bluuebunny/crossref_metadata_2025 huggingface dataset:
Responsive Complementary Feeding Practices in Rural Muhanga District of Rwanda: A Mixed Methods Study
Authors: Ahishakiye Jeanine , Vaandrager Lenneke , Matsiko Eric , Kwizera Philemon , Koelen Maria
Published: July 2024

Background

Responsive feeding among infants and young children (IYC) determines their food acceptance and adequate dietary intake, which enhances growth and developmental opportunities. However, little is known about responsive feeding practices among IYC in Rwanda. This study explored the status and barriers of responsive feeding practices among mothers from rural areas of Muhanga District in Rwanda.

Method

This descriptive longitudinal and exploratory mixed methods study was conducted among 29 mothers from 2 rural health centers in Muhanga District. Mothers were interviewed, and their interactions with children during lunch meals at 6, 9, and 12 months were observed. The interviews were recorded, transcribed, and thematically analyzed using Atlas.ti software.

Results

The study shows that the number of mothers who reported to verbally encourage their children to eat during feeding increased with the child's age. Less than half of mothers, at all three time points of data collection (at 6, 9, and 12 months), reported and were observed allowing their children to self‐feed, smiling and talking to them during feeding. The perceived major barriers to mother–child interaction during feeding were lack of time due to the burden of other responsibilities, and poverty. In addition, fear of messing up and food waste were barriers to child self‐feeding opportunities.

Conclusion

Findings indicate that responsive feeding was less practiced among study mothers due to lack of time, poverty, and fear of food waste during child self‐feeding. Nutrition interventions in this community should consider raising awareness of responsive feeding practices through education and encouraging mothers to devote sufficient time to interact with their children during feeding episodes.
Soil development and ancient Maya land use in the tropical karst landscape: Case of Busiljá, Chiapas, México
Authors: García‐Ramírez P. , Guillén K. , Sedov S. , Golden C. , Morell‐Hart S. , Scherer A. , Pi T. , Solleiro‐Rebolledo E. , Dine H. , Rivera Y.
Published: July 2024

The soil mantle of the tropical karstic landscapes of Southern Mexico was shaped by specific processes of pedogenesis and long‐term human impacts of ancient Maya agriculture. To understand the interaction between natural and human‐induced soil‐forming processes in the calcareous mountains of Chiapas state, we studied soil toposequences around the Classic Maya site of Budsilhá and related them to the archaeological evidence of settlement and land‐use distribution. Soil chemical analysis, micromorphological observations, and clay mineral identification were carried out in key soil profiles at the main geoforms. Limestone hills are occupied by shallow Rendolls which are usually perceived as incipient soils. However, high content of silicate clay composed of kaolinite and vermiculite and ferruginous clayey soil material observed at macro‐ and microscale backed the hypothesis that these soils were formed from the residues of thick Terra Rossa after their erosion. Swampy lowlands are occupied by thick clayey gleyic soils with clay mineral assemblages similar to those in the upland Rendolls. We suppose that the mineral matrix of the lowland soils is largely derived from the pedosediments of eroded upland Terra Rossa, which lost original ferruginous pigmentation and aggregation due to redoximorphic processes. Some wetland soils contain neoformed gypsum that is atypical for humid tropics; sulfide‐sulfate transformation under fluctuating redox conditions could promote gypsum synthesis. Ancient Maya land use was closely related to soil‐geomorphic conditions: settlements with homegardens occupied calcareous hills, whereas the primary agricultural domain was developed on lowland soils after their drainage by artificial canals.
Kinetic Studies on Ruthenium(III) Chloride‐Catalyzed Oxidation of Benzyl and Homobenzyl Alcohols Using Cerium(IV) Sulfate under Acidic Medium
Authors: Yadav Suresh C. , Srivastav Shalini , Singh Alok K. , Pandey Vijay , Tandon Praveen K. , Chandra Ajeet
Published: July 2024

This study investigates the kinetics of oxidative conversion of benzyl and homobenzyl alcohols to carbonyls using cerium(IV) sulfate in the presence of ruthenium(III) complex under mild acidic conditions. The results revealed that the low concentration of both alcohols and cerium(IV) ions drives the reaction to a first‐order kinetics, whereas a higher concentration induces zero‐order kinetics. In addition, the kinetics of the reaction were altered by the additives of hydrogen ions, cerium(III) ions, and chloride ions. We hope this study will be helpful in understanding the reaction kinetics of the oxidation of primary alcohols.
Nanotubes from Transition Metal Dichalcogenides: Recent Progress in the Synthesis, Characterization and Electrooptical Properties
Authors: Yadgarov Lena , Tenne Reshef
Published: July 2024

Inorganic layered compounds (2D‐materials), particularly transition metal dichalcogenide (TMDC), are the focus of intensive research in recent years. Shortly after the discovery of carbon nanotubes (CNTs) in 1991, it was hypothesized that nanostructures of 2D‐materials can also fold and seam forming, thereby nanotubes (NTs). Indeed, nanotubes (and fullerene‐like nanoparticles) of WS2 and subsequently from MoS2 were reported shortly after CNT. However, TMDC nanotubes received much less attention than CNT until recently, likely because they cannot be easily produced as single wall nanotubes with well‐defined chiral angles. Nonetheless, NTs from inorganic layered compounds have become a fertile field of research in recent years. Much progress has been achieved in the high‐temperature synthesis of TMDC nanotubes of different kinds, as well as their characterization and the study of their properties and potential applications. Their multiwall structure is found to be a blessing rather than a curse, leading to intriguing observations. This concise minireview is dedicated to the recent progress in the research of TMDC nanotubes. After reviewing the progress in their synthesis and structural characterization, their contributions to the research fields of energy conversion and storage, polymer nanocomposites, andunique optoelectronic devices are being reviewed. These studies suggest numerous potential applications for TMDC nanotubes in various technologies, which are briefly discussed.
Photothermal responsive porous hollow microneedles as Chinese medicine versatile delivery system for wound healing
Authors: Zhang Wanyue , Cai Lijun , Gan Jingjing , Zhao Yuanjin
Published: July 2024

