bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic modeling of degenerative diseases and mechanisms of neuronal regeneration in the zebrafish cerebellum
Authors: Namikawa Kazuhiko , Pose-Méndez Sol , Köster Reinhard W.
Published: December 2024

The cerebellum is a highly conserved brain compartment of vertebrates. Genetic diseases of the human cerebellum often lead to degeneration of the principal neuron, the Purkinje cell, resulting in locomotive deficits and socio-emotional impairments. Due to its relatively simple but highly conserved neuroanatomy and circuitry, these human diseases can be modeled well in vertebrates amenable for genetic manipulation. In the recent years, cerebellar research in zebrafish has contributed to understanding cerebellum development and function, since zebrafish larvae are not only molecularly tractable, but also accessible for high resolution in vivo imaging due to the transparency of the larvae and the ease of access to the zebrafish cerebellar cortex for microscopy approaches. Therefore, zebrafish is increasingly used for genetic modeling of human cerebellar neurodegenerative diseases and in particular of different types of Spinocerebellar Ataxias (SCAs). These models are well suited to address the underlying pathogenic mechanisms by means of in vivo cell biological studies. Furthermore, accompanying circuitry characterizations, physiological studies and behavioral analysis allow for unraveling molecular, structural and functional relationships. Moreover, unlike in mammals, zebrafish possess an astonishing ability to regenerate neuronal populations and their functional circuitry in the central nervous system including the cerebellum. Understanding the cellular and molecular processes of these regenerative processes could well serve to counteract acute and chronic loss of neurons in humans. Based on the high evolutionary conservation of the cerebellum these regeneration studies in zebrafish promise to open therapeutic avenues for counteracting cerebellar neuronal degeneration. The current review aims to provide an overview over currently existing genetic models of human cerebellar neurodegenerative diseases in zebrafish as well as neuroregeneration studies using the zebrafish cerebellum. Due to this solid foundation in cerebellar disease modeling and neuronal regeneration analysis, the zebrafish promises to become a popular model organism for both unraveling pathogenic mechanisms of human cerebellar diseases and providing entry points for therapeutic neuronal regeneration approaches.
Unified Framework for Continuity of Sandwiched Rényi Divergences
Authors: Bluhm Andreas , Capel Ángela , Gondolf Paul , Möbus Tim
Published: December 2024

In this work, we prove uniform continuity bounds for entropic quantities related to the sandwiched Rényi divergences such as the sandwiched Rényi conditional entropy. We follow three different approaches: The first one is the “almost additive approach”, which exploits the sub-/superadditivity and joint concavity/convexity of the exponential of the divergence. In our second approach, termed the “operator space approach”, we express the entropic measures as norms and utilize their properties for establishing the bounds. These norms draw inspiration from interpolation space norms. We not only demonstrate the norm properties solely relying on matrix analysis tools but also extend their applicability to a context that holds relevance in resource theories. By this, we extend the strategies of Marwah and Dupuis as well as Beigi and Goodarzi employed in the sandwiched Rényi conditional entropy context. Finally, we merge the approaches into a mixed approach that has some advantageous properties and then discuss in which regimes each bound performs best. Our results improve over the previous best continuity bounds or sometimes even give the first continuity bounds available. In a separate contribution, we use the ALAFF method, developed in a previous article by some of the authors, to study the stability of approximate quantum Markov chains.
The impact of primers for wood bonding on beech wood’s Young’s modulus
Authors: Böger Thomas , Engelhardt Max , Richter Klaus , Sanchez-Ferrer Antoni
Published: December 2024

When producing load-bearing timber products with one-component polyurethane adhesives and certain wood species, e.g., beech or larch, primers can be used to obtain stronger and more durable bonds. The active chemicals of three existing primer systems, hydroxymethylated resorcinol formaldehyde (HMR), polysorbate 20 (PS20), and poly(ethylene glycol) (PEG), were used to impregnate beech wood. Young’s modulus (E) in the radial direction was determined in tensile mode. A modified E can influence the deformation and stress distribution at the wood-glue interface. Compared to the untreated wood, the average E was reduced by 7% for the water-treated reference and the HMR treatment. With the PS20 treatment, the average E was reduced by 16%, compared to the untreated wood, and by 45% with the PEG treatment.
Aiding narrative generation in collaborative data utilization by humans and AI agents
Authors: Sekiguchi Kaira , Ohsawa Yukio
Published: December 2024

Narrative generation is growing in importance for data utilization, particularly in the context of co-creation with artificial intelligence (AI) agents. Narratives can, for example, bridge theoretical objects with social understanding and promote human actions. Furthermore, clarifying the narrative generation mechanism is essential for constructing effective relationships between humans and AI agents. However, the narrative generation mechanism in data utilization processes has not been fully elucidated. In this study, we developed a framework called the hierarchical narrative representation (HieNaR) to systematize the structure of narrative generation in data utilization processes. HieNaR comprises twelve levels, ranging from the set of texts down to the particle level (e.g., text, sentence, word, character, and stroke), allowing for a comprehensive analysis of narrative structures. We evaluated the usefulness of HieNaR through case studies, examining both individual user experiences and collaborative work between humans and an AI agent. The results demonstrated that the data utilization process interprets data by inquiring whether it satisfies higher-level expectations. In collaboration, AI agents can be understood as co-creative partners in data utilization, possessing their own worldviews. Through these findings, this study not only elucidates the mechanism of narrative generation in data utilization processes but also provides a foundation for improving human–AI collaboration.
Accelerating antiviral drug discovery: early hazard detection with a dual zebrafish and cell culture screen of a 403 compound library
Authors: Truong Lisa , Bieberich Andrew A. , Fatig Raymond O. , Rajwa Bartek , Simonich Michael T. , Tanguay Robyn L.
Published: December 2024

