bluuebunny/crossref_metadata_2025 huggingface dataset:
The New NormalIndia’s Quest for the ‘Credible’ in Nuclear Deterrence
Authors: Kampani Gaurav
Published: September 2024

This chapter analyzes India’s transition into a “normal” nuclear weapons power. The normality signifies India’s rejection of nuclear minimalism in favor of the classic Triad architecture of nuclear forces and the adoption of institutional practices that signify quicker responsiveness, flexibility, and enhanced deterrence. In sum, the current Indian nuclear force, its numbers, its architecture, its institutional practices, and its use doctrine, is turning into the antithesis of its purported imaginings in the 1980s and 1990s. Compared to the past, this growing force represents a radical inflection point in India’s presumed nuclear trajectory. But it can also be viewed as a normal where strategic logic, demands of credibility, technological pressures, and institutional self-realizations force states’ technics and organizational practices into a rough symmetry across the international system.
Stability and Volatility in Cultural Models of Contention
Authors: Gøtzsche-Astrup Oluf , Gøtzsche-Astrup Johan
Published: September 2024

How stable are the public’s assumptions about the legitimacy of contentious tactics? Previous studies show that the public hold a set of assumptions about what counts as legitimate and illegitimate tactics. We enrich this literature by studying the stability of these assumptions through the case of partisan protesting in the United States. Leveraging panel data collected during the 2020 Black Lives Matter and anti-lockdown protests as well as two preregistered survey experiments, we provide the first methodologically rigorous study of the short-term stability of these assumptions. We find that tactics are understood as inherently more legitimate when they are currently carried out by members of the partisan ingroup as opposed to its outgroup. However, although we do find an effect of contention, this is relatively moderate. The assumptions remain remarkably stable. This underscores the consolidated nature of the tactics in the United States and tempers fears of democratic decline in the realm of contention.
Social Crisis and Islamist Transformation: Iraq’s Sadrism Through Bourdieu’s Homology
Authors: Robin-D’Cruz Benedict
Published: September 2024

This article theorizes Islamist transformations by mapping the evolution of Sadrism in contemporary Iraq through a period of state collapse, war, and political consolidation. Using Pierre Bourdieu, this perspective emphasizes how field-based crises can synchronize and amplify homological relations between the deep-lying structures which differentiate religious from political spheres of Islamist activity. The article identifies these homological processes and structures and explains how they have patterned underlying morphologies of Sadrist politics. This differs from existing literature on Islamist movements where religion has often been contextualized in terms of material social conditions, or priority ascribed to political struggles and structures and emphasis placed on surface-level symbolic practices. By contrast, a Bourdieusian lens provides a theoretically robust approach to study the relationship between religion and politics, and an evaluative framework for Islamist transformations which is less normative than some alternatives and more generalizable beyond the context of Islamism and Islam.
Bridging mathematical and microeconomic perspectives: a praxeological analysis of the Lagrange multiplier method
Authors: Landgärds-Tarvoll Ida , Göller Daniel
Published: September 2024

This article investigates the challenges that economics students face when they make the transition from service mathematics course (s) to microeconomics courses with a focus on how the concept of the Lagrange multiplier method is used in constrained utility maximization problems. The study aims to identify and understand discrepancies in the application of the Lagrange multiplier method as introduced in the mathematics course and subsequently applied within the microeconomics course. For this purpose, we conducted a comparative praxeological analysis of textbooks used in the two courses. The analysis reveals significant differences in the techniques and technologies used in both textbooks, which may cause difficulties for students in their transition between the courses. Additionally, the analysis revealed total mismatches in praxeologies within the textbooks. The article concludes with suggestions on topics for service mathematics teachers to address for aligning their instruction with the microeconomics application of the Lagrange multiplier method.
A toxicogenomics-based identification of potential mechanisms and signaling pathways involved in PFCs-induced cancer in human
Authors: Dehghani Zahra , Ranjbar Sara , Shahabinezhad Farbod , Sabouri Pooria , Bardbori Afshin Mohammadi
Published: September 2024

Introduction

The number of new diagnosed cancer cases and cancer deaths are increasing worldwide. Perfluorinated compounds (PFCs) are synthetic chemicals, which are possible inducers of cancer in human and laboratory animals. Studies showed that PFCs induce breast, prostate, kidney, liver and pancreas cancer by inducing genes being involved in carcinogenic pathways.

Methodology

This study reviews the association between PFCs induced up-regulation/down-regulation of genes and signaling pathways that are important in promoting different types of cancer. To obtain chemical-gene interactions, an advanced search was performed in the Comparative Toxicogenomics Database platform.

Results

Five most prevalent cancers were studied and the maps of their signaling pathways were drawn, and colored borders indicate significantly differentially expressed genes if there had been reports of alterations in expression in the presence of PFCs.

