bluuebunny/crossref_metadata_2025 huggingface dataset:
Covariance loss, Szemeredi regularity, and differential privacy
Authors: Boedihardjo March , Strohmer Thomas , Vershynin Roman
Published: January 2025

We show how randomized rounding based on Grothendieck’s identity can be used to prove a nearly tight bound on the covariance loss–the amount of covariance that is lost by taking conditional expectation. This result yields a new type of weak Szemeredi regularity lemma for positive semidefinite matrices and kernels. Moreover, it can be used to construct differentially private synthetic data.
Introduction
Authors: Scheffler Samuel
Published: January 2025

This chapter introduces the book’s organizing question: what is it to lead a life? It begins by rehearsing several commonsense convictions that bear on this question. These convictions, despite their commonsense character, seem to be rejected by traditions of thought that advocate a form of detachment from our ordinary perspective. Two kinds of reasons are often said to count in favor of detachment: epistemological reasons, or reasons to free ourselves from false beliefs, and ataraxic reasons, or reasons to free ourselves from suffering. The chapter raises a dilemma: either advocates of detachment repudiate forms of attachment normally taken to be part of a good life; or they merely repudiate attachment that is pathological, thereby reproducing common sense. After reviewing the place of detachment in recent philosophy, the chapter introduces the alternative that the book defends, an attachment-sensitive conception of leading a life. It ends with an outline of the book.
Interactional Ordering: Reconstructing Lon Fuller’s Theory of Private Law
Authors: Balganesh Shyamkrishna
Published: January 2025

While Lon Fuller is best remembered for his contributions to the fields of general jurisprudence and contract law, his work in each has long been seen as unrelated to the other. This Article shows that in a significantly underappreciated body of work, Fuller did connect the two and, in the process, developed the outlines of a robust theory of private law, best characterized as “interactional ordering.” Driven by Fuller’s efforts to develop a jurisprudence of form that was derived from conventionalism and natural law thinking, interactional ordering sees all normativity as originating in horizontal interactions between individuals in society, seeking to realize their freedom socially. This horizontal normativity forms the very substantive and structural basis for the common law as a mechanism of enforcement, and emerges as the principal end that all other forms of legal and social ordering are ultimately structured around. This Article reconstructs the central tenets of interactional ordering from Fuller’s work and shows how it represents a sophisticated account of how private law normativity operates, one that abjures commitments to both Legal Positivism and Legal Realism, a move that was central to Fuller’s overall jurisprudential worldview.
To disclose or not to disclose: Exploring the risk of being transparent about GenAI use in second language writing
Authors: Tan Xiao , Wang Chaoran , Xu Wei
Published: January 2025

With the increasingly popular use of generative artificial intelligence (GenAI) tools in writing, a common policy regarding GenAI use requires students to self-disclose such use in writing. However, many students, especially second language (L2) writers, are concerned that disclosing GenAI use might negatively impact how teachers evaluate their work. This study, therefore, intends to investigate the potential impact of GenAI disclosure on L2 writing assessment. This study employs a mixed-method design to measure the statistical differences between grades received under different disclosure conditions and explore potential reasons for discrepancies. The quantitative analysis shows that teachers tend to score the essays lower when they are informed that GenAI tools are involved in the writing process. The interview data suggest that teachers might make assumptions about the student author’s writing ability and GenAI’s influence on writing, with some participants acknowledging their bias against GenAI use in writing. The study lends empirical evidence to the concern about GenAI disclosure and provides suggestions for improving mutual trust between teachers and students and rethinking L2 writing assessment in the age of GenAI.
Contribution of linguistic complexity to L2 learners’ perception on Chinese text comprehensibility and reading speed: a comparative judgment approach
Authors: Zhang Xiaopeng
Published: January 2025

This study delved into how linguistic complexity, gauged through various lexical, syntactic, and discoursal indices, correlates with the perception of text difficulty among learners acquiring Chinese as a second language (L2). This perception of difficulty underwent scrutiny via a comparative judgment task, wherein L2 raters appraised text comprehensibility and reading speed. A corpus of 250 Chinese texts was targeted, with 170 Chinese L2 learners participating as raters. Among these, eighty-five raters adjudicated pairs of texts, discerning the text posing greater comprehension challenge within each duo, while another eighty-five raters determined the text they could read faster within each pair. Stepwise linear regression models, which incorporate a range of linguistic indices, accounted for a substantial proportion of the variance in L2 learners’ judgments of comprehensibility and reading speed, respectively. Insights garnered from this study hold promise in enriching our comprehension of the elements influencing text difficulty in Chinese-L2 learners.
Social Determinants of Health and Cross-Sectional Cognitive Intra-Individual Variability in Adults from the Deep South Living with HIV
Authors: Del Bene Victor A , Fazeli Pariya L , Blake Jason A , Li Wei , Collette Christopher , Triebel Kristen L , Byun Jun Y , Jacob Alexandra E , Kamath Vidyulata , Vance David E
Published: January 2025