Chinese medicine is identified as a candidate for wound healing. Attempts in this field tend to develop efficient dosage forms for delivering Chinese medicine with low side effects. In this paper, we proposed novel photothermal responsive porous hollow microneedles (PRPH‐MNs) as a versatile Chinese medicine delivery system for efficient antibacterial wound treatment. The PRPH‐MNs are composed of porous resin shells with good mechanical property, hydrogel cores, and a photothermal graphene oxide hybrid substrate. The hollow structure provides sufficient space for loading the drug dispersed hydrogel, while the porous resin shells could not only block the direct contact between drugs and wound sites but also provide channels for facilitating the drug release from the core. In addition, benefiting from the photothermal effect of their substrate, the PRPH‐MNs could be heated under near‐infrared (NIR) irradiation for controllable promotion of drug release. Based on these features, we have proved that the antibacterial Chinese medicine Rhein loaded PRPH‐MNs were effective in promoting wound healing due to their good antibacterial property and on‐demand drug release. Thus, we believe that the proposed PRPH‐MNs are valuable for delivery of different drugs for clinical applications.
Inflow turbulence generator for large eddy simulation based on a novel block‐vorticity vortex method: Application on a tall building wind effect
Authors: Shen Lian , Han Yan , Wang Peijie , Zhou Pinhan , Cai C. S. , Deng Shuwen
Published: July 2024

Accurately simulating turbulent wind fields is a significant challenge in wind engineering. This study proposes a novel block‐vorticity method aimed at overcoming the limitations of traditional turbulence generation methods. By superimposing a blocked vortex field at the inlet boundary of large eddy simulation (LES), the proposed method enables the generation of highly precise and anisotropic turbulent wind fields. To validate the effectiveness of the proposed method, the study investigates wind pressures on a high‐rise building structure and performs a comparative analysis with LES narrowband synthesis random flow generator (NSRFG), traditional LES, and SST k‐ω turbulence inlet models. The results demonstrate that the proposed method can effectively simulate turbulence characteristics of atmospheric boundary layer flow, including vortex structure and stochastic fluctuating wind field. Compared to traditional methods, the wind field characteristics of turbulence intensity, instantaneous vorticity, and turbulence self‐equilibrium had obvious advantages over traditional methods. Moreover, the LES vortex method is more accurate in simulating the mean wind pressure and fluctuating wind pressure of the high‐rise building compared to traditional models and is closer to the wind tunnel test results. The proposed method provides an effective approach for generating turbulent wind fields with anisotropic characteristics and can be used to predict the wind‐induced response of civil engineering structures.
Isolation of camel single domain antibodies against Yersinia pestis V270 antigen based on a semi‐synthetic single domain antibody library and development of a VHH‐based lateral flow assay
Authors: Wang Bo , Wang Chunsheng , Li Bo , Yang Jin , Lin Pengfei , Jin Xuefeng , Niu Yaojie , Zhang Wei , Zhang Xinshi , Huang Ying
Published: July 2024

Background

Antibodies have been proven effective as diagnostic agents for detecting zoonotic diseases. The variable domain of camel heavy chain antibody (VHH), as an antibody derivative, may be used as an alternative for traditional antibodies in existing immunodiagnostic reagents for detecting rapidly spreading infectious diseases.

Objectives

To expedite the isolation of specific antibodies for diagnostic purposes, we constructed a semi‐synthetic camel single domain antibody library based on the phage display technique platform (PDT) and verified the validity of this study.

Methods

The semi‐synthetic single domain antibody sequences consist of two parts: one is the FR1‐FR3 region amplified by RT‐PCR from healthy camel peripheral blood lymphocytes (PBLs), and the other part is the CDR3‐FR4 region synthesised as an oligonucleotide containing CDR3 randomised region. The two parts were fused by overlapping PCR, resulting in the rearranged variable domain of heavy‐chain antibodies (VHHs). Y. pestis low‐calcium response V protein (LcrV) is an optional biomarker to detect the Y. pestis infection. The semi‐synthetic library herein was screened using recombinant (LcrV) as a target antigen.

Results

After four cycles of panning the library, four VHH binders targeting 1–270 aa residues of LcrV were isolated. The four VHH genes with unique sequences were recloned into an expression vector and expressed as VHH‐hFc chimeric antibodies. The purified antibodies were identified and used to develop a lateral flow immunoassay (LFA) test strip using latex microspheres (LM) for the rapid and visual detection of Y. pestis infection.