Conclusion

In general, PFCs are capable of inducing cancer in human via altering PPARα and PI3K pathways, evading apoptosis, inducing sustained angiogenesis, alterations in proliferation and blocking differentiation. However, more epidemiological data and mechanistic studies are needed to better understand the carcinogenic effects of PFCs in human.
Preventing delirium in post-acute care
Authors: Spear Rebecca A. , Martin-Plank Lori , Crist Janice D.
Published: September 2024

Older adults admitted to post-acute care often are frail with multiple comorbidities, making them particularly vulnerable to developing delirium. The purpose of this quality improvement project was to create, implement, and evaluate an NP-led, evidence-based delirium prevention protocol in a skilled nursing facility (SNF). The incidence of new-onset delirium was assessed pre- and postimplementation; following implementation, no patients were diagnosed with new-onset delirium, and nurses and certified nursing assistants reported changes to their practice. Based on project design, the approximately 42,000 NPs in the US with nursing home or long-term-care facility privileges are optimally positioned to lead SNFs in the prevention of new-onset delirium.
Assessment Tools for Patient Notes in Medical Education: A Scoping Review
Authors: Kelly William F. , Hawks Matthew K. , Johnson W. Rainey , Maggio Lauren A. , Pangaro Louis , Durning Steven J.
Published: September 2024

Purpose

Physician proficiency in clinical encounter documentation is a universal expectation of medical education. However, deficiencies in note writing are frequently identified, which have implications for patient safety, health care quality, and cost. This study aimed to create a compendium of tools for educators’ practical implementation or future research.

Method

A scoping review was conducted using the Arksey and O’Malley framework. PubMed, Embase, Ovid All EBM Reviews, Web of Science, and MedEdPORTAL were searched for articles published from database inception to November 16, 2023, using the following search terms: documentation, note-writing, patient note, electronic health record note, entrustable professional activity 5, and other terms. For each note-writing assessment tool, information on setting, section(s) of note that was assessed, tool properties, numbers and roles of note writers and graders, weight given, if used in grading, learner performance, and stakeholder satisfaction and feasibility was extracted and summarized.

Results

A total of 5,257 articles were identified; 32 studies with unique tools were included in the review. Eleven studies (34.4%) were published since 2018. Twenty-two studies (68.8%) outlined creating an original assessment tool, whereas 10 (31.2%) assessed a curriculum intervention using a tool. Tools varied in length and complexity. None provided data on equity or fairness to student or resident note writers or about readability for patients. Note writers often had missing or incomplete documentation (mean [SD] total tool score of 60.3% [19.4%] averaged over 25 studies), often improving after intervention. Selected patient note assessment tool studies have been cited a mean (SD) of 6.3 (9.2) times. Approximately half of the tools (17 [53.1%]) or their accompanying articles were open access.

Conclusions

Diverse tools have been published to assess patient notes, often identifying deficiencies. This compendium may assist educators and researchers in improving patient care documentation.
Imaging of Cervical Spine Trauma
Authors: Warstadt Melissa , Winegar Blair , Shah Lubdha M.
Published: September 2024

Imaging of cervical spine trauma most commonly begins with computed tomography (CT) for initial osseous and basic soft tissue evaluation, followed by magnetic resonance imaging (MRI) for complementary evaluation of the neural structures (i.e., spinal cord, nerves) and soft tissues (i.e., ligaments). Although CT and conventional MRI sequences have been the mainstay of trauma imaging for decades, there have been significant advances in CT processing, imaging sequences and techniques made possible by hardware and software development, and artificial intelligence. These advancements may provide advantages in increasing sensitivity for detection of pathology as well as in decreasing imaging and interpretation time. Unquestionably, the most important role of imaging is to provide information to help direct patient care, including diagnosis, next steps in treatment plan, and prognosis. As such, there has been a growing body of research investigating the clinical relevance of imaging findings to clinical outcomes in the setting of spinal cord injury. This article will focus on these recent advances in imaging of cervical spinal trauma.
Limbal Stem Cell Deficiency After Treatment of Ocular Surface Squamous Neoplasia
Authors: Devebacak Ali , Yaman Banu , Palamar Melis
Published: September 2024

Purpose:

To investigate limbal stem cell deficiency (LSCD) in patients surgically treated for ocular surface squamous neoplasia (OSSN).

Methods:

This retrospective case–control study investigated clinical and histological data from patients with OSSN surgically treated in a referral center.

Results:

The study included 98 patients (58 male, 40 female) with a mean age of 61.1 (23–86) years. Less than 3 clock hours were involved by OSSN in 48 eyes (49.0%), 3–6 clock hours in 32 eyes (32.7%), 6–9 clock hours in 12 eyes (12.2%), and more than 9 clock hours in 6 eyes (6.1%). Limbal stem cell deficiency was identified in 36 patients (36.7%) after surgery. The severity of LSCD was mild in 17 eyes, moderate in 11, and severe in 8. The prevalence of LSCD increased significantly in groups with 6 clock hours or more of OSSN involvement (p < 0.001). The affected limbal side (superior, inferior, nasal, or temporal) had no significant association with the prevalence of LSCD (p = 0.869). Patients with recurrent OSSN had a higher LSCD prevalence (p = 0.003). The higher the tumor stage, the more likely it was to develop LSCD (p < 0.001). Patients with corneal involvement were also more likely to develop LSCD (p = 0.021). The prevalence of LSCD was raised with increasing histopathological grade (p = 0.019). Furthermore, solely the number of clock hours affected by OSSN was an independent risk factor in multivariate analyses (p < 0.001).

