bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety and efficacy of remimazolam tosilate for general anaesthesia in paediatric patients undergoing elective surgery: a multicentre, randomised, single‐blind, controlled trial
Authors: Fang Yu‐Bo , Zhong John Wei , Szmuk Peter , Lyu Yun‐Long , Xu Ying , Qu Shuangquan , Du Zhen , Shangguan Wangning , Liu Hua‐Cheng
Published: November 2024

Introduction

Remimazolam is an ultra‐short‐acting benzodiazepine sedative drug. This study aimed to compare the efficacy and safety of remimazolam with propofol for induction and maintenance of general anaesthesia in children undergoing elective surgery.

Methods

Children (aged 3–6 y, ASA physical status 1 or 2, BMI 14–25 kg.m‐2) undergoing elective surgery under general anaesthesia with tracheal intubation were eligible for inclusion. Children were allocated randomly using a web‐based system to receive either remimazolam or propofol in a 3:1 ratio. After receiving fentanyl 3 μg.kg‐1, children received their allocated drug for both induction and maintenance of general anaesthesia. Induction doses were remimazolam 0.3 mg.kg‐1 or propofol 2.5 mg.kg‐1, with a second dose given should they not achieve loss of consciousness. After neuromuscular blockade and tracheal intubation, maintenance anaesthesia was achieved with an infusion either remimazolam 1–3 mg.kg‐1.h‐1 or propofol 4–12 mg.kg‐1.h‐1, alongside a remifentanil infusion (0.1–0.5 μg.kg‐1.min‐1) titrated to surgical stimulus and haemodynamic parameters. Primary outcomes were the incidence of successful induction and maintenance of anaesthesia. Secondary outcomes included: time to loss of consciousness, awakening and tracheal extubation; incidence of emergence delirium and moderate or severe pain in post‐anaesthesia care unit; incidence of negative behaviour change after surgery at postoperative day 3; and incidence of adverse events.

Results

A total of 187 children were analysed (140 allocated to remimazolam and 47 to propofol). All children achieved successful induction of anaesthesia. Successful maintenance of anaesthesia was achieved in 139 (99%) children who received remimazolam compared with 46 (98%) who received propofol (rate difference 1.4%, 95%CI ‐2.9–5.8%, p = 0.441). Adverse events occurred in 27 (19%) children who received remimazolam and 23 (49%) who received propofol.

Discussion

Remimazolam was well tolerated for the induction and maintenance of general anaesthesia in pre‐school‐age children and was non‐inferior to propofol.
Testicular histopathology and its association with germ cell numbers, serum concentrations of reproductive hormones, and semen quality
Authors: Saritas Gülizar , Mørup Nina , Johannsen Trine H. , Juul Anders , Aksglaede Lise , Winge Sofia B. , Almstrup Kristian
Published: November 2024

Background

It is well‐established that spermatogenesis, semen quality, and reproductive hormones are interlinked. It is, however, less well‐described how various specific testicular histopathologies are linked to reproductive hormones and semen quality.

Objectives

To describe the detailed relationship between specific testicular histopathologies and the serum concentrations of reproductive hormones and semen quality.

Materials and methods

Descriptive histological patterns on testicular biopsies from 4245 patients referred for andrological workup in our clinic between 1990 and 2022 were grouped according to a published histological coding system: (1) complete spermatogenesis (completeSPG, n = 3171), (2) reduced spermatogenesis (reducedSPG, n = 657), (3) heterogeneous (hetArrest, n = 226), and (4) homogeneous (homArrest, n = 191) spermatogenic arrest at the spermatocyte or spermatid stage. As a proxy for the number of spermatogonia, spermatocytes, and spermatids, immunohistochemical staining for MAGE‐A4, PIWIL1, and TNP1 were quantified on a representative set of biopsies (n = 100). Serum concentrations of FSH, LH, T, SHBG, and inhibin B (n = 1813) and semen parameters (n = 833) were available.

Results

Compared with the completeSPG group, the number of spermatogonia was only reduced in the hetArrest group, while the number of spermatocytes and spermatids were lower in all groups. All groups had significantly higher FSH and LH and lower T, free T, and inhibin B concentrations when compared with the completeSPG group, except for the homArrest group, where inhibin B was unaffected. The hetArrest group had the lowest number of germ cells, the most pronounced change in reproductive hormones, and the lowest sperm counts. We found a strong correlation between the number of germ cells present and the corresponding serum concentrations of FSH, LH, T, and inhibin B.

Discussion and Conclusions

A histopathological pattern of heterogeneous spermatogenic arrest is associated with a more severe phenotype than a pattern of homogeneous arrest, and the group with reduced spermatogenesis showed the mildest phenotype.
Lung function outcomes in adults born extremely preterm across three decades of advancing perinatal medicine
Authors: Bårdsen Tonje , Satrell Emma , Drange Røksund Ola , Røineland Benestad Merete , Hufthammer Karl Ove , Clemm Hege , Bruun Mikalsen Ingvild , Øymar Knut , Halvorsen Thomas , Vollsæter Maria
Published: November 2024

Aim

Advances in perinatal medicine from 1980 to 2000 improved survival in extremely preterm (EP) neonates. Long‐term effects of these developments remain unclear, and we aimed to investigate potential cohort effects on adult lung function.

Methods

Three 18‐year‐old population‐based cohorts born at ≤28 weeks gestation or with birthweight ≤1000 g during 1982–85, 1991–92 and 1999–2000 and term‐controls underwent spirometry, body plethysmography, and tests of lung diffusing capacity, bronchodilator reversibility, and airway hyperresponsiveness. We used Welch's t‐tests to compare term‐ with EP‐born as a group and split by bronchopulmonary dysplasia (BPD), and regression models to test group/cohort interactions.