Conclusions

These data demonstrate the great potential of the semi‐synthetic library for use in isolation of antigen‐specific nanobodies and the isolated specific VHHs can be used in antigen‐capture immunoassays.
A Novel Surrogated Approach for Optimizing a Vertical Axis Wind Turbine With Straight Blades
Authors: Sanaye Sepehr , Rezaeian Parsa , Farvizi Armin
Published: July 2024

Vertical axis wind turbine (VAWT) has a rotating axis perpendicular to the wind direction. This type of wind turbine that is suitable for urban environments has low wind direction dependency and noise. In this research, a novel surrogated approach for optimizing a VAWT is proposed, used, tested, and verified, which is not reported in literature. The proposed method consisted of 3D computational fluid dynamics (CFD) analysis of wind flow through the wind turbine with FLUENT software by solving the unsteady turbulent equations. However, 3D CFD analysis was time and cost consuming to obtain the output result (power coefficient) from input values (airfoil chord length, pitch angle, and tip speed ratio as turbine design variables). Thus, artificial neural network (ANN) was applied to obtain weight functions to correlate FLUENT software inputs and outputs after learning process. Finally, genetic algorithm was used for maximizing the turbine power coefficient considering three defined design variables. The optimum value of power coefficient was improved to 0.244, and the optimum values of design variables for blade chord length, blade pitch angle, and blade tip speed ratio were 0.218, −0.453, and 1.24, respectively. This novel surrogated method reduced the computational time and cost of VAWT optimizing considerably.
Wind Tunnel Tests of a Thick Wind Turbine Airfoil
Authors: Mouton Sylvain , Peter Schaffarczyk Alois , Timmer Nando
Published: July 2024

This article reports about a wind‐tunnel experiment carried out in the ONERA F2 low‐speed wind tunnel on a model of the DU 97‐W‐300Mod airfoil designed for wind turbine application. The wind tunnel, the airfoil model, and experimental techniques used are presented, with special emphasis on the data processing and corrections required to derive airfoil forces and pressure distribution. To better document the flow physics at play, the results are illustrated by infrared thermography and surface oil flow visualization. The test allowed investigating Reynolds number effects between 1 and 3.8 millions. To ameliorate the understanding of the benefits and limitations of such airfoil testing, one section is devoted to the comparison of present results with previous experiments in other wind tunnels. Some of the difficulties arising in airfoil testing are evidenced and discussed to contribute to the improvement of test methods.
Axial anomalies of maximally supersymmetric tensor theories
Authors: Yi Piljin , Zhang Yi
Published: July 2024

Abstract

We revisit anomalies of (4, 0) and (3, 1) maximally supersymmetric tensor theories in d = 6. A (4, 0) on-shell tensor multiplet descends to that of the d = 5 maximal supergravity upon a dimensional reduction, hypothesized to offer a strong-coupled UV completion of the latter in the same sense of (2, 0) theories as the UV completion of d = 5 $$ \mathcal{N} $$
N
= 2 pure Yang-Mills. The gravitational anomalies, found to be nonvanishing, had been computed, although its relevance in the absence of the d = 6 metric is not obvious. We perform a comprehensive anomaly computation for (4, 0) and (3, 1) tensor supermultiplets, respectively, for Sp(4) and Sp(3) × Sp(1) R-symmetry anomalies and the mixed R-gravitational anomaly thereof, and find that anomalies involving R-symmetries cancel out identically. We close with questions on how to address the anomaly in this class of theories with no general covariance.
Algebras and their covariant representations in quantum gravity
Authors: Bahiru Eyoab
Published: July 2024

Abstract

We study a physically motivated representation of an algebra of operators in gravitational and non gravitational theories called the covariant representation of an algebra. This is a representation where the symmetries of the operator algebra are implemented unitarily on the Hilbert space. We emphasize the very close similarity of this representation to the crossed product of an algebra. In fact, as an example of (and sometimes identified with) a covariance algebra, the crossed product of an algebra is in one to one correspondence with the covariant representation of the algebra. This will in turn illuminate physically what the crossed product algebra is in the context of quantum gravity.
Canonical Typicality for Other Ensembles than Micro-canonical
Authors: Teufel Stefan , Tumulka Roderich , Vogel Cornelia
Published: July 2024

We generalize Lévy’s lemma, a concentration-of-measure result for the uniform probability distribution on high-dimensional spheres, to a much more general class of measures, so-called GAP measures. For any given density matrix $$\rho $$
ρ
on a separable Hilbert space $${\mathcal {H}}$$
H
, $${\textrm{GAP}}(\rho )$$

GAP
(
ρ
)

is the most spread-out probability measure on the unit sphere of $${\mathcal {H}}$$
H
that has density matrix $$\rho $$
ρ
and thus forms the natural generalization of the uniform distribution. We prove concentration-of-measure whenever the largest eigenvalue $$\Vert \rho \Vert $$

‖
ρ
‖

of $$\rho $$
ρ
is small. We use this fact to generalize and improve well-known and important typicality results of quantum statistical mechanics to GAP measures, namely canonical typicality and dynamical typicality. Canonical typicality is the statement that for “most” pure states $$\psi $$
ψ
of a given ensemble, the reduced density matrix of a sufficiently small subsystem is very close to a $$\psi $$
ψ
-independent matrix. Dynamical typicality is the statement that for any observable and any unitary time evolution, for “most” pure states $$\psi $$
ψ
from a given ensemble the (coarse-grained) Born distribution of that observable in the time-evolved state $$\psi _t$$

ψ
t

is very close to a $$\psi $$
ψ
-independent distribution. So far, canonical typicality and dynamical typicality were known for the uniform distribution on finite-dimensional spheres, corresponding to the micro-canonical ensemble, and for rather special mean-value ensembles. Our result shows that these typicality results hold also for $${\textrm{GAP}}(\rho )$$