Conclusions:

The size and severity of OSSN and the presence of recurrent OSSN are associated with an increased likelihood of developing LSCD. Furthermore, the extent of the limbal area involved by the OSSN is identified as an independent risk factor of the development of LSCD.
Sublingual hematoma as a rare complication of warfarin therapy in a patient with rheumatic heart disease: a case report
Authors: Idrees Muhammad , Jain Hritvik , Masood Abdullah , Usama Rana Muhammad , Odat Ramez M. , Bin Abid Hamza , Khalid Umair , Mahmood Armghan , Jain Jyoti , Hanifa Hamdah
Published: September 2024

Introduction and importance:

Warfarin prevents thromboembolic events by acting as a vitamin-K antagonist. Close monitoring with an international normalized ratio (INR) is required to avoid bleeding-related complications. One of its rare complications is sublingual hematoma, with potentially life-threatening conditions such as severe airway obstruction. The authors present a rare case of sublingual hematoma after warfarin therapy in a patient with rheumatic heart disease (RHD).

Case presentation:

The authors report a case of a 44-year-old female with rheumatic heart disease who developed sublingual hematoma following warfarin therapy. She presented with difficulty swallowing and speaking due to pain and swelling under her tongue. Her INR was elevated. After discontinuing the drug, the patient received fresh frozen plasma and intravenous vitamin K. Her symptoms resolved within 24 h, and she was discharged without any complications. As per our understanding, this is the first case of sublingual hematoma secondary to warfarin therapy that has been reported in Pakistan.

Clinical discussion:

Warfarin remains a cornerstone anticoagulant in developing countries despite bleeding risks, with management of complications like sublingual hematoma involving INR normalization and conservative treatment. Timely intervention and monitoring of drug interactions are critical in preventing serious outcomes and reducing mortality associated with warfarin therapy.

Conclusion:

Warfarin is a commonly prescribed oral anticoagulant for a variety of conditions. Despite being rare, sublingual hematoma should be considered by the treating physician as a potential complication.
Giant ovarian mucinous cystadenoma complicating term pregnancy: a rare case report
Authors: Manh Thang Nguyen , Thi Huyen Anh Nguyen , Thanh Quang Huynh
Published: September 2024

Introduction:

Adnexal masses in pregnancy are identified at a rate of 2 to 20 in 1000, which mostly are benign simple cysts. Although the majority of adnexal masses will resolve spontaneously by the beginning of the second trimester, some cases are persistent forms which can result in complications for both mother and fetus.

Presentation of case:

A 31-year-old pregnant woman was diagnosed with a left ovarian mucinous cystadenoma. The ovarian cyst was first detected in the 8th week of pregnancy, measured 5×5 cm and reached 40×30 cm at 38 weeks of gestation. The patient underwent an elective cesarean delivery along with a left salpingo-oophorectomy at term. An alive female baby of 3000 g was delivered with good APGAR scores at the first and fifth minutes. Histologic examination confirmed the diagnosis of a benign mucinous cystadenoma.

Dicussion:

The option of surgical intervention versus conservative management should be tailored to the patient’s physical symptoms, characteristics of the tumor, and gestational age. An elective cesarean section along with salpingo-oophorectomy can be adopted for a giant ovarian cyst complicating term pregnancy. There is a risk of recurrence after a removal of ovarian mucinous cystadenoma.

Conclusion:

Ovarian cysts coexisting with pregnancy should be followed up properly by routine ultrasound and regular antenatal care. The decision to postpone surgical management of a complex mass until the time of delivery must balance the risks and benefits for mother and fetus. After surgery, the patient needs to be provided an appropriate follow-up care to manage postoperative recurrence.
Characteristics of Patients Admitted to Vascular Surgery Service for a Major Lower Limb Amputation From 2017 to 2021 With Present on Admission Pressure Injuries
Authors: Ratliff Catherine R. , Rovnyak Virginia
Published: September 2024

PURPOSE

The purpose of this study was to describe characteristics of patients admitted from 2017 to 2021 with peripheral arterial disease (PAD) who required a below knee amputation (BKA) or above knee amputation (AKA), including present on admission pressure injuries (POA-PIs).

DESIGN

Descriptive, cross-sectional retrospective research design.

SUBJECTS AND SETTING

The sample comprised 196 patients who underwent 258 major lower limb amputations. A majority (65.9 %n = 170) underwent BKAs and 88 (34.1 %) underwent AKAs. Coronary artery disease was present in 107 (54.6 %) and 143 (73.0%) had diabetes mellitus. The study site was a 670-bed level 1 trauma center in the Mid-Atlantic region of the United States.

METHODS

A retrospective chart review of patients undergoing major lower limb amputations using CPT codes 27880 BKA, and 27590 AKA was completed. Variables extracted included age, sex, race, and comorbid conditions such as smoking, cardiovascular disease, diabetes mellitus, end stage renal disease requiring dialysis, and POA-PI. Descriptive statistics (frequencies, percentages, and means) were used to describe the sample.

RESULTS

There were 25 (12.8%) individuals with POA-PI compared with 171 (87.2%) who did not have POA-PI. None of the characteristics reviewed significantly differed when patients with or without POA-PI were compared. Age was closest to statistical significance (P = .052). In addition, analysis revealed that 73% (n = 143) of individuals had diabetes mellitus in addition to having PAD.