Results

In all EP‐born cohorts, z‐scores for FEV1, FEV1/FVC, FEF25%–75%, DLCO and KCO were reduced compared with term‐born. For the 82–85, 91–92 and 99–00 cohorts, deficits for z‐FEV1 and z‐DLCO were 1.23 and 0.53; 0.68 and 0.92; and 0.51 and 0.57, respectively (p ≤0.01 for all). Cohort analyses showed stable lung function across the three cohorts overall, but improvements across cohorts for the BPD subgroups in z‐FEV1, z‐FEV1/FVC, and z‐FEF25%–75%.

Conclusion

Adults born EP across three formative decades of neonatal care had stable lung function overall, with notable improvements in BPD subgroups across cohorts.
The impact of domestic market fragmentation on China's food import prices
Authors: Sun Lin , Xu Li , Reed M. R.
Published: November 2024

As the China's imported food volume is increasing for more than 10 years, the higher import prices and price differences in various regions are attracting more attention. Based on the micro‐firm database of China Customs from 2004 to 2015, this study explores the impact of market fragmentation on food import prices at the HS8. The study finds that fragmentation of the domestic market has a positive effect on import food prices. Domestic market fragmentation has created a favourable environment for price discrimination, resulting in the food import price difference in various domestic regions. Foreign firms export food to high‐income regions with high‐quality in order to set higher price, which eventually led to the high and rising food import price in China. For this reason, actively promoting the domestic cycle and deepening the market integration of the domestic food market are the two key points to maintain high‐quality development of China's import food industry.
Randomized evaluation of the loss‐of‐function carboxylesterase 1 (CES1) G143E variant on clopidogrel and ticagrelor pharmacodynamics
Authors: Lewis Joshua P. , Ryan Kathleen A. , Streeten Elizabeth A. , Whitlatch Hilary B. , Daue Melanie , Tanner Keith , Perry James A. , O'Connell Jeffrey R. , Shuldiner Alan R. , Mitchell Braxton D.
Published: November 2024

Antiplatelet therapy with a P2Y12 receptor inhibitor, in combination with aspirin, is standard of care for medical management of patients with coronary artery disease, and flexibility in prescribing options among these medications offers great potential for individualizing patient care. Previously, we showed that a loss‐of‐function missense mutation (G143E) in carboxylesterase 1 (CES1), the primary enzyme responsible for clopidogrel degradation, significantly impacts on‐clopidogrel platelet aggregation and recurrent cardiovascular event risk. In the current investigation, we conducted a prospective randomized crossover study of clopidogrel (75 mg/day for 7 days) and ticagrelor (180 mg/day for 7 days) in 50 individuals stratified by CES1 G143E genotype (N = 34 143GG and 16 143GE) to determine the effect of drug choice on inhibition of platelet aggregation (IPA). Consistent with prior reports, we observed strong association between G143E and adenosine diphosphate‐stimulated platelet aggregation following clopidogrel administration (IPA = 71.6 vs. 48.0% in 143E‐allele carriers vs. non‐carriers, respectively, p = 3.8 × 10−5). Similar significant effects on platelet aggregation were also noted between 143E‐allele carriers versus non‐carriers in response to stimulation with arachidonic acid (45.8 vs. 25.8%, p = 0.04), epinephrine (44.4 vs. 18.8%, p = 0.03), and collagen (5 μg/mL, 25.8 vs. 11.4%, p = 3.7 × 10−3). In contrast, no relationship between CES1 G143E and IPA was observed following ticagrelor administration regardless of the platelet agonist used. Collectively, these data suggest that on‐clopidogrel platelet aggregation is substantially modified by CES1 G143E genotype, that this variant does not modify ticagrelor pharmacodynamics, and that more consistent inhibition of platelet aggregation may be achieved by using ticagrelor in patients who carry clopidogrel response‐modifying alleles in CES1.
All That Glitters is Not Gold: Viewer Understanding of Felix Gonzalez‐Torres's Candy Spill Installations
Authors: Trusty Rachel
Published: November 2024

The push to “queer the museum” calls for an increase in the inclusion of LGBT+ artworks and artists as an intervention into the heterosexual museum and canon. While popular, the display of queer, abstract objects is complicated as many museum visitors do not perceive the LGBT+ themes. In this article, I present the data on audience interpretation of two candy spill installations, Untitled (L.A.) (1991) and Untitled (Placebo‐Landscape‐for‐Roni) (1993), when they were featured in exhibitions at Crystal Bridges Museum of American Art in Bentonville, AR. Participant observation of and interviews with visitors demonstrate that while they understood the piece as a disruption to the site, no LGBT+ content was perceived. I make specific recommendations to museums based on the findings that argue the installation display, label text and placement, and museum staff training impact the viewer's understanding. As museums continue to participate in the queer turn, more should be considered when tackling the ethical display of LGBT+ works.
Evidence of Natural Reproduction of North American Rainbow Trout (Oncorhynchus mykiss) in Three Alpine Rivers in Bavaria, Germany
Authors: Mueller Melanie , Egg Leonhard , Ruff Tobias , Haas Andreas , Schubert Michael , Gum Bernhard
Published: November 2024

