bluuebunny/crossref_metadata_2025_split huggingface dataset:
Habitat edges decrease plant reproductive output in fragmented landscapes
Authors: Hulting Katherine A. , Brudvig Lars A. , Damschen Ellen I. , Levey Douglas J. , Resasco Julian , Tewksbury Joshua J. , Haddad Nick M. 
Published: November 2024

Abstract

Habitat loss is a major threat to biodiversity, but the effects of habitat fragmentation are less clear. Examining drivers of key demographic processes, such as reproduction, will clarify species‐level responses to fragmentation and broader effects on biodiversity. Yet, understanding how fragmentation affects demography has been challenging due to the many ways landscapes are altered by co‐occurring habitat loss and fragmentation, coupled with the rarity of experiments to disentangle these effects.

In a large, replicated fragmentation experiment with open savanna habitats surrounded by pine plantation forests, we tested the effects of inter‐patch connectivity, patch edge‐to‐area ratio, and within‐patch distance from an edge on plant reproductive output. Using five experimentally planted species of restoration interest—three wind‐pollinated grass species and two insect‐pollinated forb species—we measured plant flowering, pollination rate, and seed production.

All plant species were more likely to flower and produce more flowering structures farther from the forest edge. Connectivity and distance from an edge, however, had no effect on the pollination rate (regardless of pollination mode). Despite no influence of fragmentation on pollination, plant seed production increased farther from the edge for four of five species, driven by the increase in flower production.

Synthesis. Altogether, we demonstrate that plant reproductive output (seed production) is decreased by habitat fragmentation through edge effects on flowering. Our work provides evidence that an important contributor to plant demography, reproductive output, is altered by edge effects in fragmented patches. These species‐level impacts of fragmentation may provide insight into the mechanisms of fragmentation effects on community‐level changes in biodiversity.
Craft in an age of creativity: disengagement as a new mode of craftsmanship among traditional potters in Japan
Authors: Lee Shilla 
Published: November 2024

AbstractEmbedded within Japan's demographic and economic stagnation, traditional craftsmanship unexpectedly aligns with the discourse of creativity. This study delves into the intricacies of this convergence through ethnographic details, shedding light on how endeavours to preserve local crafts intertwine with the burgeoning discourse of creativity within public policy frameworks, thereby shaping a nuanced understanding of craftsmanship. The study draws on fieldwork conducted in 2018‐19 in Tamba Sasayama, Japan, focusing on the participation of Tamba potters in a regional revitalization initiative promoting the slogan of rural creativity. Initially, promotional activities were perceived as distractions hindering their ability to maintain the pace of their work, such as monitoring the changing state of the clay through various stages of the craft (i.e. throwing, drying, and firing), an aspect they considered fundamental to craftsmanship. However, the growing acknowledgement of public support accompanying their engagement prompted a reassessment, transforming distraction into a skill emblematic of flexible ‘disengagement’. The analysis of disengagement as a new virtue of craftsmanship reveals the pragmatic approach the potters uphold and the creative trajectory of traditional craftsmanship amidst the demographic crisis.
Effect of Transferrin‐Modified Fe3O4 Nanoparticle Targeted Delivery miR‐15a‐5p Combined With Photothermal Therapy on Lung Cancer
Authors: Lan Xiaoxu , Wang Xiao , Shao Liying , An Jiayue , Rong Simin , Yang Xiancong , Sun Hongfang , Liang Yan , Wang Ranran , Xie Shuyang , Li Youjie 
Published: November 2024

ABSTRACTBackgroundExisting studies have shown that transferrin receptor (TfR) is highly expressed on the surface of lung cancer cells, and nanoparticles (NPs) have been widely used as delivery vehicles. The aim of this study was to investigate the effect of the targeted delivery of Fe3O4 NPs modified with transferrin (Tf) compared with photothermal treatment for lung cancer.MethodsThe morphology and properties of Fe3O4 NPs modified with Tf were tested by internal morphological characterization experiments including transmission electron microscopy, particle size meter infrared spectrometer and other experiments. The delivery of materials was investigated by cell proliferation and apoptosis experiments, and western blot experiment was used to detect yes‐associated protein 1(YAP1) protein expression changes after delivering miR‐15a‐5p. In addition, animal models were constructed to further explore the targeting properties of the material.ResultsThe results demonstrated that the nanomaterial has good stability and targeting properties. Meanwhile, we also discovered that the miR‐15a‐5p carried by NPs can inhibit cell growth after its entry to the lung cancer cells. The effect became more evident when the nanomaterials were assisted with laser therapy, as verified by in vivo and in vitro experiments. In terms of the related mechanism, miR‐15a‐5p inhibited YAP1 expression, which affected cell proliferation and apoptosis.ConclusionIn this study, Fe3O4 NPs modified with Tf delivered miR‐15a‐5p in combination with photothermal therapy for lung cancer. In future research, the targeted delivery of Tf and the photothermal synergy of nanomaterials will provide a theoretical basis for cancer treatment.
Epigenetic age acceleration predicts subject‐specific white matter degeneration in the human brain
Authors: Newman Benjamin T. , Danoff Joshua S. , Lynch Morgan E. , Giamberardino Stephanie N. , Gregory Simon G. , Connelly Jessica J. , Druzgal T. Jason , Morris James P. 
Published: November 2024