GAP
(
ρ
)

, provided the density matrix $$\rho $$
ρ
has small eigenvalues. Since certain GAP measures are quantum analogs of the canonical ensemble of classical mechanics, our results can also be regarded as a version of equivalence of ensembles.
Standardized Innovative Polygon Trend Analysis for Climate Change Assessment (S-IPTA)
Authors: Alashan Sadık , Abu Arra Ahmad , Şişman Eyüp
Published: July 2024

Research and applications on trend analysis have recently been on the agenda and are top priorities in many disciplines due to the effects of climate change. After a thorough evaluation of the literature, it is noted that different hydro-meteorological variables, such as precipitation, temperature, etc., are studied and analyzed individually. This research proposes a new innovative polygon trend analysis application (S-IPTA) using the standardization concept to fill this gap in classical trend applications and comprehensively compare the trends of different variables to temporal and spatial patterns. Firstly, using statistical standardization, S-IPTA adjusts the original data sets and makes them dimensionless. Then, the innovative trend analyses are conducted and interpreted on one single graph (S-IPTA). The S-IPTA methodology is applied to monthly precipitation and temperature time series of Konya Basin in Türkiye at ten meteorological stations between 1959 and 2022. For precipitation, the S-IPTA did not exhibit a consistent polygon across all stations within the study area, while the temperature polygon was more regular, indicating that the temperature mean was generally stable with a positive trend. Also, S-IPTA shows the difference between the average value for each month and the newly proposed long-term average value (0). S-IPTA also provides a basis for a better interpretation of climate change and its effects by providing a common denominator for various trend characteristics, such as trend magnitudes and trend transitions in different hydro-meteorological time series.
The use of technology in type 2 diabetes and prediabetes: a narrative review
Authors: Liarakos Alexandros L. , Lim Jonathan Z. M. , Leelarathna Lalantha , Wilmot Emma G.
Published: July 2024

The increasing incidence of type 2 diabetes, which represents 90% of diabetes cases globally, is a major public health concern. Improved glucose management reduces the risk of vascular complications and mortality; however, only a small proportion of the type 2 diabetes population have blood glucose levels within the recommended treatment targets. In recent years, diabetes technologies have revolutionised the care of people with type 1 diabetes, and it is becoming increasingly evident that people with type 2 diabetes can also benefit from these advances. In this review, we describe the current knowledge regarding the role of technologies for people living with type 2 diabetes and the evidence supporting their use in clinical practice. We conclude that continuous glucose monitoring systems deliver glycaemic benefits for individuals with type 2 diabetes, whether treated with insulin or non-insulin therapy; further data are required to evaluate the role of these systems in those with prediabetes (defined as impaired glucose tolerance and/or impaired fasting glucose and/or HbA1c levels between 39 mmol/mol [5.7%] and 47 mmol/mol [6.4%]). The use of insulin pumps seems to be safe and effective in people with type 2 diabetes, especially in those with an HbA1c significantly above target. Initial results from studies exploring the impact of closed-loop systems in type 2 diabetes are promising. We discuss directions for future research to fully understand the potential benefits of integrating evidence-based technology into care for people living with type 2 diabetes and prediabetes.

Graphical Abstract
Temporal evolution of suicide by levels of rurality and deprivation among Japanese adults aged 20 years or over between 2009 and 2022
Authors: Yoshioka Eiji , Hanley Sharon J. B. , Sato Yukihiro , Saijo Yasuaki
Published: July 2024

Purpose

Previous studies have reported that levels of rurality and deprivation are factors associated with suicide risk. Reports on the association between rurality, deprivation and suicide incidence during the COVID-19 pandemic are scarce. The study aims to investigate how suicide rates evolved in areas with different levels of rurality and deprivation among Japanese adults aged 20 years or older between 2009 and 2022.

Methods

This study used population density in 2020 as an indicator of rurality and per capita prefectural income in 2019 as a proxy for deprivation in Japan’s 47 prefectures. Joinpoint regression analysis was performed to analyze secular trends in suicide rates by rurality and deprivation.

Results

Suicide rates for both men and women at different levels of rurality and deprivation remained roughly parallel during the research period. Suicide rates for men and women at all levels of rurality and deprivation were on a downward trend until around 2019, just before the onset of the pandemic. Following this, suicide rates in women showed a clear upward trend, while the trend in suicide rates for men also changed around 2019, with a slightly increasing or flat trend thereafter. Changes in suicide rates were greater among women and those aged 20–59 years.

Conclusions

In Japan, time trends in suicide rates for both men and women have changed before and after the pandemic, but levels of rurality and deprivation across the 47 prefectures do not appear to have contributed much to these changes.
Diagnostic shift in adolescents with first episode psychosis: findings from the 2-year follow-up of the “Parma Early Psychosis” program
Authors: Pelizza Lorenzo , Plazzi Enrico , Leuci Emanuela , Leucci Anna Caterina , Quattrone Emanuela , Azzali Silvia , Pupo Simona , Paulillo Giuseppina , Pellegrini Pietro , Menchetti Marco
Published: July 2024

Purpose

Diagnostic stability for people with First Episode Psychosis (FEP) is essential for treatment, but it remains poorly investigated, especially in adolescents and within a prospective design. The aims of this research were: (a) to examine diagnostic change in Italian adolescents with FEP treated within an “Early Intervention in Psychosis” program during a 2-year follow-up period and (b) to investigate any sociodemographic and clinical predictors at baseline.

