier , Martínez-Lizaga Natalia , Bogaert Petronille , Schutte Nienke , Van Eycken Liesbet , Van Damme Nancy , Henau Kris , Lyons Ronan A , Aldridge Sarah J , Faragalli Andrea , Carle Flavia , Gesuita Rosaria , Palmieri Luigi , Misiņš Jānis , Thiβen Martin , Bernal-Delgado Enrique
Published: July 2024

Background

The indirect impact of the coronavirus disease 2019 pandemic on healthcare services was studied by assessing changes in the trend of the time to first treatment for women 18 or older who were diagnosed and treated for breast cancer between 2017 and 2021.

Methods

An observational retrospective longitudinal study based on aggregated data from four European Union (EU) countries/regions investigating the time it took to receive breast cancer treatment. We compiled outputs from a federated analysis to detect structural breakpoints, confirming the empirical breakpoints by differences between the trends observed and forecasted after March 2020. Finally, we built several segmented regressions to explore the association of contextual factors with the observed changes in treatment delays.

Results

We observed empirical structural breakpoints on the monthly median time to surgery trend in Aragon (ranging from 9.20 to 17.38 days), Marche (from 37.17 to 42.04 days) and Wales (from 28.67 to 35.08 days). On the contrary, no empirical structural breakpoints were observed in Belgium (ranging from 21.25 to 23.95 days) after the pandemic's beginning. Furthermore, we confirmed statistically significant differences between the observed trend and the forecasts for Aragon and Wales. Finally, we found the interaction between the region and the pandemic's start (before/after March 2020) significantly associated with the trend of delayed breast cancer treatment at the population level.

Conclusions

Although they were not clinically relevant, only Aragon and Wales showed significant differences with expected delays after March 2020. However, experiences differed between countries/regions, pointing to structural factors other than the pandemic.
The effect of successive summer drought periods on bacterial diversity along a plant species richness gradient
Authors: de Souza Yuri Pinheiro Alves , Siani Roberto , Albracht Cynthia , Huang Yuanyuan , Eisenhauer Nico , Vogel Anja , Wagg Cameron , Schloter Michael , Schulz Stefanie
Published: July 2024

Drought is a major stressor to soil microbial communities, and the intensification of climate change is predicted to increase hydric stress worldwide in the coming decades. As a possible mitigating factor for the consequences of prolonged drought periods, above and belowground biodiversity can increase ecosystem resistance and resilience by improving metabolic redundancy and complementarity as biodiversity increases. Here, we investigated the interaction effect between plant richness and successive, simulated summer drought on soil microbial communities during a period of 9 years.To do that, we made use of a well-established biodiversity experiment (The Jena Experiment) to investigate the response of microbial richness and community composition to successive drought periods alongside a plant richness gradient, which covers 1-, 2-, 4-, 8-, 16-, and 60-species plant communities. Plots were covered from natural precipitation by installing rain shelters 6 weeks every summer. Bulk soil samples were collected 1 year after the last summer drought was simulated. Our data indicate that bacterial richness increased after successive exposure to drought, with the increase being stable along the plant richness gradient. We identified a significant effect of plant species richness on the soil microbial community composition and determined the taxa significantly impacted by drought at each plant richness level. Our data successfully demonstrates that summer drought might have a legacy effect on soil bacterial communities.
Duplications and Retrogenes Are Numerous and Widespread in Modern Canine Genomic Assemblies
Authors: Nguyen Anthony K , Blacksmith Matthew S , Kidd Jeffrey M
Published: July 2024

