bluuebunny/crossref_metadata_2025 huggingface dataset:
In vitro
investigations on the impact of fermented dairy constituents on fecal microbiota composition and fermentation activity
Authors: Li Qing , Marietou Angeliki , Andersen Freja Foget , Hosek Jiri , Scavenius Carsten , Zhang Jianbo , Schwab Clarissa
Published: February 2025

Fermented dairy constitutes a major dietary source and contains lactose as the main carbohydrate and living starter cultures, which can encounter the intestinal microbiota after ingestion. To investigate whether dairy-related nutritional and microbial modulation impacted intestinal microbiota composition and activity, we employed static fecal microbiota fermentations and a dairy model system consisting of lactose and
Streptococcus thermophilus
wild type and β-galactosidase deletion mutant. In addition, we conducted single-culture validation studies. 16S rRNA gene-based microbial community analysis showed that lactose increased the abundance of
Bifidobacteriaceae
and
Anaerobutyricum
and
Faecalibacterium
spp. The supplied lactose was hydrolyzed within 24 h of fermentation and led to higher expression of community-indigenous β-galactosidases. Targeted protein analysis confirmed that bifidobacteria contributed most β-galactosidases together with other taxa, including
Escherichia coli
and
Anaerobutyricum hallii
. Lactose addition led to higher (
P
< 0.05) levels of butyrate compared to controls, likely due to lactate-based cross-feeding and direct lactose metabolism by butyrate-producing
Anaerobutyricum
and
Faecalibacterium
spp. Representatives of both genera used lactose to produce butyrate in single cultures. When supplemented at around 5.5 log cells mL
−1
,
S. thermophilus
or its β-galactosidase-negative mutant outnumbered the indigenous
Streptococcaceae
population at the beginning of fermentation but had no impact on lactose utilization and final short-chain fatty acid profiles.

IMPORTANCE

The consumption of fermented food has been linked to positive health outcomes, possibly due to interactions of food components with the intestinal microbiota. This study brings forward new insights into how major constituents of fermented dairy affect intestinal microbial ecology and activity when supplied together or alone. We provide evidence that lactose availability increased the production of butyrate by fecal microbiota through cross-feeding and did not observe a contribution of starter cultures to lactose metabolism, possibly due to a lack of competitiveness. The methodological setup used in this study can be implemented in future investigations to determine the impact of other fermented foods and their major components on intestinal microbiota composition and activity.
Detection of tick-borne pathogens in blood-fed ticks from animals across nine Asian countries
Authors: Byun Hye-Ryung , Rieu Mi-Sun , Ji Seong-Ryeong , Nam Hyun-Young , Seo Seulgi , Choi Chang-Yong , Linh Bui Khanh , Thanh Hien Le , Kaewthamasorn Morakot , Sahara Ana , Galay Remil L. , Wang Shang-Lin , Erdenechimeg Tuvshinjargal , Batbayar Nyambayar , Matsui Shin , Kawaji Noritomo , Avais Muhammad , Chae Joon-Seok
Published: February 2025

Climate change, land development, and increased outdoor human activity have increased the prevalence and distribution of tick-borne pathogens, causing public health issues. Asia is a pivotal region of emerging infectious diseases caused by zoonotic disease. Therefore, this study aimed to construct effective surveillance systems and establish preventive strategies against novel tick-borne diseases. Next-generation sequencing (NGS) was performed to detect tick-borne pathogens from animal blood-fed ticks. Ticks (
n
= 261) were collected from different animals across nine Asian countries between 2022 and 2023. Five genera of adults and nymphal ticks were used, namely,
Amblyomma
,
Haemaphysalis
,
Hyalomma
,
Rhipicephalus
, and
Ixodes
. The animals from which the ticks were collected were wild, domestic animals, birds, and reptiles, living in the natural environment. After NGS, clean reads of 18,382,262–30,460,619 DNA viruses, 22,744,384–32,400,471 RNA viruses, 134,506–286,282 16S rRNA of bacteria, and 147,154–352,826 18S rRNA of protozoa were obtained from nine Asian countries. After analysis of the species, 28 RNA, 13 DNA viruses, 16 bacteria, and 4 protozoa were detected. Several tick-borne pathogens, including those in families that cause zoonotic diseases, such as
Phenuiviridae
,
Nairoviridae
,
Rickettsiaceae
, and
Borreliaceae
, were identified. This study is distinctive in that it involved cooperative studies with nine Asian countries to prevent the spread of tick-borne diseases. The results suggest that pathogens, which were detected in animal blood-fed ticks, can circulate in animals and may be transmitted to humans. In addition, this study can provide a basis for effective surveillance systems to prevent novel pathogens.

IMPORTANCE

Surveillance systems against novel tick-borne diseases are significant for global health. Climate and other environmental changes have contributed to an expanding range of ticks and tick-borne diseases. Areas in Asia constitute key areas of emerging infectious diseases. Through analysis of blood-fed ticks, collected from various animals living in the natural environment, we suggest that tick-borne pathogens may harbor animals and environment and have potential risk of transmission in humans. Understanding the distribution of tick-borne pathogens requires cooperative studying and, thus, can construct standardized surveillance systems.
Carbon footprinting and environmental impact of gastrointestinal endoscopy procedures at a tertiary care institution: a prospective multi-dimensional assessment
Authors: Rughwani Hardik , Kalapala Rakesh , Katrevula Anudeep , Jagtap Nitin , Desai Madhav , Campos Sara Teles de , Ramchandani Mohan , Lakhtakia Sundeep , Talukdar Rupjyoti , Darisetty Santosh , Memon Sana Fatima , Rao Guduru Venkat , Bruno Marco , Sharma Prateek , Reddy D Nageshwar
Published: February 2025

Background

Given the imperative to combat climate change, reducing the healthcare sector’s implications on the environment is crucial.

Objective

This study aims to offer a comprehensive assessment of the environmental impact of gastrointestinal endoscopy (GIE) procedures, specifically focusing on greenhouse gas (GHG) emissions and waste generation.

