bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of antiresorptive/antiangiogenic therapy on the surgical treatment outcomes of experimentally induced peri-implantitis lesions
Authors: Ramanauskaite Ausra , Krüger Nadine , Obreja Karina , Borchert Fanya , Dahmer Iulia , Schwarz Frank
Published: October 2023

Objective

To investigate the influence of various antiresorptive and antiangiogenic medications on the resolution of experimentally induced peri-implantitis lesions after different surgical treatment approaches.

Materials and methods

Forty-eight albino rats randomly received a dual application of the following medications: (1) amino-bisphosphonate (zoledronate (Zo)) (n = 8), (2) RANKL inhibitor (denosumab (De)) (n = 8), (3) antiangiogenic (bevacizumab (Be)) (n = 8), (4) Zo + Be (n = 8), (5) De + Be (n = 8), or (6) no medication (control (Co)) (n = 8). Ligature-induced peri-implantitis lesions were established at 2 maxillary implants over 16 weeks. Afterward, animals were randomly treated either with open flap debridement (OFD) or reconstructive therapy (RT). Treatment procedures were followed by a 12-week healing period. The histological outcomes included residual defect length (DL); defect width (DW) at the bone crest (BC-DW); 25%, 50%, and 75% of the DL; and areas of inflammatory cell infiltrate (ICT). When present, areas of bone sequester (BS) were assessed considering the animal as a statistical unit.

Results

A total of 21 animals were analyzed (Zo: RT = 3, OFD = 1; De: RT = 3, OFD = 2; Be: OFD = 1; Zo + Be: RT = 2, OFD = 2; Co: RT = 3, OFD = 2). Implant loss rates were comparable among the experimental groups. Except for the 25% and 75% DW values that were significantly higher in the Zo + Be group compared to the Co group (p = 0.04 and p = 0.03, respectively), no significant differences were found among the experimental groups for the DL (lowest—Be: 0.56 mm; highest—Co: 1.05 mm), BC-DW (lowest—De: 0.86 mm, highest—Co: 1.07 mm), 50% DW (lowest—De: 0.86 mm; highest—Be + Zo: 1.29 mm), and ICT (lowest—Be: 0.56 mm2; highest—Be + Zo: 1.65 mm2). All groups, except for the Zo and Be following RT, showed presence of BS.

Conclusions

The present findings did not reveal a marked effect of various antiresorptive/antiangiogenic medications on the resolution of experimentally induced peri-implantitis lesions, regardless of the surgical approach employed (OFD and RT).

Clinical relevance

Resolution of peri-implantitis lesions may not be affected by the investigated antiresorptive/antiangiogenic medications.
Comprehensive kinetostatic modeling and morphology characterization of cable-driven continuum robots for in-situ aero-engine maintenance
Authors: Yang Zheshuai , Yang Laihao , Sun Yu , Chen Xuefeng
Published: October 2023

In-situ maintenance is of great significance for improving the efficiency and ensuring the safety of aeroengines. The cable-driven continuum robot (CDCR) with twin-pivot compliant mechanisms, which is enabled with flexible deformation capability and confined space accessibility, has emerged as a novel tool that aims to promote the development of intelligence and efficiency for in-situ aero-engine maintenance. The high-fidelity model that describes the kinematic and morphology of CDCR lays the foundation for the accurate operation and control for in-situ maintenance. However, this model was not well addressed in previous literature. In this study, a general kinetostatic modeling and morphology characterization methodology that comprehensively contains the effects of cable-hole friction, gravity, and payloads is proposed for the CDCR with twin-pivot compliant mechanisms. First, a novel cable-hole friction model with the variable friction coefficient and adaptive friction direction criterion is proposed through structure optimization and kinematic parameter analysis. Second, the cable-hole friction, all-component gravities, deflection-induced center-of-gravity shift of compliant joints, and payloads are all considered to deduce a comprehensive kinetostatic model enabled with the capacity of accurate morphology characterization for CDCR. Finally, a compact continuum robot system is integrated to experimentally validate the proposed kinetostatic model and the concept of in-situ aero-engine maintenance. Results indicate that the proposed model precisely predicts the morphology of CDCR and outperforms conventional models. The compact continuum robot system could be considered a novel solution to perform in-situ maintenance tasks of aero-engines in an invasive manner.
Geographies of Public Deliberation: A Closer Look at the Ingredient of Space
Authors: Awuh Harrison Esam
Published: October 2023

Since its inception, public deliberation has been largely seen as an effective tool of inclusion and transformation within democratic politics. However, this article argues that public deliberation is not necessarily inclusive and transformative. These aspirations can only be achieved if certain conditions are met. The qualitative analyses drawn upon in this public deliberation study included virtual and face-to-face conversations between participants (N = 70) about opinions on eating together. The article examines factors that can impede food system transformation initiatives. This can be particularly problematic in low- and middle-income countries because corruptibility can reduce the stringency of food system transformation policy. This study was conducted with participants from the Dutch cities of Almere and Amsterdam. The article argues that public deliberation can be truly transformative when (1) it is institutionally sanctioned, and (2) participants in the deliberation are given more time to make their arguments and reconsider these arguments in light of what others have to say.
Update on the Obesity Epidemic: After the Sudden Rise, Is the Upward Trajectory Beginning to Flatten?
Authors: Koliaki Chrysi , Dalamaga Maria , Liatis Stavros
Published: October 2023

Purpose of Review

To provide an update on current obesity prevalence trends and summarize the available evidence suggesting a possible plateau or stabilization in obesity rates after the previous sudden global rise.