Rainbow trout have been translocated from North America worldwide for more than 150 years, but have not reproduced in the wild in Europe in the last 100 years. In recent decades, several examples of successful reproduction have become public. This study reports scientific evidence of natural reproduction of North American rainbow trout (Oncorhynchus mykiss) in three alpine rivers in Bavaria, Germany. Eggs collected from spawning redds were determined to be rainbow trout in all study rivers. In the river Leitzach, where spawning was exclusively observed in spring, electrofishing revealed a balanced length‐frequency distribution with a high abundance of rainbow trout and a high proportion of individuals < 10 cm. In the rivers Isar and Traun, spawning was observed in winter and supposedly also in spring, according to local reports. Rainbow trout < 10 cm were also observed in these two rivers during electrofishing surveys but were less abundant than in the river Leitzach. Genetic factors and river‐specific environmental and climatic conditions may have contributed to the success or failure of rainbow trout reproduction. Effects of rainbow trout on native fish vary widely, from severe negative impacts to minimal niche overlap, so further studies of genetic and environmental factors that determine rainbow trout naturalisation are needed to better inform fisheries management.
Fisheries Co‐Management Strengthen the Effectiveness of Protected Areas in Amazonian Floodplain Lakes
Authors: Carvalho Giulia Cristina Lopes , Zuanon Jansen , Morales Bruno Ferezim , Barros Gabriel Gazzana , Borba Gabriel Costa , Amadio Sidineia Aparecida , Röpke Cristhiana Paula , Shibuya Akemi , Farago Thatyla Luana Beck , Freitas Carlos Edwar de Carvalho , de Deus Claudia Pereira , Siqueira‐Souza Flávia Kelly
Published: November 2024

Aquatic protected areas and co‐management have been proposed as strategies for conserving fisheries resources in several world regions. We analyzed the effects of different levels of governance on yield of experimental fisheries in Amazonian floodplain lakes. Sampling between 2018 and 2022 used gill nets deployed for 24 h during flooding and receding water phases. Generalized linear models (GLMs) were fitted to catch per unit effort (CPUE) and covariates, river level, time, sampling sites, level of management of the collection sites, and lake fishery management type. CPUE was significantly related to governance, management type, sampling site, and water level. Our results indicated that areas of sustainable use where community‐based co‐management was implemented were more effective for promoting high fishery yield.
REVISITING MONTAILLOU
Authors: DOMANSKA EWA
Published: November 2024

Based on extensive scholarship in English and French, this article offers an analytical survey of both the laudatory and critical reception of Emmanuel Le Roy Ladurie's Montaillou (1975). I revisit the Latin text of Jacques Fournier's register and compare it with relevant fragments in the French and English translations of Montaillou. This comparison provides a starting point to comment on Le Roy Ladurie's novelistic writing style and the “hypnotic effect of narrative” achieved by the book. It also enables me to address historians’ criticisms of how Le Roy Ladurie used historical sources. In the second part of the article, I discuss anthropological history and the history of mentality as subdisciplines of contemporary historical writing, and I situate Montaillou within this tradition. Following Charles Tilly, I argue that Le Roy Ladurie's work is an example of “retrospective ethnography,” a term that more accurately describes Le Roy Ladurie's traditional approach to anthropological research, particularly the method of participatory observation. I also highlight prosopography as a method in Le Roy Ladurie's study of social relations in the medieval village. In conclusion, I reflect on the contemporary relevance of Montaillou for supporting human dignity and agency as well as the “humanity of history” needed in times of social and political upheaval.
On the collateral consequences of fine default: The Brazilian case study
Authors: Fortes Gabriel Brollo , Faraldo Cabana Patricia
Published: November 2024

The collateral consequences of the non‐payment of fines have merited much attention in jurisdictions such as the USA or Australia, yet they are relatively unexplored in countries of the Global South. In this article, we analyse Brazil as a case study. Although Brazil has the third largest prison population in the world, its criminal justice system has received little attention. We intend to fill this gap by addressing the legal framework and practices surrounding the non‐payment of fines in a country whose draconian policies cause social exclusion and impede rehabilitation.
Hair‐based minimally invasive barcoding of bumblebees
Authors: Rongstock Lydia , Schardt Leonie , Maihoff Fabienne , Grünewald Bernd , Bálint Miklós
Published: November 2024

A common method in bumblebee monitoring is the capturing and immobilisation of animals to morphologically determine their species. This usually requires researchers to kill the specimens to examine small details under an optics setup. To circumvent this, molecular methods like cytochrome oxidase subunit I–based barcoding have been well established, which support monitoring efforts without the need to keep voucher specimens. The most common way of sampling tissue from living bumblebees for DNA barcoding remains the clipping of tarsal tips. However, the possible effects of this sampling method on the specimens, especially reproductives, have not been studied in detail.

Here, we tested a minimally invasive sampling method for barcode‐based species identification, using hair from living as well as collection‐derived specimens. Our study consists of three different experimental parts, which aimed at adapting the method from controlled experimental to field conditions.

Our results indicate that hair‐based barcoding of bumblebees is possible. In a controlled experiment, there were no negative effects on the survival of sampled individuals. However, sample processing must be handled more carefully than traditional tarsal sampling to avoid sample contamination. Nevertheless, hair is a promising sampling material for supporting difficult identifications in bumblebee monitoring.