Recent years have seen a dramatic increase in the number of canine genome assemblies available. Duplications are an important source of evolutionary novelty and are also prone to misassembly. We explored the duplication content of nine canine genome assemblies using both genome self-alignment and read-depth approaches. We find that 8.58% of the genome is duplicated in the canFam4 assembly, derived from the German Shepherd Dog Mischka, including 90.15% of unplaced contigs. Highlighting the continued difficulty in properly assembling duplications, less than half of read-depth and assembly alignment duplications overlap, but the mCanLor1.2 Greenland wolf assembly shows greater concordance. Further study shows the presence of multiple segments that have alignments to four or more duplicate copies. These high-recurrence duplications correspond to gene retrocopies. We identified 3,892 candidate retrocopies from 1,316 parental genes in the canFam4 assembly and find that ∼8.82% of duplicated base pairs involve a retrocopy, confirming this mechanism as a major driver of gene duplication in canines. Similar patterns are found across eight other recent canine genome assemblies, with metrics supporting a greater quality of the PacBio HiFi mCanLor1.2 assembly. Comparison between the wolf and other canine assemblies found that 92% of retrocopy insertions are shared between assemblies. By calculating the number of generations since genome divergence, we estimate that new retrocopy insertions appear, on average, in 1 out of 3,514 births. Our analyses illustrate the impact of retrogene formation on canine genomes and highlight the variable representation of duplicated sequences among recently completed canine assemblies.
Association Between Subclinical Thyroid Dysfunction and Cognitive Decline: Findings From the ELSA-Brasil Study
Authors: Gomes Gonçalves Natalia , Szlejf Claudia , Lotufo Paulo Andrade , Bensenor Isabela M , Suemoto Claudia Kimie
Published: July 2024

Background

Thyroid dysfunction has been associated with cognitive decline and dementia. However, the role of subtle thyroid hormone alterations in cognitive function is still debatable.

Methods

Participants without overt thyroid dysfunction aged 35–74 years at baseline were evaluated in 3 study waves (2008–2010, 2012–2014, and 2017–2019). We assessed baseline thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3). Cognitive performance was evaluated every 4 years in each wave using 10-word immediate and late recall, word recognition, semantic (animals category) and phonemic (letter f) verbal fluency, and the trail-making B-version tests. A global composite z-score was derived from these tests. The associations of TSH, FT4, and FT3 levels with cognitive decline over time were evaluated using linear mixed-effect models adjusted for sociodemographic, clinical, and lifestyle variables.

Results

In 9 524 participants (mean age 51.2 ± 8.9 years old, 51% women, 52% White), there was no association between baseline TSH, FT4, and FT3 levels and cognitive decline during the follow-up. However, increase in FT4 levels over time was associated with faster memory (β = −0.004, 95% CI = −0.007; −0.001, p = .014), verbal fluency (β = −0.003, 95% CI = −0.007; −0.0005, p = .021), executive function (β = −0.004, 95% CI = −0.011; −0.003, p < .001), and global cognition decline (β = −0.003, 95% CI = −0.006; −0.001, p = .001). Decrease in FT4 levels over time was associated with faster verbal fluency (β = −0.003, 95% CI = −0.007; −0.0004, p = .025) and executive function (β = −0.004, 95% CI = −0.007; −0.0003, p = .031) decline.

Conclusions

An increase or decrease in FT4 levels over time was associated with faster cognitive decline in middle-aged and older adults without overt thyroid dysfunction during 8 years of follow-up.
On head-to-head results as tie-breaker and consequent opportunities for collusion
Authors: Csató László
Published: July 2024

Accepted by: Phil Scarf

The outcome of some football matches has benefited both teams at the expense of a third team because head-to-head results were used for breaking ties. Inspired by these examples, our mathematical analysis identifies all possible collusion opportunities caused by this particular ranking rule in a single round-robin tournament with four teams. According to a simulation model based on the 2024 UEFA European Football Championship, merely the tie-breaking rule increases the probability of reaching a situation vulnerable to collusion by between 11.5 and 14.8 percentage points. This risk can scarcely be mitigated by a static match schedule. Therefore, tournament organizers are strongly encouraged to choose goal difference as the primary tie-breaking rule, similar to the official policy of FIFA.
Insights from utilizing data of different quality levels for simulating barley performance under Nordic conditions: The Agricultural Production Systems SIMulator model evaluation
Authors: Appiah Mercy , Bracho-Mujica Gennady , Svane Simon , Styczen Merete , Kersebaum Kurt-Christian , Rötter Reimund P
Published: July 2024

