bluuebunny/crossref_metadata_2025 huggingface dataset:
Collagen type III formation but not degradation is associated with risk of kidney disease progression and mortality after acute kidney injury
Authors: Sparding Nadja , Genovese Federica , Karsdal Morten Asser , Selby Nicholas M
Published: December 2024

Background

Acute kidney injury (AKI), a rapid decrease in kidney function, is associated with increased risk of adverse outcomes including development and progression of CKD. Kidney fibrosis is one of the pathological processes central to this AKI-to-CKD transition. Here we investigate the association of biomarkers of collagen type III turnover with adverse outcome following AKI.

Methods

We measured three biomarkers reflecting collagen type III (PRO-C3) formation and degradation (C3M and C3C) in plasma samples collected 1 year after an episode of AKI in 800 patients (392 patients with AKI and 408 non-AKI controls) from the prospective AKI Risk in Derby (ARID) study. Patients were followed until 3 years after the episode of AKI and the following outcomes were assessed: kidney disease progression, mortality, heart failure, cardiovascular events, and hospital readmission.

Results

PRO-C3 levels were elevated in the AKI group compared with the controls (P < .001), whereas C3M and C3C levels were not different between groups. In multivariate models including common risk factors, PRO-C3 was prognostic for kidney disease progression and mortality in the AKI group and for heart failure in the control group. C3M and C3C were not prognostic for any of the investigated outcomes.

Conclusions

Circulating PRO-C3, a biomarker of fibroblast activity, was prognostic for kidney disease progression and mortality when measured 1 year after an episode of AKI. Biomarkers of fibroblast activity may help patient stratification after an episode of AKI by identifying patients at higher risk of kidney disease progression.
Only the Bluesky is the limit: ten tips for a trending #Skytorial
Authors: Sethi Jasmine , Stauss Madelena , Mirioglu Safak , Floyd Lauren , Woywodt Alexander
Published: December 2024

Threaded online medical education first emerged on X (formerly Twitter) in early 2018 following the introduction of a threading feature in December 2017, with nephrologists quickly becoming enthusiastic adopters. However, changes like paid features and weakened content moderation have led many nephrologists and allied professionals to migrate to other platforms, which offer the potential for a more suitable environment for learning and discussion. The 2024 US presidential election and growing disillusionment with X has accelerated this shift. By late November 2024, Bluesky appears to have reached critical mass, and we propose that it will become a major social media platform in nephrology. To this end, we provide 10 tips to compose educational material for use on Bluesky. We suggest a clean break with regards to terminology and propose the term ‘skytorial’. Starter packs can help rebuild networks on Bluesky. Skytorials need to be planned with thought given to audience and scope. The first post is important: like a hook in fishing, it needs to interest the audience and establish contact. Emojis and visual content can be used to generate interest. Skytorials need to be concise and less is often more. Tagging and the use of hashtags is important, as is a good take-home message. Finally, it is important to check the entire skytorial before posting it. The arena of social media is constantly evolving and the future is difficult to predict. However, given the rapidly growing popularity of Bluesky, we believe nephrologists should now explore the opportunities of the new platform.
Predictive factors for failure of neoadjuvant docetaxel, cisplatin, and 5-fluorouracil therapy in esophageal squamous cell carcinoma
Authors: Terayama Masayoshi , Okamura Akihiko , Oki Akira , Kuriyama Kengo , Takahashi Naoki , Tamura Masahiro , Kanamori Jun , Udagawa Shohei , Shimozaki Keitaro , Osumi Hiroki , Fukuoka Shota , Ogura Mariko , Chin Keisho , Watanabe Masayuki
Published: December 2024

Recently, neoadjuvant chemotherapy comprising docetaxel, cisplatin, and 5-fluorouracil showed promising efficacy for esophageal squamous cell carcinoma. However, some patients do not achieve curative resection despite neoadjuvant chemotherapy using these drugs. This study aimed to clarify the pretherapeutic characteristics of these patients. We included 113 patients who underwent neoadjuvant chemotherapy with docetaxel, cisplatin, and 5-fluorouracil for potentially resectable esophageal squamous cell carcinoma and compared the clinical characteristics between patients who achieved curative resection (curative group) and those who failed to achieve curative resection after planned neoadjuvant chemotherapy (noncurative group). Moreover, we determined the factors predicting noncurative outcomes. Ninety-one (81%) and 22 patients (19%) were in the curative and noncurative groups, respectively. The noncurative group had significantly more tumors located in the upper third of the esophagus, larger-sized tumors, and borderline resectable tumors than the curative group (P = 0.003, 0.049, and <0.001, respectively). Moreover, the noncurative group had significantly higher serum squamous cell carcinoma antigen concentrations than the curative group (P = 0.008). Multivariable analysis identified tumor location in the upper third of the esophagus (odds ratio 7.31, P = 0.002), tumor size ≥50 mm (odds ratio 4.71, P = 0.037), and borderline resectable tumors (odds ratio 6.65, P = 0.003) as independent predictors for noncurative outcomes. Tumor location in the upper third of the esophagus, larger-sized tumors, and borderline resectable tumors might be significant predictors for noncurative outcomes in patients who received neoadjuvant chemotherapy with docetaxel, cisplatin, and 5-fluorouracil.
Impact of intraoperative recurrent laryngeal nerve monitoring on minimally invasive esophagectomy outcomes for esophageal cancer: a meta-analysis of case–control studies
Authors: Peyser Cardoso Rayner , Agarwal Lokesh , Cardoso Swizel Ann , Agarwal Ayushi , Varshney Vaibhav , Soni Subhash , Selvakumar B , Varshney Peeyush
Published: December 2024