AbstractEpigenetic clocks provide powerful tools for estimating health and lifespan but their ability to predict brain degeneration and neuronal damage during the aging process is unknown. In this study, we use GrimAge, an epigenetic clock correlated to several blood plasma proteins, to longitudinally investigate brain cellular microstructure in axonal white matter from a cohort of healthy aging individuals. A specific focus was made on white matter hyperintensities, a visible neurological manifestation of small vessel disease, and the axonal pathways throughout each individual's brain affected by their unique white matter hyperintensity location and volume. 98 subjects over 55 years of age were scanned at baseline with 41 returning for a follow‐up scan 2 years later. Using diffusion MRI lesionometry, we reconstructed subject‐specific networks of affected axonal tracts and examined the diffusion cellular microstructure composition of these areas, both at baseline and longitudinally, for evidence of cellular degeneration. A chronological age‐adjusted version of GrimAge was significantly correlated with baseline WMH volume and markers of neuronal decline, indicated by increased extracellular free water, increased intracellular signal, and decreased axonal signal within WMH. By isolating subject‐specific axonal regions “lesioned” by crossing through a WMH, age‐adjusted GrimAge was also able to predict longitudinal development of similar patterns of neuronal decline throughout the brain. This study is the first to demonstrate WMH lesionometry as a subject‐specific precision imaging technique to study degeneration in aging and the first to establish a relationship between accelerated epigenetic GrimAge and brain cellular microstructure in humans.
Ultrasound visualization and blood flow velocity measurements of the adrenal arteries in the fetus
Authors: Bergøy Øystein , Kiserud Torvid , Kessler Jørg , Dalen Ingvild , Økland Kristine Moi , Sande Ragnar Kvie 
Published: November 2024

AbstractIntroductionDetection and surveillance of fetal growth restriction (FGR) is well established, but there is still room for improvement. Animal studies indicate that compromised fetuses increase adrenal blood flow. Modern ultrasound equipment allows us to measure vascular impedance in the fetal adrenal arteries despite their modest size. However, extensive anatomical variance is a challenge to standardizing measurements. We set out to improve this.Material and MethodsWe included 75 low‐risk pregnant women in a prospective cross‐sectional study aiming to develop a reliable technique to visualize and measure flow velocity in human fetal adrenal arteries. We used commercially available ultrasound equipment: a GE Voluson 10 2019 with a C2‐9 probe (GE Healthcare, Zipf, Austria), and a Philips Epiq Elite with a V9‐2 probe (Philips Medical Systems International B.V., Best, The Netherlands), exploiting the modern sensitive power Doppler modes in both scanners to visualize small vessels.ResultsAmong 72 fetuses, the inferior adrenal artery was the most consistently visualized and measured artery to the gland. Doppler velocimetry was achieved in 66 (92%) participants. We found the anatomical variation described previously but were able to develop visualization strategies to identify the common arteries and use a consistent Doppler technique for the second half of pregnancy.ConclusionsIt is possible to visualize and measure flow velocity in the adrenal arteries of human fetuses. The success rate was highest for the inferior adrenal artery making this vessel a candidate for clinical studies.
Impact of Nonalcoholic Fatty Liver Disease on the Survival of People Living With HIV
Authors: Macias Juan , Frias Mario , Pineda Juan Antonio , Corona‐Mata Diana , Corma‐Gomez Anais , Rivero‐Juarez Antonio , Santos Marta , García‐Deltoro Miguel , Rivero Antonio , Ricart‐Olmos Carmen , Gonzalez‐Serna Alejandro , Real Luis Miguel 
Published: November 2024