Design

A prospective study was conducted at the Asian Institute of Gastroenterology (AIG Hospitals), Hyderabad, India, from 29 May to 10 June 2023, including all consecutive GIE procedures. Carbon emissions for various variables involved were calculated with specific emission factors using ‘The GHG Protocol’.

Results

Based on data from 3244 consecutive patients undergoing 3873 procedures, the study revealed a total carbon footprint of 148 947.32 kg CO2e or 38.45 kg CO2e per procedure. Excluding patient travel, the emissions were 6.50 kg CO2e per procedure. The total waste generated was 1952.50 kg, averaging 0.504 kg per procedure, far less than 2–3 kg per procedure in the West. The waste disposal breakdown was 9.5% direct landfilling, 64.8% incineration, then landfilling and 25.7% recycling, which saved 380 kg CO2e. India effectively recycles 25.7% of hospital-related waste, which undergoes landfilling in the West. The primary contributors to GHG emissions were patient travel (83.09%), electricity consumption (10.42%), medical gas transport and usage (3.63%) and water consumption (1.86%). Diagnostic procedures generate less waste and lower carbon footprint than therapeutic procedures.

Conclusion

This study highlights the significant environmental footprint of GIE procedures, emphasising the importance of optimising practices to reduce patient travel and repeat procedures, alongside improving electricity and water management for sustainable healthcare.
Effects of dietary Pleurotus geesteranus stem supplementation on growth performance, anti-inflammation activity, intestinal function, and meat quality in pigs
Authors: Ju Ying , Sun Sheng , Lin Shengli , Huang Liling , Liu Xuzhou , Qi Liangliang
Published: February 2025

The study evaluated the effects of Pleurotus geesteranus stem (PGS), an agricultural waste rich in bioactive components, on pig growth, antioxidant status, anti-inflammatory responses, short-chain fatty acid (SCFA) production, fecal microbiota, intestinal function, and meat quality across different stages. In Exp. 1, 108 weaned piglets (7.80 ± 0.41 kg) were randomly assigned to three dietary treatments: control (basal diet), 1.5% PGS, and 3% PGS. In Exp. 2, 108 growing-finishing pigs (76.97 ± 5.91 kg) were subjected to the same treatments. Results showed that diets supplemented with PGS increased the average daily gain (ADG) (P<0.05) and fecal total SCFA contents (P<0.05) of piglets. PGS supplementation reduced serum interleukin-6 (IL-6) content (P<0.05) and fecal Escherichia coli counts (P<0.05) in piglets. The PGS addition could enhance ileal mucosal mucin 1 and mucin 2 expression (P<0.05), decrease drip loss (P<0.05), and increase pH45min value (P<0.05) of longissimus dorsi muscle (LDM), and down-regulate ACC expression (P<0.05) in LDM of growing-finishing pigs. Overall, PGS supplementation positively influenced growth performance, inflammation control, SCFA production, intestinal health, and meat quality.
Novel Approach to Optimizing Express-Local Metro Train Timetable Considering Multiple Train Stopping Patterns
Authors: Ye Mao , Zhang Renjie , Lai Yuanwen , Easa Said M. , Zhan Yuchao , Lan Wenhai
Published: February 2025

A traditional hybrid operational mode of a metro system usually combines the express and local trains. The stopping patterns of express trains are generally assumed to be the same. To provide a diverse service, this paper aims to explore the train timetable optimization method when the express trains have different stopping patterns. A passenger-oriented timetabling model for reducing passenger waiting time is established, which is proved to be a quadratic programming problem. Then, an Interior Point Method is applied to obtain the best timetable. A case study based on the Guangzhou Metro Network is conducted, symbolizing different operation strategies. The results indicate that the proposed model can efficiently reduce the passenger waiting time by 16.8% and the number of stranded passengers by 15.9%. The practical implications of this research are significant, as it introduces a new approach to train timetable optimization that can be applied to real-world metro systems.
Provincial diffusion, national acceptance: the transfer of conservation easement policy in Canada
Authors: Hisey Forrest
Published: February 2025

Conservation easements (CEs) are a private land conservation (PLC) tool, with landowners voluntarily selling property rights to an outside entity (governmental or nongovernmental). Pioneered in the USA, CEs were operationalized in the late 1980s, and by 2001, legislation had swept across Canada. I asked how did subnational Canadian CE policy develop? I analyzed Hansard records and interviewed government officials, finding coercion from the Federal government and environmental nongovernmental organizations (eNGOs), with transfer being ideologically, geographically, and temporally uneven. CE legislation reveals a fundamental shift in how subnational governments were trying to enhance biodiversity conservation, specifically by legitimizing PLC and non-state partners. Interestingly, this study both confirms, and pushes back against, previous Canadian policy transfer studies. I found a lack of formal subnational policy networks and an increased role of subnational policy innovators unlike previous studies, while the substantial U.S. influence align with older policy cases. ENGOs were the most active proponents to push for CE legislation, not policymakers or foreign states. Ultimately, Canadian federalism creates unique subnational policy arenas that require further study to understand the movement of conservation policy, especially with the crises of biodiversity and climate.
Drivers of high rates of carbon burial in a riverine-influenced freshwater marsh in the Long Point Walsingham Priority Place of southern Ontario
Authors: Loder Amanda L. , Gillespie Adam , Ardakani Omid Haeri , Oviedo Cecilia Cordero , Finkelstein Sarah A.
Published: February 2025

Reported rates of soil organic carbon (SOC) accumulation in wetlands are markedly higher over recent versus longer timescales, caused by SOC losses through decomposition, paleoenvironmental changes, and recent increases in sedimentation or biomass production. Explaining changes in SOC sequestration rates and determining the time horizon over which high rates are sustained are both critical for accurately measuring the potential for wetland conservation as a natural climate solution. Here, we present analyses on a 4-m core from a riverine-influenced marsh in Big Creek watershed, southern Ontario, to track changes in SOC accumulation regimes. Since wetland initiation ∼5700 years ago, mean long-term (pre-industrial) rates of SOC accumulation were 24 g C m−2 year−1, and recent rates up to four times higher. We demonstrate that elevated recent rates of SOC accumulation are largely explained by more labile carbon in surficial soils, and are sustained for less than a century before transitioning to slower burial rates of predominantly recalcitrant organic matter. However, there are exceptions to this trend, such as when labile SOC was buried intermittently during Holocene Lake Erie highstands. Our research underscores the importance of organic matter type and hydroclimatic context in predicting long-term potential for marsh soils to stabilize atmospheric carbon.
Weak gravity conjecture validation with photon spheres of quantum corrected Reissner–Nordstrom–AdS black holes in Kiselev spacetime
Authors: Alipour Mohammad Reza , S. Afshar Mohammad Ali , Noori Gashti Saeed , Sadeghi Jafar
Published: February 2025