Cognitive intra-individual variability (IIV) is a sensitive marker of neuropathology and is increased in people with HIV (PWH). In a sample of PWH from the United States Deep South, we examined the relationship of cognitive IIV with cognitive impairment and social determinants of health (SDoH). This secondary analysis included 131 PWH from a larger cognitive training protocol. Our primary outcome measure was the coefficient of variation (CoV). We also included the individual standard deviation (iSD), with both calculated from demographically adjusted T-scores and unadjusted sample–based scores. Mixed-effects models investigated the relationship between IIV and cognitive impairment severity (i.e., Global Rating Score), SDoH, and clinical variables. Bivariate correlations were used to further explore these relationships. Greater cognitive IIV was associated with greater cognitive impairment in PWH, when accounting for demographic factors. When IIV is calculated from the sample, then IIV is no longer associated with cognitive impairment, but is associated with race (>IIV in Black and African American participants). Demographically adjusted IIV is associated with global cognition, Wide Range Achievement Test–Fourth Edition reading score, and viral load (iSD only). No correlations were significant when using the unadjusted sample–based IIV metrics. In PWH from the Deep South, greater cognitive variability is seen in those with greater cognitive impairment, in Black participants, and in those with lower reading scores. Further research on the psychometric properties of IIV in HIV and other populations is needed, as results varied depending on the normative adjustments.
RNA-TorsionBERT: leveraging language models for RNA 3D torsion angles prediction
Authors: Bernard Clément , Postic Guillaume , Ghannay Sahar , Tahi Fariza
Published: January 2025

Motivation

Predicting the 3D structure of RNA is an ongoing challenge that has yet to be completely addressed despite continuous advancements. RNA 3D structures rely on distances between residues and base interactions but also backbone torsional angles. Knowing the torsional angles for each residue could help reconstruct its global folding, which is what we tackle in this work. This paper presents a novel approach for directly predicting RNA torsional angles from raw sequence data. Our method draws inspiration from the successful application of language models in various domains and adapts them to RNA.

Results

We have developed a language-based model, RNA-TorsionBERT, incorporating better sequential interactions for predicting RNA torsional and pseudo-torsional angles from the sequence only. Through extensive benchmarking, we demonstrate that our method improves the prediction of torsional angles compared to state-of-the-art methods. In addition, by using our predictive model, we have inferred a torsion angle-dependent scoring function, called TB-MCQ, that replaces the true reference angles by our model prediction. We show that it accurately evaluates the quality of near-native predicted structures, in terms of RNA backbone torsion angle values. Our work demonstrates promising results, suggesting the potential utility of language models in advancing RNA 3D structure prediction.

Availability and implementation

Source code is freely available on the EvryRNA platform: https://evryrna.ibisc.univ-evry.fr/evryrna/RNA-TorsionBERT.
High-throughput proteomics identifies inflammatory proteins associated with disease severity and genetic ancestry in patients with hidradenitis suppurativa
Authors: Dimitrion Peter M , Krevh Rachel , Veenstra Jesse , Ge James , Siddiqui Aamir , Ferguson Deangelo , Hans Aakash , Zuniga Bobby , Sidhu Kermanjot , Daveluy Steven , Hamzavi Iltefat , Zhou Li , Adrianto Indra , Mi Qing-Sheng
Published: January 2025

Background

Hidradenitis Suppurativa (HS) is a chronic inflammatory skin condition with a greater prevalence and disease burden in patients who identify as African American and those with a family history of HS, suggesting a strong genetic component to its pathogenesis.

Objective

To evaluate the relationship between plasma inflammatory protein expression, HS disease severity, and genetic ancestry in a diverse cohort of patients with Hidradenitis Suppurativa.

Methods

We performed a case-control study of patients with HS compared to age-, sex-, and ethnicity-matched healthy controls. We profiled circulating inflammatory proteins using Olink High-throughput proteomics and determined genetic ancestry from whole-genome sequencing data.

Results

Using linear regression, we identified novel proteins associated with HS after adjusting for age, sex, and ethnicity. Our analysis also revealed differences in the inflammatory proteome linked to disease severity. Specifically, we found that plasma IL6 levels can distinguish between different Hurley stages, indicating that IL6 may serve as a marker of disease severity. Additionally, we observed variations in inflammatory protein levels based on genetic ancestry: patients with predominantly African ancestry exhibited higher levels of inflammatory proteins associated with neutrophilic inflammation, while those with predominantly European ancestry showed increased levels of Th1-related inflammatory proteins.

Limitations

Single-center study. Limited sample size. Unable to account for treatment status or comorbidities that may influence the level of inflammatory cytokines.

Conclusion

Genetic ancestry and disease severity influence the plasma inflammatory profile in patients with HS.
Dermatologic surgery: An update on Secondary Intention Healing and Adjuncts: Part 2
Authors: Potluru Aparna , Barlow Richard , Pawlik Olga , Veitch David , Wernham Aaron
Published: January 2025

Secondary intention healing (SIH) is utilised by various surgical specialities. The formation of granulation tissue is crucial for initiating the healing process, necessitating robust support at this stage. Numerous adjunct therapies are available, with new developments aimed at treating both acute and chronic wounds undergoing SIH. This article continues from part 1, examining the efficacy of various adjunct therapies in promoting SIH. This article continues from part 1, examining the efficacy of various adjunct therapies in promoting SIH.
Intravenous Steroids Do Not Improve Short-Term Outcomes of Patients With Crohn’s Disease Presenting With an Acute Small Bowel Obstruction
Authors: Garcia Mariely , Debebe Anketse , Mahmood Farhan , Nirenberg Sharon , Rendon Alexa , Yang Eunyoung , Xiang Jiani , Colombel Jean-Frédéric , Kahan Tamara , Ghiasian Ghoncheh , Faye Adam S , Levine Irving , Farber Michael , Ramada Michael , Omoakhe Tisor , Sultan Keith , Sachar David B
Published: January 2025

Background

Intravenous (IV) steroids are commonly used to treat acute flares of Crohn’s disease (CD). However, it is unclear if they are beneficial in the setting of uncomplicated small bowel obstruction (SBO). We sought to examine if IV steroid administration improved short-term outcomes in patients with CD hospitalized for acute, uncomplicated SBO across three New York City hospital systems.