Our study is an example of establishing minimally invasive sampling methods for hairy pollinators. The method might be used to reduce the number of specimens killed in monitoring campaigns and to avoid damaging precious museum specimens.
The Impacts of Guided and Unguided Mobile‐Mediated Concept Mapping on EFL Learners’ Vocabulary Learning and Strategy Awareness
Authors: Kaveh Ardalan
Published: November 2024

Although several studies have provided positive evidence concerning the impacts of technology‐mediated language learning on learners’ vocabulary acquisition, few studies have investigated concept mapping in this field. This study intended to examine the impacts of guided and unguided mobile‐mediated concept mapping on learners’ vocabulary acquisition outside of English as a foreign language (EFL) classrooms. Moreover, the vocabulary acquisition strategies of students were examined. Sixty EFL learners in three intact classes were assigned to guided and unguided mobile‐mediated concept mapping conditions as well as one control group. The participants in the guided mobile‐mediated concept mapping group were provided with fill‐in‐blank concept mapping of words, and they were asked to fill in the nodes through their smartphones. The participants of the unguided mobile‐mediated concept mapping group were asked to draw concept maps of words via their mobile phones without receiving fill‐in‐blank concept mapping. The control group's participants were required to understand and memorize the words given to the experimental conditions conventionally, and they did not receive mobile‐mediated concept maps. Analyses of the learners’ post‐ and also delayed posttests indicated that both guided and unguided mobile‐mediated concept mapping were equally beneficial for increasing EFL learners’ vocabulary learning. Moreover, findings revealed that guided and unguided mobile‐mediated concept mapping promoted learners’ vocabulary learning strategy awareness outside of EFL settings.
Physical, but not laboratory, treatment‐related adverse events are associated with favorable outcomes of enfortumab vedotin for advanced urothelial carcinoma: A landmark analysis
Authors: Taguchi Satoru , Kawai Taketo , Ambe Yoshiki , Kishitani Kenjiro , Noda Michio , Kaneko Tomoyuki , Miyakawa Jimpei , Nakamura Yu , Hoshina Hayato , Obinata Daisuke , Yamaguchi Kenya , Kakutani Shigenori , Furuya Yoshitsune , Sato Yujiro , Adachi Yume , Sugimoto Kazuma , Sato Keigo , Tabata Mariko , Tanaka Takehiro , Nara Katsuhiko , Uemura Yukari , Kamei Jun , Akiyama Yoshiyuki , Sato Yusuke , Yamada Yuta , Niimi Aya , Yamada Daisuke , Takada Tappei , Takahashi Sayuri , Yamada Yukio , Miyazaki Hideyo , Enomoto Yutaka , Nishimatsu Hiroaki , Fujimura Tetsuya , Fukuhara Hiroshi , Nakagawa Tohru , Takahashi Satoru , Kume Haruki
Published: November 2024

Background

While the occurrence of immune‐related adverse events has been recognized as a prognostic marker in patients receiving immune checkpoint inhibitors, the prognostic significance of treatment‐related adverse events (trAEs) in patients undergoing antibody–drug conjugates such as enfortumab vedotin (EV) is controversial.

Methods

We reviewed 106 patients with advanced urothelial carcinoma who were treated with EV therapy at 10 institutions between 2021 and 2023. Associations of clinical parameters with overall survival and progression‐free survival were assessed using the Cox proportional hazards model. For the assessment of trAEs, landmark analysis was conducted to minimize immortal time bias.

Results

Of 106 patients, 55 (51.9%) experienced disease progression and 44 (41.5%) died during the follow‐up period. Any grade and grade ≥3 trAEs occurred in 94 (88.7%) and 44 (41.5%) patients, respectively. Common trAEs included skin disorders (74.5%), gastrointestinal disorders (62.3%), fatigue (50.0%), peripheral neuropathy (36.8%), and hematological disorders (37.7%). One patient died of interstitial pneumonia (grade 5). According to landmark analysis using 88 patients who survived for 2 months or more, trAEs were significantly associated with longer survival. Furthermore, when trAEs were classified into “physical trAEs” such as skin disorders and “laboratory trAEs” such as hematological disorders, the former were associated with longer survival while the latter were associated with shorter survival.

Conclusions

Physical, but not laboratory, trAEs are associated with favorable outcomes of EV therapy for advanced urothelial carcinoma. Both managing trAEs and utilizing them as prognostic markers are key points in the use of antibody–drug conjugates such as EV.
Inpatient Burden of Respiratory Syncytial Virus Infection and Influenza in Children Younger Than 5 Years in Japan, 2011–2022: A Database Study
Authors: Arashiro Takeshi , Kramer Rolf , Jin Jing , Kano Munehide , Wang Fangyuan , Miyairi Isao
Published: November 2024

Background

Respiratory syncytial virus (RSV) and influenza virus are major viral etiologies of pediatric lower respiratory tract infection, but comparative data on inpatient burden are lacking.

Methods

Using a large‐scale health claims database in Japan, we identified patients under 5 years of age with a confirmed RSV or influenza diagnosis as an outpatient or inpatient between 2011 and 2022. Hospitalization rate, inpatient characteristics, various in‐hospital outcomes/complications, and healthcare resource utilization were described.

Results

A total of 176,911 RSV‐confirmed outpatients, 153,383 influenza‐confirmed outpatients, 90,413 RSV‐confirmed hospitalizations, and 11,186 influenza‐confirmed hospitalizations were identified. Among outpatients, 24.7% of RSV infection and 2.8% of influenza cases required hospitalization within 1 week. There was no co‐morbidities/prematurity for 95.0% of RSV hospitalizations and 96.5% of influenza hospitalizations. Proportions of in‐hospital outcomes/complications were (RSV infection vs. influenza): oxygen use 47.6% vs. 14.8%, mechanical ventilation 2.1% vs. 0.7%, pneumonia 33.6% vs. 12.8%, otitis media 7.7% vs. 2.3%, febrile seizure 1.5% vs. 34.4%, encephalitis/encephalopathy 0.1% vs. 0.5%, myocarditis < 0.1% vs. 0.6%, antibiotics prescription 48.0% vs. 24.4%. The mean inpatient stay was 6.1 vs. 4.3 days at direct medical costs of 435,744 vs. 315,809 JPY/patient. These trends held true in age‐stratified data. In‐hospital death occurred in 31 RSV infection and 6 influenza cases.