The constant emergence of new viral pathogens underscores the need for continually evolving, effective antiviral drugs. A key challenge is identifying compounds that are both efficacious and safe, as many candidates fail during development due to unforeseen toxicity. To address this, the embryonic zebrafish morphology, mortality, and behavior (ZBE) screen and the SYSTEMETRIC® Cell Health Screen (CHS) were employed to evaluate the safety of 403 compounds from the Cayman Antiviral Screening Library. Of these compounds, 114 were FDA-approved, 17 were discontinued, and 97 remained on the market. CHS identified 25% (104 compounds) as toxic, with a Cell Health Index™ (CHI) > 0.5. The embryonic zebrafish model identified an additional 20% as toxic (79), bringing the total to 183. ZBEscreen flagged 19 toxic hits among compounds still on the market, seven of which were also identified by CHS. The combined use of CHS and zebrafish models enhanced hazard detection. Together, CHS and ZBEscreen identified 45.5% of the library as potentially hazardous. Notably, the zebrafish non-hazardous compounds correlated strongly with over-the-counter or prescribed antiviral drugs, confirming their known safety profile. Over 130 hazard-associated compounds warranted further investigation. Using self-organizing maps, six distinct neighborhoods of compound similarity were identified. This dual approach streamlined the early detection of hazards associated with promising leads and is expected to facilitate faster, safer antiviral discovery.
Convergence speed for Fekete points on uniformly polynomially cuspidal sets
Authors: Ahn Hyunsoo , Nguyen Ngoc Cuong
Published: December 2024

We obtain the convergence speed for Fekete points on uniformly polynomially cuspidal compact sets introduced by Pawłucki and Pleśniak. This is done by showing that these sets are

$$(\mathscr {C}^{\alpha }, \mathscr {C}^{\alpha '})$$

(

C
α

,

C

α
′

)

-regular in the sense of Dinh, Ma and Nguyen.
Substrate expansion of Geotrichum candidum alcohol dehydrogenase towards diaryl ketones by mutation
Authors: Tang Zhongyao , Takagi Yuuki , Koesoema Afifa Ayu , Matsuda Tomoko
Published: December 2024

Chiral diaryl alcohols, such as (4-chlorophenyl)(pyridin-2-yl)methanol, are important intermediates for pharmaceutical synthesis. However, using alcohol dehydrogenases (ADHs) in the asymmetric reduction of diaryl ketones to produce the corresponding alcohols is challenging due to steric hindrance in the substrate binding pockets of the enzymes. In this study, the steric hindrance of the ADH from Geotrichum candidum NBRC 4597 (G. candidum acetophenone reductase, GcAPRD) was eliminated by simultaneous site-directed mutagenesis of Phe56 (in the large pocket) and Trp288 (in the small pocket). As a result, two double mutants, Phe56Ile/Trp288Ala, and Phe56Ala/Trp288Ala, exhibited much higher specific activities towards 2-(4′-chlorobenzoyl)pyridine (4.5 μmol/min/mg and 3.4 μmol/min/mg, respectively) than the wild type (< 0.2 μmol/min/mg). In whole-cell-catalyzed asymmetric reductions of diaryl ketones, Phe56Ile/Trp288Ala significantly increased the isolated yields, which were over 90% for the reactions of most of the tested substrates. Regarding enantioselectivity, Phe56Ile/Trp288Ala and Phe56Ala/Trp288Ala, and Trp288Ala generally exhibited similar selectivity to produce (R)-alcohols with up to 97% ee.

Key points

• Phe56 in Geotrichum reductase (GcAPRD) was mutated to eliminate steric hindrance.

• Mutation at Phe56 increased enzymatic activity and expanded substrate specificity.

• Phe56Ile/Trp288Ala showed high activity and (R)-selectivity towards diaryl ketones.

Graphical Abstract
Cystic lesions and their mimics involving the intrahepatic bile ducts and peribiliary space: diagnosis, complications, and management
Authors: Khot Rachita , Ganeshan Dhakshinamoorthy , Sundaram Karthik M. , Depetris Jena N. , Ludwig Daniel R.
Published: December 2024