In this study, we investigate the Weak Gravity Conjecture (WGC) in the context of quantum-corrected Reissner–Nordstrom–AdS (RN-AdS) black holes within Kiselev spacetime. Our focus is on photon spheres, which serve as markers for stable and unstable photon spheres. We confirm the validity of the WGC by demonstrating that quantum corrections do not alter the essential charge-to-mass ratio, thereby supporting the conjecture’s universality. Our analysis reveals that black holes with a charge greater than their mass

$$(Q > M)$$

(
Q
>
M
)

possess photon spheres or exhibit a total topological charge of the photon sphere

$$(\text {PS} = -1),$$

(
PS
=
-
1
)
,

which upholds the WGC. This finding is significant as it reinforces the conjecture’s applicability even in the presence of quantum corrections. Furthermore, we examine various parameter configurations to understand their impact on the WGC. Specifically, we find that configurations with

$$\omega = -\frac{1}{3}$$

ω
=
-

1
3

and

$$\omega = -1$$

ω
=
-
1

maintain the conjecture, indicating that these values do not disrupt the charge-to-mass ratio required by the WGC. However, for

$$\omega = -\frac{4}{3},$$

ω
=
-

4
3

,

the conjecture does not hold, suggesting that this particular parameter value leads to deviations from the expected behavior. These results open new directions for research in quantum gravity, as they highlight the importance of specific parameter values in maintaining the WGC. The findings suggest that while the WGC is robust under certain conditions, there are scenarios where it may be challenged, prompting further investigation into the underlying principles of quantum gravity.
Dark I-Love-Q
Authors: Wu Jing-Yi , Li Wei , Huang Xin-Han , Zhang Kilar
Published: February 2025

For neutron stars, there exist universal relations insensitive to the equation of states, the so called I-Love-Q relations, which show the connections among the moment of inertia, tidal Love number and quadrupole moment. In this paper, we show that these relations also apply to dark stars, bosonic or fermionic. The relations can be extended to higher ranges of the variables, clarifying the deviations for dark stars in the literature, as those curves all approximate the ones generated by a polytropic equation of state, when taking the low density (pressure) limit. Besides, we find that for equation of states with scaling symmetries, the I-Love-Q curves do not change when adjusting the scaling parameters.
Prediction of mass and radii of anisotropic polytropic compact objects with Buchdahl-I metric
Authors: Mardan S. A. , Zahra A. , Riaz Muhammad Bilal , Manzoor Rubab , Malik Adnan
Published: February 2025

In this article, we discuss several compact objects (GW 190814, PSR J0952-0607, PSR J0030+0451, PSR J0740+6620,   GW 170817,   PSR J1614-2230,   PSR J2215+5135, and 4U 1608-52) to predict their masses and radii. A generalized polytropic stellar model within the framework of general relativity is derived by employing the Buchdahl-I metric. All the physical quantities such as energy density, radial, and tangential pressure are well behaved, continuous and no singularity is observed. The obtained results are compatible with observational data for compact objects under consideration. The physical stability of this model is determined by using generalized hydrostatic equilibrium condition, energy conditions, causality conditions and Herrera’s cracking technique. We observe that our model fulfills all of the requirements for being a physically realistic model.
Perturbative construction of equilibrium states for interacting fermionic field theories Semiclassical Maxwell equation and the Debye screening length
Authors: Galanda Stefano
Published: February 2025

In this paper, we aim to extend to interacting massive and massless fermionic theories the recent perturbative construction of equilibrium states developed within the framework of perturbative algebraic quantum field theory on Lorentzian spacetime. We analyze the case of interactions which depend on time by a smooth switch-on function and on space by a suitably bounded function that multiplies an interaction Lagrangian density constructed with the field of the theory. The construction is achieved by first considering the case of compact support and, in a second step, by removing the space cutoff with a suitable limit (adiabatic limit). As an application, we consider a Dirac field interacting with a classical stationary background electromagnetic potential, and we compute at first perturbative order (linear response) the expectation value of the conserved current on the equilibrium state for the interacting theory. The resulting expectation value is written as a convolution, in the space coordinates, between the electromagnetic potential and an integral kernel which, at vanishing conjugate momentum, gives the inverse of the square Debye screening length at finite temperature. The corresponding Debye screening effect is visible in the backreaction treated semiclassically of this current on the classical background electromagnetic potential sourced by a classical external current.
Almost non-positive Kähler manifolds
Authors: Zhang Yuguang
Published: February 2025

This paper proves that the universal covering of a compact Kähler manifold with small positive sectional curvature in a certain sense is contractible.
Undergirding Bonding Curves: Supply-sovereign Automated Market Makers Enabling Liquidity and Sustainable Financing
Authors: Kirste Daniel , Poddey Alexander , Sunyaev Ali
Published: February 2025

Conventional exchanges and market makers facilitating initial public offerings and market making of tokens are prone to illicit practices. Automated market makers (AMMs) and, especially, supply-sovereign AMMs (sAMMs) seem to tackle those challenges by employing persistent and transparent market making strategies.

AMM designs typically serve two purposes: (1) facilitating the exchange of tokens not issued by the AMM and (2) enabling the issuance and exchange of tokens by the AMM itself, known as supply-sovereign AMMs).