Recent Findings

The escalating global obesity epidemic represents one of the most serious public health challenges. There have been some indications that in high-income populations, the rate of obesity increase in adults has been stabilized after the decade 2000–2010, suggesting a possible plateau. Current evidence also suggests that obesity rates have been stabilized in children and adolescents of most economically advanced countries since 2000, which is possibly related to healthier dietary habits and increased levels of physical activity. On the other hand, there is a steady uninterrupted rise in low-income nations, and the universal trend is obesity escalation rather than slowdown, mainly driven by sharp increases in the obesity prevalence of low-income populations. Furthermore, an increasing number of high- and middle-income countries are currently experiencing an epidemic of severe obesity. In high-income populations, severe obesity is expected to double its prevalence from 10 to 20% between 2020 and 2035, posing an enormous threat for healthcare systems. Even if transiently stabilized, the obesity prevalence remains globally at unacceptably high levels, and there is no guarantee that the current stability (if any) will be maintained for long.

In this review, we explore the underlying drivers of the global obesity epidemic; we provide possible explanations for the reported slowdown of the obesity rates in some countries; and we overall take a critical perspective on the obesity plateau hypothesis, emphasizing the urgent need for immediate effective actions at population and regional level in order to halt the alarming obesity escalation and its serious health risks.
An Independent Art Library for Naarm/Melbourne
Authors: Fraser Nell
Published: October 2023

Melbourne Art Library was established in 2020, during the early days of the COVID-19 pandemic in Australia, as a uniquely independent art library in Australia. The library's development – which may be equated to a kind of practice-lead-research exploring what a library is – has not been without its difficulties. Yet, despite this, the library is three years strong and provides a specialised lending collection of over 3000 books, a reading room, and an active program of public events.
Europe’s political constitution
Authors: Somek Alexander , Paar Elisabeth
Published: October 2023

Pluralism is a defining feature of European human rights law and of the European constitution. Contestability and conditional deference determine how participating states eventually calibrate their relation to international and supranational authority. This structure gives rise to differences of opinion that reverberate throughout a public sphere that is composed of a growing number of scholars. They increasingly rely on digital media to exchange their ideas. A major role has come to be played by blogs such as the Verfassungsblog. Since its inception, its focus has rested on defending the values of constitutionalism vis-à-vis ‘backsliding’ Member States. The constitutional culture that results from this is somewhat reminiscent of Germany during the period of the Weimar Republic (1919–1933). While the rise of authoritarianism is a major issue, public law scholarship appears to become increasingly partisan. As European constitutional law emerges against the backdrop of an expanding public sphere, scholarly interventions are drawn into the vortex of politics. Unsurprisingly, scholarship begins to face up to its politicisation by reflecting on its proper task.
Stochastic differential equation approximations of generative adversarial network training and its long-run behavior
Authors: Cao Haoyang , Guo Xin
Published: October 2023

This paper analyzes the training process of generative adversarial networks (GANs) via stochastic differential equations (SDEs). It first establishes SDE approximations for the training of GANs under stochastic gradient algorithms, with precise error bound analysis. It then describes the long-run behavior of GAN training via the invariant measures of its SDE approximations under proper conditions. This work builds a theoretical foundation for GAN training and provides analytical tools to study its evolution and stability.
CHRONOLOGY OF THE VOLCHIA GRIVA MEGAFAUNAL LOCALITY AND PALEOLITHIC SITE (WESTERN SIBERIA) AND THE ISSUE OF HUMAN OCCUPATION OF SIBERIA AT THE LAST GLACIAL MAXIMUM
Authors: Kuzmin Yaroslav V , Leshchinskiy Sergey V , Zenin Vasily N , Burkanova Elena M , Zazovskaya Elya P , Samandrosova Aleksandra S
Published: October 2023

A summary of the chronology for the key paleontological and archaeological site of Volchia Griva in the southern part of the West Siberian Plain is presented. Currently, 42 reliable 14C values have been generated on animal bones (37 14C dates) and charcoal (5 14C dates). Three stratigraphic levels of animal bones are established. The 14C ages of the fossils are as follows: the upper level—ca. 10,620–12,520 BP; the middle level—ca. 13,700–17,800 BP; and the lower level—ca. 18,230–19,790 BP. The majority of animal fossils and artifacts are associated with the lower level. Based on the results obtained, we suggest that Upper Paleolithic people occupied the Volchia Griva site during the second part of the Last Glacial Maximum (LGM), ca. 18,200–19,800 BP, and perhaps occasionally afterwards. It is obvious that these humans were well adapted to the cold and dry climate of the LGM, as well as numerous other populations in Siberia south of 58°N. It is noteworthy that the youngest 14C values on woolly mammoth are of ca. 10,620–11,815 BP, and this makes the Volchia Griva one of the latest mammoth refugia in northern Eurasia outside of the Arctic.
Do you see the pattern? Make the most of sensor data in dairy cows
Authors: Kok Akke , Ternman Emma , Thorup Vivi M.
Published: October 2023