Biliary and peribiliary cystic lesions represent a diverse group of abnormalities, often discovered incidentally during imaging for unrelated conditions. These lesions, typically asymptomatic, necessitate precise imaging modalities to characterize their nature and determine subsequent clinical actions, such as follow-up imaging, biopsy, or surgical referral. The anatomic location of these cystic lesions, whether biliary or peribiliary, influences both diagnostic and prognostic outcomes. Biliary cystic lesions, such as mucinous cystic neoplasms, intraductal papillary neoplasms of the bile duct, and Caroli disease, require careful monitoring due to their propensity to develop malignancy. In contrast, peribiliary cysts are often associated with chronic liver disease and may indicate disease progression through a gradual increase in cyst size. Accurate differentiation of these lesions from other clinical entities that have overlapping features on imaging, such as microabscesses, bilomas, Langerhans cell histiocytosis, neurofibromatosis, and vascular anomalies such as cavernous transformation of the portal vein, is essential given the divergent management for each. This article focuses on intrahepatic biliary and peribiliary cystic lesions and their mimics, highlighting their imaging characteristics with an emphasis on magnetic resonance imaging and magnetic resonance cholangiopancreatography, differential diagnosis, potential associated complications, and clinical management.
Discrepancy between radiography and magnetic resonance imaging in Japanese Investigation Committee classification type C osteonecrosis of the femoral head
Authors: Otaka Keiji , Osawa Yusuke , Takegami Yasuhiko , Funahashi Hiroto , Imagama Shiro
Published: December 2024

Purpose

The Japanese Investigation Committee (JIC) classification for osteonecrosis of the femoral head (ONFH) is based on the necrotic area relative to the weight-bearing surface on anteroposterior (AP) radiographs or central coronal MRI. Discrepancies exist between these methods, potentially related to the AP necrosis area. This study evaluated these discrepancies and the extent of AP necrotic lesions.

Methods

We retrospectively reviewed 139 patients (188 hips) with nontraumatic ONFH, JIC type C1 or C2 on radiography, and collapse < 3 mm. Cases with and without discrepancies between radiography and MRI were designated as discrepancy and consistent groups, respectively. We assessed the proportion of patients in the discrepancy group and survival rates in both groups, with femoral head collapse > 3 mm as the endpoint. The cutoff value for AP necrotic regions on lateral radiographs identifying discrepancies was calculated using ROC curve analysis.

Results

The discrepancy group comprised 28 hips (14.9%) vs. 160 hips in the consistent group. Five-year survival rates were 73.3% vs. 31.9% (P < 0.01), and AP necrotic region extent was 61.2 vs. 73.8 mm (P < 0.001) in discrepancy vs. consistent groups. The cutoff value for necrotic region extent revealing discrepancies was 66.9% (AUC 0.833, sensitivity 83.8%, specificity 82.4%).

Conclusion

Patients with AP necrotic regions < 66.9% were more likely to show discrepancies between radiography and MRI in type classification. This study can help improve accuracy in assessing ONFH severity and prognosis.
Regression of bilateral persistent primitive ophthalmic artery: a case report
Authors: Takeuchi Issei , Izumi Takashi , Nishihori Masahiro , Goto Shunsaku , Hanyu Taketo , Suzuki Keita , Takayanagi Kai , Kawasaki Yuichi , Saito Ryuta
Published: December 2024

Purpose

We report a case of regression of a 2-year-old girl with bilateral primitive ophthalmic arteries (POAs).

Case report

The patient presented with a headache and had no visual impairment or visual field abnormalities. Magnetic resonance angiography (MRA) revealed arteries originating bilaterally from the cavernous internal carotid artery segments, diagnosed as persistent POAs.

Conclusion

Six months later, MRA revealed decreased origin delineation and five years later, MRA revealed bilateral origin disappearance from the orbit to the periphery.
Predictors of treatment duration in conservative management of developmental dysplasia of hip -a retrospective cohort study
Authors: Kraus Tanja , Hammerschmid Anita , Guggenberger Bernhard , Novak Michael , Schappacher-Tilp Gudrun , Svehlik Martin
Published: December 2024

Developmental dysplasia of the hip is a prevalent condition in newborns. However, predicting the duration of conservative treatment remains challenging. This study aimed to determine the duration of treatment more precisely by analyzing associated factors. We conducted a retrospective analysis and developed a linear regression model based on 503 patients treated at our institution over the last 10 years. A linear regression model (GLM) was used for predicting treatment duration (df residuals 371, df model 3, Pearson Chi2 78.9, Number of iterations 15). The baseline scenario thereby feature a child with an average age at the beginning of treatment (35th day of life), both sides pathologically affected, and a minimum alpha angle of 29 degrees. The GLM identified age at treatment onset, alpha angle, and bilaterality as significant predictors of treatment duration. A four-week delay in treatment initiation extended the duration by one week, while a 5-degree increase in the alpha angle reduced it by two weeks. Bilaterality added 19 days to treatment duration. However, sex and clinical hip instability did not significantly affect the treatment time. These findings enable the calculation of treatment duration based on identified factors, potentially improving the management and planning of conservative therapies for developmental dysplasia of the hip in newborns.
Celiac in the twenty-first century—the change in BMI of children at diagnosis over the last two decades
Authors: Kasem Ali Sliman Rim , Stein Nili , Elenberg Alter Yigal
Published: December 2024