Esophagectomy and lymphadenectomy for esophageal cancer carry an inherent risk of recurrent laryngeal nerve (RLN) injury. Intraoperative nerve monitoring (IONM) may help prevent RLN damage, though evidence on its effectiveness is still limited. This systematic review and meta-analysis (SRMA) evaluate the feasibility and efficacy of IONM during minimally invasive esophagectomy (MIE) for esophageal cancer. This SRMA followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines, with a registered protocol on PROSPERO (CRD42022367916). Two independent authors conducted a comprehensive literature search across multiple databases, screening studies on MIE for esophageal cancer using IONM. Case–control studies were included, focusing on the RLN palsy (RLNP) rate as the primary outcome. A total of 11 studies involving 1907 patients (IONM group: 752 patients; non-IONM group: 1155 patients) were included in the SRMA. IONM significantly reduced the incidence of RLNP (OR = 0.47, P < 0.001). Length of hospital stay (LOHS) and lower respiratory tract infection (LRTI) rates were significantly reduced with IONM use. No significant differences were observed in anastomotic leak, chylothorax, total number of lymph nodes dissected, operation time, aspiration rates, or intraoperative blood loss. The pooled sensitivity and specificity of IONM for detecting RLN injury were 83.3% and 81%, respectively. IONM during MIE significantly reduces the incidence of RLNP, postoperative LRTI, and shortens the LOHS, without adding operative risks. Further research is needed to evaluate its long-term survival benefits and cost-effectiveness.
When is it subfunctionalization and when is it not?
Authors: Birchler James A
Published: December 2024

New genes arise from duplication followed by divergence. The most common fate of a duplication is one copy is deleted to return to a single copy. But if divergence occurs, the function of the gene can be split between the two copies, which is called subfunctionalization, or a new function can arise, which is called neofunctionalization. Changes in expression between the two copies does not necessarily suggest that subfunctionalization has occurred. In this commentary, the caveats and criteria for subfunctionalization are discussed.
The hybrid history of zebrafish
Authors: McCluskey Braedan M , Batzel Peter , Postlethwait John H
Published: December 2024

Since the description of zebrafish (Danio rerio) in 1822, the identity of its closest living relative has been unclear. To address this problem, we sequenced the exomes of 10 species in genus Danio, using the closely related Devario aequipinnatus as outgroup, to infer relationships across the 25 chromosomes of the zebrafish genome. The majority of relationships within Danio were remarkably consistent across all chromosomes. Relationships of chromosome segments, however, depended systematically upon their genomic location within zebrafish chromosomes. Regions near chromosome centers identified Danio kyathit and/or Danio aesculapii as the closest relative of zebrafish, while segments near chromosome ends supported only D. aesculapii as the zebrafish sister species. Genome-wide comparisons of derived character states revealed that danio relationships are inconsistent with a simple bifurcating species history but support an ancient hybrid origin of the D. rerio lineage by homoploid hybrid speciation. We also found evidence of more recent gene flow limited to the high recombination ends of chromosomes and several megabases of chromosome 20 with a history distinct from the rest of the genome. Additional insights gained from incorporating genome structure into a phylogenomic study demonstrate the utility of such an approach for future studies in other taxa. The multiple genomic histories of species in the genus Danio have important implications for comparative studies in these morphologically varied and beautiful species and for our understanding of the hybrid evolutionary history of zebrafish.
Convergent Evolution Has Led to the Loss of Claw Proteins in Snakes and Worm Lizards
Authors: Holthaus Karin Brigit , Steinbinder Julia , Sachslehner Attila Placido , Eckhart Leopold
Published: December 2024

The evolution of cornified skin appendages, such as hair, feathers, and claws, is closely linked to the evolution of proteins that establish the unique mechanical stability of these epithelial structures. We hypothesized that the evolution of the limbless body anatomy of the Florida worm lizard (Rhineura floridana) and the concomitant loss of claws had led to the degeneration of genes with claw-associated functions. To test this hypothesis, we investigated the evolution of three gene families implicated in epithelial cell architecture, namely type I keratins, type II keratins, and genes of the epidermal differentiation complex in R. floridana in comparison with other squamates. We report that the orthologs of mammalian hair and nail keratins have undergone pseudogenization in R. floridana. Likewise, the epidermal differentiation complex genes tentatively named EDYM1 and EDCCs have been lost in R. floridana. The aforementioned genes are conserved in various lizards with claws, but not in snakes. Proteomic analysis of the cornified claws of the bearded dragon (Pogona vitticeps) confirmed that type I and type II hair keratin homologs, EDYM1 and EDCCs, are protein components of claws in squamates. We conclude that the convergent evolution of a limbless body was associated with the convergent loss of claw keratins and differentiation genes in squamates.
Application of the reverberation waveform inversion for the high-resolution sediment layer structure in the Pacific
Authors: Kim HyeJeong , Kawakatsu Hitoshi , Akuhara Takeshi , Takeuchi Nozomu , Isse Takehi , Shiobara Hajime , Sugioka Hiroko , Utada Hisashi , Kim YoungHee , Lee Sang-Mook
Published: December 2024