Sensors are increasingly being used to monitor animal behaviour. Data handling methods have, however, lagged behind the continuous data stream to some extent, often being limited to summarizing data into daily averages at group level. This research reflection presents our opinion of the neglected application of 24-h pattern analysis. Recent studies of dairy cow behaviour have demonstrated that additional ways of analysing data improve our understanding of animal behaviour and add value to data that were already retrieved. The terminology for the described 24-h patterns differs between these studies, making them difficult to compare. Thus, diurnal, circadian, daily, periodicity and 24-h pattern are all terms used to describe dairy cow activities over a 24-h period. Several studies have shown that the 24-h behavioural pattern at herd level is relatively consistent over time, and that with well-established management routines, a specific herd signature will be evident. However, within a herd, individual cows may have individual 24-h patterns with more or less variability. Recent studies suggest that deviations from herd and/or individual 24-h patterns can be used to describe cow robustness, as well as to predict disease. We strongly believe that individual and herd 24-h patterns provide a great deal of information about behaviour and that these patterns offer opportunity for more precise and timely health management and welfare monitoring.
Long-term outcomes of bilateral medialisation thyroplasty in patients with vocal fold atrophy with or without sulcus
Authors: van den Broek Emke MJM , Heijnen Bas J , van der Valk Jens C , Hendriksma Martine , Langeveld Antonius PM , van Benthem Peter Paul G , Sjögren Elisabeth V
Published: October 2023

Objective

Evaluate long-term voice outcome after bilateral medialisation thyroplasty in glottic insufficiency due to vocal fold atrophy with or without sulcus.

Methods

Patients after medialisation thyroplasty for vocal fold atrophy with or without sulcus were identified. Long-term post-operative subjective voice outcomes (> 1 year) using Voice Handicap Index-30, subjective ratings on voice aspects and study-specific questionnaire were compared to pre-operative and shorter-term (1 year) values.

Results

Thirty-six patients were identified, of which 26 were included (16 atrophy, 10 sulcus) with median follow up of 6.7 years. Mean Voice Handicap Index score at > 1 year (40.0) showed clinically relevant (≥ 15 for groups) and statistically significant improvement compared to pre-operative score (58.1) and remained stable compared to post-operative score (35.7) at one year. Ten patients (56 per cent) reported clinically relevant improvement (≥ 10) after more than five years.

Conclusion

Long-term improvement in subjective voice outcomes is attainable in a significant proportion of patients undergoing bilateral medialisation thyroplasty for atrophy with or without sulcus.
Graphic codes, language, and the computational niche
Authors: Winters James
Published: October 2023

Human language looms large in the emergence and evolution of graphic codes. Here, I argue that language not only acts as a strong constraint on graphic codes, but it is also a precondition for their emergence and their evolution as computational devices.
Emoji use validates the potential for meaning standardization among ideographic symbols
Authors: Feldman Laurie Beth
Published: October 2023

Technological innovations for online communication reduce the impact of signal transience on meaning standardization while boosting access to reliable patterning across multiple linguistic and nonlinguistic contexts – both asynchronous and synchronous. We classify emojis as ideographic symbols, examine their interdependence with surrounding words when reading/writing, and argue that emoji use validates the potential for meaning standardization in ideographs.
Improving Content Analysis: Tools for Working with Undergraduate Research Assistants
Authors: Goehring Benjamin
Published: October 2023

Undergraduate research assistants (URAs) perform important roles in many political scientists’ research projects. They serve as coauthors, survey respondents, and data collectors. Despite these roles, there is relatively little discussion about how best to train and manage URAs who are working on a common task: content coding. Drawing on insights from psychology, text analysis, and business management, as well as my own experience in managing a team of nine URAs, this article argues that supervisors should train URAs by pushing them to engage with their own mistakes. Via a series of simulation exercises, I also argue that supervisors—especially supervisors of small teams—should be concerned about the effects of errant post-training coding on data quality. Therefore, I contend that supervisors should utilize computational tools to monitor URA reliability in real time. I provide researchers with a new R package, ura, and a web-based application to implement these suggestions.
CHD8 regulates gut epithelial cell function and affects autism-related behaviors through the gut-brain axis
Authors: Chatterjee Ipsita , Getselter Dmitriy , Ghanayem Nasreen , Harari Ram , Davis Liron , Bel Shai , Elliott Evan
Published: October 2023

Autism is a neurodevelopmental disorder characterized by early-onset social behavioral deficits and repetitive behaviors. Chromodomain helicase DNA-binding protein (CHD8) is among the genes most strongly associated with autism. In addition to the core behavioral symptoms of autism, affected individuals frequently present with gastrointestinal symptoms that are also common among individuals harboring mutations in the gene encoding CHD8. However, little is known regarding the mechanisms whereby CHD8 affects gut function. In addition, it remains unknown whether gastrointestinal manifestations contribute to the behavioral phenotypes of autism. The current study found that mice haploinsufficient for the large isoform of Chd8 (Chd8L) exhibited increased intestinal permeability, transcriptomic dysregulation in gut epithelial cells, reduced tuft cell and goblet cell counts in the gut, and an overall increase in microbial load. Gut epithelial cell-specific Chd8 haploinsufficiency was associated with increased anxiety-related behaviors together with a decrease in tuft cell numbers. Antibiotic treatment of Chd8L haploinsufficient mice attenuated social behavioral deficits. Together, these results suggest Chd8 as a key determinant of autism-related gastrointestinal deficits, while also laying the ground for future studies on the link between GI deficits and autism-related behaviors.
Velusetrag rescues GI dysfunction, gut inflammation and dysbiosis in a mouse model of Parkinson’s disease
Authors: Grigoletto Jessica , Miraglia Fabiana , Benvenuti Laura , Pellegrini Carolina , Soldi Sara , Galletti Serena , Cattaneo Antonino , Pich Emilio Merlo , Grimaldi Maria , Colla Emanuela , Vesci Loredana
Published: October 2023