CONCLUSION

Approximately 13% of a group of patients with PAD had POA-PI when admitted to hospital for major limb amputation. Analysis of multiple factors found that none significantly differed between patients with or without POA-PI. Age came nearest to statistical significance and we hypothesize that older age may increase the risk for POA-PI; additional research in samples with greater power to detect this effect are needed. Findings also indicate that diabetes mellitus is a common risk factor for major lower limb amputation. It is important to educate staff/patients/caregivers on the importance of PI prevention especially in the elderly vascular population who are at risk for undergoing major lower limb amputations.
Activity of forkhead box P2-positive neurons is associated with tadpole begging behaviour
Authors: Ludington Sarah C. , McKinney Jordan E. , Butler Julie M. , Goolsby Billie C. , Callan Ashlyn A. , Gaines-Richardson Maiah , O’Connell Lauren A.
Published: September 2024

Motor function is a critical aspect of social behaviour in a wide range of taxa. The transcription factor forkhead box P2 (FoxP2) is well studied in the context of vocal communication in humans, mice and songbirds, but its role in regulating social behaviour in other vertebrate taxa is unclear. We examined the distribution and activity of FoxP2-positive neurons in tadpoles of the mimic poison frog (
Ranitomeya imitator
). In this species, tadpoles are reared in isolated plant nurseries and are aggressive to other tadpoles. Mothers provide unfertilized egg meals to tadpoles that perform a begging display by vigorously vibrating back and forth. We found that FoxP2 is widely distributed in the tadpole brain and parallels the brain distribution in mammals, birds and fishes. We then tested the hypothesis that FoxP2-positive neurons would have differential activity levels in begging or aggression contexts compared to non-social controls. We found that FoxP2-positive neurons showed increased activation in the striatum and cerebellum during begging and in the nucleus accumbens during aggression. Overall, these findings lay a foundation for testing the hypothesis that FoxP2 has a generalizable role in social behaviour beyond vocal communication across terrestrial vertebrates.
Evaluating exposure to vehicle pollutants using physics-informed immersive reality models
Authors: Si Run , Stafford Jason
Published: September 2024

Major health risks and chronic diseases are caused by exposure to unregulated particle pollutants from road, tyre and brake sources. Here, we use large-eddy simulations to identify local exposure to these harmful pollutants and build a physics-informed immersive reality experience to communicate outcomes with the general public for health guidance. Our analysis reveals that exposure to non-exhaust pollution is greatest at the end of braking phases, when deceleration rates are above 3 m s
−2
, diminishes to background levels for pedestrians located 1.5 m away from a car, and is reasonably insensitive to the car type. We show that by using immersive reality models to visualize pollution data in a human-centric format, people could identify pollutant sources and health risks, and understand how to navigate urban spaces for reduced exposure. This was achieved without any prerequisite knowledge and with minimal dependency on educational background, suggesting the approach can support public health guidance, policymakers and urban planners towards improving air quality in urban environments.
An existence theorem for generalized Abelian Higgs equations and its application
Authors: Cao Lei , Chen Shouxin
Published: September 2024

In this note, we construct self-dual vortices and cosmic strings from the generalized Abelian Higgs theory in which the Higgs potential is a polynomial whose degree depends on the number

m

. When

|
m
|
>
0

, we obtain sharp existence theorems for vortices and strings corresponding to the absence and presence of gravity, respectively, over the whole plane. In the absence of gravity, we prove the existence of vortices by using a monotone iteration method. When gravity is taken into account, a regularization method and a fixed-point theorem are used to show that multiple string solutions exist under a sufficient condition imposed only on the total number of strings. In addition, a series of properties with respect to vortices and strings have also been established.
Immunological feedback loops generate parasite persistence thresholds that explain variation in infection duration
Authors: Cressler Clayton E. , Metz Daniel C. G. , Chang van Oordt David A. , Graham Andrea L.
Published: September 2024

Infection duration affects individual host fitness and between-host transmission. Whether an infection is cleared or becomes chronic depends on the complex interaction between host immune responses and parasite growth. Empirical and theoretical studies have suggested that there are critical thresholds of parasite dose that can determine clearance versus chronicity, driven by the ability of the parasite to manipulate host immunity. However, the mammalian immune response is characterized by strong positive and negative feedback loops that could generate duration thresholds even in the absence of direct immunomodulation. Here, we derive and analyse a simple model for the interaction between T-cell subpopulations and parasite growth. We show that whether an infection is cleared or not is very sensitive to the initial immune state, parasite dose and strength of immunological feedbacks. In particular, chronic infections are possible even when parasites provoke a strong and effective immune response and lack any ability to immunomodulate. Our findings indicate that the initial immune state, which often goes unmeasured in empirical studies, is a critical determinant of infection duration. This work also has implications for epidemiological models, as it implies that infection duration will be highly variable among individuals, and dependent on each individual’s infection history.
Independent operations of appetitive and aversive conditioning systems lead to simultaneous production of conflicting memories in an insect
Authors: Rahman Sadniman , Terao Kanta , Hashimoto Kohei , Mizunami Makoto
Published: September 2024