Methods

At baseline, 66 adolescents with FEP was recruited. Their primary diagnosis was formulated both at baseline and at the end of follow-up. At presentation, FEP adolescents completed the Health of the Nation Outcome Scales for Children and Adolescents (HoNOSCA). As for diagnostic stability, the Kappa statistic was calculated. The associations of diagnostic change with baseline clinical and sociodemographic features were analyzed using a logistic model with the diagnostic shift as dependent variable. A propensity score was finally calculated based on logistic analysis results.

Results

38 (57.6%) FEP adolescents changed their opening diagnosis. The highest prospective diagnostic stability was for initial diagnosis of schizophrenia (95.4%) and affective spectrum psychoses (75%). Diagnostic instability was high for opening diagnosis of psychosis not otherwise specified, brief psychosis and schizophreniform disorder (100%). The best predictors of diagnostic change were fewer years of education, shorter duration of untreated psychosis and higher baseline levels of psychiatric symptoms.

Conclusion

Diagnostic stability is crucial for treatment and clinical decision making. Addressing instability in FEP diagnoses is an important challenge for future diagnostic development in early psychosis, especially in adolescence.
Bringing Order to Chaos: The Case of Collision-Resistant Chameleon-Hashes
Authors: Derler David , Samelin Kai , Slamanig Daniel
Published: July 2024

Chameleon-hash functions, introduced by Krawczyk and Rabin (NDSS’00), are trapdoor collision-resistant hash functions parametrized by a public key. If the corresponding secret key is known, arbitrary collisions for the hash function can be found efficiently. Chameleon-hash functions have prominent applications in the design of cryptographic primitives, such as lifting non-adaptively secure signatures to adaptively secure ones. Recently, this primitive also received a lot of attention as a building block in more complex cryptographic applications, ranging from editable blockchains to advanced signature and encryption schemes. We observe that, in latter applications, various different notions of collision-resistance are used, and it is not always clear if the respective notion really covers what seems intuitively required by the application. Therefore, we revisit existing collision-resistance notions in the literature, study their relations, and by means of selected applications discuss which practical impact different notions of collision-resistance might have. Moreover, we provide a stronger, and arguably more desirable, notion of collision-resistance than what is known from the literature (which we call full collision-resistance). Finally, we present a surprisingly simple, and efficient, black-box construction of chameleon-hash functions achieving this strong notion of full collision-resistance.
Identity and political corruption: a laboratory experiment
Authors: Cubel Maria , Papadopoulou Anastasia , Sánchez-Pagés Santiago
Published: July 2024

This paper explores the role of identity in voters’ decision to retain corrupt politicians. We build up a model of electoral accountability with pure moral hazard and bring it to the lab. Politicians must decide whether to invest in a public project with uncertain returns or to keep the funds for themselves. Voters observe the outcome of the project but not the action of the politician; if the project is unsuccessful, they do not know whether it was because of bad luck or because the politician embezzled the funds. We run two treatments; a control and a treatment where subjects are assigned an identity using the minimal group paradigm. Our main result is that, upon observing a failed project, voters approve politicians of their same identity group significantly more often than in the control and compared to politicians of a different identity group. This is partially driven by a belief on same-identity politicians being more honest. We also observe that subjects acting as politicians embezzle funds less often than expected by the equilibrium prediction.
GSDME-mediated pyroptosis promotes anti-tumor immunity of neoadjuvant chemotherapy in breast cancer
Authors: Fu Changfang , Ji Wenbo , Cui Qianwen , Chen Anling , Weng Haiyan , Lu Nannan , Yang Wulin
Published: July 2024

Paclitaxel and anthracycline-based chemotherapy is one of the standard treatment options for breast cancer. However, only about 6–30% of breast cancer patients achieved a pathological complete response (pCR), and the mechanism responsible for the difference is still unclear. In this study, random forest algorithm was used to screen feature genes, and artificial neural network (ANN) algorithm was used to construct an ANN model for predicting the efficacy of neoadjuvant chemotherapy for breast cancer. Furthermore, digital pathology, cytology, and molecular biology experiments were used to verify the relationship between the efficacy of neoadjuvant chemotherapy and immune ecology. It was found that paclitaxel and doxorubicin, an anthracycline, could induce typical pyroptosis and bubbling in breast cancer cells, accompanied by gasdermin E (GSDME) cleavage. Paclitaxel with LDH release and Annexin V/PI doubule positive cell populations, and accompanied by the increased release of damage-associated molecular patterns, HMGB1 and ATP. Cell coculture experiments also demonstrated enhanced phagocytosis of macrophages and increased the levels of IFN-γ and IL-2 secretion after paclitaxel treatment. Mechanistically, GSDME may mediate paclitaxel and doxorubicin-induced pyroptosis in breast cancer cells through the caspase-9/caspase-3 pathway, activate anti-tumor immunity, and promote the efficacy of paclitaxel and anthracycline-based neoadjuvant chemotherapy. This study has practical guiding significance for the precision treatment of breast cancer, and can also provide ideas for understanding molecular mechanisms related to the chemotherapy sensitivity.
High expression of PD-L1 on conventional dendritic cells in tumour-draining lymph nodes is associated with poor prognosis in oral cancer
Authors: Eric Hjalmarsson , Piersiala Krzysztof , Lagebro Vilma , Farrajota Neves Da Silva Pedro , Petro Marianne , Starkhammar Magnus , Elliot Alexandra , Bark Rusana , Margolin Gregori , Kumlien Georén Susanna , Cardell Lars-Olaf
Published: July 2024

Introduction

Oral squamous cell carcinoma (OSCC), while common and with a favorable prognosis in early stages, presents a marked reduction in survival rate upon metastasis to lymph nodes. Early detection of lymph node metastasis via biomarkers could enhance the therapeutic strategy for OSCC. Here, we explored dendritic cells (DCs) and cytotoxic T-cells in tumour-draining lymph nodes (TDLNs) as potential biomarkers.