Methods

This retrospective study included patients ≥ 18 years old admitted between January 1, 2011, and December 31, 2019, with Crohn’s disease and an admission diagnosis of uncomplicated acute SBO, defined as cases without adhesions, fistula, phlegmon, and sepsis. Primary endpoints (length of stay and frequency of surgery) were compared between patients who received IV steroids upon admission and those who did not.

Results

Our analysis included 674 unique patients. Ninety-two (14%) received IV steroids, and 582 (86%) did not. IV steroid use did not result in shorter hospital stays (median days [IQR]: 3.0 (2.0-5.5) days vs 3.0 (2.0-6.0) days in the no-steroid group, P = .65) or reduce the need for surgery (4 patients (4.4%) vs 28 patients (4.8%) in the no-steroid group, P = .85). Sex, age, disease duration, concomitant biologic therapy, and NG tube placement did not independently contribute to either outcome.

Conclusions

These findings suggest that IV steroid administration for uncomplicated SBO in CD patients does not decrease hospital length of stay or need for surgery. Further research may help identify specific obstruction patterns or other therapies associated with different outcomes.
Efficacy and Safety of Mirikizumab in the Treatment of Moderately to Severely Active Ulcerative Colitis Regardless of Baseline Modified Mayo Score: Results From the Phase 3 LUCENT Trials
Authors: Abraham Bincy , Wu Jianmin , Vermeire Séverine , Melmed Gil , Ungaro Ryan , Charabaty Aline , Moses Richard , Chan-Diehl Faye , Paulissen Jerome , Zhu Baojin , Barnes Edward L , Ehrlich Adam C , Rubin David T
Published: January 2025

Background

The modified Mayo score (mMS) is a measure for ulcerative colitis (UC) disease activity. Recent US Food and Drug Administration guidance for moderately to severely active UC trials suggests that patients should have baseline mMS of 5–9 including an endoscopy score of at least 2, opposed to the previous range of 4–9. This disclosure reports results from patients with UC with baseline mMS of 5–9 who received mirikizumab, a monoclonal antibody directed against the interleukin-23 p19 subunit, or placebo in the phase 3 LUCENT trials.

Methods

Mirikizumab was evaluated in the randomized, double-blind, placebo-controlled LUCENT-1 (NCT03518086) and LUCENT-2 (NCT03524092) trials, and the ongoing long-term LUCENT-3 (NCT03519945) trial, which use mMS 4-9. Analyses for patients with baseline mMS of 5-9 (excluding patients with mMS of 4) were conducted according to LUCENT trial statistical analysis plans. Categorical efficacy endpoints were summarized using proportions and confidence intervals. Continuous efficacy endpoints are presented as least-squares mean (standard error) changes from baseline.

Results

Mirikizumab demonstrated efficacy for the primary endpoint of clinical remission and major secondary endpoints including clinical response, endoscopic improvement, histologic–endoscopic mucosal improvement/remission, bowel urgency remission, and corticosteroid-free remission. Importantly, mirikizumab exhibited greater improvements versus placebo in the Inflammatory Bowel Disease Questionnaire, fatigue, symptomatic remission, and work productivity. Finally, mirikizumab demonstrated long-term (104-week) sustained, durable efficacy across all studied endpoints. No new safety signals were identified during 2-year follow-up.

Conclusions

Mirikizumab delivered significant clinical benefit for patients with baseline mMS of 5-9 and demonstrated a favorable safety profile.
Endocrine dysfunction in long-term survivors of pediatric head and neck rhabdomyosarcoma
Authors: Morfouace Michele , Schoot Reineke A , Hol Marinka L F , Minard-Colin Veronique , Kolb Frederic , Bollé Stephanie , Kayembe Matumba T , Gaze Mark N , Sandler Eric , Knops Rutger R G , Merks Johannes H M , Smeele Ludwig E , Indelicato Daniel J , Slater Olga , van Santen Hanneke M
Published: January 2025

Objective

Survivors of pediatric head and neck rhabdomyosarcoma (HNRMS) are at risk of developing endocrinopathies following local treatment, resulting from radiation damage to the pituitary gland, hypothalamus, or thyroid gland, often at a young age. Our aim was to determine the prevalence of endocrine dysfunction in long-term HNRMS survivors and compare the prevalence of anterior pituitary insufficiency (API) among different local treatment strategies: external beam radiation with photons, external beam radiation with protons, microscopically radical surgery combined with external irradiation, and macroscopic radical surgery combined with brachytherapy.

Design and methods

Head and neck rhabdomyosarcoma survivors treated between 1993 and 2017, with ≥2 years of follow-up, without recurrent disease or secondary malignancy were eligible for this study. The presence of any endocrine dysfunction was assessed cross-sectionally using Common Terminology Criteria of Adverse Events grading, anthropometrics, and biochemical testing. Retrospective chart review was added to this clinical assessment.

Results

Ninety-six survivors with long follow-up time (median, 9 years) were included. Any endocrinopathy was present in 35% of survivors, with 88% having pituitary, 6% peripheral (thyroid), and 6% combined insufficiencies. None had gonadal insufficiency. Growth hormone deficiency was diagnosed in 31 (32%) survivors, with additional pituitary insufficiencies in 12 (39%). In 8%, central precocious puberty preceded API. None of the survivors given brachytherapy had API.