Pavlovian conditioning is a ubiquitous form of associative learning that enables animals to remember appetitive and aversive experiences. Animals possess appetitive and aversive conditioning systems that memorize and retrieve appetitive and aversive experiences. Here, we addressed a question of whether integration of competing appetitive and aversive information takes place during the encoding of the experience or during memory retrieval. We developed novel experimental procedures to address this question using crickets (
Gryllus bimaculatus
), which allowed selective blockade of the expression of appetitive and aversive memories by injecting octopamine and dopamine receptor antagonists. We conditioned an odour (conditioned stimulus 1, CS1) with water and then with sodium chloride solution. At 24 h after conditioning, crickets retained both appetitive and aversive memories, and the memories were integrated to produce a conditioned response (CR). Importantly, when a visual pattern (CS2) was conditioned with CS1, appetitive and aversive memories formed simultaneously. This indicates that appetitive and aversive second-order conditionings are achieved at the same time. The memories were integrated for producing a conditioned response. We conclude that appetitive and aversive conditioning systems operate independently to form parallel appetitive and aversive memories, which compete to produce learned behaviour in crickets.
Species morphology better predicts plant–hummingbird interactions across elevations than nectar traits
Authors: Maglianesi María A. , Brenes Emanuel , Chaves-Elizondo Nelson , Zuniga Krystal , Castro Jiménez Alejandro , Barreto Elisa , Duchenne François , Graham Catherine H.
Published: September 2024

Species traits greatly influence interactions between plants and pollinators where floral nectar is the primary energy source fostering this mutualism. However, very little is known about how nectar traits mediate interactions in pollination networks compared with morphological traits. Here, we evaluated the role of morphological and nectar traits in shaping plant–hummingbird interaction networks along an elevation gradient. For this, we assessed patterns in floral phenotypic traits and network properties of plant species across elevations in Costa Rica. We also analysed whether plant species with generalized flower traits are ecological generalists and how morphological trait matching versus nectar traits affect interactions. We found marked variation in floral phenotypic traits and flower abundance of hummingbird-visited plant species across 10 sites along the elevation gradient. We did not find evidence for a relationship between flower morphology and nectar traits or between morphological and ecological generalization of plant species. Plant–hummingbird interaction frequency increased when the lengths of hummingbird bill and flower corolla were similar, indicating morphological matching, whereas nectar traits were unrelated to interactions. While nectar may play a difficult-to-detect secondary role within plant–hummingbird networks, our results reinforce the idea that morphological matching is an important factor in structuring ecological communities.
Evolution of odorant receptor repertoires across Hymenoptera is not linked to the evolution of eusociality
Authors: Gautam Shubham , McKenzie Sean , Katzke Julian , Hita Garcia Francisco , Yamamoto Shûhei , Economo Evan P.
Published: September 2024

Communication is essential for social organisms. In eusocial insects, olfaction facilitates communication and recognition between nestmates. The study of certain model organisms has led to the hypothesis that odorant receptors are expanded in eusocial Hymenoptera. This has become a widely mentioned idea in the literature, albeit with conflicting reports, and has not been tested with a broad comparative analysis. Here we combined existing genomic and new neuroanatomical data, including from an approximately 100 Myr old fossil ant, across a phylogenetically broad sample of hymenopteran lineages. We find no evidence that variation in the size and evolutionary tempo of odorant receptor repertoires is related to eusociality. Post hoc exploration of our data hinted at loss of flight as a possible factor shaping some of the variation in OR repertoires in Hymenoptera. Nevertheless, our analyses revealed a complex pattern of evolutionary variation, and raise new questions about the ecological, behavioural and social factors that shape olfactory abilities.
Production of green synthesized iron oxide /graphene magnetic nanocomposite as a novel antibacterial material
Authors: kazazi Mohammad , Moomivand Ali , Mahmoodvand Ali
Published: September 2024

Synthesis of green iron magnetic nanoparticles (Nps) based on graphene is an environmentally friendly method in nanotechnology. In this method, graphene is synthesized via electrochemical process from graphite. Then, a homogeneous solution of graphene in a mixture of water and alcohol is prepared, and iron magnetic Nps are synthesized using iron(II) chloride and iron(III) chloride in a 1:2 ratio. Finally, the antibacterial property of the synthesized nanocomposite was investigated, and analyses including SEM, XRD, FT-IR, EDAX, and VSM were performed.
Upregulation of Reward Mesolimbic Activity via fMRI-Neurofeedback Improves Vaccination Efficiency in Humans
Authors: Lubianiker Nitzan , Koren Tamar , Djerasi Meshi , Sirotkin Margarita , Singer Neomi , Jalon Itamar , Lerner Avigail , Sar-el Roi , Sharon Haggai , Azulay-Debby Hilla , Rolls Asya , Hendler Talma
Published: September 2024