ABSTRACTBackgroundNonalcoholic fatty liver disease (NAFLD) is an increasing concern for people living with HIV (PLWH). However, information on the impact of NAFLD on the prognosis of PLWH is very scarce.AimsTo investigate the influence of NAFLD on the overall and liver‐related mortality in PLWH.MethodsPLWH followed in three Spanish centres were included in a prospective cohort at the date of the first transient elastography evaluation. Survival data were recorded, and the causes of death were centrally monitored. The risk of all‐cause death and liver‐related death was evaluated by applying time‐to‐event analyses.ResultsA total of 2151 PLWH were included in the cohort and followed for a median (Q1–Q3) of 7.3 (3.5–10.4) years. There were 174 (8.1%) deaths. The probability of overall death and liver‐related death was associated with liver stiffness measurement (LSM) and with FibroScan‐AST (FAST) score. Among 844 PLWH with potential for NALFD, LSM was independently associated with all‐cause mortality (adjusted hazard ratio [AHR], by 1 kPa increase: 1.06; 95% confidence interval [95% CI]: 1.04–1.08; p < 0.001). In a separate model and after adjustment, FAST score ≥ 0.67 was related to survival (AHR: 1.87; 95% CI: 1.40–2.50; p < 0.001). The AUROC (95% CI) of the models were based on LSM, 0.812 (0.739–0.885); and FAST, 0.825 (0.753–0.897) (p = 0.386).ConclusionsFor PLWH, advanced liver fibrosis increases the risk of overall death and liver‐related death. LSM and the FAST score are similar predictors of survival for PLWH with potential for NAFLD.
Inequalities in geographic barriers and patient representation in lymphoma clinical trials across England
Authors: Jones David A. , Spencer Katie , Ramroth Johanna , Probert Jake , Roope Laurence S. J. , Shakir Rebecca , Broggio John , Burroughs Frank , Collins Graham P. , Clarke Philip M. , Wolstenholme Jane L. , Cutter David J. 
Published: November 2024

SummaryThe distribution of trial site locations may lead to disparities in geographic access and affect patient representativeness in clinical trials. We utilised trial data covering 1993–2022 from the National Institute for Health and Care Research (NIHR) Open Data Platform, 2011 and 2021 English Census and geographic data and English individual‐patient cancer registry data for patients diagnosed with lymphoma between 1997 and 2017. To assess representation, we compared patient age and sex between trial participants and the incident population. We mapped the distance and travel times of English lower layer super output areas (LSOAs) to their nearest research active NHS Trusts and assessed associations between distance and travel times and the geographic and sociodemographic characteristics of the LSOAs. Trial participants were younger than the incident population and more likely to be male. The closest NHS Trust to more than half of English LSOAs was not research active. Greater LSOA mean age, male percent, White British percent, rurality and coastal/border status were positively associated with distance and travel time (at prespecified p < 0.05 level), while greater deprivation was negatively associated. Female and older lymphoma patients in England are underrepresented in trials, with the latter facing a higher burden of geographic barriers.
Efficacy and safety of bendamustine, rituximab and bortezomib treatment in relapsed/refractory Waldenstrom Macroglobulinaemia: results of phase 2 single‐arm FIL‐BRB trial
Authors: Benevolo Giulia , Drandi Daniela , Villivà Nicoletta , Castiglione Anna , Monaco Federico , Boccomini Carola , Dessi Daniela , Califano Catello , Curreli Luigi , Cavallo Federica , Conconi Annarita , Gaidano Gianluca , Rossi Francesca Gaia , Caravita di Toritto Tommaso , Ferrante Martina , Mannina Donato , Tosi Patrizia , Pietrantuono Giuseppe , Musuraca Gerardo , Merli Michele , Sartori Roberto , Tani Monica , Freilone Roberto , Varettoni Marzia , Ferrero Simone 
Published: November 2024