Conclusions

The prevalence of pituitary dysfunction in HNRMS survivors is high, emphasizing the importance of systematic endocrine assessment during follow-up, including pubertal development and growth. Efforts should be made to further reduce extraneous irradiation to endocrine organs to prevent dysfunction later in life.
Fine-scale spatial variation in fitness, inbreeding, and inbreeding depression in a wild ungulate
Authors: Hewett Anna M , Johnston Susan E , Albery Gregory F , Morris Alison , Morris Sean J , Pemberton Josephine M
Published: January 2025

Environmental stress can exacerbate inbreeding depression by amplifying differences between inbred and outbred individuals. In wild populations, where the environment is often unpredictable and stress can be highly detrimental, the interplay between inbreeding depression and environmental variation is potentially important. Here, we investigate variation in inbreeding level, fitness and strength of inbreeding depression across a fine-scale geographic area (~12 km2) in an individually monitored population of red deer (Cervus elaphus). We show that northern regions of the study area have lower birth weights, lower juvenile survival rates, and higher inbreeding coefficients. Such fine-scale differences in inbreeding coefficients could be caused by the mating system of red deer combined with female density variation. We then tested for an inbreeding depression-by-environment interaction (ID × E) in birth weight and juvenile survival, by fitting an interaction term between the inbreeding coefficient and geographic location. We find that inbreeding depression in juvenile survival is stronger in the harsher northern regions, indicating the presence of ID × E. We also highlight that the ability to infer ID × E is affected by the variation in inbreeding within each geographic region. Therefore, for future studies on ID × E in wild populations, we recommend first assessing whether inbreeding and traits vary spatially or temporally. Overall, this is one of only a handful of studies to find evidence for ID × E in a wild population—despite its prevalence in experimental systems—likely due to intense data demands or insufficient variation in environmental stress or inbreeding coefficients.
The Correlation Between Fecal Amino Acids, Colonic Mucosal Taste Receptors, and Clinical Features and Indicators of Ulcerative Colitis: A Multicenter Exploratory Study
Authors: Liu Yixin , Sha Sumei , Ran Qiuju , Shi Haitao , Ma Juan , Qin Bin , Li Yingchao , Wang Ning , Liu Xin , Wang Jinhai , Li Lu , Liu Na , Quan Xiaojing
Published: January 2025

Background

Patients with ulcerative colitis (UC) exhibit abnormal amino acid (AA) metabolism. Taste receptors play a crucial role in the detection of intestinal AAs. Nevertheless, it remains unclear whether UC patients exhibit abnormal expression of these receptors in the colon.

Methods

An observational, multicenter study was conducted involving adult patients with active UC and healthy controls (HCs), recruited from July 2023 to March 2024. Fresh feces and rectosigmoid mucosal tissues were obtained from each participant. The concentrations of fecal AAs and the expression of taste receptors, including calcium-sensing receptor (CaSR), G protein-coupled receptor family C group 6 member A (GPRC6A), taste receptor type 1 member 1 (T1R1), and metabotropic glutamate receptor 4 (mGLuR4), in the colon were measured. Additionally, the correlation between colonic mucosal taste receptors and clinical characteristics was evaluated.

Results

Except for GPRC6A, the expression levels of CaSR, mGLuR4, and T1R1 in the colonic mucosa of UC patients were significantly elevated compared to HC. The expression of CaSR was negatively correlated with C-reactive protein and erythrocyte sedimentation rate (ESR). T1R1 expression positively correlated with defecation frequency and an Improved Mayo Endoscopic Score. The total and subtype concentrations of fecal AAs were elevated in UC patients and demonstrated a negative correlation with ESR and fecal calprotectin.

Conclusions

The increased levels of taste receptors and fecal AAs in the colon of UC patients suggest an abnormal nutrient-sensing mechanism, potentially playing a crucial role in the development of the disease.
Pharmacokinetics and pharmacodynamics of an innovative psychedelic N,N-dimethyltryptamine/harmine formulation in healthy participants: a randomized controlled trial
Authors: Mueller Michael J , Aicher Helena D , Dornbierer Dario A , Marten Laurenz , Suay Dila , Meling Daniel , Elsner Claudius , Wicki Ilhui A , Müller Jovin , Poetzsch Sandra N , Caflisch Luzia , Hempe Alexandra , Steinhart Camilla P , Puchkov Maxim , Kost Jonas , Landolt Hans-Peter , Seifritz Erich , Quednow Boris B , Scheidegger Milan
Published: January 2025

Background

Recent interest in the clinical use of psychedelics has highlighted plant-derived medicines like ayahuasca showing rapid-acting and sustainable therapeutic effects in various psychiatric conditions. This traditional Amazonian plant decoction contains N,N-dimethyltryptamine (DMT) and β-carboline alkaloids such as harmine. However, its use is often accompanied by distressing effects like nausea, vomiting, and intense hallucinations, possibly due to complex pharmacokinetic/pharmacodynamic (PK-PD) interactions and lack of dose standardization.

Methods

This study addresses these limitations by testing a novel pharmaceutical formulation containing pure forms of DMT and harmine in a double-blind, randomized, placebo-controlled trial with 31 healthy male volunteers. We evaluated PK-PD by monitoring drug and metabolite plasma levels, subjective effects, adverse events, and cardiovascular parameters. Each participant received 3 randomized treatments: (1) 100 mg buccal harmine with 100 mg intranasal DMT, (2) 100 mg buccal harmine with intranasal placebo, and (3) full placebo, using a repeated-intermittent dosing scheme, such that 10 mg of DMT (or placebo) was administered every 15 minutes.