Conclusions

Although both infections resulted in substantial burden, RSV infection led to more frequent hospitalizations, worse in‐hospital outcomes, longer inpatient stays, higher medical costs, and more frequent antibiotics prescription compared to influenza. Most RSV hospitalizations occurred among healthy term children, emphasizing the need for prevention measures in all children.
The French connection: Multiple records of Strait of Gibraltar killer whales (Orcinus orca) (2003–2023) in the Bay of Biscay, France
Authors: Pouey‐Santalou Victoria , Moreno‐Godoy Paula , Ducret Mathieu , Dramet Maéva , Toulot Aurore , Eriksson Ida , De Weerdt Joëlle
Published: November 2024

Documenting species occurrence and distribution patterns is fundamental for effective conservation strategies, particularly for endangered species facing various threats. Killer whales (Orcinus orca) are distributed worldwide, yet some populations, such as the critically endangered Strait of Gibraltar subpopulation, lack comprehensive distribution data. This study focuses on documenting the occurrence of Strait of Gibraltar killer whales along the French coast of the Bay of Biscay using twenty years (2003–2023) of scientific and citizen science data. Analysis of 34 sightings revealed seasonal patterns, with most sightings occurring between June and November. Also, killer whales are observed more often in the area since 2015. Photo‐identification methods allowed for the identification of 11 individuals, eight of which were recaptured in Spanish and Portuguese catalogs, confirming their affiliation with the Strait of Gibraltar subpopulation. Some individuals have been sighted over several years, regularly travelling together, suggesting potential site fidelity to the Bay of Biscay. Overall movement patterns showed associations with Atlantic bluefin tuna distribution. However, disruptive behaviors observed in some individuals highlight conservation challenges. This study provides novel insights into the distribution and movements of a critically endangered killer whale subpopulation, informing future conservation efforts in the region.
Left nationalism in the French Basque Country: From civic opposition to critical participation
Authors: Chevallier Thomas , Itçaina Xabier
Published: November 2024

Research on territories which have long been subjected to nationalist violence has tended to focus on the most radical manifestations of these struggles and their electoral and institutional consequences. In certain configurations, the involvement of nationalist entrepreneurs in socio‐economic initiatives, environmental causes or women's mobilisations reveals a broadening of activism to a larger political scope. This broadening can contribute to diluting or, conversely, reinforcing purely nationalist demands while creating new opportunities for alliances with non‐nationalist mobilisations. The French Basque region illustrates such a discussion. Basque nationalist politics has not only taken the form of a political movement but has also constituted a culture of citizen opposition in which the nationalist demand is as much an end as support for other struggles, notably socio‐economic ones. The article adopts a socio‐historical approach by going back to the main arenas in which Basque nationalism was formed and the struggles that have shaped it. Once having defined the concept of the culture of civic opposition, the article analyses three historical sequences from the 1970s until the 2020s.
Machine learning‐based identification of general transcriptional predictors for plant disease
Authors: Sia Jayson , Zhang Wei , Cheng Mingxi , Bogdan Paul , Cook David E.
Published: November 2024

This study investigated the generalizability of Arabidopsis thaliana immune responses across diverse pathogens, including Botrytis cinerea, Sclerotinia sclerotiorum, and Pseudomonas syringae, using a data‐driven, machine learning approach.

Machine learning models were trained to predict disease development from early transcriptional responses. Feature selection techniques based on network science and topology were used to train models employing only a fraction of the transcriptome. Machine learning models trained on one pathosystem where then validated by predicting disease development in new pathosystems.

The identified feature selection gene sets were enriched for pathways related to biotic, abiotic, and stress responses, though the specific genes involved differed between feature sets. This suggests common immune responses to diverse pathogens that operate via different gene sets.

The study demonstrates that machine learning can uncover both established and novel components of the plant's immune response, offering insights into disease resistance mechanisms. These predictive models highlight the potential to advance our understanding of multigenic outcomes in plant immunity and can be further refined for applications in disease prediction.
The impact of behavioral weight management interventions on eating behavior traits in adults with overweight or obesity: A systematic review and meta‐analysis
Authors: Kudlek Laura , Eustachio Colombo Patricia , Ahern Amy , Tait Struan , Reid Natasha , Wickramarachchi Milindu , Lakshmi Aiswarya , Sharp Stephen J. , Spreckley Marie , Mueller Julia , Jones Rebecca A.
Published: November 2024

Eating behavior traits (EBTs), defined as personal tendencies determining food intake, can be useful targets for behavioral weight management interventions. Previous reviews have examined the impact of specific intervention types on EBTs, not reflecting the breadth of interventions used in practice. This systematic review and meta‐analysis synthesized evidence on the impact of all types of behavioral weight management interventions on EBTs. We searched seven databases and included randomized controlled trials reporting EBT outcomes following behavioral weight management interventions delivered to adults with overweight or obesity. Using random‐effects meta‐analyses, we synthesized findings from 27 trials at the end of intervention and 12 months (±3 months) post intervention. We found evidence to suggest that interventions improved uncontrolled eating, external eating, susceptibility to hunger, restraint and intuitive eating at intervention end when compared with waitlist, minimal or usual care control. We found no evidence of effects on emotional eating, disinhibition, and hedonic hunger. At follow‐up, effects on restraint remained, but we found no evidence of an effect on emotional eating, hedonic hunger and uncontrolled eating. Findings were limited by low numbers of contributing trials. More high‐quality trials reporting EBTs are needed to better understand the impact of adult behavioral weight management interventions on EBTs.