The placebo response is associated with a positive expectation of recovery. Recent studies in mice uncovered a potential underlying mechanism of placebo effects, by demonstrating the involvement of the dopaminergic mesolimbic pathway, previously implicated in reward expectation, in immune modulation. Yet, it is not known whether an analogous brain-immune regulatory mechanism exists in humans, and whether it employs conscious positive expectations. Here, we employed fMRI-neurofeedback to train healthy participants to increase their reward mesolimbic activity by using self-chosen mental strategies, followed by Hepatitis B Virus (HBV) vaccination. We found that stronger Ventral Tegmental Area (VTA) activity, but not control regions activation, was associated with higher post-vaccination HBV antibody titer. Interestingly, higher VTA activity before vaccination was associated with mental strategies characterized by positive expectation. Thus, our results establish a relationship between reward system activity, positive expectation and immunity in humans and reveal a potential neuropsychological mechanism for non-invasive immune modulation.

https://clinicaltrials.gov/study/NCT03951870.
Sex Differences in Home-Cage Ethanol Drinking and Operant Self-Administration in C57BL/6J Mice with Equivalent Regulation by Glutamate AMPAR Activity
Authors: Faccidomo Sara , Eastman Vallari R , Santanam Taruni S , Swaim Katarina S , Taylor Seth M , Hodge Clyde W
Published: September 2024

Introduction

Considering sex as a biological variable (SABV) in preclinical research can enhance understanding of the neurobiology of alcohol use disorder (AUD). However, the behavioral and neural mechanisms underlying sex-specific differences remain unclear. This study aims to elucidate SABV in ethanol (EtOH) consumption by evaluating its reinforcing effects and regulation by glutamate AMPA receptor activity in male and female mice.

Methods

C57BL/6J mice (male and female) were assessed for EtOH intake under continuous and limited access conditions in the home cage. Acute sensitivity to EtOH sedation and blood clearance were evaluated as potential modifying factors. Motivation to consume EtOH was measured using operant self-administration procedures. Sex-specific differences in neural regulation of EtOH reinforcement were examined by testing the effects of a glutamate AMPA receptor antagonist on operant EtOH self-administration.

Results

Female C57BL/6J mice exhibited a time-dependent escalation in EtOH intake under both continuous and limited access conditions. They were less sensitive to EtOH sedation and had lower blood levels post-EtOH administration (4 g/kg) despite similar clearance rates. Females also showed increased operant EtOH self-administration and progressive ratio performance over a 30-day baseline period compared to males. The AMPAR antagonist GYKI 52466 (0–10 mg/kg, IP) dose-dependently reduced EtOH-reinforced lever pressing in both sexes, with no differences in potency or efficacy.

Discussion

These findings confirm that female C57BL/6J mice consume more EtOH than males in home-cage conditions and exhibit reduced acute sedation, potentially contributing to higher EtOH intake. Females demonstrated increased operant EtOH self-administration and motivation, indicating higher reinforcing efficacy. The lack of sex differences in the relative effects of GYKI 52466 suggests that AMPAR activity is equally required for EtOH reinforcement in both sexes.
Learning-Augmented Sketching Offers Improved Performance for Privacy Preserving and Secure GWAS
Authors: Xu Junyan , Zhu Kaiyuan , Cai Jieling , Kockan Can , Dokmai Natnatee , Cho Hyunghoon , Woodruff David P. , Sahinalp S. Cenk
Published: September 2024

The introduction of trusted execution environments (TEEs), such as secure enclaves provided by the Intel SGX technology has enabled secure and privacy-preserving computation on the cloud. The stringent resource limitations, such as memory constraints, required by some TEEs necessitates the development of computational approaches with reduced memory usage, such as sketching. One example is the SkSES method for GWAS on a cohort of case and control samples from multiple institutions, which identifies the most significant SNPs in a privacy-preserving manner without disclosing sensitive genotype information to other institutions or the cloud service provider. Here we show how to improve the performance of SkSES on large datasets by augmenting it with a learning-augmented approach. Specifically, we show how individual institutions can perform smaller scale GWAS on their own datasets and identify two sets of variants according to certain criteria, which are then used to guide the sketching process to more accurately identify significant variants over the collective dataset. The new method achieves up to 40% accuracy gain compared to the original SkSES method under the same memory constraints on datasets we tested on. The code is available athttps://github.com/alreadydone/sgx-genome-variants-search.

Contact

cenk.sahinalp@nih.gov
Characterizing trachoma elimination using serology
Authors: Kamau Everlyn , Ante-Testard Pearl Anne , Gwyn Sarah , Blumberg Seth , Abdalla Zeinab , Aiemjoy Kristen , Amza Abdou , Aragie Solomon , Arzika Ahmed M. , Awoussi Marcel S. , Bailey Robin L. , Butcher Robert , Callahan E. Kelly , Chaima David , Dawed Adisu Abebe , Saboyá Díaz Martha Idalí , Domingo Abou-Bakr Sidik , Drakeley Chris , Elshafie Belgesa E. , Emerson Paul M. , Fornace Kimberley , Gass Katherine , Goodhew E. Brook , Hammou Jaouad , Harding-Esch Emma M. , Hooper PJ , Kadri Boubacar , Kalua Khumbo , Kanyi Sarjo , Kasubi Mabula , Kello Amir B. , Ko Robert , Lammie Patrick J. , Lescano Andres G. , Maliki Ramatou , Masika Michael Peter , Migchelsen Stephanie J. , Nassirou Beido , Nesemann John M. , Parameswaran Nishanth , Pomat Willie , Renneker Kristen , Roberts Chrissy , Rymil Prudence , Sata Eshetu , Senyonjo Laura , Seife Fikre , Sillah Ansumana , Sokana Oliver , Srivathsan Ariktha , Tadesse Zerihun , Taleo Fasihah , Taylor Emma Michelle , Tekeraoi Rababe , Togbey Kwamy , West Sheila K. , Wickens Karana , William Timothy , Wittberg Dionna M. , Yeboah-Manu Dorothy , Youbi Mohammed , Zeru Taye , Keenan Jeremy D. , Lietman Thomas M. , Solomon Anthony W. , Nash Scott D. , Martin Diana L. , Arnold Benjamin F.
Published: September 2024