This study examined the prevalence of different BMI categories among newly diagnosed pediatric celiac disease (CD) patients in Israel from 2002 to 2018. A retrospective cross-sectional study using the database of Clalit Health Services in Israel included 5520 newly diagnosed CD children aged 2–18 between 2002 and 2018. Data on BMI, gender, ethnicity, and socioeconomic status (SES) were collected and analyzed Of the 5520 CD patients, 57.5% were female, 39.7% had low SES, and 77.1% were Jewish. At diagnosis, 13.1% were underweight, 73% had normal BMI, 9.1% overweight, and 4.8% were obese. Underweight and obese patients tended to be older at diagnosis (9 years) compared with normal and overweight patients (8 years) (P < 0.001). A higher proportion of Arab patients were underweight, while more Jewish patients were obese. Lower SES was significantly associated with increased underweight risk (P < 0.001). Over time, diagnosed patients had improved SES and were less underweight (P < 0.001). Male gender increased obesity risk (OR 1.36 [95% CI 1.06–1.74], P = 0.017), while Arab ethnicity was protective for obesity (OR 0.67 [95% CI, (0.45–0.99)], P = 0.047)

Conclusion: Underweight prevalence significantly decreased in the second decade, but no significant change in overweight and obesity was noted. Underweight was associated with older age at diagnosis, poverty, and Arab ethnicity. Obesity was associated with older age and was more frequent in Jewish and male patients. Physicians should have a low threshold for CD screening regardless of BMI status to enable timely diagnosis and treatment to prevent long-term health consequences.

What Is Known:
• Celiac disease is traditionally associated with underweight due to malabsorption, but recent reports suggest an increasing prevalence of overweight and obesity in pediatric patients at diagnosis
What Is New:
• This study found that underweight prevalence decreased significantly over time, while overweight and obesity prevalence remained unchanged. Underweight was associated with older age, poverty, and Arab ethnicity, while obesity was more common in Jewish and male patients
Seismic velocity changes from repetitive seismicity at Mauna Loa prior to and during its 2022 eruption
Authors: Hotovec-Ellis Alicia J.
Published: December 2024

Mauna Loa’s short-lived eruption from late November to early December 2022 marked the culmination of nearly a decade of elevated seismic activity and geodetic inflation. The volcano has been monitored by a network of permanent, short period and broadband seismometers. I used the continuous waveform data from that network starting in 2012 to generate a catalog of seismicity that enhances the US Geological Survey Hawaiian Volcano Observatory’s public seismic catalog with four times the number of earthquakes, which were then grouped by waveform similarity. Analysis of subtle delays in the timing of arrivals of scattered waves between pairs of earthquakes in this catalog yields a history of small changes in the shallow seismic velocity structure of the volcano. Seismic velocities have been shown at other volcanoes to change during unrest and eruption. My results show a decrease in seismic velocity centered on the summit beginning in September 2022, corresponding to the onset of a vigorous precursory swarm of seismic activity and shallow inflation. During the eruption itself, I observe large changes due likely to dike opening along the northeast rift zone and deflation of the summit reservoir. However, seismic velocity changes associated with non-volcanic sources such as ground shaking from large earthquakes and meteorological influences at seasonal and diurnal time scales are also observed, and these dominate the velocity changes prior to the eruption. Proper accounting of these effects will be a requirement for use in real-time monitoring, and this work serves as a starting point in that endeavor for Mauna Loa.
Childhood idiopathic nephrotic syndrome: recent advancements shaping future guidelines
Authors: Chan Eugene Yu-hin , Boyer Olivia
Published: December 2024

Childhood idiopathic nephrotic syndrome is an important pediatric kidney disease associated with significant morbidities and even mortality. Several guidelines have been developed to standardize the terminology and patient care among the pediatric nephrology community. Since the publication of these guidelines, there have been major breakthroughs in the disease management and the understanding of underlying pathogenesis through multi-omics investigations, including the identification of anti-nephrin autoantibodies, genetic susceptibility loci, and the pathogenic role of B cell subsets. In this educational review, we summarize the recent major advancements in idiopathic nephrotic syndrome and attempt to provide potential therapeutic approaches in both steroid-sensitive and steroid-resistant nephrotic syndrome that may shape future guideline development.

Graphical abstract
Measuring the biomechanical properties of cell-derived fibronectin fibrils
Authors: Dalton Caleb J. , Dhakal Soma , Lemmon Christopher A.
Published: December 2024

Embryonic development, wound healing, and organogenesis all require assembly of the extracellular matrix protein fibronectin (FN) into insoluble, viscoelastic fibrils. FN fibrils mediate cell migration, force generation, angiogenic sprouting, and collagen deposition. While the critical role of FN fibrils has long been appreciated, we still have an extremely poor understanding of their mechanical properties and how these mechanical properties facilitate cellular responses. Here, we demonstrate the development of a system to probe the mechanics of cell-derived FN fibrils and present quantified mechanical properties of these fibrils. We demonstrate that: fibril elasticity can be classified into three phenotypes: linearly elastic, strain-hardening, or nonlinear with a “toe” region; fibrils exhibit pre-conditioning, with nonlinear “toe” fibrils becoming more linear with repeated stretch and strain-hardened fibrils becoming less linear with repeated stretch; fibrils exhibit an average elastic modulus of roughly 8 MPa; and fibrils exhibit a time-dependent viscoelastic behavior, exhibiting a transition from a stress relaxation response to an inverse stress relaxation response. These findings have a potentially significant impact on our understanding of cellular mechanical responses in fibrotic diseases and embryonic development, where FN fibrils play a major role.
Oral Sex May Serve as Low Mate Value Compensation Among Men: Evidence from a Pre-registered Study
Authors: Frankowska Natalia , Szymkow Aleksandra , Galbarczyk Andrzej
Published: December 2024