Method

Dendritic cells and cytotoxic T-cells in 33 lymph nodes were analyzed with multi-parameter flow cytometry in TDLNs, regional non-TDLNs surgically excised from 12 OSCC patients, and compared to 9 lymph nodes from patients with benign conditions.

Results

Our results displayed a higher proportion of conventional cDC1s with immunosuppressive features in TDLN. Further, high PD-L1 expression on cDC1 in TDLNs was associated with metastasis and/or recurrent disease risk. Also, elevated levels of memory CD8+ T-cells and terminally exhausted PD-1+TCF-1−CD8+ T-cells were observed in TDLNs and non-TDLNs compared to healthy lymph nodes.

Conclusions

We conclude that TDLNs contain cells that could trigger an anti-tumor adaptive response, as evidenced by activated cDC1s and progenitor-like TCF-1+ T-cells. The detection of high PDL1 expression on cDC1s was indicative of TDLN metastasis and an adverse prognosis, proposing that PD-L1 on dendritic cells in TDLN could serve as a predictive biomarker of OSCC patients with a worse prognosis.
Tumor-intrinsic IFNα and CXCL10 are critical for immunotherapeutic efficacy by recruiting and activating T lymphocytes in tumor microenvironment
Authors: Cheng Chun-Chia , Chang Jungshan , Ho Ai-Sheng , Sie Zong-Lin , Peng Cheng-Liang , Wang Chih‑Liang , Dev Kapil , Chang Chun-Chao
Published: July 2024

Tumor immunotherapies targeting PD-(L)1 exhibit anti-tumor efficacy in only 10–30% of patients with various cancers. Literature has demonstrated that a “hot tumor” which contains high T lymphocytes in the tumor microenvironment exhibits a better response to immunotherapies than a “cold tumor.” This study aimed to investigate whether tumor-intrinsic IFNα and CXCL10 determine the recruitment and activation of CD8+ T cells to become “hot tumor.” In this study, we found that CXCL10 overexpressed in a variety of tumors including lung, colon, and liver tumors with a correlation with PD-L1. High PD-L1 and CXCL10 are associated with better survival rates in tumor patients receiving immunotherapies. IFNs-downstream transcriptional factor IRF-1 and STAT1 were correlated with PD-L1 and CXCL10 expression. We demonstrated that IRF-1 and STAT1 were both bound with the promoters of PD-L1 and CXCL10, sharing the same signaling pathway and determining IFNs-mediated PD-L1 and CXCL10 expression. In addition, IFNα significantly increased activation marker IFNγ in PBMCs, promoting M1 type monocyte differentiation, CD4+ T, and CD8+ T cell activation. Particularly, we found that CD8+ T lymphocytes abundantly expressed CXCR3, a receptor of CXCL10, by flow cytometry, indicating that tumor-intrinsic CXCL10 potentially recruited CD8+ T in tumor microenvironment. To demonstrate the hypothesis, immunotherapy-sensitive CT26 and immunotherapy-resistant LL/2 were used and we found that CT26 cells exhibited higher IFNα, IFNγ, CXCL10, and PD-L1 levels compared to LL/2, leading to higher IFNγ expression in mouse splenocytes. Moreover, we found that CD8+ T cells were recruited by CXCL10 in vitro, whereas SCH546738, an inhibitor of CXCR3, inhibited T cell migration and splenocytes-mediated anti-tumor effect. We then confirmed that CT26-derived tumor was sensitive to αPD-L1 immunotherapy and LL/2-tumor was resistant, whereas αPD-L1 significantly increased T lymphocyte activation marker CD107a in CT26-derived BALB/c mice. In conclusion, this study revealed that CXCL10 expression is correlated with PD-L1 in tumors, sharing the same signaling pathway and associating with better immunotherapeutic efficacy. Further evidence in the syngeneic tumor models demonstrated that immunotherapy-sensitive CT26 intrinsically exhibited higher IFNα and CXCL10 compared to immunotherapy-resistant LL/2 to recruit and activate CD8+ T cells in the tumor microenvironment, exhibiting “hot tumor” characteristic of sensitizing αPD-L1 immunotherapies.
The performance status gap in immunotherapy for frail patients with advanced non-small cell lung cancer
Authors: Wu Julie Tsu-Yu , Corrigan June , Su Chloe , Dumontier Clark , La Jennifer , Khan Aparjita , Arya Shipra , Harris Alex H. S. , Backhus Leah , Das Millie , Do Nhan V. , Brophy Mary T. , Han Summer S. , Kelley Michael , Fillmore Nathanael R.
Published: July 2024

Purpose

In advanced non-small cell lung cancer (NSCLC), immune checkpoint inhibitor (ICI) monotherapy is often preferred over intensive ICI treatment for frail patients and those with poor performance status (PS). Among those with poor PS, the additional effect of frailty on treatment selection and mortality is unknown.