In patients with Parkinson’s disease (PD), constipation is common, and it appears in a prodromal stage before the hallmark motor symptoms. The present study aimed to investigate whether Velusetrag, a selective 5‑HT4 receptor agonist, may be a suitable candidate to improve intestinal motility in a mouse model of PD. Five months old PrP human A53T alpha-synuclein transgenic (Tg) mice, which display severe constipation along with decreased colonic cholinergic transmission already at 3 months, were treated daily with the drug for 4 weeks. Velusetrag treatment reduced constipation by significantly stimulating both the longitudinal and circular-driven contractions and improved inflammation by reducing the level of serum and colonic IL1β and TNF-α and by decreasing the number of GFAP-positive glia cells in the colon of treated mice. No significant downregulation of the 5-HT4 receptor was observed but instead Velusetrag seemed to improve axonal degeneration in Tgs as shown by an increase in NF-H and VAChT staining. Ultimately, Velusetrag restored a well-balanced intestinal microbial composition comparable to non-Tg mice. Based on these promising data, we are confident that Velusetrag is potentially eligible for clinical studies to treat constipation in PD patients.
Soil carbon storage capacity of drylands under altered fire regimes
Authors: Pellegrini Adam F. A. , Reich Peter B. , Hobbie Sarah E. , Coetsee Corli , Wigley Benjamin , February Edmund , Georgiou Katerina , Terrer Cesar , Brookshire E. N. J. , Ahlström Anders , Nieradzik Lars , Sitch Stephen , Melton Joe R. , Forrest Matthew , Li Fang , Hantson Stijn , Burton Chantelle , Yue Chao , Ciais Philippe , Jackson Robert B.
Published: October 2023

The determinants of fire-driven changes in soil organic carbon (SOC) across broad environmental gradients remains unclear, especially in global drylands. Here we combined datasets and field sampling of fire-manipulation experiments to evaluate where and why fire changes SOC and compared our statistical model to simulations from ecosystem models. Drier ecosystems experienced larger relative changes in SOC than humid ecosystems—in some cases exceeding losses from plant biomass pools—primarily explained by high fire-driven declines in tree biomass inputs in dry ecosystems. Many ecosystem models underestimated the SOC changes in drier ecosystems. Upscaling our statistical model predicted that soils in savannah–grassland regions may have gained 0.64 PgC due to net-declines in burned area over the past approximately two decades. Consequently, ongoing declines in fire frequencies have probably created an extensive carbon sink in the soils of global drylands that may have been underestimated by ecosystem models.
Multilevel visual motion opponency in Drosophila
Authors: Ammer Georg , Serbe-Kamp Etienne , Mauss Alex S. , Richter Florian G. , Fendl Sandra , Borst Alexander
Published: October 2023

Inhibitory interactions between opponent neuronal pathways constitute a common circuit motif across brain areas and species. However, in most cases, synaptic wiring and biophysical, cellular and network mechanisms generating opponency are unknown. Here, we combine optogenetics, voltage and calcium imaging, connectomics, electrophysiology and modeling to reveal multilevel opponent inhibition in the fly visual system. We uncover a circuit architecture in which a single cell type implements direction-selective, motion-opponent inhibition at all three network levels. This inhibition, mediated by GluClα receptors, is balanced with excitation in strength, despite tenfold fewer synapses. The different opponent network levels constitute a nested, hierarchical structure operating at increasing spatiotemporal scales. Electrophysiology and modeling suggest that distributing this computation over consecutive network levels counteracts a reduction in gain, which would result from integrating large opposing conductances at a single instance. We propose that this neural architecture provides resilience to noise while enabling high selectivity for relevant sensory information.
Elongation roadblocks mediated by dCas9 across human genes modulate transcription and nascent RNA processing
Authors: Zukher Inna , Dujardin Gwendal , Sousa-Luís Rui , Proudfoot Nick J.
Published: October 2023

Non-cleaving Cas9 (dCas9) is widely employed to manipulate specific gene loci, often with scant regard for unintended transcriptional effects. We demonstrate here that dCas9 mediates precise RNA polymerase II transcriptional pausing followed by transcription termination and potential alternative polyadenylation. By contrast, alternative splicing is unaffected, likely requiring more sustained alteration to elongation speed. The effect on transcription is orientation specific, with pausing only being induced when dCas9-associated guide RNA anneals to the non-template strand. Targeting the template strand induces minimal effects on transcription elongation and thus provides a neutral approach to recruit dCas9-linked effector domains to specific gene regions. In essence, we evaluate molecular effects of targeting dCas9 to mammalian transcription units. In so doing, we also provide new information on elongation by RNA polymerase II and coupled pre-mRNA processing.
HCG supplement did not accelerate tunica albuginea remodeling to facilitate penile growth
Authors: Li Tao , Tian Yuan , Zhong Quliang , Chen Peng , Zhang Junhao , Du Guangshi , Li Lei , Jiang Yiting , Jiang Kehua
Published: October 2023