This study presents the velocity structures of the seafloor sediment across the Pacific using teleseismic body waves recorded by arrays of ocean bottom seismometers (OBSs). We apply the method inverting the multicomponent stacked autocorrelation functions and radial-component waveform of teleseismic body waves. We analyze OBSs distributed across the Pacific Ocean, through a wide range of water depths and equipped with various sensor types. The inverted models agreeing with measurements of seafloor drilling samples demonstrate the broad applicability of employing the inversion method to resolve sediment thicknesses ranging from <100 m to a few kilometers. In addition to various broad-band OBSs, we confirm our method works also for short-period sensors, since our retrieved the model using data from a short-period sensor in Northeast Japan agrees with active-source seismic survey analyses. The constrained models show various numbers of intrasediment discontinuities across different locations. Furthermore, the newly characterized sediment models have higher values of P-wave to S-wave velocity ratio (${{V}_P}$/${{V}_S}$) than the previously known scaling relationships, which suggests a larger effect of sediment-layer reverberation on the body-wave analysis than we have anticipated. The sediment velocity models obtained in this study produce Rayleigh-wave admittances that are consistent with those in previous studies but with much finer structural details within the sediment layer. The reverberation waveform inversion method will enable improved predictions of the impact of the water and sediment layers in body-wave records from existing and future OBS observations.
Coseismic deformation and kinematic rupture process of the 2023 Türkiye MW7.8–7.5 earthquake doublet deduced from high-rate GNSS observations
Authors: Dong Zhihua , Meng Guojie , Xu Yueyi , Wu Weiwei , Wei Congmin , Yang Yancong , Wang Yufan
Published: December 2024

On 2023 February 6, a devastating earthquake doublet struck in Türkiye, which caused tremendous damage including about 54 000 fatalities. We use high-rate global navigation satellite system (GNSS) data to study the coseismic static and kinematic displacement, and invert for fault slip distribution of the earthquake doublet. The maximum static coseismic displacements for the Mw7.8 (EQ1) and Mw7.5 earthquake (EQ2) are 0.38 and 4.4 m, respectively. The kinematic displacement recorded by GNSS stations reflect clearly the earthquake rupture process in more detail. We utilize 1-Hz GNSS waveforms, GNSS static displacements and surface rupture measurements to invert for the kinematic rupture model of the earthquake doublet. Our results show a rupture duration of ∼80 s, faulting length ∼350 km and maximum slip ∼7.4 m for EQ1, and a rupture duration of ∼35 s, rupture length ∼190 km and maximum slip ∼9.2 m for EQ2. The slip distributions inverted solely from GNSS coseismic deformation are basically consistent with the results from multisource data. The rupture velocity of EQ1 towards east is about 4.5 km s−1 towards the east and 3.2 km s−1 towards the west. EQ2 nucleates on Çardak fault with bilateral supershear rupture velocity of 5.0∼5.5 km s−1 within the first 0–12 s, subsequently transitioning to subshear rupture at a speed of 1.2 km s−1 towards the east and 3.0 km s−1 towards the west. Our finding of the bilateral supershear ruptures of EQ2 contrasts with the results of unilateral westward supershear rupture of previous studies. We think that this discrepancy could be attributed to the utilization of more geodetic data of the relatively denser GNSS stations in the east flank of EQ2’s epicentre and calculating the mean velocities for individual rupture intervals in this study.
Modelling the impact of hypoxia on critical essential fish habitats throughout the life cycle of exploited marine species
Authors: Champagnat Juliette , Brown Elliot John , Rivot Etienne , Le Pape Olivier
Published: December 2024

Spawning grounds and juvenile habitats are critical essential fish habitats (CEFH) facing multiple anthropogenic pressures. Yet the impacts of these pressures on fish population dynamics are poorly quantified. In this study, we address the impact of hypoxia on CEFH and its consequences on the productivity of exploited marine fish populations. Our approach relies on an age- and stage-structured simulation model, including habitat effects on egg, juvenile, or spawner mortalities to integrate the impact of hypoxia on spawning and juvenile habitats. We applied this framework in the Baltic Sea (BS) to explore population responses of cod, plaice, and herring, which face hypoxic conditions in their CEFH. All scenarios lead to modifications in fishing mortality, population size, and yield at maximum sustainable yield, but with different magnitudes depending on the impacted life stage. Perturbations of spawning habitats that result in higher mortality of eggs had the least impact, while the more direct effect on spawners themselves had the largest impact. Within each scenario, the responses also depended upon species and life history traits, with contrast in steepness and lifespan that explain most of the differences between species. Cumulative impacts of pressures in both CEFH were also investigated and revealed mainly nonadditive responses. Our framework is a generic tool, transferable to a large panel of case studies, to quantify the relative impact of CEFH degradation/restoration for the dynamics of marine exploited populations.
Impact of Late–Rainy Season Indoor Residual Spraying on Holoendemic Malaria Transmission: A Cohort Study in Northern Zambia
Authors: Martin Anne C , Chaponda Mike , Muleba Mbanga , Lupiya James , Gebhardt Mary E , Berube Sophie , Shields Timothy , Wesolowski Amy , Kobayashi Tamaki , Norris Douglas E , Impoinvil Daniel E , Chirwa Brian , Zulu Reuben , Psychas Paul , Ippolito Matthew , Moss William J ,   for the Southern and Central Africa International Center of Excellence for Malaria Research, Impoinvil Daniel E , Chirwa Brian , Zulu Reuben , Psychas Paul
Published: December 2024