Methods

Patients in the veterans affairs national precision oncology program from 1/2019–12/2021 who received first-line ICI for advanced NSCLC were followed until death or study end 6/2022. Association of an electronic frailty index with treatment selection was examined using logistic regression stratified by PS. We also examined overall survival (OS) on intensive treatment using Cox regression stratified by PS. Intensive treatment was defined as concurrent use of platinum-doublet chemotherapy and/or dual checkpoint blockade and non-intensive as ICI monotherapy.

Results

Of 1547 patients receiving any ICI, 66.2% were frail, 33.8% had poor PS (≥ 2), and 25.8% were both. Frail patients received less intensive treatment than non-frail patients in both PS subgroups (Good PS: odds ratio [OR] 0.67, 95% confidence interval [CI] 0.51 − 0.88; Poor PS: OR 0.69, 95% CI 0.44 − 1.10). Among 731 patients receiving intensive treatment, frailty was associated with lower OS for those with good PS (hazard ratio [HR] 1.53, 95% CI 1.2 − 1.96), but no association was observed with poor PS (HR 1.03, 95% CI 0.67 − 1.58).

Conclusion

Frail patients with both good and poor PS received less intensive treatment. However, frailty has a limited effect on survival among those with poor PS. These findings suggest that PS, not frailty, drives survival on intensive treatment.
Heat-altered scent marks of males of a fossorial reptile still allow recognition by females but lose information on male quality
Authors: Martín José , Navarro-Castilla Álvaro , de la Concha Alejandro , Cuervo José Javier , Barja Isabel , López Pilar
Published: July 2024

The efficacy of sexual signals in communication is often maximized under specific environmental conditions. Anthropic alterations of these conditions might, thus, negatively affect communication during reproductive behavior. In fossorial animals, inhabiting visually restricted environments, chemical senses are very important. We examined whether climatic episodes of heat-waves with unusual high temperatures may affect the information provided to females by the sexual chemical signals of males of a fossorial reptile, the amphisbaenian Blanus cinereus. The results showed that experimentally heat-altered substrate scent marks of males can still provide information to females about the presence of a male. Females spent more time on males’ scent marks, irrespective of the temperature treatment, than on control clean ones. However, heat-altered scent marks did not seem to convey information about the health state (immune response) of the producer. Females spent more time on unaltered scent marks of healthier males (probably indicating mating preferences for these males), while female preferences for some heat-altered scent marks were not related to size or immune response of the same individual males. Chemical analyses indicated that the overall chemical profile of precloacal secretions (used for scent marking) did not change with increased temperatures. However, the relationship between proportions of some compounds in secretions and males’ immune response found in unaltered secretions was lost in heat-altered ones. We conclude that unusual increased environmental temperatures may decrease the efficacy of underground sexual chemical signals in this amphisbaenian (i.e., a loss of information on male quality), and consequently, may negatively affect sexual selection and reproduction.
Long-Term Outcomes of Balloon TACE for HCC: An European Multicentre Single-Arm Retrospective Study
Authors: Lucatelli Pierleone , Rocco Bianca , De Beare Thierry , Verset Gontran , Fucilli Fabio , Damato Elio , Paccapelo Alexandro , Braccischi Lorenzo , Taninokuchi Tomassoni Makoto , Bucalau Ana-Maria , Catalano Carlo , Mosconi Cristina
Published: July 2024

Purpose

To report response rates (using mRECIST), overall survival (OS), progression-free survival and local tumour recurrence-free survival (LRFS) of balloon-occluded transarterial chemoembolisation (bTACE) for hepatocellular carcinoma (HCC).

Materials and Methods

Patients from five European centres treated with conventional or drug-eluting microsphere bTACE for HCC were included, and patients already lost to follow-up before 12 months were excluded. Possible factors contributing to LRFS and OS were evaluated with Cox proportional hazards models.

Results

Seventy-three patients were enrolled. The mean number of nodules per patient was 2.07(± 1.68), and the average maximum diameter of the nodules was 37 ± 19.9 mm. The response of the target lesion at 6 months was complete response (CR) in 58.9%, partial response (PR) in 28.8%, stable disease (SD) in 6.8% and progressive disease (PD) in 5.5%. The median follow-up time was 31 months; at the last follow-up, target tumour response was CR in 49.3%, PR in 12.3%, SD in 5.5% and PD 32.9%. Overall response at the last follow-up was CR in 17.8%, PR in 9.6%, SD 2.7% and PD in 69.9% (for new lesions in 37% of patients). Median OS was not reached; mean overall survival was 50.0 months, while median LRFS was 31.0 months. At uni- and multivariable analysis, only tumour maximum diameter was related to LRFS (hazard ratio [HR] = 1.021; 95% CI 1.004–1.038, P = 0.015).

Conclusions

bTACE demonstrated high efficacy for HCC, with a complete response in 58.9% of patients, a median local recurrence-free survival of 31.0 months and a mean overall survival of 50.0 months.

Graphical Abstract
Posttraumatische Verbitterung bei ehemals politisch Inhaftierten der Sowjetischen Besatzungszone und Deutschen Demokratischen Republik
Authors: Quensel Paula , Maslahati Tolou , Arnhold Lisa , Dreyer Anne , Galve Gómez Milagros , Donth Stefan , Heuser-Collier Isabella , Roepke Stefan
Published: July 2024

Hintergrund

Betroffene politischer Haft der Sowjetischen Besatzungszone (SBZ) und Deutschen Demokratischen Republik (DDR) haben zahlreiche Situationen als ungerecht und herabwürdigend erlebt, wodurch Verbitterungsgefühle ausgelöst werden können. Diese Studie untersucht die Ausprägung der posttraumatischen Verbitterung sowie mögliche damit zusammenhängende Faktoren bei ehemals politisch Inhaftierten der SBZ/DDR.