Penile size is closely concerned and short penis contributes serious sexual dysfunction and tremendous psychological problems to couples. Androgen is essential for penile development and testosterone replacement is recommended to patients with micropenis. We previously proved that inhibiting activity of lysyl oxidase (Anti-lysyl oxidase, Anti-LOX) combined with vacuum erectile device (VED) lengthened penis by remodeling tunica albuginea. We thus explored whether HCG supplement could accelerate tunica albuginea remodeling (induced by Anti-LOX + VED) to promote penile growth. Forty-two SD male rats (4 weeks old) were purchased and divided into 7 groups: control, Anti-LOX, HCG, VED (with a negative aspirated pressure of − 300 mmHg), Anti-LOX + VED, HCG + VED, and Anti-LOX + HCG + VED. After an intervention for 4 weeks, all rats’ penile length, exposed penile length, and erectile function were measured. Serum samples were collected to detect hormone levels and penile corpus cavernosum were harvested for histo-pathological analysis. All intervention groups showed significantly longer penis than controlled rats. Anti-LOX sharply increased penile length and exposed length by 15% and 9% respectively, this lengthening effect was more obvious in Anti-LOX + VED group (26% and 19%, respectively). Although HCG promoted penile length by 8%, this effect was slight for exposed length (3%). Moreover, Anti-LOX + HCG + VED dramatically increased penile length and exposed length by 22% and 18%, respectively, which was similar with that in Anti-LOX + VED (26% and 19%, respectively). HCG dramatically stimulated testosterone and dihydrotestosterone secretions than control group, whether with or without Anti-LOX and VED; while it induced more AR expression than other groups. Finally, all procedures did not improve or deteriorate normal erectile function. Although we verified that Anti-LOX + VED lengthened penis by inducing tunica albuginea remodeling, however, HCG supplement did not synergize with Anti-LOX + VED to accelerate albuginea remodeling to facilitate penile growth.
An integrative and multi-indicator approach for wildlife health applied to an endangered caribou herd
Authors: Aguilar Xavier Fernandez , Leclerc Lisa-Marie ,   Kugluktuk Angoniatit Association,   Ekaluktutiak Hunters & Trappers Organization,   Olokhaktomiut Hunters & Trappers Committee, Mavrot Fabien , Roberto-Charron Amélie , Tomaselli Matilde , Mastromonaco Gabriela , Gunn Anne , Pruvot Mathieu , Rothenburger Jamie L. , Thanthrige-Don Niroshan , Jahromi Elham Zeini , Kutz Susan
Published: October 2023

Assessing wildlife health in remote regions requires a multi-faceted approach, which commonly involves convenient samplings and the need of identifying and targeting relevant and informative indicators. We applied a novel wildlife health framework and critically assessed the value of different indicators for understanding the health status and trends of an endangered tundra caribou population. Samples and data from the Dolphin and Union caribou herd were obtained between 2015 and 2021, from community-based surveillance programs and from captured animals. We documented and categorized indicators into health determinants (infectious diseases and trace elements), processes (cortisol, pathology), and health outcomes (pregnancy and body condition). During a recent period of steep population decline, our results indicated a relatively good body condition and pregnancy rates, and decreasing levels of stress, along with a low adult cow survival. We detected multiple factors as potential contributors to the reduced survival, including Brucella suis biovar 4, Erysipelothrix rhusiopathiae and lower hair trace minerals. These results remark the need of targeted studies to improve detection and investigations on caribou mortalities. We also identified differences in health indicators between captured and hunter sampled caribou, highlighting the importance of accounting for sampling biases. This integrative approach that drew on multiple data sources has provided unprecedented knowledge on the health in this herd and highlights the value of documenting individual animal health to understand causes of wildlife declines.
Histologic subtype-based evaluation of recurrence and survival outcomes in patients with adenocarcinoma of the ampulla of Vater
Authors: Park Se Jun , Shin Kabsoo , Hong Tae Ho , Lee Sung Hak , Kim In-Ho , Kim Younghoon , Lee MyungAh
Published: October 2023

Patients with ampulla of Vater adenocarcinoma exhibit diverse outcomes, likely since these malignancies can originate from any of the three converging epithelia at this site. Such variability presents difficulties in clinical decision-making processes and in devising therapeutic approaches. In this study, the potential clinical value of histomolecular phenotypes was determined by integrating histopathological analysis with protein expression (MUC1, CDX2, CK20, and MUC2), in a cohort of 87 patients diagnosed with stage IB to III ampulla of Vater adenocarcinoma who underwent curative surgical resection. Of the 87 patients, 54 were classified as pancreato-biliary (PB) subtype and 33 as intestinal subtype. The median follow-up time for all patients was 32.8 months (95% CI, 25.3–49.2). Patients with a histomolecular PB phenotype (CDX2 negative, MUC1 positive, MUC2 negative, and irrespective of the CK20 results) were associated with poor prognostic outcomes in both disease-free survival (DFS) (HR = 1.81; 95% CI, 1.04–3.17; p = 0.054) and overall survival (OS) (HR = 2.01; 95% CI, 1.11–3.66; p = 0.039) compared to those with histomolecular intestinal carcinomas. Patients with the PB subtype were more likely to have local recurrence alone (11 of 37, 29.7%) compared to those with the intestinal subtype (1 of 15, 6.7%). In the context of systemic disease, a notably greater proportion of patients exhibiting elevated carbohydrate antigen 19–9 levels were observed in the PB subtype compared to the intestinal subtype (p = 0.024). In the cohort of 38 patients who received first-line palliative chemotherapy, a diminished median overall survival (OS) was observed in the PB group compared to the intestinal group (10.3 vs. 28.3 months, HR = 2.47; 95% CI, 1.23–4.95; p = 0.025). By integrating histopathologic and molecular criteria, we can identify distinct and clinically relevant histomolecular phenotypes in adenocarcinomas of the ampulla of Vater, which could have considerable impact on existing therapeutic approaches.
Electronic strengthening mechanism of covalent Si via excess electron/hole doping
Authors: Noda Hiroki , Sakaguchi Shumpei , Fujita Ryoga , Minami Susumu , Hirakata Hiroyuki , Shimada Takahiro
Published: October 2023