In this work, we establish the foundations of bonding curve representations for these two AMM designs and explore their relationships. We introduce
undergirding bonding curve
(UBC)-based sAMMs, a novel design of sAMMs well suited to represent continuous value growth and to support all project phases, from raising capital to mature and late phases. This is achieved by the novel type of shape-adapting bonding curve in our sAMM, enabling incentive-compatible value accumulation and distribution to shareholders. The provided formalized analysis shows that UBC-based sAMMs implement desirable characteristics of conventional share-based companies with accumulated future value derived from generated revenues.
The Once and Future Gas: Methane's Multifunctional Roles in Earth's Evolution and Potential as a Biosignature
Authors: Glass Jennifer B. , Hörst Sarah M.
Published: February 2025

Methane (CH4) is a simple molecule that, due to its radiative forcing, wields an outsized impact on planetary heat balance. Methane is formed by diverse abiotic pathways across a range of pressures and temperatures. Biological methanogenesis for anaerobic respiration uses a terminal nickel-containing enzyme and is limited to the archaeal domain of life. Methane can also be produced in aerobic microbes during bacterial methylphosphonate and methylamine degradation and via nonenzymatic reactions during oxidative stress. Abiotic CH4 is produced via thermogenic reactions and during serpentinization reactions in the presence of metal catalysts. Reconstructions of methane cycling over geologic time are largely inferential. Throughout Earth's history, methane has probably been the second most important climate-forcing greenhouse gas after carbon dioxide. Biological methanogenesis has likely dominated CH4 flux to Earth's atmosphere for the past ∼3.5 billion years, during which time CH4 is thought to have generally declined as atmospheric oxygen has risen. Here we review the evolution of the CH4 cycle over Earth's history, showcasing the multifunctional roles CH4 has played in Earth's climate, prebiotic chemistry, and microbial metabolisms. We also discuss the future of Earth's atmospheric CH4, the cycling of CH4 on other planetary bodies in the Solar System (with special emphasis on Titan), and the potential of CH4 as a biosignature on Earth-like extrasolar planets.

▪

Before life arose on Earth, abundant atmospheric CH4 in Earth's early atmosphere was likely key for establishment of habitable conditions and production of organic molecules for prebiotic chemistry.

▪

Biological methanogenesis for anaerobic respiration is only known to exist in some groups of anaerobic archaea, but CH4 can also be produced via enzymatic and nonenzymatic biological pathways that are not directly coupled to energy conservation. The relative importance of each of these pathways to the global CH4 cycle is a topic of active research, but archaeal methanogenesis dominates all other biological pathways for CH4 generation.

▪

As atmospheric O2 rose over Earth history, models suggest that atmospheric CH4 declined; in the distant deoxygenated future, atmospheric CH4 is predicted to rise again.

▪

Future missions to Titan will aid in understanding the complex organic chemistry on the only other planetary body in our Solar System with an active methane cycle.
Reaction Coordinates Are Optimal Channels of Energy Flow
Authors: Ma Ao , Li Huiyu
Published: February 2025

Reaction coordinates (RCs) are the few essential coordinates of a protein that control its functional processes, such as allostery, enzymatic reaction, and conformational change. They are critical for understanding protein function and provide optimal enhanced sampling of protein conformational changes and states. Since the pioneering work in the late 1990s, identifying the correct and objectively provable RCs has been a central topic in molecular biophysics and chemical physics. This review summarizes the major advances in identifying RCs over the past 25 years, focusing on methods aimed at finding RCs that meet the rigorous committor criterion, widely accepted as the true RCs. Importantly, the newly developed physics-based energy flow theory and generalized work functional method provide a general and rigorous approach for identifying true RCs, revealing their physical nature as the optimal channels of energy flow in biomolecules.
Transarterial Chemoembolization with Radiofrequency Ablation versus Surgical Resection for Small Late-Recurrence Hepatocellular Carcinoma
Authors: Zhang Yao-Jun , Chen Jinbin , Zhou Zhongguo , Hu Dandan , Wang Juncheng , Pan Yangxun , Fu Yizhen , Hu Zili , Xu Li , Chen Min-Shan
Published: February 2025

In patients with small late-recurrence hepatocellular carcinoma, combined transarterial chemoembolization with radiofrequency ablation did not result in better survival outcomes compared with surgical resection alone but could be a safer option.
Elucidating Factors Governing the Discrepancy of Oxygen Vacancy Concentration Between La0.6Sr0.4Co1−yFeyO3−δ (y = 0, 0.2, 0.4, 0.6, 0.8, 1) Dense Film and Bulk Electrodes
Authors: Oi Daichi , Miyashita Nanaha , Budiman Riyan Achmad , Develos-Bagarinao Katherine , Kimura Yuta , Nakamura Takashi , Yashiro Keiji , Amezawa Koji , Kawada Tatsuya
Published: February 2025

Dense film electrodes are used to understand the reaction mechanisms of solid oxide cells. However, the oxygen vacancy concentration, δ, in films differ from that in bulk materials, which can mislead the understanding of the reaction mechanism. Therefore, a comprehensive study was conducted to elucidate the differences in δ for the air electrode, La0.6Sr0.4Co1−y
Fe
y
O3−δ
(LSCF, y = 0, 0.2, 0.4, 0.6, 0.8, and 1), between film and bulk electrodes. Two key findings emerged: (1) For Co-rich compositions (y ≤ 0.5), significant differences in δ were observed between films and bulk electrodes, while (2) for Fe-rich compositions (y ≥ 0.6), there was almost no difference in δ. Plausible reasons for these discrepancies were investigated: (1) lattice stress in the film, (2) compositional variation within the film electrode, and (3) changes in the electronic conduction. High-temperature X-ray diffraction revealed no significant differences in lattice constant between films and bulk electrodes, and X-ray photoelectron spectroscopy and X-ray absorption spectroscopy indicated no changes in electronic structure. However, scanning transmission electron microscopy/energy dispersive X-ray spectroscopy revealed the presence of Co3 O4 formation within the film, suggesting local compositional variations. Therefore, the results indicate that local compositional differences are the most likely factor affecting δ in LSCF films.
Dopant Sensitive Electrolytic Etching of Germanium with High Selectivity
Authors: Wood Joseph G. , Carpenter Arthur , Hunt Charles E. , van Benthem Klaus
Published: February 2025