From the evolutionary perspective, maintaining a committed relationship is beneficial for reproductive success but involves risks such as losing a partner or infidelity. People typically prefer partners with similar mate value (MV) to avoid rejection. However, when a mate value discrepancy (MVD) arises, the partner with lower MV might employ mate retention strategies to maintain the relationship. This study investigated whether men with lower MV compared to their female partners used cunnilingus more often and whether this effect was mediated by their motivation to satisfy the partner. Additionally, it tested the moderating role of men’s perceived vulnerability to disease (PVD), predicting that men less concerned about disease would show a stronger link between MVD and cunnilingus frequency, given the health risks associated with oral sex. Data from 540 men in committed heterosexual relationships confirmed that a higher MVD—where the man's MV was lower than his partner's—led to more frequent cunnilingus, and this relationship was mediated by a greater motivation to sexually satisfy the partner. However, the moderating role of PVD was not confirmed. We explore the evolutionary perspective that men may perform oral sex on their partners as a mate retention strategy. This behavior potentially serves as a benefit-provisioning mechanism, compensating for discrepancies in mate value.
Understanding Taphonomy Through 3D and 2D Records: A Case Study from the Tropical Maya Area
Authors: De Tomassi Mirko , Lercari Nicola
Published: December 2024

Mortuary archaeology in the Maya region is complicated by both cultural and natural factors. Distinctive funerary depositional and post-depositional secondary activities, in addition to tropical climate, contribute to the complexity of pre-Hispanic Maya funerary practices. This paper proposes to merge 2D and 3D recording data to obtain a comprehensive understanding of the taphonomic phenomena that affect heavily altered burials at the site of Palenque, Mexico. Employing an archaeothanatological approach, we argue that careful 3D imaging, integrated with earlier produced legacy data, provides additional insight into the formation processes of funerary contexts compared to previous methods. Digital photogrammetric analyses improve our capacity to reconstruct joint articulations of the body and its original funerary deposition in situ. The results of this research elucidate the intentional activities that led to the archaeological arrangement of the grave assemblage. By noticing the degree of articulation and clarifying the pace at which bodies decomposed, these results showcase the depositional sequence of one collective mixed burial from Group IV, a domestic compound in Palenque. These results suggest the viability of 3D methodologies in assessing post-depositional disturbances and movements of the body, both for illuminating funerary taphonomic practices and serving as important recording procedures for the future.
Neuronal traveling waves form preferred pathways using synaptic plasticity
Authors: Butler Kendall , Cruz Luis
Published: December 2024

Traveling waves of neuronal spiking activity are commonly observed across the brain, but their intrinsic function is still a matter of investigation. Experiments suggest that they may be valuable in the consolidation of memory or learning, indicating that consideration of traveling waves in the presence of plasticity might be important. A possible outcome of this consideration is that the synaptic pathways, necessary for the propagation of these waves, will be modified by the waves themselves. This will create a feedback loop where both the traveling waves and the strengths of the available synaptic pathways will change. To computationally investigate this, we model a sheet of cortical tissue by considering a quasi two-dimensional network of model neurons locally connected with plastic synaptic weights using Spike-Timing Dependent Plasticity (STDP). By using different stimulation conditions (central, stochastic, and alternating stimulation), we demonstrate that starting from a random network, traveling waves with STDP will form and strengthen propagation pathways. With progressive formation of traveling waves, we observe increases in synaptic weight along the direction of wave propagation, increases in propagation speed when pathways are strengthened over time, and an increase in the local order of synaptic weights. We also present evidence that the interaction between traveling waves and plasticity can serve as a mechanism of network-wide competition between available pathways. With an improved understanding of the interactions between traveling waves and synaptic plasticity, we can approach a fuller understanding of mechanisms of learning, computation, and processing within the brain.
Phosphorous determination in nuclear reactor materials: dysprosium titanate, titanium dioxide and uranium oxide
Authors: Verma Poonam , Thakur U. K. , Jeyakumar S.
Published: December 2024

A reliable analytical methodology is developed to determine phosphorus as phosphate in nuclear matrices viz uranium oxide, TiO2 and dysprosium titanate by spectrophotometric molybdenum blue method. Refractory matrices (TiO2 and dysprosium titanate) are dissolved employing microwave technique. Calibration is linear in the concentration range from 0.1 to 1.0 ppm of phosphorous with r2 better than 0.9989. LOD obtained is 0.03 ppm. Method and instrumental RSD is 1 and 0.3%, respectively at 0.33 ppm level. Recovery of P at 0.33 ppm level is better than 95%. The developed method is validated by comparing results obtained by ion chromatography.
First evidence of predation on the native endangered Iberian desman (Galemys pyrenaicus) and Iberian water shrews (Neomys anomalus) by the invasive species American mink using eDNA tools in Extremadura (Spain)
Authors: Ripa Adriana , Palacios-Gonzalez María Jesús , Díaz-Caballero José A. , Espinosa Antonio , Zalba Francisco Javier , García-Zapata Juan Luis , Fernádez-García José Luis
Published: December 2024

Background

Wildlife conservation and management aims to restore population declines, it is the vulnerable or endangered populations who require the greatest conservation efforts. In this context, non-invasive sampling has been evaluated as an option for reporting prey/predator impact. Galemys pyrenaicus is currently threatened throughout its range, and cohabits with Nemys anomalus, in Extremadura (Spain). Predation by American mink and otter has been suggested, but the first one is considered a serious conservation problem. This study has focused on the use of molecular methods based on RT-PCR and DNA sequencing, as it can inform on how invasive predators are harming the desman or the Iberian water shrew, and how these genetic tools can be used to detect predation.