PROSPERO registration number: CRD42022367505.
A Comparative Historical Sociology of Corruption
Authors: Garrido Marco , Zaloznaya Marina , Wilson Nicholas Hoover
Published: November 2024

A view of corruption as disembedded from society and history is predominant today. In this view, corruption is basically the same thing everywhere and inherently a bad thing because it gets in the way of proper processes. In opposition to this view, we argue for understanding corruption as socially and historically embedded. While there are many viable ways to embed corruption, we advocate a comparative historical sociology of corruption in particular. This approach has in mind a view of corruption as “a moving object,” that is, as subject to variation across social space and transformation over time. It focuses on the processes through which a course of action is worked out in relation to historically specific structural conditions. By tracing these processes and embedding “corrupt” practices in the situations where they were developed and make sense, we gain a deeper understanding of these practices and are in a better position to evaluate them. We are also able to make better comparisons, comparing objects shaped by similar processes rather than objects identified by definition alone. We proceed, first, by situating our intervention in the context of the rise of a disembedded approach to corruption. Second, we review a selection of more or less embedded approaches in anthropology and sociology. Third, we describe what a comparative historical sociology of corruption entails. Finally, we highlight the costs of a disembedded view in terms of ineffective and pathologizing anti‐corruption efforts.
Measuring position sense
Authors: Proske Uwe
Published: November 2024

Position sense is arguably more important than any of the other proprioceptive senses, because it provides us with information about the position of our body and limbs in relationship to one another and to our surroundings; it has been considered to contribute to our self‐awareness. There is currently no consensus over the best method of measuring position sense. We have recently measured position sense with three commonly used methods. These were two‐arm matching, one‐arm pointing and one‐arm repositioning, all carried out by blindfolded subjects with their lightly loaded forearms moving in the sagittal plane. It is currently believed that muscle spindles are the principal position sensors. We posed the question, was there evidence for spindles participating in the generation of position sense with each method? The indicator of spindle activity we used was the presence of thixotropic errors in the position signal, in response to conditioning voluntary contractions of forearm muscles. Based on this criterion, there was evidence of spindles contributing to position sense with all three methods. It was concluded that the spindle contribution to the position signal and the extent to which this was processed centrally was different with each method. It is argued that a case could be made for the existence of more than one position sense. Differences between the methods have implications for their meaning in a clinical setting.
Single-cell multi-omics sequencing uncovers region-specific plasticity of glioblastoma for complementary therapeutic targeting
Authors: Wang Xin , Sun Qian , Liu Tianbin , Lu Haoran , Lin Xuyi , Wang Weiwen , Liu Yang , Huang Yunting , Huang Guodong , Sun Haixi , Chen Qianxue , Wang Junmin , Tian Daofeng , Yuan Fan’en , Liu Longqi , Wang Bo , Gu Ying , Liu Baohui , Chen Liang
Published: November 2024

Glioblastoma (GBM) cells are highly heterogeneous and invasive, leading to treatment resistance and relapse. However, the molecular regulation in and distal to tumors remains elusive. Here, we collected paired tissues from the tumor core (TC) and peritumoral brain (PTB) for integrated snRNA-seq and snATAC-seq analyses. Tumor cells infiltrating PTB from TC behave more like oligodendrocyte progenitor cells than astrocytes at the transcriptome level. Dual-omics analyses further suggest that the distal regulatory regions in the tumor genome and specific transcription factors are potential determinants of regional heterogeneity. Notably, while activator protein 1 (AP-1) is active in all GBM states, its activity declines from TC to PTB, with another transcription factor, BACH1, showing the opposite trend. Combined inhibition of AP-1 and BACH1 more efficiently attenuates the tumor progression in mice and prolongs survival than either single-target treatment. Together, our work reveals marked molecular alterations of infiltrated GBM cells and a synergy of combination therapy targeting intratumor heterogeneity in and distal to GBM.
Zircon trace element evidence for early hydrothermal activity on Mars
Authors: Gillespie Jack , Cavosie Aaron J. , Fougerouse Denis , Ciobanu Cristiana L. , Rickard William D. A. , Saxey David W. , Benedix Gretchen K. , Bland Phil A.
Published: November 2024

Finding direct evidence for hydrous fluids on early Mars is of interest for understanding the origin of water on rocky planets, surface processes, and conditions essential for habitability, but it is challenging to obtain from martian meteorites. Micro- to nanoscale microscopy of a unique impact-shocked zircon from the regolith breccia meteorite NWA7034 reveals textural and chemical indicators of hydrothermal conditions on Mars during crystallization 4.45 billion years ago. Element distribution maps show sharp alternating zoning defined by marked enrichments of non-formula elements, such as Fe, Al, and Na, and ubiquitous nanoscale magnetite inclusions. The zoning and inclusions are similar to those reported in terrestrial zircon crystallizing in the presence of aqueous fluid and are here interpreted as primary features recording zircon growth from exsolved hydrous fluids at ~4.45 billion years. The unique record of crustal processes preserved in this grain survived early impact bombardment and provides previously unidentified petrological evidence for a wet pre-Noachian martian crust.
High-order direct modulation terahertz communications with a wideband time-coding metachip modulator
Authors: Wang Lan , Dai Jun Yan , Ding Ke Seng , Zeng Hong Xin , Cheng Qiang , Yang Zi Qiang , Zhang Ya Xin , Cui Tie Jun
Published: November 2024