Results

N,N-dimethyltryptamine produced consistent PK profiles with Cmax values of 22.1 ng/mL and acute drug effects resembling the psychological effects of ayahuasca with a duration of 2–3 hours. Likewise, buccal harmine produced sustained-release PK profiles with Cmax values of 32.5 ng/mL but lacked distinguishable subjective effects compared to placebo. All drug conditions were safe and well tolerated, indicating the formulation’s suitability for clinical applications.

Conclusions

This study underscores the potential of a patient-oriented pharmaceutical formulation of DMT and harmine to reduce risks and improve therapeutic outcomes in treating mental health disorders.

Clinical trial registration number

Neurodynamics of prosocial emotional processing following serotonergic stimulation with N,N-dimethyltryptamine (DMT) and harmine in healthy subjects (NCT04716335) https://clinicaltrials.gov/ct2/show/NCT04716335
The role of pallidal substance P and neurokinin receptors in the consolidation of spatial memory of rats
Authors: Kertes Erika , Péczely László , Ollmann Tamás , László Kristóf , Berta Beáta , Kállai Veronika , Zagorácz Olga , Kovács Anita , Szabó Ádám , Karádi Zoltán , Lénárd László
Published: January 2025

Background

The tachykinin substance P (SP) facilitates learning and memory processes after its central administration. Activation of its different receptive sites, neurokinin-1 receptors (NK1Rs), as well as NK2Rs and NK3Rs, was shown to influence learning and memory. The basal ganglia have been confirmed to play an important role in the control of memory processes and spatial learning mechanisms, and as part of the basal ganglia, the globus pallidus (GP) may also be involved in this regulation. SP-immunoreactive fibers and terminals, as well as NK1Rs and NK3Rs, were shown to be present in the GP.

Methods

The present study aimed to examine whether the SP administered into the GP can influence spatial memory consolidation in the Morris water maze (MWM). Therefore, male Wistar rats received a post-trial microinjection of 0.4 µLf 10 ng SP, 100 ng SP, or vehicle solution. The possible involvement of pallidal NK1Rs and NK3Rs in the SP effects was also studied by applying WIN51708 for NK1R antagonism and SR142801 as a selective NK3R antagonist.

Results

Our results showed that the lower dose of SP significantly decreased escape latency on the second day compared to control animals, while the higher dose was ineffective. Prior treatment with the NK1R antagonist WIN51708 could not block, while the NK3R antagonist SR142801 inhibited the effects of SP on memory consolidation in the MWM.

Conclusions

Our results are the first to demonstrate that SP improves consolidation of spatial memory in the GP, and this effect is mediated through NK3Rs but not NK1Rs.
Effectiveness of mRNA COVID-19 Vaccines and Hybrid Immunity in Preventing SARS-CoV-2 Infection and Symptomatic COVID-19 Among Adults in the United States
Authors: Feldstein Leora R , Ruffin Jasmine , Wiegand Ryan E , Borkowf Craig B , James-Gist Jade , Babu Tara M , Briggs-Hagen Melissa , Chappell James , Chu Helen Y , Englund Janet A , Kuntz Jennifer L , Lauring Adam S , Lo Natalie , Carone Marco , Lockwood Christina , Martin Emily T , Midgley Claire M , Monto Arnold S , Naleway Allison L , Ogilvie Tara , Saydah Sharon , Schmidt Mark A , Schmitz Jonathan E , Smith Ning , Sohn Ine , Starita Lea , Talbot H Keipp , Weil Ana A , Grijalva Carlos G
Published: January 2025

Background

Understanding protection against SARS-CoV-2 infection by vaccine and hybrid immunity is important for informing public health strategies as new variants emerge.

Methods

We analyzed data from 3 cohort studies spanning 1 September 2022 to 31 July 2023 to estimate COVID-19 vaccine effectiveness (VE) against SARS-CoV-2 infection and symptomatic COVID-19 among adults with and without prior infection in the United States. Participants collected weekly nasal swabs irrespective of symptoms, participated in annual blood draws, and completed periodic surveys, which included vaccination status and infection history. Swabs were tested molecularly for SARS-CoV-2. VE was estimated by Cox proportional hazards models for the hazard ratios of infections, adjusting for covariates. VE was calculated considering prior infection and recency of vaccination.

Results

Among 3344 adults, the adjusted VE of a bivalent vaccine against infection was 37.2% (95% CI, 12.3%–55.7%) within 7 to 59 days of vaccination and 21.1% (95% CI, −0.5% to 37.1%) within 60 to 179 days of vaccination when compared with participants who were unvaccinated or had received an original monovalent vaccine dose ≥180 days prior. Overall, the adjusted VE of a bivalent vaccine against infection, in conjunction with prior infection, was 62.2% (95% CI, 46.0%–74.5%) within 7 to 179 days of vaccination and 39.4% (95% CI, 12.5%–61.6%) at ≥180 days when compared with naive participants who were unvaccinated or had received a monovalent vaccine dose ≥180 days prior.