Crop model-aided ideotyping can accelerate the breeding of resilient barley cultivars. Yet, the accuracy of process descriptions in the crop models still requires substantial improvement, which is only possible with high-quality (HQ) experimental data. Despite being demanded frequently, such data are still rarely available, especially for Northern European barley production. This study is one of the first to contribute to closing this existing data gap through the targeted collection of HQ experimental data in pluri-annual, multi-location spring barley field trials in Denmark. With this data, the prediction accuracy of Agricultural Production Systems SIMulator significantly increased in contrast to commonly utilized lower quality datasets. Using this data for model calibration resulted in more accurate predictions of in-season plant development and important state variables (e.g. final grain yield and biomass). The model’s prediction accuracy can ultimately be further improved by examining remaining model weaknesses that were discoverable with the HQ data. Process descriptions regarding, for example, early and late leaf development, soil water dynamics and respective plant response appeared to require further improvement. By illustrating the effect of data quality on model performance we reinforce the need for more model-guided field experiments.
Use of a commercial feed supplement based on diatom earth and yeast products on oxidative status and in vitro immune response in buffaloes during peripartum
Authors: Maggiolino Aristide , Sgarro Maria Federica , Casalino Elisabetta , Latronico Tiziana , Liuzzi Grazia Maria , De Palo Pasquale
Published: July 2024

The transition period is a critical metabolic phase for dairy ruminants, especially those with high production levels. In spite of this, little is still known about dairy water buffalo. The aim of this study was to evaluate the effect of a commercial feed additive based on diatomaceous earth and hydrolyzed yeasts on health status, milk quality, and immune response of buffalo cows during the transition period. Eighty healthy Water buffaloes (Bubalus bubalis) of Italian Mediterranean breed were included in the trial. They were subdivided into two groups: one group received the additive (n = 40) while the control group (n = 40) received a placebo. The trial lasted 120 d, from 60 d before calving to 60 d in milk. Blood samples were collected from each buffalo at −60 (60 d from the expected calving), −30, 0 (calving), +15, +30, and +60 d (respectively, i.e., 15, 30, and 60 d in milking). The biochemical as well as the oxidative profile, and the antioxidant power and enzymatic activity were evaluated in the samples obtained. Moreover, acute phase proteins, reactive proteins, and interleukin plasma levels were determined. Peripheral blood mononuclear cells (PBMCs) and monocytes were isolated and viability, reactive oxygen species (ROS), and reactive nitrogen species were measured on PBMC and monocytes. The introduction of additives enhanced the total antioxidant capacity and enzyme activity, while no differences were observed in oxidation products throughout the trial. Additionally, it significantly reduced the synthesis of ROS in polymorphonuclear cells, supporting a potential positive response in animals experiencing inflammation. The impact of oxidation on the products was not evident. Despite higher enzyme levels in plasma, this did not necessarily correspond to significantly increased enzymatic activity but rather indicated a higher potential. From these results, it was evident that the transition period in buffaloes differs notably from what reported in the literature for cows, probably due to the absence of common postpartum production diseases in dairy cows and lower metabolic challenges linked to lower milk production in buffaloes. Few parameters exhibited notable changes during the transition period in buffaloes, notably certain antioxidant enzymes, PBMC viability, PBMC ROS production, and Hp levels.
Inspiring or demoralizing? Deservingness perceptions help determine why emerging adults experience positive or negative effects from envy-inducing social media posts
Authors: Montes Enoch , DeAndrea David C
Published: July 2024