Methods and results

Five samples (faecal and stomach contents) were received and RT-PCR assays were performed using TaqMan probes simultaneously targeting the cytochrome b (cytb) genes of G. pyrenaicus and N. anomalus, and the presence of both micromammals as prey was assessed. The predator was identified by Sanger sequencing using the nuclear IRBP gene. The assays provide a powerful tool for identification of invasive species, as in this case, but further confirmation by comparative sequence alignment by BLAST search was also necessary.

Conclusions

This study contributes to highlight simultaneously monitor and discriminate predation on specific micromammals with faecal samples of predators. Also supports the use of highly sensitive DNA analysis from samples obtained from predators as an additional methodology to monitor their effects on prey populations.
Understanding and how-possibly explanations: Why can’t they be friends?
Authors: Verreault-Julien Philippe , Grüne-Yanoff Till
Published: December 2024

In the current debate on the relation between how-possibly explanations (HPEs) and understanding, two seemingly irreconcilable positions have emerged, which either deny or assert HPEs’ contribution to understanding. We argue, in contrast, that there is substantial room for reconciliation between these positions. First, we show that a shared assumption is unfounded: HPEs can be interpreted as being correct explanations. Second, we argue that what we call the standard account is actually compatible with the claim that HPEs may improve understanding. Our analysis not only indicates that there is room for reconciliation, but also specifies the potential remaining disagreements.
Centenarians—the way to healthy vascular ageing and longevity: a review from VascAgeNet
Authors: Summer Sabrina , Borrell-Pages Maria , Bruno Rosa-Maria , Climie Rachel E. , Dipla Konstantina , Dogan Aysenur , Eruslanova Kseniia , Fraenkel Emil , Mattace-Raso Francesco , Pugh Christopher J. A. , Rochfort Keith D. , Ross Mark , Roth Lynn , Schmidt-Trucksäss Arno , Schwarz Dennis , Shadiow James , Sohrabi Yahya , Sonnenberg Jannik , Tura-Ceide Olga , Guvenc Tuna Bilge , Julve Josep , Dogan Soner
Published: December 2024

The prevalence of centenarians, people who lived 100 years and longer, is steadily growing in the last decades. This exceptional longevity is based on multifaceted processes influenced by a combination of intrinsic and extrinsic factors such as sex, (epi-)genetic factors, gut microbiota, cellular metabolism, exposure to oxidative stress, immune status, cardiovascular risk factors, environmental factors, and lifestyle behavior. Epidemiologically, the incidence rate of cardiovascular diseases is reduced in healthy centenarians along with late onset of age-related diseases compared with the general aged population. Understanding the mechanisms that affect vascular ageing in centenarians and the underlying factors could offer valuable insights for developing strategies to improve overall healthy life span in the elderly. This review discusses these key factors influencing vascular ageing and how their modulation could foster healthy longevity.
Interfacial mechanical behavior of epoxy-quartz: MD nanoindentation and nanoscratching study
Authors: Wei Pengchang , Yin Zhen-Yu , Hicher Pierre-Yves , Xu Wangqi
Published: December 2024

Fiber-reinforced polymer (FRP) is widely used in various engineering fields due to its several outstanding properties. In geotechnical engineering, the interactions between FRP and soil play an essential role. In this paper, molecular dynamics (MD) simulation method has been performed to study the interfacial mechanical behavior of epoxy-quartz interface as a subsystem of FRP-soil structure. Uniaxial traction on bulk epoxy was conducted to verify the accuracy of the model. The nanoindentation and nanoscratching mechanisms of epoxy-quartz interface were analyzed, considering the effect of loading rate, sliding velocity, and indentation depth. Abrasion models have been proposed based on the relationship between forces and displacements. Simulation results indicated that the indenter force and the indentation hardness of epoxy substrate increased with the loading rate during nanoindentation, and the relationship between indenter force and indentation depths could be expressed by a power law. The forces along three directions increased with the sliding velocity or indentation depths during nanoscratching, the sliding force and the sliding distance following an exponential function. The numerical simulations demonstrated that the surface wear of the epoxy substrate had the shape of a groove in nanoindentation and a fan-shaped distribution during the nanoscratching process.
Technology-Based Substance Use Interventions for Emerging Adults and College Students: A Systematic Review and Meta-Analysis
Authors: Hai Audrey Hang , Curran Laura , Simons Jocelyn N. , Carey Kate B. , Bordnick Patrick S.
Published: December 2024

Objective

To synthesize randomized controlled trial evidence on technology-based interventions’ (TBIs) effectiveness for substance use among emerging adults (EA)/college students (CS).

Methods

Nine electronic databases were searched. Two reviewers independently screened studies, extracted data, and assessed evidence quality. We used robust variance estimation in meta-regression for effect size synthesis and moderator analysis.