Trachoma is targeted for global elimination as a public health problem by 2030. Measurement of IgG antibodies in children is being considered for surveillance and programmatic decision-making. There are currently no guidelines for applications of serology, which represents a generalizable problem in seroepidemiology and disease elimination. We collatedChlamydia trachomatisPgp3 and CT694 IgG measurements (63,911 children ages 1–9 years) from 48 serosurveys, including surveys across Africa, Latin America, and the Pacific Islands to estimate population-level seroconversion rates (SCR) along a gradient of trachoma endemicity. We propose a novel, generalizable approach to estimate the probability that populationC. trachomatistransmission is below levels requiring ongoing programmatic action, or conversely is above levels that indicate ongoing interventions are needed. We provide possible thresholds for SCR at a specified level of certainty and illustrate how the approach could be used to inform trachoma program decision-making using serology.
Functional impact of the hyperduplication genomophenotype in high copy number endometrial cancer
Authors: Florio Angela , Smadbeck James , Johnson Sarah H. , Lin Wan-Hsin , Sadeghian Dorsay , Sotiriou Sotiris , Salvatori Rebeca , Feathers Ryan W. , Berry Taylor , Kinsella Lindsey , Harris Faye R. , McCune Alexa F. , Murphy Stephen J. , Ali Mohamed F. , Pezeshki Abdulmohammad , Barrett Michael T. , Grcevich Leah , Capasso Ilaria , De Vitis Luigi Antonio , Schivardi Gabriella , Occhiali Tommaso , Larish Alyssa M. , Weroha John , Borad Mitesh J. , Cheville John , Anastasiadis Panos Z. , Mariani Andrea , Vasmatzis George
Published: September 2024

High copy number endometrial cancers (HCNEC) are dominated by excessive duplications scattered across the genome, termed here as theHyperDuplicationGenomoPhenotype (HDGP). Although correlated with cancer progression, its biological significance and implications for therapy have not yet been established. We identified locations and sizes of duplications in 171 endometrial cancer cases and designated 71 HCNEC cases as HDGP. We also investigated the response to the pan-ERBB inhibitor afatinib in a subset of HDGP-EC cases withERBB2/ERBB3duplications using a patient-derived three-dimensional culture model. Our analysis demonstrates that beyond tandem duplications there is a more general pattern involving coordinated duplication of multiple distant regions of the genome, demonstrating preferential selectivity to over-expressed potential oncogenes within a broad network. This suggests that HDGP increases tumor fitness and resistance to therapy by perturbing important gene networks in concert rather than only driver genes, suggesting a mechanistic basis for the ineffectiveness of targeted drugs in these patients and highlighting the need for combination therapies in these highly aggressive cases.
Ectoine production through a marine methanotroph-microalgae culture allows complete biogas valorization
Authors: Ruiz-Ruiz Patricia , Mohedano-Caballero Patricia , De Vrieze Jo
Published: September 2024

Methanotrophs have recently emerged as a promising platform for producing bio-based chemicals, like ectoine, from biogas, offering an economical alternative to glucose. However, most studies have focused solely on CH4consumption, often overlooking the CO2, which is both produced by methanotrophs and present in biogas, despite its potential as a carbon source for microorganisms, such as microalgae. In this study, marine methanotrophic-microalgal cultures were enriched from environmental samples collected at the North Sea coast to explore ectoine production from both CH4and CO2in biogas. The sediment-derived culture exhibited the highest CH4removal efficiency and CO2uptake, and was selected for further experiments. The culture was primarily composed ofMethylobacter marinus,Methylophaga marina, and the microalgaPicochlorum oklahomensis. Gas consumption, growth, and ectoine production were evaluated under varying salinity levels and osmotic stress. The NaCl concentrations above 6% negatively impacted CH4oxidation and inhibited ectoine synthesis, while osmotic shocks enhanced ectoine accumulation, with a maximum ectoine content of 51.3 mgectoinegVSS−1at 4.5% NaCl. This study is the first to report ectoine production from methanotroph-microalgal cultures, showing its potential for biogas valorization into high-value bio-based chemicals, like ectoine, marking a significant step toward sustainable biogas utilization.