This study extends pain-driven dual envy theory to explain why emerging adults who do not attend college might experience uplifting or hostile reactions to the social media posts of their college-attending peers. Employing a 2 × 2 experiment (N = 233; Mage   = 21.87), we examined how deservingness perceptions (deserving versus undeserving) and social approval cues (high versus low) affect the type of envy emerging adults experience from viewing college success posts on social media. Results indicated that the more participants perceived the college success of their peers to be deserved, the more they experienced benign envy. Conversely, the more participants appraised the college success of their peers to be undeserved, the more they experienced malicious envy. Results also indicated that posts with higher social approval indirectly triggered more pain for participants. Overall, findings help clarify why social media users can experience both positive and negative effects from online social comparisons.
The evolution of judicial standards: evidence from litigated merger trials
Authors: Macher Jeffrey T , Mayo John W , Sappington David E M , Whitener Mark
Published: July 2024

A popular narrative suggests that, in the wake of the rise of the Chicago School, the judiciary has grown increasingly lax, making it difficult for antitrust agencies to successfully challenge mergers in court. We develop a theoretical framework to yield propositions regarding merger challenges, settlements, and outcomes under varying judicial standards. We then undertake an empirical investigation of all mergers, challenges, and litigated outcomes in the United States over 1982–2021 to test for the presence of shifting judicial standards. Contrary to the popular narrative, we find evidence that judicial standards have become increasingly pro-enforcement over the past four decades.
Immunomodulatory effects of Yu-Ping-Feng formula on primary Sjögren syndrome: interrogating the T-cell response
Authors: Yu Sulan , Zhou Xinyao , Liu Ruihua , Xu Xiaoyu , Ma Danbao , Feng Yun , Lin Xiang
Published: July 2024

Ethnopharmacological treatments have shown beneficial effects in the clinical practice of autoimmune disorders. However, the underlying mechanism of immunomodulatory effects remains challenging, given the complicate composition of herbal medicines. Here, we developed an immunological approach to interrogate the T helper cell response. Through data mining, we hypothesized that Chinese medicine formula Yu-Ping-Feng might be a promising candidate for treating primary Sjögren syndrome, a common autoimmune disease manifested by exocrine gland dysfunction. We took advantage of a mouse model of experimental Sjögren syndrome that we previously established for Yu-Ping-Feng formula treatment. Yu-Ping-Feng therapy ameliorated the experimental Sjögren syndrome pathology in mice with active disease, showing improved salivary function and decreased serum levels of autoantibodies. Phenotypic analysis suggested that both effector T and B cells were significantly suppressed. Using coculture assay and adoptive transfer models, we demonstrated that Yu-Ping-Feng formula directly restrained effector/memory T-cell expansion and differentiation into Th17 and T follicular helper cells, the key subsets in experimental Sjögren syndrome pathogenesis. Importantly, we recruited 20 patients with primary Sjögren syndrome and conducted a pilot study of 8-wk therapy of Yu-Ping-Feng formula. Yu-Ping-Feng treatment effectively improved fatigue symptoms and exocrine gland functions, as well as reduced serum IgG/IgA levels, while effector T- and B-cell subsets were significantly decreased. There was a trend of reduction on disease activity, but not statistically significant. Together, our findings suggest a novel approach to assess the immunomodulatory effects of Yu-Ping-Feng formula, which may be favorable for patients with autoimmune disorders.
Cancers with epidemiologic signatures of viral oncogenicity among immunocompromised populations in the United States
Authors: Haas Cameron B , Shiels Meredith S , Pfeiffer Ruth M , D’Arcy Monica , Luo Qianlai , Yu Kelly , Austin April A , Cohen Colby , Miller Paige , Morawski Bozena M , Pawlish Karen , Robinson William T , Engels Eric A
Published: July 2024

Background

Immunosuppressed individuals have elevated risk of virus-related cancers. Identifying cancers with elevated risk in people with HIV and solid organ transplant recipients, 2 immunosuppressed populations, may help identify novel etiologic relationships with infectious agents.