Conclusions

Adults with prior infection and recent vaccination had high protection against infection and symptomatic illness. Recent vaccination alone provided moderate protection.
Safety and efficacy of long-acting cabotegravir/rilpivirine versus standard oral antiretroviral therapy: a systematic review and meta-analysis
Authors: Manalu Samuel Bungaran Partahi Saud , Perez Navarro Andrea , Fairhead Cassandra , Hill Andrew
Published: January 2025

Background

In 2023, there were 39.9 million people living with HIV (PLWH) worldwide and 630 000 deaths related to HIV. New strategies are needed, and long-acting antiretrovirals (LAAs) are now widely considered to have great potential to help end the HIV epidemic. This systematic review and meta-analysis compare the safety and efficacy of LAA versus standard oral treatment (SOT) for HIV.

Methods

PubMed and Embase databases, supplemented by ClinicalTrials.gov and grey literature, were searched. Randomized controlled trials (RCTs) reporting efficacy and/or safety of LAA versus SOT for PLWH until June 2024 were included. Efficacy (HIV RNA < 50 copies/mL) and HIV RNA ≥ 50 copies/mL, adverse events (AEs), treatment discontinuation, CD4 count, metabolic parameters and drug resistance were assessed. Prespecified subgroup analyses were conducted. The risk of bias was assessed with Cochrane RoB 2.0. Certainty of evidence was assessed using GRADE.

Results

Six RCTs were eligible for inclusion, involving 2829 participants. LAA was non-inferior to SOT in suppressing HIV RNA < 50 copies/mL [Risk Difference (RD), −0.00; 95% CI, −0.03–0.02; P = 0.83; I2 = 51%; high quality of evidence (QoE)]. LAA was associated with higher drug resistance (percentage pooled estimate, 57%; 95% CI, 33%–78% versus 9%; 95% CI, 2%–30%; moderate QoE) and risk of grade 1–4 AEs than SOT [Risk Ratio (RR), 1.22; 95% CI, 1.12–1.33; P < 0.001; I2 = 62%; moderate QoE].

Conclusions

LAA has non-inferior efficacy compared to SOT. However, participants receiving LAA were at a higher risk of developing drug resistance, cross-resistance and AEs.
Optimizing decision-making potential, cost, and environmental impact of traps for monitoring olive fruit fly Bactrocera oleae (Rossi) (Diptera: Tephritidae)
Authors: Moreno-Alcaide Flora , Quesada-Moraga Enrique , Valverde-García Pablo , Yousef-Yousef Meelad
Published: January 2025

This work aimed to optimize olive fruit fly (OFF) Bactrocera oleae (Rossi) (Diptera: Tephritidae) monitoring and integrated management, thereby ensuring optimal and less-costly decision-making and timely intervention. Field trials in Andalusia (Spain) were undertaken over 2 years to optimize trap model, color, size, and density for the accurate determination of pest spatial distribution and damage as a function of olive cultivar. McPhail traps and yellow sticky panels outperformed the other 4 models with respect to the number of OFF captured. However, McPhail traps caught more natural enemies than yellow sticky panels and so sticky panels were selected to unravel the effect of color on the number of both OFF and natural enemies [hymenopteran parasitoids (Psyttalia concolor) and lacewings (Chrysopidae)] captured. Yellow sticky panels outperformed white, green, and blue ones for the number of OFF captured and captured the fewest natural enemies. When comparing the surface area of yellow sticky panels, 20 × 25 and 10 × 25 cm double-sided panels were equally effective at catching OFF. However, large double-sided yellow sticky panels caught significantly more natural enemies than the small double-sided panels, a key result for developing a less costly and environmentally friendly monitoring system. Furthermore, it was shown that the damage curve had a cultivar-based shape, i.e., for the same population size of OFF the damage caused varied depending on cultivar. Finally, 15 sticky panels per hectare were the optimal number for estimation of OFF spatial distribution. The present research provides key information for new trap design, OFF forecasting, and IPM development.
Establishing best practices for insect resistance management: a new paradigm for genetically engineered toxins in cotton expressing Mpp51Aa2
Authors: Reisig Dominic , Huseth Anders
Published: January 2025

Debate over resistance management tactics for genetically engineered (GE) crops expressing insecticidal toxins is not new. For several decades, researchers, regulators, and agricultural industry scientists have developed strategies to limit the evolution of resistance in populations of lepidopteran and coleopteran pests. A key attribute of many of these events was insecticide resistance management (IRM) strategies designed around a presumed high-dose expression sufficient to kill 99.5% of exposed larvae for some of the main target pests in corn, Zea mays L. and cotton, Gossypium hirsutum L. In contrast, other target pests did not meet this high-dose criterion. Similarly, the recent release of ThryvOn cotton that expresses thysanopteran and hemipteran active Mpp51Aa2.834_16 toxin is not high dose, working on a combination of behavioral and sublethal effects to suppress populations. This unique mode of control has generated considerable uncertainty about what IRM strategies will be most effective to limit field-evolved resistance to this unique spectrum of pests. The goal of this manuscript is to present several knowledge gaps that exist in proposed Mpp51Aa2 IRM plans, focusing on its activity on thrips, Frankliniella spp. Addressing these gaps will be crucial to limit resistance and preserve the benefits that this technology may provide by alleviating reliance on conventional insecticides and seed treatments. Broadly, these considerations will be important for future GE events that are non-high dose but remain valuable components of a more holistic insect management programs that integrate multiple tactics to reduce conventional insecticide use for challenging pests.
Development and reproduction of Grapholita molesta (Lepidoptera: Tortricidae) on the 3 artificial diets in the laboratory
Authors: Sun Xiaoting , Ge Shishuai , Chu Bo , He Wei , Yang Xianming , Wu Kongming
Published: January 2025