Terahertz communication technology based on on-off keying (OOK) direct modulation is vital for sixth-generation communication systems, especially in short-distance and high-rate applications. However, low-order OOK modulation often leads to suboptimal anti-interference capabilities and a heightened demodulation threshold. Here, we propose a high-order direct modulation terahertz communication framework using a wideband time-coding metachip modulator. The modulator leverages the electromagnetic resonance properties within the metaunit structure, with control enabled by gallium arsenide Schottky diodes. By manipulating the timing of voltage pulses applied to these diodes, the equivalent electromagnetic resonance distributions can be precisely regulated in the time domain. This enables independent and accurate control over the amplitude and phase of terahertz harmonics. Leveraging this technique, three high-order modulation schemes—quadrature phase-shift keying, 16-phase-shift keying, and 16-quadrature amplitude modulation— are achieved in a direct modulation and direct detection system, demonstrating the real-time image transmission. The proposed method offers an important way to develop integrated and low-complexity terahertz wireless communication systems.
Monoamine transporter ubiquitination and inward-open conformation synergistically maximize transporter endocytosis
Authors: Sorkina Tatiana , Bagalkot Tarique , Cheng Mary Hongying , Guthrie Daryl A. , Newman Amy Hauck , Watkins Simon C. , Sorkin Alexander
Published: November 2024

Monoamine transporters function in neuronal membranes to control extracellular concentrations of their substrates. Cell-surface expression of transporters is regulated by substrates and intracellular signaling, but the underlying mechanisms remain unclear. Here, we found that substrates of the dopamine transporter (DAT), amphetamine and dopamine, synergize with protein kinase C (PKC)–dependent DAT ubiquitination to markedly elevate clathrin-mediated endocytosis of DAT, which is accompanied by DAT movement out of plasma membrane protrusions with a negative curvature. Disruption of the outward-open (OO) DAT conformation or its stabilization in the inward-open (IO) conformation recapitulates substrate effects on DAT endocytosis. Amphetamine strongly increases PKC-dependent endocytosis of norepinephrine transporter (NET) but not of serotonin transporter (SERT), correlating with a substantially weaker ubiquitination of SERT compared to NET. We propose a “shape-transition” model whereby shifting from convex-shaped OO conformers to IO conformers minimizes retention of transporters in negatively curved membranes, which facilitates their PKC-dependent ubiquitination and recruitment to positively invaginated clathrin-coated membranes, driving robust transporter endocytosis.
Functional anatomy of the subthalamic nucleus and the pathophysiology of cardinal features of Parkinson’s disease unraveled by focused ultrasound ablation
Authors: Rodriguez-Rojas Rafael , Máñez-Miró Jorge U. , Pineda-Pardo José A. , del Álamo Marta , Martínez-Fernández Raúl , Obeso José A.
Published: November 2024

The subthalamic nucleus (STN) modulates basal ganglia output and plays a fundamental role in the pathophysiology of Parkinson’s disease (PD). Blockade/ablation of the STN improves motor signs in PD. We assessed the topography of focused ultrasound subthalamotomy (
n
= 39) by voxel-based lesion-symptom mapping to identify statistically validated brain voxels with the optimal effect against each cardinal feature and their respective cortical connectivity patterns by diffusion-weighted tractography. Bradykinesia and rigidity amelioration were associated with ablation of the rostral motor STN subregion connected to the supplementary motor and premotor cortices, whereas antitremor effect was explained by lesioning the posterolateral STN projection to the primary motor cortex. These findings were corroborated prospectively in another PD cohort (
n
= 12). This work concurs with recent deep brain stimulation findings that suggest different corticosubthalamic circuits underlying each PD cardinal feature. Our results provide sound evidence in humans of segregated anatomy of subthalamic-cortical connections and their distinct role in PD pathophysiology and normal motor control.
LTβR deficiency causes lymph node aplasia and impaired B cell differentiation
Authors: Ransmayr Bernhard , Bal Sevgi Köstel , Thian Marini , Svaton Michael , van de Wetering Cheryl , Hafemeister Christoph , Segarra-Roca Anna , Block Jana , Frohne Alexandra , Krolo Ana , Altunbas Melek Yorgun , Bilgic-Eltan Sevgi , Kıykım Ayça , Aydiner Omer , Kesim Selin , Inanir Sabahat , Karakoc-Aydiner Elif , Ozen Ahmet , Aba Ümran , Çomak Aylin , Tuğcu Gökçen Dilşa , Pazdzior Robert , Huber Bettina , Farlik Matthias , Kubicek Stefan , von Bernuth Horst , Simonitsch-Klupp Ingrid , Rizzi Marta , Halbritter Florian , Tumanov Alexei V. , Kraakman Michael J. , Metin Ayşe , Castanon Irinka , Erman Baran , Baris Safa , Boztug Kaan
Published: November 2024