Background

Indoor residual spraying (IRS) is a malaria control strategy implemented before the rainy season. Nchelenge District, Zambia, is a holoendemic setting where IRS has been conducted since 2008 with little impact on malaria incidence or parasite prevalence. Pre–rainy season IRS may not reduce the post–rainy season peak abundance of the major vector Anopheles funestus.

Methods

A controlled, pretest-posttest, prospective cohort study assessed the impact of late–rainy season IRS on malaria prevalence, incidence, hazard, and vector abundance. A total of 382 individuals were enrolled across 4 household clusters, of which 2 were sprayed in April 2022 toward the end of the rainy season. Monthly household and individual surveys and indoor overnight vector collections were conducted through August 2022. Multivariate regression and time-to-event analyses estimated the impact of IRS on outcomes measured by rapid diagnostic tests, microscopy, and quantitative polymerase chain reaction.

Results

Among participants, 72% tested positive by rapid diagnostic test at least once, and incidence by microscopy was 3.4 infections per person-year. Residing in a household in a sprayed area was associated with a 52% reduction in infection hazard (hazards ratio, 0.48; 95% CI, .29–.78) but not with changes in incidence, prevalence, or vector abundance. The study-wide entomologic inoculation rate was 34 infectious bites per person per year.

Conclusions

Monthly tracking of incidence and prevalence did not demonstrate meaningful changes in holoendemic transmission intensity. However, hazard of infection, which provides greater power for detecting changes in transmission, demonstrated that late–rainy season IRS reduced malaria risk.
Atomic Arguments and Counter-Arguments: How Exposure to Conflicting Information Influences American Public Support for the Use of Nuclear Weapons
Authors: Sagan Scott D , Valentino Benjamin A
Published: December 2024

In this paper, we introduce a novel approach for assessing the effectiveness of messaging designed to influence public opinion on the use of nuclear weapons. We argue that messages intended to decrease support for nuclear use are most effective when they meet three conditions. First, they must present subjects with novel counter-attitudinal information or interpretations that were not likely to be already incorporated into subjects’ opinions. Second, they must provide salient information that resonates with the values and concerns of subjects. Third, since, in the real world, the public is likely to hear both arguments and counterarguments for important policy issues, effective messages must be resilient, maintaining their effect even when respondents are exposed to strong, competing messages. We use this framework to test the effects of different messages about the legality of nuclear use, the military effectiveness of nuclear weapons, and the potential for setting precedents for nuclear use by others. We find that most messages have only modest and reversible effects. Alerting subjects to the possibility that using nuclear weapons might set a precedent making American adversaries more likely to use them in the future, however, produces the most significant reduction in support for nuclear use.
In vitro activity and genomic characterization of KPC-producing Klebsiella pneumoniae clinical blood culture isolates resistant to ceftazidime/avibactam, meropenem/vaborbactam, imipenem/relebactam: an Italian nationwide multicentre observational study (2022–23)
Authors: Bianco Gabriele , Boattini Matteo , Lupo Laura , Ambretti Simone , Greco Rita , Degl’Innocenti Linda , Chiatamone Ranieri Sofia , Fasciana Teresa , Mazzariol Annarita , Gibellini Davide , Antonelli Guido , Sacco Federica , Quirino Angela , Farina Claudio , Paglietti Bianca , Comini Sara , Fiamma Maura , Broccolo Francesco , Cavallo Rossana , Costa Cristina , Gaibani Paolo
Published: December 2024

Objectives

To evaluate the in vitro activity of ceftazidime/avibactam, meropenem/vaborbactam, imipenem/relebactam and comparators against KPC-producing Klebsiella pneumoniae (KPC-Kp) clinical isolates collected from a multicentre study in Italy (2022–23) and genomic characterization of the molecular mechanisms causing resistance.

Methods

Consecutive KPC-Kp isolates from blood cultures (n = 264) were collected from 14 hospital centres in the period 2022–23. Antimicrobial susceptibility testing was performed using broth microdilution. WGS was used to investigate KPC-Kp strains resistant to the new approved β-lactam/β-lactam inhibitor combinations (BLICs).

Results

Overall, meropenem/vaborbactam (95.1% susceptible by EUCAST and 93.9% susceptible by CLSI; MIC50 = 0.5 mg/L; MIC90 = 4 mg/L) and imipenem/relebactam (97% susceptible by EUCAST and 92.8% susceptible by CLSI; MIC50 = 0.25 mg/L; MIC90 = 0.5 mg/L) showed similar activity, followed by ceftazidime/avibactam (93.9% susceptible by both EUCAST and CLSI; MIC50 = 2 mg/L; MIC90 = 8 mg/L). Ten out of 13 (76.9%) KPC-Kp resistant to ceftazidime/avibactam carried a blaKPC variant including blaKPC-31, blaKPC-205, blaKPC-203 and blaKPC-93. Among KPC-Kp resistant to meropenem/vaborbactam and imipenem/relebactam, 90.9% (10/11) and 80% (4/5) harboured a WT carbapenemase (i.e. blaKPC-2 or blaKPC-3), respectively. All strains resistant to meropenem/vaborbactam and/or imipenem/relebactam carried truncated OmpK35 and/or mutated (ins135GD) OmpK36.