The enhanced charge carrier mobility and photon absorption compared to silicon make germanium attractive for next-generation photo diodes. However, the complex oxidation behavior of germanium challenges dopant-dependent selective etching that is desired for the fabrication of backside imaging architectures. This report demonstrates electrolytic wet etching of p-doped germanium which proceeds up to 17,500x faster than etching of intrinsic germanium. Homoepitaxially grown layers of germanium were electrolytically etched in potassium hydroxide over a range of biases. Intermittent acquisition of cyclic voltammetry spectra during etching has suppressed the formation of electric double layers, maintained appreciable etch rates, and allowed for in operando process control. The observed etch rates scaled with dopant concentration. An effective etch rate of germanium removal of 2.100 ± 0.044 μm min−1 was accomplished for a boron dopant concentration of 6E18cm−3. For nominally intrinsic germanium, however, an effective etch rate of only 0.00012 ± 0.00011 μm min−1 was observed. A series of systematic electrolytic etch experiments have revealed the transfer of 4 electrons per germanium atom removed.
Cardiac health, type I collagen, and aging in the oim/oim mouse model of osteogenesis imperfecta and a cohort of adults with OI
Authors: Lafaver Brittany N. , Lee Li , Derocher Chloe E. , Levin Lawrence F. , Carter Erin M. , Sardesai Krish , Vallejo Julian A. , McAllister-Day Ali , Crawford Tara K. , Chapman Isabel M. , Wacker Michael J. , Raggio Cathleen L. , Ma Lixin , Krenz Maike , Phillips Charlotte L.
Published: February 2025

The heritable skeletal dysplasia, osteogenesis imperfecta (OI), recently recognized as a pleiotropic collagenopathy, shows growing evidence of cardiac involvement impacting lifespan. Evaluating cardiac function (magnetic resonance imaging and echocardiography) using an OI mouse model revealed increased left ventricular end-diastolic and end-systolic volumes concomitant with decreased function and reduced survival in 18-mo-old male OI mice. Additional cardiac evaluations of an adult patient cohort with OI corroborated increased incidences of valvular dysfunction in the patient population with OI.
Leptin receptor downregulation in the carotid body treats obesity-induced hypertension
Authors: Shin Mi-Kyung , Kim Lenise J. , Davaanyam Dashdulam , Amorim Mateus R. , Lee Sean M. , Tang Wan-Yee , Polotsky Vsevolod Y.
Published: February 2025

Obesity and comorbid sleep apnea are key predisposing factors to hypertension. Obesity increases circulating leptin levels and hyperleptinemia may contribute to hypertension but mechanisms are not clear. Here, we have shown that knockdown of the leptin receptor LepRb in the carotid body decreased blood pressure and treated hypertension in diet-induced obese mice. Thus, we identified a novel mechanism of obesity hypertension and a novel drug target, LepRb in the carotid body.
A Novel Micro‐Thermophotovoltaic Combustor of Hydrogen–Air to Enable Ultra‐Lean Combustion, High Thermal Output and NO Low Emissions
Authors: Mansouri Zakaria , Chouichi Lina , Azzouz Salaheddine , Settar Abdelhakim
Published: February 2025

This study presents a novel micro‐combustor (MC) design called micro‐trapped vortex combustor (MTVC) for micro‐thermophotovoltaic (MTPV) devices used in small‐scale electricity generation. Traditional MC designs struggle to operate efficiently under ultra‐lean regimes due to flame quenching, limiting their performance. The proposed MTVC incorporates the trapped vortex concept, inspired by aeronautical applications, to improve thermal performance and stability under ultra‐lean conditions. Numerical simulations, using the Navier–Stokes and energy equations for laminar and reactive flow, are conducted to compare the MTVC with conventional micro‐backward‐step combustors (MBSCs) under hydrogen (H2)–air mixture combustion. The study focuses on key performance parameters such as temperature distribution, heat recirculation, flame shape, flow topology, radiative power and emissions. The results show that the MTVC can operate at an ultra‐lean equivalence ratio of Φ = 0.5, while the MBSC experiences flame quenching below Φ = 0.7. The MTVC design achieves up to 26.51% higher radiative power and a 36% improvement in energy conversion efficiency compared to traditional combustor designs. Additionally, the MTVC produces 43% less nitrogen oxides (NOx) emissions, demonstrating its potential for both higher efficiency and reduced environmental impact in portable power applications.
Assessment of Formalin‐Fixed Bovine Larynx Asymmetry Using Geometric Morphometry
Authors: Salamanca-Carreño Arcesio , Parés-Casanova Pere M. , Vélez-Terranova Mauricio , Monroy-Ochoa Néstor Ismael
Published: February 2025

The vibrations of the larynx produce the voice. Little is known about morphology and the size of cattle larynx. The aim of the study was to quantify the shape asymmetry of the larynx in calves obtained postmortem using a geometric morphometric approach. A sample of 14 larynges from calves (in an age range 335–625 days) belonging to “Bruna dels Pirineus” breed and its F1 crosses was obtained in an abattoir during the first semester of 2021. Laringes were dissected and preserved in the laboratory until their photograph was taken Landmark sets were superimposed on images of fixed transverse sections of larynges. Using geometric morphometric techniques, we analyzed the presence of asymmetries. Asymmetry between sexes was assessed by means of a Canonical Variate Analysis on regression residuals of asymmetric components using the Mahalanobis distance, which assumes a lack of isotropy. Significant differences in the morphometric profile were found between the right and left larynx and between the sexes (p < 0.05). Results demonstrate differences between right and left larynx sides as directional asymmetry, at least in fixed structures. Our findings provide a foundation for quantifying the possible contribution of larynx asymmetry among cattle. This study can be considered the first to detect larynx asymmetries in cattle. Studies with a larger sample size are needed to validate the information in large populations. One limitation is that the present study does not have samples from adult animals, so it would be interesting to know if the results are similar among them.
Supplementary Figures from Multiomics Analysis Reveals Molecular Changes during Early Progression of Precancerous Lesions to Lung Adenocarcinoma in Never-Smokers
Authors: Chen Yun-Ching , Hsu Chia-Lang , Wang Hui-Min , Wu Shang-Gin , Chang Yih-Leong , Chen Jin-Shing , Wu Yu-Ching , Lin Yen-Ting , Yang Ching-Yao , Lin Mong-Wei , Lee Jang-Ming , Kuo Shuenn-Wen , Chen Ke-Cheng , Hsu Hsao-Hsun , Huang Pei-Ming , Huang Yen-Lin , Yu Chong-Jen , Pirooznia Mehdi , Huang Bevan E. , Yang Rob , Shih Jin-Yuan , Yang Pan-Chyr
Published: February 2025