Secondary lymphoid organs (SLOs) provide the confined microenvironment required for stromal cells to interact with immune cells to initiate adaptive immune responses resulting in B cell differentiation. Here, we studied three patients from two families with functional hyposplenism, absence of tonsils, and complete lymph node aplasia, leading to recurrent bacterial and viral infections. We identified biallelic loss-of-function mutations in
LTBR,
encoding the lymphotoxin beta receptor (LTβR), primarily expressed on stromal cells. Patients with LTβR deficiency had hypogammaglobulinemia, diminished memory B cells, regulatory and follicular T helper cells, and dysregulated expression of several tumor necrosis factor family members. B cell differentiation in an ex vivo coculture system was intact, implying that the observed B cell defects were not intrinsic in nature and instead resulted from LTβR-dependent stromal cell interaction signaling critical for SLO formation. Collectively, we define a human inborn error of immunity caused primarily by a stromal defect affecting the development and function of SLOs.
Brecciation and epithermal mineralization in the Baia Mare ore district (Romania): The Wilhelm deposit
Authors: Tămaș Călin G.
Published: November 2024

The Wilhelm deposit is part of an intermediate-sulfidation polymetallic Zn-Pb-Ag-Au vein system in the Baia Mare ore district of the Eastern Carpathians, Romania, where left-lateral tectonic displacement in an E−W-dominated fault system controlled the epithermal mineralization. The Wilhelm deposit consists of tens of vein sets, including the sub-parallel Complex veins (1−7), and is hosted by the ca. 11.6 Ma Ulmoasa dacite. The 7 Complex vein is composed of sub-vertical breccia, including marginal fine-grained rock flour breccia (Fgb), which is matrix-supported and cemented by minor interstitially precipitated minerals. This breccia is cut and re-brecciated multiple times by a clast-supported breccia (Csb) cemented by four hydrothermal mineralization stages comprising the economic ore, i.e., gray quartz−pyrite (M1); sphalerite−galena−pyrite−freibergite (M2); white calcite−electrum−freibergite (M3); and gray-blue quartz−freibergite with an unnamed Ag-mineral (Ag,Cu)8SbS5 (M4). Each mineralization stage follows its distinct brecciation event (B1 to B4). This clast-supported breccia is comminuted near contacts with unbrecciated dacitic host rock to a matrix-supported breccia with rock flour enclosing small ore and host-rock fragments (Ofb).

The rounded shape of fragments originating in the underlying sedimentary rock basement indicates the upward transport of Fgb by incipient phreatomagmatic activity. The dominant ore and gangue minerals of Csb suggest dominant hydrothermal fluid flow during ore formation. The gradual contact of Csb with Ofb and its clasts indicate that Ofb was formed by tectonic movement during the waning stage of hydrothermal activity, because both breccias are cut by pink calcite veins (mineralization stage M5). A similar evolution from phreatomagmatic breccias through repeated hydrothermal brecciation and mineralization to late tectonic brecciation is characteristic of the entire Baia Mare district. Its consistent relation to coeval calc-alkaline magmatism indicates that magmatic fluids played an essential role in ore formation. Resulting steep thermal gradients with or without mixing with surface water created a metal zonation with deep Cu-rich zones, intermediate Pb-Zn zones, and Au-rich bonanza zones due to shallow fluid boiling. The local presence of Au-rich ores also at greater depth indicates fluid de-sulfidation as an alternative mechanism for Au precipitation.
Supplemental Material: Detrital zircon provenance links between outcrop and subsurface, Rocas Verdes and Magallanes-Austral Basins, Patagonia
Authors: Almonte N. Gross , al. et
Published: November 2024

Data Set 1: U-Pb detrital zircon data table results from LA-ICP-MS. Data Set 2: U-Pb data inputs for IsoplotR weighted mean average (WMA) calculations. Data Set 3: Raw and normalized point-count data. 
Supplemental Material: Model for sinistral offset of the Cretaceous magmatic arc of southwestern North America along the Nacimiento fault system
Authors: Ingersoll Raymond V.
Published: November 2024

Two PowerPoint files displaying sequences of paleogeologic maps at 6 m.y. intervals from 0 Ma to 90 Ma.  
Induction of Alkaline Bands in Chara by External Electric Current Reveals the Influence of Plasma Membrane H+ Fluxes on Cyclosis-Mediated Signaling
Authors: Bulychev A. A. , Krupenina N. A.
Published: November 2024

Long-distant communications in plants and giant plant cells are essential for optimal cell functioning under variable environmental conditions. In characean internodal cells exposed to spotted or flickering light, the redox balance in dimly lit chloroplasts is sensitive to the reducing power produced in brightly illuminated chloroplasts of a distal cell region located upstream in the directed cytoplasmic flow. The distant communication is mediated by excessive production in the high-light region of reducing metabolites that are exported into the streaming cytoplasm and delivered by cytoplasmic flow to light-starving chloroplasts. These target chloroplasts perceive the transportable metabolic signal, which is reflected in the transient increase of modulated chlorophyll fluorescence F '. Previous studies of cyclosis-mediated F ' transients revealed that they are sensitive to natural H+ fluxes across the plasma membrane and that the signal transduction is suppressed in cell areas with massive H+ influx. In this study with Chara australis R. Br., we show that the injection of inward electric current is accompanied by proton influx sufficient for the creation of artificial alkaline band. The combined application of PAM chlorophyll microfluorometry, local light stimuli, and measurements of pericellular pH showed that the microfluidic signal transduction is notably suppressed under artificially produced alkaline band where H+ influx acidifies the cytoplasm. It is hypothesized that changes in cytoplasmic pH regulate the rates of electron flows directed to NADP reduction and O2 reduction, which may disturb long-distance redox control system involving production and consumption of reducing equivalents.