Conclusions

New BLICs were shown to be the most widely active therapeutic option against KPC-Kp clinical isolates collected in Italy. Ceftazidime/avibactam resistance is mainly driven by the expression of KPC variants, whereas the loss of function of the OmpK35 and OmpK36 porins appears to play a key but not exclusive role in the development of meropenem/vaborbactam and/or imipenem/relebactam resistance.
Impact of dietary supplementation of beef cows with rumen-protected methionine during the periconceptional period on prenatal growth and performance to weaning
Authors: Heredia Daniella , Tarnonsky Federico , Lopez-Duarte Maria C , Venturini Mauro , Podversich Federico , Ojeda-Rojas Oscar A , Peñagaricano Francisco , Chebel Ricardo C , Luchini Daniel , Hansen Peter J , DiLorenzo Nicolas , Gonella-Diaza Angela M
Published: December 2024

Changes in maternal nutrition during the periconceptional period can influence postnatal growth in cattle. This study aimed to identify the impact of supplementing beef cows with rumen-protected methionine (RP-Met) during the periconceptional period on their female progeny. In experiment 1, plasma methionine (Met) levels were analyzed in samples from 10 Angus crossbred, non-lactating beef cows. Cows were randomly assigned to receive 454 g of cottonseed meal with 15 g/d of RP-Met (RPM; Smartamine M, Adisseo) or not (CON) for 5 d and data were analyzed as a completely randomized design with repeated measures. A treatment-by-day interaction was observed (P < 0.001), where plasma Met concentrations increased in the RPM treatment yet remained basal in CON. In experiment 2, 114 cows were fed a roughage-based diet and randomized to receive 454 g/d of corn gluten supplemented with 15 g/d of RP-Met (RPM n = 56) or not (CON n = 58) from days −7 to 7 relative to timed-artificial insemination using sexed semen to obtain females. Amino acids were measured in plasma samples from days −8, 0, and 7 in cows. In the female progeny, body weight, withers height, body length, and heart girth were measured every 60 d from birth through weaning at an average age of 242 ± 5.8 d. Liver, adipose tissue, and longissimus dorsi muscle biopsies were collected at 187.88 ± 5.5 d of age and a subset of 20 random samples (CON = 10; RPM = 10) were selected for RNA-seq on each tissue. Data were analyzed using a generalized randomized block design with repeated measures. Methionine was increased (P < 0.01) in plasma from cows in the RPM treatment on days 0 and 7. After calving, 34 female calves (CON = 16; RPM = 18) remained in the study and no difference was observed in birth weights between treatments. Calves were taller at the withers for RPM than CON (P = 0.03; CON = 92 ± 1.0 cm; RPM = 95 ± 1 cm) but there were no effects of treatment on other measures of body size. A total of 30, 24, and 2 differentially expressed genes (DEGs; P < 0.01) were observed in liver, longissimus dorsi muscle, and adipose tissue respectively. In summary, feeding RP-Met to cows in the periconceptional period resulted in female calves that were taller than CON before weaning. There were DEGs in the tissue samples but no other changes in measurements associated with body size. In conclusion, supplementation of RP-Met to beef cows during the periconceptional period caused minor changes in the female offspring before weaning.
Drug detection in oral fluid and urine after single therapeutic doses of dexamphetamine, lisdexamphetamine, and methylphenidate in healthy volunteers
Authors: Helland Arne , Muller Sébastien , Spigset Olav , Krabseth Hege-Merete , Hansen Miriam , Skråstad Ragnhild Bergene
Published: December 2024

Dexamphetamine, lisdexamphetamine, and methylphenidate are central stimulant drugs widely used to treat attention-deficit/hyperactivity disorder (ADHD), but poor adherence may lead to treatment failure, and the drugs are also subject to misuse and diversion. Drug analysis in oral fluid may thus be useful for monitoring adherence and misuse. We measured drug concentrations in oral fluid and urine after controlled dosing to investigate detection windows and evaluate the chosen cutoffs. Healthy volunteers ingested single oral doses of 10 mg dexamphetamine (n = 11), 30 mg lisdexamphetamine (n = 11), or 20 mg methylphenidate (n = 10), after which they collected parallel oral fluid and urine samples every 8 h for 4–6 days. Amphetamine (analytical cutoff, oral fluid: 1.5 ng/mL; urine: 50 ng/mL), methylphenidate (oral fluid: 0.06 ng/mL), and ritalinic acid (urine: 500 ng/mL) were analyzed using fully validated chromatographic methods. The median time from ingestion to the last detection in oral fluid was 67 ± 4.9 h (lisdexamphetamine) and 69 ± 8.8 h (dexamphetamine) for amphetamine and 36 ± 2.5 h for methylphenidate. This was comparable to urine (77 ± 5.1 h for lisdexamphetamine, 78 ± 4.5 h for dexamphetamine, and 41 ± 2.4 h for ritalinic acid). The interindividual variability in detection times was large, probably in part due to pH-dependent disposition. Using a logistic regression approach, we found similar detection rates as a function of time since intake in urine and oral fluid with the chosen cutoffs, with a high degree of probability for detection at least 24 h after intake of a low therapeutic dose. This demonstrates the usefulness of oral fluid as a test matrix to assess adherence to ADHD medications, provided that the analytical method is sensitive, requiring a cutoff as low as 0.1 ng/mL for methylphenidate. Detection windows similar to those in urine may be achieved for amphetamine and methylphenidate in oral fluid.
Supernovae evidence for foundational change to cosmological models
Authors: Seifert Antonia , Lane Zachary G , Galoppo Marco , Ridden-Harper Ryan , Wiltshire David L
Published: December 2024