Brittle fracture of a covalent material is ultimately governed by the strength of the electronic bonds. Recently, attempts have been made to alter the mechanical properties including fracture strength by excess electron/hole doping. However, the underlying mechanics/mechanism of how these doped electrons/holes interact with the bond and changes its strength is yet to be revealed. Here, we perform first-principles density-functional theory calculations to clarify the effect of excess electrons/holes on the bonding strength of covalent Si. We demonstrate that the bond strength of Si decreases or increases monotonically in correspondence with the doping concentration. Surprisingly, change to the extent of 30–40% at the maximum feasible doping concentration could be observed. Furthermore, we demonstrated that the change in the covalent bond strength is determined by the bonding/antibonding state of the doped excess electrons/holes. In summary, this work explains the electronic strengthening mechanism of covalent Si from a quantum mechanical point of view and provides valuable insights into the electronic-level design of strength in covalent materials.
Visual perceptual learning modulates microsaccade rate and directionality
Authors: Hung Shao-Chin , Barbot Antoine , Carrasco Marisa
Published: October 2023

Microsaccades, incessant “fixational eye movements” (< 1°), are an important window into cognitive functions. Yet, its role in visual perceptual learning (VPL)–improvements in visual discrimination due to practice–remains practically unexplored. Here we investigated whether and how microsaccades change in VPL. Human observers performed a Landolt acuity task for 5 consecutive days and were assigned to the Neutral or Attention group. On each trial, two peripheral Landolt squares were presented briefly along a diagonal. Observers reported the gap side of the target stimulus. Training improved acuity and modified the microsaccade rate; with training, the rate decreased during the fixation period but increased during the response cue. Furthermore, microsaccade direction during the response cue was biased toward the target location, and training enhanced and sped up this bias. Finally, the microsaccade rate during a task-free fixation period correlated with observers’ initial acuity threshold, indicating that the fewer the microsaccades during fixation the better the individual visual acuity. All these results, which were similar for both the Neutral and Attention groups and at both trained and untrained locations, suggest that microsaccades could serve as a physiological marker reflecting functional dynamics in human perceptual learning.
Dark matter halo mass functions and density profiles from mass and energy cascade
Authors: Xu Zhijie
Published: October 2023

Halo abundance and structure play a central role for modeling structure formation and evolution. Without relying on a spherical or ellipsoidal collapse model, we analytically derive the halo mass function and cuspy halo density (inner slope of −4/3) based on the mass and energy cascade theory in dark matter flow. The hierarchical halo structure formation leads to halo or particle random walk with a position-dependent waiting time $$\tau _g$$

τ
g

. First, the inverse mass cascade from small to large scales leads to the halo random walk in mass space with $$\tau _g\propto m_h^{-\lambda }$$

τ
g

∝

m
h

-
λ

, where $$m_h$$

m
h

is the halo mass and $$\lambda$$
λ
is a halo geometry parameter with predicted value of 2/3. The corresponding Fokker-Planck solution for halo random walk in mass space gives rise to the halo mass function with a power-law behavior on small scale and exponential decay on large scale. This can be further improved by considering two different $$\lambda$$
λ
for haloes below and above a critical mass scale $$m_h^*$$

m
h
∗

, i.e. a double-$$\lambda$$
λ
halo mass function. Second, a double-$$\gamma$$
γ
density profile can be derived based on the particle random walk in 3D space with a position-dependent waiting time $$\tau _g \propto \Phi (r)^{-1} \propto r^{-\gamma }$$

τ
g

∝
Φ

(
r
)

-
1

∝

r

-
γ

, where $$\Phi$$
Φ
is the gravitational potential and r is the particle distance to halo center. Theory predicts $$\gamma =2/3$$

γ
=
2
/
3

that leads to a cuspy density profile with an inner slope of −4/3, consistent with the predicted scaling laws from energy cascade. The Press-Schechter mass function and Einasto density profile are just special cases of proposed models. The small scale permanence can be identified due to the scale-independent rate of mass and energy cascade, where density profiles of different halo masses and redshifts converge to the $$-4/3$$

-
4
/
3

scaling law ($$\rho _h \propto r^{-4/3}$$

ρ
h

∝

r

-
4
/
3

) on small scales. Theory predicts the halo number density scales with halo mass as $$\propto m_h^{-1.9}$$