Highlights

Methanotroph-microalgae cultures can valorize CH4and CO2from biogas into ectoine

NaCl concentrations above 6% reduced CH4uptake and inhibited ectoine synthesis

Osmotic shock at 4.5% NaCl enhanced ectoine accumulation

First report of ectoine production using methanotroph-microalgal cultures
Stimulus-modulatedapproach tosteady-state: A new paradigm for event-related fMRI
Authors: Mathew Renil , Eed Amr , Klassen L. Martyn , Everling Stefan , Menon Ravi S
Published: September 2024

Functional MRI (fMRI) studies discard the initial volumes acquired during the approach of the magnetization to its steady-state value. Here, we leverage the substantially higher temporal signal-to-noise ratio (tSNR) of these initial volumes to increase the sensitivity of event-related fMRI experiments. To do this, we introduce Acquisition Free Periods (AFPs) that allow for the full recovery of the magnetization, followed by equal-length task or baseline acquisition blocks (AB) of fMRI volumes. An appropriately placed stimulus in the AFP produces a Blood Oxygenation-Level-Dependent (BOLD) response that peaks during the initial high tSNR phase of the AB, yielding an ∼50% reduction in the number of trials (relative to conventional fMRI) needed to achieve a given statistical threshold. The AFP allows flexibility for the presentation of auditory stimuli, uncontaminated recording of electrophysiological activity, physiological gating, as well as the ability to average aperiodic fMRI data using stimulus or response-locked signal acquisition.
Towards a global barcode reference library for subterranean fauna
Authors: Guzik Michelle T , Thornhill Jacob , van der Heyde Mieke , Stringer Danielle , White Nicole , Saccò Mattia , Beasley-Hall Perry G , King Rachael , Nevill Paul , Cooper Steven , Austin Andrew
Published: September 2024

Implementation of environmental DNA (eDNA) metabarcoding for biodiversity discovery and assessment offers a unique opportunity to gain new insights into subterranean communities around the world. However, for effective and meaningful identification of species from anonymous eDNA barcodes, a library of known reference sequences with associated correct taxonomic metadata - also called a barcode reference library (BRL) - is required. Here we propose an open, publicly accessible information resource for eDNA biomonitoring of subterranean fauna following findable, accessible, interoperable and reusable (FAIR) principles that can be expanded globally. While similar proposals have been made by other authors for individual taxon groups, here we have analysed a curated BRL of subterranean fauna compiled from existing GenBank and BOLD DNA sequence databases for a minimum of four genes (COI, 18S, 12S, and 16S rRNA). We demonstrate the value of such an initiative to eDNA metabarcoding where custom libraries are used to characterise entire ecosystems under examination. To examine the effectiveness of a custom BRL, we generated metabarcoding data for an exemplar system at Bungaroo Creek in the Pilbara (Australia), a globally significant location of stygofaunal diversity. We compared results of BLAST queries of eDNA Operational Taxonomic Units (OTUs) to our BRL and the GenBank nucleotide database, and observed that for all barcoding regions, the custom BRL identified subterranean ZOTUs that could not be identified using GenBank and worked better in tandem. We use the BRL presented here to propose a four-stage plan for developing data infrastructure for subterranean fauna, especially with respect to eDNA metabarcoding data. To our knowledge, this represents the first published instance of a subterranean BRL being tested against real eDNA metabarcoding data. These findings provide a step forward towards robust DNA-based bioassessments for subterranean biodiversity and further emphasise the need for the eDNA community to work together in facilitating a global BRL.
Analytical and computational solution for the estimation of SNP-heritability in biobank-scale and distributed datasets
Authors: Qi Guo-An , Zhang Qi-Xin , Kang Jingyu , Li Tianyuan , Xu Xiyun , Zhang Zhe , Fan Zhe , Liu Siyang , Chen Guo-Bo
Published: September 2024

Estimation of heritability has been a routine in statistical genetics, in particular with the increasing sample size such as biobank-scale data and distributed datasets, the latter of which has increasing concerns of privacy. Recently a randomized Haseman-Elston regression (RHE-reg) has been proposed to estimate SNP-heritability, and given sufficient iteration (B) RHE-reg can tackle biobank-scale data, such as UK Biobank (UKB), very efficiently. In this study, we present an analytical solution that balances iterationBand RHE-reg estimation, which resolves the convergence of the proposed RHE-reg in high precision. We applied the method for 81 UKB quantitative traits and estimated their SNP-heritability and test statistics precisely. Furthermore, we extended RHE-reg into distributed datasets and demonstrated their utility in real data application and simulated data. The software for estimating SNP-heritability for biobank-scale data is released:https://github.com/gc5k/gear2.
Active segregation in binary mixtures under flow
Authors: Di Dio Giacomo , Colin Remy
Published: September 2024

Many bacterial habitats, from the gut to the soil, feature narrow channels where confined flow is a key constraint that might influence the spatial organization, and thus the functioning, of the complex, phenotypically heterogeneous communities these microbes form. Here, we investigate how a model heterogeneous bacterial community of motile and non-motileEscherichia coliorganizes under confined Poiseuille flow. We discovered a new mode of active self-organization, where the motile bacteria induce the rapid sideways segregation of the non-motile cells to one side of the channel, eventually resulting in asymmetric biofilm formation. Our experiments and modeling elucidated the purely physical segregation mechanism: the rheotactic drift of the motile cells, which stems from shear acting on their chiral flagella, induces a conveyer-belt-like backflow advecting the non-motile cells. The latter then accumulate thanks to sedimentation countering flow incompressibility. This unexpected consequence of motility can affect the organization of complex bacteria communities colonizing environments under confined flow.