We present a new, cosmologically model-independent, statistical analysis of the Pantheon$+$ Type Ia Supernovae spectroscopic data set, improving a standard methodology adopted by Lane et al. We use the Tripp equation for supernova standardization alone, thereby avoiding any potential correlation in the stretch and colour distributions. We compare the standard homogeneous cosmological model, i.e. spatially flat $\Lambda$ cold dark matter ($\Lambda$CDM), and the timescape cosmology which invokes backreaction of inhomogeneities. Timescape, while statistically homogeneous and isotropic, departs from average Friedmann–Lemaître–Robertson–Walker evolution, and replaces dark energy by kinetic gravitational energy and its gradients, in explaining independent cosmological observations. When considering the entire Pantheon$+$ sample, we find very strong evidence ($\ln B\gt 5$) in favour of timescape over $\Lambda$CDM. Furthermore, even restricting the sample to redshifts beyond any conventional scale of statistical homogeneity, $z \gt 0.075$, timescape is preferred over $\Lambda$CDM with $\ln B\gt 1$. These results provide evidence for a need to revisit the foundations of theoretical and observational cosmology.
AntiBody Sequence Database
Authors: Malesys Simon , Torchet Rachel , Saunier Bertrand , Maillet Nicolas
Published: December 2024

Antibodies play a crucial role in the humoral immune response against health threats, such as viral infections. Although the theoretical number of human immunoglobulins is well over a trillion, the total number of unique antibody protein sequences accessible in databases is much lower than the number found in a single individual. Training AI (Artificial Intelligence) models, for example to assist in developing serodiagnoses or antibody-based therapies, requires building datasets according to strict criteria to include as many standardized antibody sequences as possible. However, the available sequences are scattered across partially redundant databases, making it difficult to compile them into single non-redundant datasets. Here, we introduce ABSD (AntiBody Sequence Database, https://absd.pasteur.cloud), which contains data from major publicly available resources, creating the largest standardized, automatically updated and non-redundant source of public antibody sequences. This user-friendly and open website enables users to generate lists of antibodies based on selected criteria and download the unique sequence pairs of their variable regions.
Navigating Illumina DNA methylation data: biology versus technical artefacts
Authors: Glaser Selina , Kretzmer Helene , Kolassa Iris Tatjana , Schlesner Matthias , Fischer Anja , Fenske Isabell , Siebert Reiner , Ammerpohl Ole
Published: December 2024

Illumina-based BeadChip arrays have revolutionized genome-wide DNA methylation profiling, pushing it into diagnostics. However, comprehensive quality assessment remains challenging within a wide range of available tissue materials and sample preparation methods. This study tackles two critical issues: differentiating between biological effects and technical artefacts in suboptimal quality samples and the impact of the first sample on the Illumina-like normalization algorithm. We introduce three quality control scores based on global DNA methylation distribution (DB-Score), bin distance from copy number variation analysis (BIN-Score) and consistently methylated CpGs (CM-Score) that rely on biological features rather than internal array controls. These scores, designed to be adjustable for different analysis tools and sample cohort characteristics, were explored and benchmarked across independent cohorts. Additionally, we reveal deviations in beta values caused by different sample rankings with the Illumina-like normalization algorithm, verified these with whole-genome methylation sequencing data and showed effects on differential DNA methylation analysis. Our findings underscore the necessity of consistently utilizing a pre-defined normalization sample within the ranking process to boost reproducibility of the Illumina-like normalization algorithm. Overall, our study delivers valuable insights, practical recommendations and R functions designed to enhance reproducibility and quality assurance of DNA methylation analysis, particularly for challenging sample types.
Challenging the narrative of Alport syndrome spectrum: no link with cystic phenotype
Authors: Pagniez Marie-Sophie , Lombardi Yannis , Fages Victor , Larrue Romain , Laboux Timothée , Gatinois Clémence , Letavernier Emmanuel , Rigothier Claire , Glowacki François , Mesnard Laurent , Robert Thomas
Published: December 2024

Background

Alport syndromes (AS) are the second leading genetic cause of kidney failure. Whether the multiple kidney cysts (MKC) phenotype belongs to the AS spectrum remains debated.

Methods

This multicenter retrospective study focused on patients genotyped with pathogenic COL4A3, COL4A4, or COL4A5 variants (classified as ACMG-AMP 4 or 5) between January 2011 and January 2023 across four French university hospitals. The study aimed to compare characteristics between two groups based on the presence or absence of MKC, defined by three or more cysts per kidney. The MKC group was compared to a control group with negative exome sequencing results for undetermined kidney disease (ES-UKD) to assess the association between MKC and AS.