Methode

Bei 246 Betroffenen wurden die posttraumatische Verbitterung und psychische Störungen im Querschnitt mithilfe eines Selbstbeurteilungsbogens für posttraumatische Verbitterung und des diagnostischen Expertensystems zur Erfassung psychischer Störungen (DIA-X) erhoben. Ein vorher definierter Fragekatalog umfasste sozioökonomische, haftspezifische, aufarbeitungsbetreffende und allgemeine Gesundheitsdaten.

Ergebnisse

Es zeigten 28 % der Befragten (n = 69) klinisch relevante Verbitterungswerte („Cut-off“-Wert ≥ 2,5). Ein positiv signifikanter Zusammenhang konnte für die Faktoren chronische Erkrankung, Grad der Behinderung, affektive Störung, posttraumatische Belastungsstörung und Unzufriedenheit mit der juristischen Aufarbeitung ermittelt werden.

Schlussfolgerungen

Verbitterung spielt eine substanzielle Rolle bei politisch Inhaftierten Personen und sollte bei der Behandlung psychischer und somatischer Erkrankungen berücksichtigt werden.
Effects of low temperature on growth and metabolism of larval green sturgeon (Acipenser medirostris) across early ontogeny
Authors: Lo Vanessa K. , Zillig Kenneth W. , Cocherell Dennis E. , Todgham Anne E. , Fangue Nann A.
Published: July 2024

Southern Distinct Population Segment (sDPS) green sturgeon spawn solely in one stretch of the Sacramento River in California. Management of this spawning habitat is complicated by cold water temperature requirements for the conservation of winter-run Chinook salmon. This study assessed whether low incubation and rearing temperatures resulted in carryover effects across embryo to early juvenile life stages on scaling relationships in growth and metabolism in northern DPS green sturgeon used as a proxy for sDPS green sturgeon. Fish were incubated and reared at 11 °C and 15 °C, with a subset experiencing a reciprocal temperature transfer post-hatch, to assess recovery from cold incubation or to simulate a cold-water dam release which would chill rearing larvae. Growth and metabolic rate of embryos and larvae were measured to 118 days post hatch. Reciprocal temperature transfers revealed a greater effect of low temperature exposure during larval rearing rather than during egg incubation. While 11 °C eggs hatched at a smaller length, log-transformed length–weight relationships showed that these differences in developmental trajectory dissipated as individuals achieved juvenile morphology. However, considerable size-at-age differences persisted between rearing temperatures, with 15 °C fish requiring 60 days post-hatch to achieve 1 g in mass, whereas 11 °C fish required 120 days to achieve 1 g, resulting in fish of the same age at the completion of the experiment with a ca. 37-fold difference in weight. Consequently, our study suggests that cold rearing temperatures have far more consequential downstream effects than cold embryo incubation temperatures. Growth delays from 11 °C rearing temperatures would greatly increase the period of vulnerability to predation in larval green sturgeon. The scaling relationship between log-transformed whole-body metabolism and mass exhibited a steeper slope and thus an increased oxygen requirement with size in 11 °C reared fish, potentially indicating an energetically unsustainable situation. Understanding how cold temperatures affect green sturgeon ontogeny is necessary to refine our larval recruitment estimations for this threatened species.
Multiphysics modeling of 3D traction force microscopy with application to cancer cell-induced degradation of the extracellular matrix
Authors: Apolinar-Fernández Alejandro , Barrasa-Fano Jorge , Van Oosterwyck Hans , Sanz-Herrera José A.
Published: July 2024

3D Traction Force Microscopy (3DTFM) constitutes a powerful methodology that enables the computation of realistic forces exerted by cells on the surrounding extracellular matrix (ECM). The ECM is characterized by its highly dynamic structure, which is constantly remodeled in order to regulate most basic cellular functions and processes. Certain pathological processes, such as cancer and metastasis, alter the way the ECM is remodeled. In particular, cancer cells are able to invade its surrounding tissue by the secretion of metalloproteinases that degrade the extracellular matrix to move and migrate towards different tissues, inducing ECM heterogeneity. Typically, 3DTFM studies neglect such heterogeneity and assume homogeneous ECM properties, which can lead to inaccuracies in traction reconstruction. Some studies have implemented ECM degradation models into 3DTFM, but the associated degradation maps are defined in an ad hoc manner. In this paper, we present a novel multiphysics approach to 3DTFM with evolving mechanical properties of the ECM. Our modeling considers a system of partial differential equations based on the mechanisms of activation of diffusive metalloproteinase MMP2 by membrane-bound metalloproteinase MT1-MMP. The obtained ECM density maps in an ECM-mimicking hydrogel are then used to compute the heterogeneous mechanical properties of the hydrogel through a multiscale approach. We perform forward and inverse TFM simulations both accounting for and omitting degradation, and results are compared to ground truth reference solutions in which degradation is considered. The main conclusions resulting from the study are: (i) the inverse methodology yields results that are significantly more accurate than those provided by the forward methodology; (ii) ignoring ECM degradation results in a considerable overestimation of tractions and non negligible errors in all analyzed cases.