∝

m
h

-
1.9

, while the halo mass density scales as $$\propto m_h^{4/9}$$

∝

m
h

4
/
9

. Results were compared against the Illustris simulations. This new perspective provides a theory for nearly universal halo mass functions and density profiles.
Wood cookstove use is associated with gastric cancer in Central America and mediated by host genetics
Authors: Rifkin Samara B. , Miller Anna K. , Montalvan-Sanchez Eleazar E. , Norwood Dalton A. , Martinez Enrique , Waterboer Tim , Beasley T. Mark , Dominguez Ricardo L. , Williams Scott M. , Morgan Douglas R.
Published: October 2023

Biomass cookstove food preparation is linked to aero-digestive cancers, mediated by ingested and inhaled carcinogens (e.g., heterocyclic amines, and polycyclic aromatic hydrocarbons). We investigated the association between gastric adenocarcinoma, wood cookstove use, H. pylori CagA infection and risk modification by variants in genes that metabolize and affect the internal dose of carcinogens. We conducted a population-based, case–control study (814 incident cases, 1049 controls) in rural Honduras, a high-incidence region with a homogeneous diet and endemic H. pylori infection, primarily with the high-risk CagA genotype. We investigated factors including wood cookstove use, H. pylori CagA serostatus, and 15 variants from 7 metabolizing genes, and the interactions between wood stove use and the genetic variants. Male sex (OR 2.0, 1.6–2.6), age (OR 1.04, 1.03–1.05), wood cookstove use (OR 2.3, 1.6–3.3), and CagA serostatus (OR 3.5, 2.4–5.1) and two SNPs in CYP1B1 (rs1800440 and rs1056836) were independently associated with gastric cancer in multivariate analysis. In the final multivariate model, a highly significant interaction (OR 3.1, 1.2–7.8) was noted between wood cookstove use and the rs1800440 metabolizing genotype, highlighting an important gene-environment interaction. Lifetime wood cookstove use associates with gastric cancer risk in the high-incidence regions of Central America, and the association is dependent on the rs1800440 genotype in CYP1B1. H. pylori CagA infection, wood cookstove use and the rs1800440 genotype, all of which are highly prevalent, informs who is at greatest risk from biomass cookstove use.
Counter-intuitive penetration of droplets into hydrophobic gaps in theory and experiment
Authors: Hagg Daniel , Eifert Alexander , Dörr Aaron , Bodziony Francisco , Marschall Holger
Published: October 2023

Droplets that spontaneously penetrate a gap between two hydrophobic surfaces without any external stimulus seems counterintuitive. However, in this work we show that it can be energetically favorable for a droplet to penetrate a gap formed by two hydrophobic or in some cases even superhydrophobic surfaces. For this purpose, we derived an analytical equation to calculate the change in Helmholtz free energy of a droplet penetrating a hydrophobic gap. The derived equation solely depends on the gap width, the droplet volume and the contact angle on the gap walls, and predicts whether a droplet penetrates a hydrophobic gap or not. Additionally, numerical simulations were conducted to provide insights into the gradual change in Helmholtz free energy during the process of penetration and to validate the analytical approach. A series of experiments with a hydrophobic gap having an advancing contact angle of $$115^\circ$$

115
∘

, a droplet volume of about 10 $$\mu$$
μ
L and different gap widths confirmed the theoretical predictions. Limits and possible deviations between the analytical solution, the simulation and the experiments are presented and discussed.
Factors associated with poorer quality of life in people living with HIV in southwestern France in 2018–2020 (ANRS CO3 AQUIVIH-NA cohort: QuAliV study)
Authors: Barger Diana , Hessamfar Mojgan , Neau Didier , Farbos Sophie , Leleux Olivier , Cazanave Charles , Rouanes Nicolas , Duffau Pierre , Lazaro Estibaliz , Rispal Patrick , Dabis François , Wittkop Linda , Bonnet Fabrice
Published: October 2023

We evaluated people living with Human Immunodeficiency Virus’ (PLWH) quality of life (QoL) and assessed whether their demographic, disease-related, socioeconomic, or behavioral characteristics were associated with poorer QoL. ANRS CO3 AQUIVIH-NA cohort participants (Nouvelle Aquitaine, France) were recruited to a cross-sectional study (2018–2020) and their QoL assessed (WHOQOL-BREF). We calculated median (Q1, Q3) QoL domain scores and assessed factors associated with poorer median QoL using bivariable and multivariable quartile regression. Of the 965 PLWH included, 98.4% were on antiretroviral therapy, 94.7% were virally-suppressed, 63.5% reported good/very good QoL. Median scores (0–100) were highest for physical (69;Q1, Q3: 56, 81) and environmental (69; 56, 75) QoL and lowest for social (56; 44, 69) and psychological (56; 44, 69) QoL. PLWH with ≥ 3 comorbidities, HIV-related stigma, or income of < 1500€/month had poorer median adjusted physical, psychological, social, and environmental QoL scores compared to reference groups. While more than half of PLWH reported good/very good QoL, we have not achieved good QoL in 90% of PLWH. Multi-morbidity, HIV-related stigma, and social determinants were consistently and independently associated with poorer QoL. Addressing structural factors in addition to those indirectly related to HIV is required to attain good QoL in all PLWH.
Immobilized enzyme microreactors for analysis of tryptic peptides in β-casein and β-lactoglobulin
Authors: Rodzik Agnieszka , Railean Viorica , Pomastowski Paweł , Buszewski Bogusław , Szumski Michał
Published: October 2023