Results

Among the 257 AS patients included, 38 (14.8%) presented MKC without variation from hereditary cystic kidney panel. MKC showed a significant association with male gender (P = 0.004), cardiovascular risk factors, and loss of function variants (P = 0.012). Kidney failure onset appeared significantly later, by 6 years, in MKC patients (P = 0.035). Comparison with the ES-UKD (n = 990) control group showed no significant association between AS and MKC by univariate and multivariate analysis. Multivariate analysis identified patient age and male gender (P < 0.001) as factors linked to MKC.

Conclusions

A 14.8% prevalence of MKC was found in our cohort of 257 patients with AS. MKC-AS patients exhibited clinical and histological characteristics akin to nephroangiosclerosis. Our comprehensive analysis, incorporating a sizable ES-UKD cohort, revealed no significant association between MKC and AS, thus questioning the inclusion of MKC within the spectrum of AS.
The Emergence of Tastes
Authors: Matthen Mohan
Published: December 2024

If the purpose of art is simply to create what is beautiful, it is strange that it takes such different forms in different cultures, and that people generally respond most positively to the artistic products of their own culture. Why are there diverse art forms? I offer a genealogical explanation. In this account, art is culturally coordinated behavior, where culture is a set of shared beliefs transmitted within a community. Culture evolves within local communities by divergence from earlier cultures—this pattern of divergence accounts for diversity. Conversely, if this pattern of divergence is traced backwards in time, we arrive at the ultimate ancestral forms that were the origin of all the local forms we find today. These common ancestors explain why, amidst diversity, there is a degree of cross-cultural commonality and appreciation.
Diversity, Equity, Inclusion, and Belonging
Authors: Starks Saundra H. , Cashwell Suzie T. , Ardrey Saundra Curry
Published: December 2024

Regarding the integration of diversity, equity, inclusion, and belonging (DEIB) in social work practice, rural community strengths are often their liabilities. Rural communities often function in tight-knit groups and have intergenerational connections that perpetuate values and actions that may be counterproductive to DEIB practice. Recent current events have resulted in a call for social work to develop anti-racism strategies and to strengthen DEIB practices. Diversity, equity, inclusion, and belonging are elements that make up the basis for a humane society in which people can grow and thrive. When a segment of society is blocked, then all of society is negatively impacted. Diversity—multiple identities—must include age, race, gender, ethnicity, ability, sexual orientation, religion, political ideology, and the myriad of ways that difference shows up among people. Equity is the redistribution of power and access that enables all people to acquire resources promoting their general welfare. Inclusion ensures all voices, thoughts, ideas, and perspectives are given respect and merit, which is critical to impact the political landscape that requires reshaping for effective DEIB practice. Belonging, which requires a safe space, means that multiple cultures, voices, thoughts, ideas, and perspectives are visible, present, and celebrated. Given the dynamics of rural communities, social workers at all system levels need to find creative ways to enhance DEIB practice. The call for the profession to change the knowledge base, values, and skills to a DEIB lens is now. This chapter explores challenges while presenting several strategies for integrating DEIB practice across systems levels.
Introduction
Authors: Berry Albert
Published: December 2024

Land, the key input for economies in the earlier stages of their development, is the source of much conflict, both physical and political. Its distribution is often highly unequal, typically implying severe inequality of income and welfare, both during development and into the future, as the level of inequality typically manifests a high degree of inertia over time. Explanations for high land concentration vary widely. One argument states that whoever has political, military, or physical power gets the land (or keeps the land). Another theory posits where high concentration exists, it signals the greater efficiency of larger units. This latter perspective has been increasingly contradicted by the evidence that such concentrations typically come with lower total output and a near consensus that it raises inequality.
Land Reform under Communist Regimes
Authors: Berry Albert
Published: December 2024

The land reforms in each of Russia, China, Vietnam, and Cuba occurred after revolutions unseated the traditional ruling group. Vietnam had previously been governed by France and, in Cuba, the US had a major influence. All were highly agricultural at the time of their reforms, except for Cuba. The number of deaths experienced during the revolutions was high in Russia and China, and later deaths were even higher due to Joseph Stalin’s paranoia and brutality in Russia, and in both cases due to serious miscalculations by leaders, which caused food shortages and famine. One initial mistake in all cases was to rely on collective farming of one sort or another, which kept productivity below potential. All four countries eventually pulled back from the collective/cooperative approach and returned operational control to families. In each case, the reform was part of a policy package designed to lower inequality and improve the welfare of the common people; inequality was reduced in all cases, although in the USSR and China it eventually rose again, reaching levels higher than those prior to the revolutions. Vietnam and Cuba have retained their low levels of inequality. Economic growth and poverty reduction were eventually very fast in China and Vietnam, but less so in the USSR and in Cuba, although, in the latter case, poverty was much lower at the time of the reform than in the other three. Vietnam, arguably, underwent the most successful of the four reforms.
The Agreement
Authors: Tannam Etain
Published: December 2024