Supplementary Figures
The Mode of Action and Clinical Outcomes of Sacituzumab Govitecan in Solid Tumors
Authors: Tolaney Sara M. , Cardillo Thomas M. , Chou Chih-Chien , Dornan Carrie , Faris Mary
Published: February 2025

Sacituzumab govitecan (SG), a trophoblast cell-surface antigen-2 (Trop-2)–directed antibody–drug conjugate, is currently approved to treat metastatic triple-negative breast cancer and HR+/HER2− breast cancer and is under clinical investigation for a range of other tumor types. This review describes its mode of action, development, and clinical outcomes. SG is composed of SN-38 (a topoisomerase I inhibitor derived from irinotecan) covalently linked to an anti–Trop-2 mAb (sacituzumab; hRS7) via a hydrolyzable CL2A linker. SN-38 was chosen due to its potent antitumor activity; CL2A occupies the most effective position on SN-38 for maintaining stability during transport, with pH-sensitive payload release in the tumor, and the antigen target (Trop-2) is highly expressed on many solid tumors. SG has an ∼8:1 drug-to-antibody ratio and delivers therapeutic SN-38 concentration to Trop-2+–expressing tumor cells via rapid internalization and efficient payload release. Free SN-38 can subsequently enter the tumor microenvironment and kill adjacent tumor cells with or without Trop-2 expression (bystander effect). SN-38 induces DNA breakage and inhibits nucleic acid synthesis via a drug-induced topoisomerase 1:DNA complex that interferes with cell proliferation, causing apoptosis. Dose-finding studies support SG 10 mg/kg on days 1 and 8 of a 21-day cycle as the monotherapy dose for clinical use; this was determined by therapeutic index improvement based on efficacy and safety. Payload–linker dynamics and SG potency ensure continued tissue penetration. Neutropenia and diarrhea are the most common grade ≥3 treatment-emergent adverse events with SG, but they are manageable. The efficacy of SG has been demonstrated across a broad spectrum of solid tumors.
Figure S2 from Harnessing the Potential of FAP-IL12mut TMEkine for Targeted and Enhanced Antitumor Responses
Authors: Lee Dahea , Kim Dongsu , Kim Donggeon , Kang Jisu , Lee Kiram , Lee Hyunji , Yoon Yujin , Lee Youngin , Kim Nahmju , Cho Byoung Chul , Chang Jihoon , Lee Byoung Chul
Published: February 2025

Supplementary Figure 2. In vitro characterization of mFAP-IL12mut. A. Binding specificity of mFAP-IL12 and mFAP-IL12mut to target the cells was confirmed using flow cytometry with mouse FAP overexpressed NIH3T3-mFAP, CT26-mFAP, and B16F10-mFAP cells. NIH3T3 cells served as a negative control. Target cells were treated with the indicated antibodies and then analyzed using flow cytometry. B. Dose-dependent induction of phosphorylated STAT4 of mFAP-IL12, mFAP-IL12mut, and recombinant mouse IL12 (rmIL12) was determined by phospho-STAT4 alphaLISA assay. C. IFNγ induction assay was assessed on activated mouse splenocytes. Data are presented as mean ± SEM. ****p < 0.0001, ns., not significant, two-tailed unpaired t-test.
Supplementary Figure S3 from Characteristics of a CCL21 Gene–Modified Dendritic Cell Vaccine Utilized for a Clinical Trial in Non–Small Cell Lung Cancer
Authors: Oh Michael S. , Dumitras Camelia , Salehi-Rad Ramin , Tran Linh M. , Krysan Kostyantyn , Lim Raymond J. , Jing Zhe , Tappuni Shahed , Lisberg Aaron , Garon Edward B. , Dubinett Steven M. , Liu Bin
Published: February 2025

Supplementary Figure S3. Viability and cytokine secretion of thawed CCL21-DC vaccines.
Supplementary Figure S1 from Characteristics of a CCL21 Gene–Modified Dendritic Cell Vaccine Utilized for a Clinical Trial in Non–Small Cell Lung Cancer
Authors: Oh Michael S. , Dumitras Camelia , Salehi-Rad Ramin , Tran Linh M. , Krysan Kostyantyn , Lim Raymond J. , Jing Zhe , Tappuni Shahed , Lisberg Aaron , Garon Edward B. , Dubinett Steven M. , Liu Bin
Published: February 2025

Supplementary Figure S1. Gating strategy for flow cytometry studies.
Supplementary Figure S6. from Targeting NAD+ Metabolism Vulnerability in FH-Deficient Hereditary Leiomyomatosis and Renal Cell Carcinoma with the Novel NAMPT Inhibitor OT-82
Authors: Najera Susana S. , Ricketts Christopher J. , Schmidt Laura S. , Medina Julia I. , Saito Keita , Ileva Lilia , Brender Jeffrey R. , James Amy M. , Peer Cody J. , Gouker Brad , Karim Baktiar O. , Chernova Olga , Wells Catherine , Wei Ming-Hui , Yang Youfeng , Zhang Xiaohu , Klumpp-Thomas Carleen , Travers Jameson , Chen Lu , Wilson Kelli M. , Issaq Sameer H. , Figg William D. , Difilippantonio Simone , Kalen Joseph D. , Krishna Murali C. , Thomas Craig J. , Ceribelli Michele , Heske Christine M. , Crooks Daniel R. , Meier Jordan L.
Published: February 2025