In this study, our primary objective was to develop an effective analytical method for studying trypsin-digested peptides of two proteins commonly found in cow's milk: β-casein (βCN) and β-lactoglobulin (βLG). To achieve this, we employed two distinct approaches: traditional in-gel protein digestion and protein digestion using immobilized enzyme microreactors (μ-IMER). Both methods utilized ZipTip pipette tips filled with C18 reverse phase media for sample concentration. The μ-IMER was fabricated through a multi-step process that included preconditioning the capillary, modifying its surface, synthesizing a monolithic support, and further surface modification. Its performance was evaluated under HPLC chromatography conditions using a small-molecule trypsin substrate (BAEE). Hydrolysates from both digestion methods were analyzed using MALDI-TOF MS. Our findings indicate that the μ-IMER method demonstrated superior sequence coverage for oxidized molecules in βCN (33 ± 1.5%) and βLG (65 ± 3%) compared to classical in-gel digestion (20 ± 2% for βCN; 49 ± 2% for βLG). The use of ZipTips further improved sequence coverage in both classical in-gel digestion (26 ± 1% for βCN; 60 ± 4% for βLG) and μ-IMER (41 ± 3% for βCN; 80 ± 5% for βLG). Additionally, phosphorylations were identified. For βCN, no phosphorylation was detected using classical digestion, but the use of ZipTips showed a value of 27 ± 4%. With μ-IMER and μ-IMER–ZipTip, the values increased to 30 ± 2% and 33 ± 1%, respectively. For βLG, the use of ZipTip enabled the detection of a higher percentage of modified peptides in both classical (79 ± 2%) and μ-IMER (79 ± 4%) digestions. By providing a comprehensive comparison of traditional in-gel digestion and μ-IMER methods, this study offers valuable insights into the advantages and limitations of each approach, particularly in the context of complex biological samples. The findings set a new benchmark in protein digestion and analysis, highlighting the potential of μ-IMER systems for enhanced sequence coverage and post-translational modification detection.
Valorization of Spirodela polyrrhiza biomass for the production of biofuels for distributed energy
Authors: Romanowska-Duda Z. , Piotrowski K. , Szufa S. , Sklodowska M. , Naliwajski M. , Emmanouil C. , Kungolos A. , Zorpas A. A.
Published: October 2023

Considering the main objectives of a circular economy, Lemnaceae plants have great potential for different types of techniques to valorize their biomass for use in biofuel production. For this reason, scientific interest in this group of plants has increased in recent years. The aim of this study was to evaluate the effects of salt stress on the growth and development of S. polyrrhiza and the valorization of biomass for biofuel and energy production in a circular economy. Plants were grown in a variety of culture media, including standard 'Z' medium, tap water, 1% digestate from a biogas plant in Piaszczyna (54° 01′ 21″ N, 17° 10′ 19″ E), Poland) and supplemented with different concentrations of NaCl (from 25 to 100 mM). Plants were cultured under phytotron conditions at 24 °C. After 10 days of culture, plant growth, fresh and dry biomass, as well as physio-chemical parameters such as chlorophyll content index, gas exchange parameters (net photosynthesis, transpiration, stomatal conductance and intercellular CO2 concentration), chlorophyll fluorescence measurements were analyzed. After 10 days of the experiment, the percentage starch content of Spirodela shoot segments was determined. S. polyrrhiza was shown to have a high starch storage capacity under certain unfavorable growth conditions, such as salt stress and nutrient deficiency. In the W2 (50 mM NaCl) series, compared to the control (Control2), starch levels were 76% higher in shoots and 30% lower in roots. The analysis of the individual growth and development parameters of S. polyrrhiza plants in the experiment carried out indicates new possibilities for the use of this group of plants in biofuel and bioethanol production.
Midlife cardiovascular health factors as predictors of retirement age, work-loss years, and years spent in retirement among older businessmen
Authors: Haapanen Markus J. , Törmäkangas Timo , von Bonsdorff Monika E. , Strandberg Arto Y. , Strandberg Timo E. , von Bonsdorff Mikaela B.
Published: October 2023

Cardiovascular disease (CVD) is one of the leading causes of premature retirement. However, the relationship between CVD risk factors and workforce participation is not well known. We studied the relationship between midlife CVD risk, age at retirement, work-loss years, and survival in retirement. Middle-aged Finnish men (initial n = 3490, mean age = 47.8 years) were assessed for CVD risk factors and general health in the 1970s. They worked as business executives and provided information on their retirement status in the year 2000. Survival was followed up to the 9th decade of life with a follow-up of up to 44 years. Work-loss years were calculated as death or retirement occurring at age ≤ 65 years. Smoking, body mass index, and alcohol use were used as covariates, excluding models of CVD risk, which were adjusted for alcohol use only. Higher risk of 10-year fatal CVD was associated with 0.32 more years (relative risk < 1 vs. 1, covariate-adjusted β = 0.32, 95% CI = 0.13, 0.53) of work-loss. Higher risk of 5-year incident (covariate-adjusted time-constant HR = 1.32, 95% CI = 1.19, 1.47) and 10-year fatal (covariate-adjusted time-dependent HR = 1.55, 95% CI = 1.30, 1.85) CVD in midlife were associated with fewer years spent in retirement. Poorer self-rated health and physical fitness and higher levels of triglycerides were associated with increased hazard of earlier retirement, more work-loss years, and fewer years spent in retirement. Poorer health and greater midlife CVD risk may be associated with earlier exit from the workforce and fewer years spent in retirement. Management of CVD risk in midlife may support people to work longer.