This chapter sets out the three strands of the 1998 Belfast/Good Friday Agreement and its institutions. The Agreement’s three strands expressed the totality of relations that had permeated British–Irish strategy in Northern Ireland since Charles Haughey’s ‘teapot summit’ with Margaret Thatcher in 1980. The chapter explains how the 1998 Agreement encapsulates John Hume’s approach to resolving conflict in Northern Ireland, addressing three relationships, namely the internal nationalist–unionist relationship in Northern Ireland (Strand One), the cross-border Irish–Northern Irish relationship (North–South) (Strand Two), and the British–Irish relationship as a guardian of the totality of relations and the Agreement itself (Strand Three), and sets out conflicting concepts of sovereignty and interpretations of the Agreement.
Brexit and the European Union
Authors: Tannam Etain
Published: December 2024

This chapter provides an overview of the Brexit negotiations, the Northern Ireland Protocol that was part of its Withdrawal Agreement with the EU, and the tensions caused by it, The impact of Brexit on British–Irish relations cannot be overstated. The chapter highlights its destructive impact on the 1998 Agreement and analyses the role of the EU, the Irish government, and the UK government in the negotiations, where choices by all three at different times and to different degrees may have been ill-judged. The chapter ends by setting out the details of the Windsor Framework, highlighting how it differed from the Protocol, and the restoration of the devolved government in Northern Ireland.
Conclusion
Authors: Tannam Etain
Published: December 2024

This chapter summarises the book’s finding about the successes and failures of the 1998 and Brexit’s impact. In conclusion, it will be shown that, after 2007, the UK and Irish governments’ lack of understanding of the three-strands approach, as well as differences in interpretations of sovereignty, contributed to the Agreement’s weaknesses. The chapter ends by highlighting the salience of identity politics in the context of a referendum on a united Ireland. It emphasises the necessity of institutionalised British–Irish intergovernmental cooperation on the British–Irish Intergovernmental Conference and it recommends returning to the 1985 Intergovernmental Conference as a model to guide the governments about their roles. It also cautions against revising the Agreement.
Community Data
Authors: Bhargava Rahul
Published: December 2024

Community Data offers a new toolkit for data storytelling in community settings, one purpose-built for goals like inclusion, empowerment, and impact. Data visualization has spread into new domains it wasn’t designed for—community organizing, education, journalism, civic governance, and more. The dominant computational methods and processes, which have not changed in response, are causing significant discriminatory and harmful impacts, documented by leading scholars across a variety of populations. Informed by fifteen years of collaborations in academic and professional settings with nonprofits and marginalized populations, Community Data articulates a new approach for aligning the processes and media of data work with social good outcomes, learning from the practices of newspapers, museums, community groups, artists, and libraries. This book introduces a community-driven framework in response to the urgent need to realign data theories and methods around justice and empowerment to avoid further replicating harmful power dynamics and ensure everyone has a seat at the table in data-centered community processes. Community Data offers a broader toolbox for working with data and presenting it, pushing beyond the limited vocabulary of surveys, spreadsheets, charts, and graphs to arts-based practices such as data murals, data sculptures, data theatre, sonification, edibilization, smellification, and beyond.
The rationality of ineffective spin genus-4 theta-null loci
Authors: Zucconi Francesco
Published: December 2024

In this paper we show that the divisor in $S^{+}_g$ given by couples $[C,\theta]$, where C is a curve of genus 4 with a vanishing theta-null and θ is an ineffective theta-characteristic, is a rational variety. Actually we first show that for g = 4, the corresponding theta-null Prym divisor in ${\mathcal{R}}_4$ is rational.
Proper pushforwards on analytic adic spaces
Authors: Abe Tomoyuki , Lazda Christopher
Published: December 2024

We construct proper pushforwards for partially proper morphisms of analytic adic spaces. This generalises the theory due to van der Put in the case of rigid analytic varieties over a non-Archimedean field. For morphisms that are smooth and partially proper in the sense of Kiehl, we furthermore construct the trace map and duality pairing.
Focusing on ligamentous soft tissue inflammation for the future understanding of early axial psoriatic arthritis
Authors: Abacar Kerem , Rennie Winston J , Raychaudhuri Siba P , Chaudhari Abhijit J , McGonagle Dennis
Published: December 2024

Imaging has transformed the understanding of inflammatory and degenerative arthritis in both peripheral and axial disease. In axial inflammation, fat suppression magnetic resonance imaging (MRI) has unravelled the role of sub-fibrocartilaginous osteitis in axial spondyloarthritis and the role of peri-entheseal vertebral body osteitis and subsequent spinal new bone formation. Established or late-stage axial psoriatic arthritis (PsA) cases often exhibit impressive para-marginal or chunky syndesmophytosis on conventional X-ray that pathologically represents entheseal soft tissue ossification. However, the spinal entheseal soft tissue and contiguous ligamentous tissues are poorly visualized on MRI in subjects with early inflammatory back pain including those with axial PsA. In this article, we highlight the need for imaging modalities to discern the crucial soft tissue “ligamentous” component of axial PsA towards diagnosis, prognosis and therapy validation. We issue a clarion call to focus advanced imaging methodology on spinal ligamentous soft tissue that represents the last hidden backwater of PsA immunopathology that needs visualization to fully decipher axial PsA pathogenesis. This in combination with the existing ability to visualize ligamentous bony anchorage site osteitis is needed to define a gold standard test for axial PsA.