Grapholita molesta (Busck) (Lepidoptera: Tortricidae) is a major pest of many fruit trees. The large-scale artificial propagation technology of the insect is the basis for the field application of the sterile insect technique and biological control products based on host mass reproduction. However, a low-cost diet with easily accessible materials remains lacking. In this study, we assessed the insect rearing performance feeding on 3 artificial diets: D1: an artificial diet based on wheat bran and soybean powders; D2: an artificial diet based on soybean powder, maize powders, and tomato sauce; and D3: an artificial diet based on soybean powder, maize powder, tomato sauce, and wheat bran, with apples as a control, using 2-sex life table. At 26 ± 1 °C, 70 ± 5% humidity, and 16:8 h L:D photoperiod, the biological indicators of G. molesta fed D1 were consistent with those fed apples, with a larval stage of 14.88 d, a pupal stage of 7.57 d, adult longevity of 22.69 d, egg deposition count of 223.22, intrinsic rate of increase (r) of 0.1359, finite rate of increase (λ) of 1.1456, and net reproductive rate (R0) of 94.50. D1 was used to continuously rear G. molesta population for 5 generations, all life parameters remained normal. These results indicated that the artificial diet based on wheat bran and soybean powder could be used for rearing of the insect. This study proposes an available and cost-effective artificial diet for G. molesta, facilitating the application of green prevention and control technology.
Heterogeneity in Household Inflation Expectations and Monetary Policy
Authors: Doh Taeyoung , Lee Ji Hyung , Park Woong Yong
Published: January 2025

We empirically characterize the heterogeneity in the conditional distribution of household inflation expectations across demographic groups using the Survey of Consumer Expectations and also investigate how monetary policy shocks affect the conditional distribution. We find that, across all the groups, the peak of the group-specific distribution of household inflation expectations aligns closely with the 2% target set by the Federal Reserve, but there is substantial heterogeneity both within and across groups, primarily on the right. However, in response to a contractionary monetary policy shock identified by high-frequency financial market responses, households overall adjust their inflation expectations significantly downwards. In addition, the magnitude of the reaction is more pronounced in the upper quantile of low-income groups whose unconditional inflation expectations are less well anchored.
Acupuncture gone awry: surgical management of a popliteal artery pseudoaneurysm with concurrent abdominal aortic aneurysm
Authors: Asteguieta Sebastian , Diaz Q Carlos , Jacobs Luis P , Villeda Kelly , Estrada Sebastian
Published: January 2025

Popliteal artery pseudoaneurysms are rare, especially from acupuncture-related trauma. We report a 67-year-old male with hypertension, diabetes, chronic kidney disease, and an abdominal aortic aneurysm (AAA), who developed a popliteal pseudoaneurysm after acupuncture. Imaging confirmed the pseudoaneurysm and a 55 mm AAA. Urgent surgical repair with a Gore-Tex graft led to a smooth recovery. This case emphasizes the vascular risks of acupuncture and the importance of early diagnosis, multidisciplinary care, and personalized follow-up in patients with complex comorbidities.
Chronology of transcriptome and proteome expression during early Arabidopsis flower development
Authors: Álvarez-Urdiola Raquel , Matus José Tomás , González-Miguel Víctor Manuel , Bernardo-Faura Martí , Riechmann José Luis
Published: January 2025

The complex gene regulatory landscape underlying early flower development in Arabidopsis has been extensively studied through transcriptome profiling, and gene networks controlling floral organ development have been derived from the analyses of genome-wide binding of key transcription factors. In contrast, the dynamic nature of the proteome during the flower development process is much less understood. In this study, we characterized the floral proteome at different stages during early flower development and correlated it with unbiased transcript expression data. Shotgun proteomics and transcript profiling were conducted using an APETALA1 (AP1)-based floral induction system. A specific analysis pipeline to process the time-course proteomics data was developed. In total, 8924 proteins and 23 069 transcripts were identified. Co-expression analysis revealed that RNA–protein pairs clustered in various expression pattern modules. An overall positive correlation between RNA and protein level changes was observed, but subgroups of RNA–protein pairs with anti-correlated gene expression changes were also identified and found to be enriched in hormone-responsive pathways. In addition, the RNA-seq dataset reported here further expanded the identification of genes whose expression changes during early flower development, and its combination with previously published AP1 ChIP-seq datasets allowed the identification of additional direct and high-confidence targets of AP1.
Identification of a gene controlling levels of the copper response regulator 1 transcription factor in Chlamydomonas reinhardtii
Authors: Sun Xiaoqing , LaVoie Matthew , Lefebvre Paul A , Gallaher Sean D , Glaesener Anne G , Strenkert Daniela , Mehta Radhika , Merchant Sabeeha S , Silflow Carolyn D
Published: January 2025