SummaryThis multicentre phase II study Fondazione Italiana Linfomi (FIL)‐bortezomib plus rituximab plus bendamustine (BRB) tested a combination of bendamustine (90 mg/m2 on days 1–2), rituximab (375 mg/m2 intravenously on day 1) and bortezomib (1.3 mg/m2 sc on days 1, 8, 15, 22) every 28 days for six cycles in 38 symptomatic patients with relapsed/refractory Waldenstrom macroglobulinaemia (RR‐WM). Moreover, MYD88L265P and CXCR4S338X mutations were tested by droplet digital polymerase chain reaction (ddPCR) both at baseline and at the end of treatment in 21 patients. Overall response rate at the end of therapy was 84.6%, including 4 (11%) complete remission, 15 (39%) very good partial response, 12 (32%) partial responses according to IWWM response criteria. At 18, 24 and 30 months, progression‐free survival was 84.2% (95% CI 68.2%–92.6%), 81.5% (95%CI 65.1–90.7) and 78.8% (95%CI 62.0–88.8) respectively. At 18 months, the Overall survival was 92.1% (95%CI 77.5%–97.4%). Overall, 19 patients (50%) experienced grade 3–4 haematological toxicity, mainly thrombocytopenia, and grade 1–3 neuropathy rate was about 10% and required bortezomib dose reduction but did not result in treatment interruption. Moreover, BRB treatment induced the high rates of undetectable molecular minimal residual disease (MRD) at the end of the therapy. BRB regimen used as second line is an effective and well‐tolerated salvage treatment for relapsed refractory Waldenstrom macroglobulinaemia patients. MRD monitoring showed promising efficacy in clearing the residual disease.
Psychological needs related to civil inattention: A qualitative and quantitative view on public encounters
Authors: Diefenbach Sarah , Riehle Anna , Jannott Hannah , Vornhagen Joëlle‐Sophie , Stoll Johannes , Markhoff Lea , von Terzi Pia 
Published: November 2024

AbstractAs described by early sociological research (Goffman, 1963, Behavior in public places: Notes on the social organization of gatherings), a typical behavioural pattern in public encounters between strangers is so‐called Civil Inattention (CI). CI describes a ritual of politely communicating having noticed the other while assuring non‐communication intentions. A typical example of showing CI is initially looking at the other person but then quickly averting the gaze. As argued earlier, CI fulfils a central role in the smooth functioning of a society. Also, CI gains new relevance in the digital era, in particular regarding privacy needs. Still, previous research on CI often remained on a theoretical or descriptive level, and its psychological functions have not been explored systematically. As an advancement, our study provides a deeper understanding of CI, exploring individual narratives, relevant psychological needs, and contextual factors. We conducted a qualitative interview study (N = 25) followed by an experimental online study (N = 353) with a 2 (presence of CI) × 2 (physical distance) mixed design. It shows that CI adds to well‐being and specifically addresses needs for relatedness, security, and autonomy. However, though Study 1 suggested physical distance as a relevant contextual factor, the present experimental manipulation in Study 2 did not show significant effects.
Cross‐pathway integration of cAMP signals through cGMP and calcium‐regulated phosphodiesterases in mouse striatal cholinergic interneurons
Authors: Bompierre Ségolène , Byelyayeva Yelyzaveta , Mota Elia , Lefevre Marion , Pumo Anna , Kehler Jan , Castro Liliana R. V. , Vincent Pierre 
Published: November 2024

AbstractBackground and PurposeAcetylcholine plays a key role in striatal function. Firing properties of striatal cholinergic interneurons depend on intracellular cAMP through the regulation of Ih currents. Yet, the dynamics of cyclic nucleotide signalling in these neurons have remained elusive.Experimental approachWe used highly selective FRET biosensors and pharmacological compounds to analyse the functional contribution of phosphodiesterases in striatal cholinergic interneurons in mouse brain slices.Key ResultsPDE1A, PDE3A and PDE4 appear as the main controllers of cAMP levels in striatal cholinergic interneurons. The calcium signal elicited through NMDA or metabotropic glutamate receptors activates PDE1A, which degrades both cAMP and cGMP. Interestingly, the nitric oxide/cGMP pathway amplifies cAMP signalling via PDE3A inhibition—a mechanism hitherto unexplored in a neuronal context.Conclusions and ImplicationsThe expression pattern of specific PDE enzymes in striatal cholinergic interneurons, by integrating diverse intracellular pathways, can adjust cAMP responses bidirectionally. These properties eventually allow striatal cholinergic interneurons to dynamically regulate their overall activity and modulate acetylcholine release. Remarkably, this effect is the opposite of the cGMP‐induced inhibition of cAMP signals involving PDE2A in striatal medium‐sized spiny neurons, which provides important insights for the understanding of signal integration in the striatum.
Skipping of Exon 20 in EP300: A Novel Variant Linked to Rubinstein–Taybi Syndrome With Atypical and Severe Clinical Manifestations
Authors: Pavinato Lisa , Carestiato Silvia , Trajkova Slavica , Sorasio Lorena , Mantovani Giovanna , De Sanctis Luisa , Kerkhof Jennifer , McConkey Haley , Rzasa Jessica , Todd Emily , Balzo Maria , Cardaropoli Simona , Bruselles Alessandro , De Rubeis Silvia , Buxbaum Joseph D. , Tartaglia Marco , Sadikovic Bekim , Ferrero Giovanni Battista , Brusco Alfredo 
Published: November 2024