Real-time invasion analysis of UOK262 and UOK365 cells treated with OT-82. Real-time invasion analysis of UOK262 and UOK365 cells demonstrating cell line invasion over 5 days (120 hrs) was performed (A) to show that DMSO (used as the vehicle for OT-82) did not affect invasion in comparison to untreated cells and (B) to demonstrate the effects of OT-82 treatment at either 1 nM or 10 nM in comparison to vehicle alone (DMSO) or the non-invasive control (no serum in the lower chamber). In each case, a representative graph from one of three separate experiments is shown. (C) The invasion inhibition for three repeats at each dose is shown for each cell line. The average invasion inhibition is shown as a percentage compared to the vehicle alone (DMSO) invasion and T-tests were performed comparing each dose to the vehicle alone (DMSO).
Supplementary Methods and Tables from OBI-992, a Novel TROP2-Targeted Antibody–Drug Conjugate, Demonstrates Antitumor Activity in Multiple Cancer Models
Authors: Li Wan-Fen , Chiang Ming-Feng , Weng Hao-Cheng , Yang Jhih-Jie , Wu Hsin-Shan , Wu Szu-Yu , Chen Yu-Jung , Lu Chi‐Huan , Tu Jyy-Shiuan , Hsu Ren-Yu , Shia Chi-Sheng , Huang Teng-Yi , Lai Ming-Tain
Published: February 2025

Supplemental Methods Table S1; Table S2; Table S3; Table S4; Table S5; Table S6; Table S7; Table S8
Figure S4 from OBI-992, a Novel TROP2-Targeted Antibody–Drug Conjugate, Demonstrates Antitumor Activity in Multiple Cancer Models
Authors: Li Wan-Fen , Chiang Ming-Feng , Weng Hao-Cheng , Yang Jhih-Jie , Wu Hsin-Shan , Wu Szu-Yu , Chen Yu-Jung , Lu Chi‐Huan , Tu Jyy-Shiuan , Hsu Ren-Yu , Shia Chi-Sheng , Huang Teng-Yi , Lai Ming-Tain
Published: February 2025

Supplementary Figure S4
Figure S1 from OBI-992, a Novel TROP2-Targeted Antibody–Drug Conjugate, Demonstrates Antitumor Activity in Multiple Cancer Models
Authors: Li Wan-Fen , Chiang Ming-Feng , Weng Hao-Cheng , Yang Jhih-Jie , Wu Hsin-Shan , Wu Szu-Yu , Chen Yu-Jung , Lu Chi‐Huan , Tu Jyy-Shiuan , Hsu Ren-Yu , Shia Chi-Sheng , Huang Teng-Yi , Lai Ming-Tain
Published: February 2025

Supplementary Figure S1
Figure S6 from HPV and p53 Status as Precision Determinants of Head and Neck Cancer Response to DNA-PKcs Inhibition in Combination with Irradiation
Authors: Hayrapetyan Liana , Roth Selina M. , Quintin Aurélie , Hovhannisyan Lusine , Medo Matúš , Riedo Rahel , Ott Julien G. , Albers Joachim , Aebersold Daniel M. , Zimmer Yitzhak , Medová Michaela
Published: February 2025

In-vivo tissue immunohistochemistry: (A) Tumor collection day post treatment (top panel), growth control (bottom) and (B) Ki67 (proliferation), TUNEL (DNA fragmentation), and β-gal (senescence) stainings (representative pictures (top panels) and quantification (bottom)) of UM-SCC-74A xenografts post indicated treatments (Longitudinal cohort, n = 7). (C) Tumor collection day post treatment (top panel), growth control (bottom) and (D) Ki67, TUNEL, and β-gal stainings (representative pictures (top) and quantification (bottom)) of UD-SCC-2 xenografts post indicated treatments (Longitudinal cohort, n = 7). Data has been analyzed with one-way ANOVA with post hoc multiple comparisons and is represented as mean ± SEM; ns – nonsignificant, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.
Figure S5 from HPV and p53 Status as Precision Determinants of Head and Neck Cancer Response to DNA-PKcs Inhibition in Combination with Irradiation
Authors: Hayrapetyan Liana , Roth Selina M. , Quintin Aurélie , Hovhannisyan Lusine , Medo Matúš , Riedo Rahel , Ott Julien G. , Albers Joachim , Aebersold Daniel M. , Zimmer Yitzhak , Medová Michaela
Published: February 2025

In-vivo tumor growth: (A) In-vivo study treatment setup (Created with BioRender.com) (B) Tumor growth curves for each individual animal (n = 7) in all experimental and treatment groups. (C) Average animal weight gain (Mean (%) ± SEM) throughout the experiment. (D) Xenograft tumor slices of UD-SCC-2 and UM-SCC-74A cell lines stained for proliferation and apoptosis show opposite staining patterns.
Table S1 from Preclinical Characterization of XB002, an Anti–Tissue Factor Antibody–Drug Conjugate for the Treatment of Solid Tumors
Authors: Kantak Seema , Faggioni Raffaella , Cai Allen G. , Bhatti Maryam M. , Li Jing , Vainshtein Inna , Cheng Jackie , Mendelsohn Brian A. , Gaudreault Jacques , Migone Thi-Sau , Theunissen Jan-Willem
Published: February 2025

Factor VII binding to TF in presence of 25A3
Table S1 from Development and Characterization of a Lysosome-Targeting SLC3A2/PD-L1 Bispecific Antibody–Drug Conjugate for Enhanced Antitumor Efficacy in Solid Tumors
Authors: Wang Zeng , Zheng Meijun , Li Mengyao , Lu Huaqing , Liu Nanxi , Chen Yongdong , Yang Nian , Zeng Wanqin , Dong Yijun , Li Jia , Zhu Zhixiong , Yang Chen , Zhang Zongliang , Lu Qizhong , Li Hexian , Zhou Liangxue , Yang Hui , Tong Aiping
Published: February 2025