Methods

We used 2 linkages of population-based cancer registries with HIV and transplant registries in the United States. Cancer entities were systematically classified according to site and histology codes. Standardized incidence ratios were used to compare risk in people with HIV and solid organ transplant recipients with the general population. For selected cancer entities, incidence rate ratios were calculated for indicators of immunosuppression within each population.

Results

We identified 38 047 cancer cases in solid organ transplant recipients and 53 592 in people with HIV, yielding overall standardized incidence ratios of 1.66 (95% confidence interval [CI] = 1.65 to 1.68) and 1.49 (95% CI = 1.47 to 1.50), respectively. A total of 43 cancer entities met selection criteria, including conjunctival squamous cell carcinoma (people with HIV standardized incidence ratio = 7.1, 95% CI = 5.5 to 9.2; solid organ transplant recipients standardized incidence ratio = 9.4, 95% CI = 6.8 to 12.6). Sebaceous adenocarcinoma was elevated in solid organ transplant recipients (standardized incidence ratio = 16.2, 95% CI = 14.0 to 18.6) and, among solid organ transplant recipients, associated with greater risk in lung and heart transplant recipients compared with recipients of other organs (incidence rate ratio = 2.3, 95% CI = 1.7 to 3.2). Salivary gland tumors, malignant fibrous histiocytoma, and intrahepatic cholangiocarcinoma showed elevated risk in solid organ transplant recipients (standardized incidence ratio = 3.9,  4.7, and  3.2, respectively) but not in people with HIV. However, risks for these cancers were elevated following an AIDS diagnosis among people with HIV (incidence rate ratio = 2.4, 4.3, and  2.0, respectively).

Conclusions

Elevated standardized incidence ratios among solid organ transplant recipients and people with HIV, and associations with immunosuppression within these populations, suggest novel infectious causes for several cancers including conjunctival squamous cell carcinoma, sebaceous adenocarcinoma, salivary gland tumors, malignant fibrous histiocytoma, and intrahepatic cholangiocarcinoma.
TikTok and teen mental health: an analysis of user-generated content and engagement
Authors: Lau Nancy , Srinakarin Kavin , Aalfs Homer , Zhao Xin , Palermo Tonya M
Published: July 2024

Background

TikTok is a social media mobile application that is widely used by adolescents, and has the potential to serve as a revolutionary platform for public and mental health discourse, education, and intervention.

Objective

Our study aimed to describe the content and engagement metrics of the hashtag #teenmentalhealth on TikTok.

Methods

In this study, we: (a) conducted a directed content analysis of the Top 100 TikTok videos tagged with #teenmentalhealth, and (b) collected data on video engagements (views, likes, saves, and shares) and computed view-based engagement rates.

Results

The videos collectively garnered 144,320,591 views; 28,289,655 likes; 219,780 comments; 1,971,492 saves; and 478,696 shares. Most of the generated content were from teens and therapists. Engagement metrics revealed strong user engagement rates across user types. The most prevalent content categories represented across videos were personal experience, coping techniques or treatment, humor, interpersonal relationships, and health campaign. The content categories with the highest engagement rates were relatable media representation, health campaign, social isolation, and humor. Only a single video incorporated evidence-based treatment content.

Conclusion

TikTok facilitates communication and information dissemination on teen mental health. Future research should focus on improving the quality and credibility of digital content while maintaining engagement through creativity, self-expression, and relatability. Use of popular social media platforms and community-engaged research to disseminate evidence-based content may help bridge the translational research gap.
Post-malaria delayed cerebellar ataxia in a traveller
Authors: Davoli Caterina , Sponga Pietro , Angheben Andrea , Gobbi Federico G
Published: July 2024

An Italian traveller returning from Kenya was diagnosed and treated for malaria. Fourteen days later, he developed cerebellar symptoms and was diagnosed with delayed cerebellar ataxia (DCA), a rare, self-limiting post-malarial neurological complication with a favourable prognosis that may appear after effectively treated malaria.