ABSTRACTRubinstein–Taybi syndrome (RSTS) is a rare autosomal dominant neurodevelopmental disorder linked to haploinsufficiency of CREBBP (RSTS1) and EP300 (RSTS2) genes. Characteristic features often include distinctive facial traits, broad thumbs and toes, short stature, and various degrees of intellectual disability. The clinical presentation of RSTS is notably variable, making it challenging to establish a clear genotype–phenotype correlation, except for specific variants which cause the allelic Menke–Hennekam syndrome. Trio exome analysis, data collection via networking and GeneMatcher platforms, transcript processing analysis, and DNA methylation profiling were performed. We identified two unrelated patients with de novo variants in EP300 (NM_001429.4: c.3671+5G>C; c.3671+5_3671+8delGTAA) predicted to cause in‐frame exon 20 skipping, confirmed in one patient. In silico 3D protein modeling suggested that exon 20 deletion (comprising 27 amino acids) likely alters the structural conformation between the RING_CBP‐p300 and HAT‐KAT11 domains. Clinically, both patients displayed severe RSTS2‐like clinical features, including autism spectrum disorder, speech delay, hearing loss, microcephaly, developmental delay, and intellectual disability, alongside ocular, respiratory, and cardiovascular abnormalities. Additionally, one patient developed early‐onset colorectal cancer. DNA methylation profiling in Subject #1 confirmed RSTS but did not align with the specific episignatures for RSTS1 or RSTS2. We propose that skipping of exon 20 in EP300 is associated with a distinct form of Rubinstein–Taybi syndrome featuring clinical characteristics not fully aligning with RSTS1 or RSTS2. Our findings increase the understanding of RSTS genetic and molecular basis and stress the need for further research to establish definitive genotype–phenotype correlations.
High‐protein vegan and omnivorous diets improve peripheral insulin sensitivity to a similar extent in people with type 2 diabetes
Authors: Whelehan Gráinne , Dirks Marlou L. , West Sam , Abdelrahman Doaa R. , Murton Andrew J. , Finnigan Tim J. A. , Wall Benjamin T. , Stephens Francis B. 
Published: November 2024

AbstractBackgroundHigh‐protein diets have been recognized as a potential strategy in the nutritional management of type 2 diabetes (T2D). Mycoprotein is a high‐fibre, high‐protein food ingredient previously shown to improve acute glycaemic control. We determined whether incorporating mycoprotein into a high‐protein vegan diet would improve glycaemic control to a greater extent than an isonitrogenous omnivorous diet in people with T2D.MethodsSeventeen adults (f = 5, age = 58.3 ± 8.3 years, BMI = 32.9 ± 4.7 kg∙m−2, HbA1c = 60 ± 15 mmol∙mol−1) with T2D were randomly allocated to a 5‐week eucaloric high‐protein (30% energy from protein) diet, either an omnivorous diet (OMNI; 70% protein from omnivorous sources) or an isonitrogenous, mycoprotein‐rich, vegan diet (VEG; 50% protein from mycoprotein). Glycaemic control was assessed using a two‐step hyperinsulinaemic‐euglycaemic clamp (HEC) with D‐[6,6‐2H2] glucose infusion, a mixed‐meal tolerance test (MMTT) and continuous glucose monitoring.ResultsThe rate of glucose disappearance (RdT), glucose disposal rate and endogenous glucose production, as well as postprandial time‐course of blood glucose, serum insulin and C‐peptide were assessed during the HEC and MMTT, respectively. Both groups had improved peripheral insulin sensitivity (intervention effect, p = 0.006; increased RdT/Insulin of 1.0 ± 0.6 and 1.0 ± 0.3 mg kg−1 min−1 in OMNI and VEG, respectively), HbA1c (intervention; p = 0.001) and glycaemic variability (intervention; p = 0.040; increased time in‐range of 11.8 ± 9.3% and 23.3 ± 12.9% in OMNI and VEG). There were no improvements in hepatic insulin sensitivity or in postprandial blood glucose and serum C‐peptide (p > 0.05) during the MMTT.ConclusionsHigh‐protein diets, whether predicated on vegan or omnivorous proteins, can improve glycaemic control by increasing peripheral insulin sensitivity in people with T2D.