Supplementary Table 1. The expression profile of SLC3A2 and PD-L1 on surface of tumor cell lines.
Figure S4 from Development and Characterization of a Lysosome-Targeting SLC3A2/PD-L1 Bispecific Antibody–Drug Conjugate for Enhanced Antitumor Efficacy in Solid Tumors
Authors: Wang Zeng , Zheng Meijun , Li Mengyao , Lu Huaqing , Liu Nanxi , Chen Yongdong , Yang Nian , Zeng Wanqin , Dong Yijun , Li Jia , Zhu Zhixiong , Yang Chen , Zhang Zongliang , Lu Qizhong , Li Hexian , Zhou Liangxue , Yang Hui , Tong Aiping
Published: February 2025

Supplementary Figure 4. LC-MS analysis and average DAR value of antibody-drug conjugates. A, LC-MS analysis of SLC3A2/PD-L1 BsADC. LC-MS, liquid chromatography-MS. The average DAR of SLC3A2/PD-L1 BsADC was 0.82. B, LC-MS analysis of SLC3A2 ADC. The average DAR of SLC3A2/PD-L1 BsADC was 1.63. C, LC-MS analysis of PD-L1 ADC. The average DAR of PD-L1 ADC was 0.93.
Figure S2 from Preclinical Characterization of XB002, an Anti–Tissue Factor Antibody–Drug Conjugate for the Treatment of Solid Tumors
Authors: Kantak Seema , Faggioni Raffaella , Cai Allen G. , Bhatti Maryam M. , Li Jing , Vainshtein Inna , Cheng Jackie , Mendelsohn Brian A. , Gaudreault Jacques , Migone Thi-Sau , Theunissen Jan-Willem
Published: February 2025

Binding affinity of 25A3 to TF-expressing cell lines
Supplementary Figure S3 from Modeling the Acute Mucosal Toxicity of Fractionated Radiotherapy Combined with the ATM Inhibitor WSD0628
Authors: Garcia Darwin A. , Rathi Sneha , Connors Margaret A. , Grams Michael , Vaubel Rachael A. , Bakken Katrina K. , Ott Lauren L. , Carlson Brett L. , Hu Zeng , Decker Paul A. , Eckel-Passow Jeanette E. , Burgenske Danielle M. , Zhong Wei , Trzasko Joshua D. , Herman Michael G. , Elmquist William F. , Remmes Nicholas B. , Sarkaria Jann N.
Published: February 2025

Supplementary Figure S3 shows effect of irradiating different lengths of esophagus. Additionally, higher magnitude images of esophageal H&E images.
Supplementary Data from Soluble CD146 Cooperates with VEGFa to Generate an Immunosuppressive Microenvironment in CD146-Positive Tumors: Interest of a Combined Antibody-Based Therapy
Authors: Joshkon Ahmad , Traboulsi Wael , Terme Magali , Bachelier Richard , Fayyad-Kazan Hussein , Dignat-George Françoise , Foucault-Bertaud Alexandrine , Leroyer Aurelie S. , Bardin Nathalie , Blot-Chabaud Marcel
Published: February 2025

Supplementary Data
Suppl Figure 9 from Soluble CD146 Cooperates with VEGFa to Generate an Immunosuppressive Microenvironment in CD146-Positive Tumors: Interest of a Combined Antibody-Based Therapy
Authors: Joshkon Ahmad , Traboulsi Wael , Terme Magali , Bachelier Richard , Fayyad-Kazan Hussein , Dignat-George Françoise , Foucault-Bertaud Alexandrine , Leroyer Aurelie S. , Bardin Nathalie , Blot-Chabaud Marcel
Published: February 2025

Suppl Figure 9
Suppl Figure 4 from Soluble CD146 Cooperates with VEGFa to Generate an Immunosuppressive Microenvironment in CD146-Positive Tumors: Interest of a Combined Antibody-Based Therapy
Authors: Joshkon Ahmad , Traboulsi Wael , Terme Magali , Bachelier Richard , Fayyad-Kazan Hussein , Dignat-George Françoise , Foucault-Bertaud Alexandrine , Leroyer Aurelie S. , Bardin Nathalie , Blot-Chabaud Marcel
Published: February 2025

Suppl Figure 4
Suppl Figure 3 from Soluble CD146 Cooperates with VEGFa to Generate an Immunosuppressive Microenvironment in CD146-Positive Tumors: Interest of a Combined Antibody-Based Therapy
Authors: Joshkon Ahmad , Traboulsi Wael , Terme Magali , Bachelier Richard , Fayyad-Kazan Hussein , Dignat-George Françoise , Foucault-Bertaud Alexandrine , Leroyer Aurelie S. , Bardin Nathalie , Blot-Chabaud Marcel
Published: February 2025

Suppl Figure 3
Supplementary Figure S6 from Pancreatic CAF-Derived Autotaxin Drives Autocrine CTGF Expression to Modulate Protumorigenic Signaling
Authors: Volat Fanny , Medhi Ragini , Maggs Lauren Z. , Deken Marcel A. , Price Alice , Andrews Lauren , Clark Jonathan , Taylor Diane , Carruthers Alan , Taylor-Smith Ewan , Pacheco Natalia , Rudge Simon A. , Fraser Amy , Lopez-Clavijo Andrea F. , Sousa Bebiana C. , Johnson Zoë , Di Conza Giusy , van der Veen Lars , Shah Pritom , Sandig Hilary , Sharpe Hayley J. , Farrow Stuart
Published: February 2025

Supplementary Figure S6 shows LLPs expression in PDAC cancer and CAFs cells.
Supplementary Figure S3 from Pancreatic CAF-Derived Autotaxin Drives Autocrine CTGF Expression to Modulate Protumorigenic Signaling
Authors: Volat Fanny , Medhi Ragini , Maggs Lauren Z. , Deken Marcel A. , Price Alice , Andrews Lauren , Clark Jonathan , Taylor Diane , Carruthers Alan , Taylor-Smith Ewan , Pacheco Natalia , Rudge Simon A. , Fraser Amy , Lopez-Clavijo Andrea F. , Sousa Bebiana C. , Johnson Zoë , Di Conza Giusy , van der Veen Lars , Shah Pritom , Sandig Hilary , Sharpe Hayley J. , Farrow Stuart
Published: February 2025

Supplementary Figure S3 shows ATX antibody validation and ATX detection in cancer and CAF co-cultures.