Results

Based on 130 studies, the overall between-group effect size was 0.23 (95% CI = 0.18, 0.28). The effect sizes for comparing TBIs with no treatment, standard care, and non-technology interventions were 0.25 (CI = 0.19, 0.31), 0.23 (CI = 0.15, 0.32), and 0.12 (CI = -0.02, 0.25), respectively. Older participants showed significantly larger effect sizes, and interventions using multiple technologies had larger effects than smartphone-based ones.

Conclusion

TBIs are effective in reducing substance use in EA/CS, with outcomes comparable to non-technology interventions and advantages over no treatment and standard care. Future research should address drug-related outcomes, multi-technology approaches, age-appropriate designs, and cultural diversity.
When am I Accountable for What Others do? The Causal Accounts and the Explanatory Challenge
Authors: Oidermaa Meradjuddin Khan
Published: December 2024

The majority of authors in the complicity literature claim that causal accounts of complicity are inadequate because they fail to handle cases of causal overdetermination (Kutz, 2000, 2007, 2020; Lawson, 2013; Driver, 2015a, b; Bazargan-Forward, 2013, 2017, 2022; Mellema, 2016; Aragon and Jaggar, 2018; Williams 2019; Bennett, 2021; Donohue, 2021; Knowles, 2021). However, it has recently been argued that causal accounts can handle such cases (Lepora and Goodin, 2013; Petterson, 2013; Jensen, 2020). In this paper I scrutinize these defenses. I argue while they make some progress towards overcoming the standard overdetermination challenge, they are not fully satisfactory. More importantly, I present a novel challenge raised by cases of overdetermination—the explanatory challenge. I argue that, not only do these recent defenses not overcome this challenge, it is unlikely that any causal account can overcome it. Finally, I suggest that since causal accounts of complicity are inadequate, pluralism about complicity must be correct, because we cannot fully dispense with causation from our understanding of complicity.
Evaluating air leakage from staple line reinforcements in anatomical pulmonary resection (AIRSTOP): a prospective randomized controlled trial protocol
Authors: Yusa Jotaro , Tanaka Kazuhisa , Takahashi Kohei , Shiko Yuki , Sugawara Takeshi , Yoshino Ichiro , Suzuki Hidemi
Published: December 2024

Background

Air leakage during pulmonary resection is a major complication in thoracic surgery. It frequently occurs at sites of adhesion dissection, due to lung manipulation, and along the staple lines of automatic suturing devices, particularly in cases of pulmonary fragility such as those of emphysema and interstitial pneumonia. Persistent postoperative air leakage prolongs chest tube indwelling and extends hospitalization time. Staplers with absorbable tissue reinforcements have been introduced for pulmonary resection to prevent intraoperative stapler-related air leakage. This phase II prospective, open-label, randomized, parallel-group trial aims to validate the efficacy of staplers with or without absorbable tissue reinforcements in controlling stapler-related air leakage during anatomical pulmonary resections.

Methods

Overall, 120 patients will be randomized into two groups: one that will undergo conventional anatomical pulmonary resection and the other in which staplers with absorbable tissue reinforcements will be used. The primary endpoint will be intraoperative stapler-related air leakage. Data will be analyzed between 2024 and 2025.

Discussion

This trial will validate the effectiveness and safety of staple line reinforcements in controlling intraoperative air leakage during anatomical pulmonary resections, potentially leading to optimized strategies for patients with conditions such as emphysema and interstitial pneumonia.

Trial registration

This trial has been registered with the Japan Registry of Clinical Trials 1032220620 (https://jrct.niph.go.jp/latest-detail/jRCTs031230224).
Disease Network-Based Approaches to Study Comorbidity in Heart Failure: Current State and Future Perspectives
Authors: Gomez-Ochoa Sergio Alejandro , Lanzer Jan D. , Levinson Rebecca T.
Published: December 2024

Purpose of Review

Heart failure (HF) is often accompanied by a constellation of comorbidities, leading to diverse patient presentations and clinical trajectories. While traditional methods have provided valuable insights into our understanding of HF, network medicine approaches seek to leverage these complex relationships by analyzing disease at a systems level. This review introduces the concepts of network medicine and explores the use of comorbidity networks to study HF and heart disease.

Recent Findings

Comorbidity networks are used to understand disease trajectories, predict outcomes, and uncover potential molecular mechanisms through identification of genes and pathways relevant to comorbidity. These networks have shown the importance of non-cardiovascular comorbidities to the clinical journey of patients with HF. However, the community should be aware of important limitations in developing and implementing these methods.

Network approaches hold promise for unraveling the impact of comorbidities in the complex presentation and genetics of HF. Methods that consider comorbidity presence and timing have the potential to help optimize management strategies and identify pathophysiological mechanisms.
Beyond the herd: investigating livestock feeding strategies in the Iron Age Iberian Peninsula (3rd c. BC) through a multi-isotope analysis
Authors: Messana Chiara , Tornero Carlos , Colominas Lídia
Published: December 2024