Oxygen prevents hydrogen production in Chlamydomonas (Chlamydomonas reinhardtii), in part by inhibiting the transcription of hydrogenase genes. We developed a screen for mutants showing constitutive accumulation of iron hydrogenase 1 (HYDA1) transcripts in normoxia. A reporter gene required for ciliary motility placed under the control of the HYDA1 promoter conferred motility only in hypoxia. By selecting for mutants able to swim even in normoxia, we obtained strains that constitutively express the reporter gene. One identified mutant was affected in a gene encoding an F-box protein 3 (FBXO3) that participates in ubiquitylation and proteasomal degradation pathways in other eukaryotes. Transcriptome profiles revealed that the mutation, termed cehc1-1 (constitutive expression of hydrogenases and copper-responsive genes), triggers the upregulation of genes known to be targets of copper response regulator 1 (CRR1), a transcription factor involved in the nutritional copper signaling pathway and in the hypoxia response pathway. CRR1 was required for upregulating the HYDA1 reporter gene expression in response to hypoxia and for the constitutive expression of the reporter gene in cehc1-1 mutant cells. The CRR1 protein, normally degraded in Cu-supplemented cells, was stabilized in cehc1-1 cells, supporting the conclusion that CEHC1 facilitates CRR1 degradation. Our results describe a previously unknown pathway for CRR1 inhibition and possibly other pathways leading to complex metabolic changes.
The effect of conditional incentives in an email–web valuation survey of recreational anglers
Authors: Carter David W , Lovell Sabrina , Records David , Liese Christopher
Published: January 2025

Web surveys often suffer from low response rates when invitations are sent via email. We conducted an experiment testing the effects of a $5 Starbucks gift card incentive on response rates and survey results from an email–web survey of Gulf of Mexico recreational anglers. Half the sample was randomly assigned to be offered the incentive for completion of the survey. Despite this, response rates were nearly identical between the incentivized (12 percent) and non-incentivized (13 percent) groups. Respondent demographics, fishing trip characteristics, and econometric estimates were highly consistent across groups. Statistical tests could not reject the null of no difference between the incentive treatments. Our results suggest foregoing small conditional non-monetary incentives can be cost-effective for this type of specialized recreation survey using an email protocol. However, generalizability to other populations, incentives, and protocols requires further research. The non-monetary incentive did not meaningfully impact response rates or estimates in this context.
The Possible effect of Bosentan on the methotrexate-induced salivary gland changes in male rats: histological and Immunohistochemical study
Authors: Attarbashee Rana Khairi , Hamodat Heba Faiz , Mammdoh Jawnaa Khalid , Ridha-Salman Hayder
Published: January 2025

Methotrexate (MTX) is an antimetabolite drug utilized for managing a variety of cancers and autoinflammatory conditions. MTX may trigger detrimental effects in mout, h tissues, including salivary gland impairment. Bosentan (BOS), a drug that blocks endothelin receptors, has strengthened antioxidant, anti-inflammatory, and anti-apoptotic properties. The study aimed to estimate the protective effect of BOS on MTX-exacerbated salivary changes in Wistar Albino rats. Thirty male rats were arbitrarily sorted into three groups of ten animals each. The control group received a normal saline for 18 days. The MTX (induction) group received MTX (25 mg/kg) intraperitoneally on the 7th day of the experiment once daily for 6 consecutive days. The MTX + BOS group received BOS (50 mg/kg) orally once a day for 18 days: 6 days before induction, 6 days 2-h after induction, and 6 days post-induction. Animals were euthanized on day 19, and salivary gland tissues were dissected for biochemical, histopathological, and immunohistochemical analyses. BOS dramatically improved MTX-aggravated biochemical and histopathological abnormalities, as evidenced by diminished Bax, caspase 3, TNF-α, IL-1β, MDA, and MPO levels, increased SOD, GSH, and GPX levels, and reduced degenerative changes in the granular convolute tubule, mucous acini, and striate duct. BOS further substantially upregulated MTX-induced decline of the Ki-67 and Bcl-2, as indicated by immunohistochemistry scoring methods. The anti-oxidative, ant-inflammatory, and antiapoptotic properties of BOS are a promising strategy for ameliorating the toxic effect of MTX on submandibular glandular tissues.
A Supervised Home-Based Exercise Program to Improve Functional Performance in Women With Breast Cancer (Home-Pac): A Randomized Controlled Trial
Authors: Ramos Pedro G.F. , Júdice Pedro B. , Valadas Gabriela , Bento Alexandra , Nobre Inês , Rodrigues Bruno , Carraça Eliana V.
Published: January 2025

Background:

Endocrine therapy’s effects may hinder the functional performance and quality of life of women with breast cancer. Physical activity can counteract these effects, but this population does not regularly adopt it. This study aimed to test the impact of a 12-week home-based exercise intervention with a supervised component on the functional performance, quality of life, and physical activity of women with breast cancer undergoing endocrine therapy.

Methods:

Twenty-one women were initially randomized. Three participants were missing at random before the intervention started, leaving 18 with breast cancer stage I to III diagnosis, aged 18 to 75 years, receiving endocrine therapy, and reporting low to moderate activity levels. The study comprised a weekly online exercise session and, an exercise booklet intervention, and control group. Functional performance, quality of life, and physical activity were assessed. ANOVAs with repeated measures and Bonferroni-adjusted pairwise comparisons were conducted.

Results:

High adherence to program was observed (80%). Significant group-by-time interactions, favoring the intervention group, were found for functional performance—sit-to-stand (F = 19.64; P < .001; Eta2 = .55), arm curl (F = 13.01; P = .002; Eta2 = .45), and timed-up-go (F = 12.22; P = .003; Eta2 = .43); quality of life—insomnia (F = 6.05; P = 0.026; Eta2 = .27) and global health status (F = 6.81; P = .020; Eta2 = .31); and total physical activity (F = 5.95; P = .027; Eta2 = .27).

Conclusion:

The findings suggest that home-based exercise programs might be feasible and improve strength and overall mobility. These programs may contribute to increasing physical activity and quality of life of women with breast cancer. Further studies with larger samples are needed to confirm these findings.