During the Iron Age, north-eastern Iberian communities relied on crop cultivation and animal husbandry for their subsistence. The latter was mainly focused on caprine, with sheep being prominent due to their suitability to the Mediterranean climate, orography, and environment. Despite the pivotal role of sheep in livestock husbandry, information on Iberian communities’ feeding strategies for this species is limited. To address this lacuna, this study investigates the livestock feeding habits at four Catalan sites dating back to the 3rd century BC: Mas Castellar de Pontós, Tossal de Baltarga, Sant Esteve d’Olius, and Turó de la Rovira. Bulk carbon and nitrogen isotope analyses (δ13C and δ15N) of bone collagen and sequential carbon and oxygen analyses (δ13C and δ18O) of dental enamel were performed on 74 remains (43 bones, 31 teeth) from 51 sheep. Additionally, 153 bone remains from other domestic and wild species from the four sites were analysed. Our results revealed the complex and adaptive livestock feeding strategies of Iron Age Iberian populations. Sheep exhibited minimal diet variations, mainly consuming C3 plants across the four sites. Nevertheless, their feeding habits changed seasonally depending on pasture availability and settlement requirements. The other main domestic species were subject to individualised and variable feeding strategies within the same settlement. This diversified feeding management unveiled the complex and adaptive nature of the husbandry practices employed by Iron Age Iberian communities. Finally, the extensive number of remains analysed provides the first data on livestock feeding strategies for the Middle/Late Iron Age in the north-eastern Iberian Peninsula.
Ionic liquids as stabilisers of therapeutic protein formulations: a review of insulin and monoclonal antibodies
Authors: Tien Samuel , Kayser Veysel
Published: December 2024

Therapeutic proteins such as insulin and monoclonal antibodies (mAbs) have become an essential part of the modern healthcare system and play a crucial role in the treatment of various diseases including cancer and autoimmune disorders. However, their long-term stability is a significant concern, affecting efficacy, shelf-life, and safety. Ionic liquids (ILs) have emerged as promising additives to enhance protein stability and address the aforementioned issues. Indeed, recent studies indicate that biocompatible ILs, particularly choline-based ILs, have significant potential to improve stability while preserving proteins’ functionality. For instance, choline valinate has been shown to increase the melting temperature of insulin by almost 13 °C (Judy and Kishore Biochimie 207:20-32, 2023), while choline dihydrogen phosphate has increased the melting temperature of trastuzumab by over 21 °C (Reslan et al. Chem Commun 54:10622-10625, 2018). However, it is worth noting that the use of some ILs introduces a complex trade-off: while they can increase thermal stability, they may also promote protein unfolding, thereby reducing conformational stability. Moreover, selecting the most suitable IL and its optimal concentration is challenging, as different protein formulations may exhibit varying effects. This review provides a comprehensive overview of the existing literature on ILs as stabilisers for insulin and mAbs, documenting specific IL-protein combinations and conditions to identify potential future stabilising agents for biologics in general.
The PARPscore system using poly (ADP-ribose) polymerase (PARP) family features and tumor immune microenvironment in glioma
Authors: Zhang Cheng , Feng Juan , Zhou Xia , Zhang Jie , Tao Chuming , Zhou Hongwei
Published: December 2024

The immune response plays a pivotal role in tumor progression and therapy. However, the influence of protein PAR polymerases (PARPs) modifications on cell infiltration within the tumor microenvironment (TME) remains insufficiently understood. In this study, the Clinical and RNA sequencing data we performed a comprehensive analysis of PARPs modification patterns, exploring their associations with TME cell infiltration were acquired from the Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) database. To quantify PARPs modification in individual tumors, we developed a novel metric, the PARPscore, derived using principal component analysis. Our findings revealed three distinct PARPs modification patterns, each correlated with unique TME infiltration characteristics and tumor immunophenotypes. These patterns demonstrated predictive value for various clinical parameters, including inflammation stage, tumor subtypes, TME matrix activity, genetic variations, and patient prognosis. Notably, the high PARPscore subtype exhibited features of stromal activation and reduced immune infiltration, indicative of a non-inflamed, immune-excluded TME phenotype, and was associated with poorer survival outcomes. Conversely, lower PARPscore subtypes corresponded to substantial therapeutic benefits and improved outcomes in two independent immunotherapy cohorts. This study underscores the critical role of PARPs modification in shaping the diverse and dynamic TME. By delineating tumor-specific PARPs modification patterns, we provide valuable insights into TME complexity and its implications for immunotherapy.
Effects of Treated Effluent Discharge on Tree Growth and Water use in a Cypress Swamp
Authors: Schexnayder Devin , Wolfe Brett T.
Published: December 2024

When municipal effluent is discharged into swamps, baldcypress trees (Taxodium distichum) generally respond with increased growth. This growth increase may be associated with increased transpiration (E), but if functional traits are also affected, they may modulate the response of E to environmental conditions such as atmospheric vapor pressure deficit (VPD). We measured tree growth and sap flux to assess water-use traits and daily E in mature baldcypress trees that received effluent discharge and compared them to nearby trees that did not receive effluent. Basal area increment and foliar N:P were higher in trees that received effluent. For any given tree size, E was 5.8 L day−1 higher in trees receiving effluent. Sap-flux-based whole-tree canopy conductance at the reference VPD of 1 kPa and its sensitivity to VPD were both positively related to foliar N:P, suggesting that effluent discharge shifted trees to higher water use when VPD was relatively low, but that water use was more sensitive to VPD. Our results suggest that when effluent discharge increases forested wetland productivity it can also increase E, but these effects may be diminished by high VPD.