bluuebunny/crossref_metadata_2025 huggingface dataset:
Aspekte der Versorgungsgerechtigkeit im UseCase Depressionsbehandlung des Digitalen FortschrittsHubs DECIDE
Authors: Riedinger Dirk , Huetter Sophia , Husemann Ronja , Momtahen Nicoletta , Uhl Francesca , Panholzer Torsten , Sandkämper Lucas , Scherrer Alexander , Pilz Maximilian , Flechsig Jonas , Simon Perikles , Tüscher Oliver , Hölzel Lars P. , Lieb Klaus , Wiegand Hauke Felix
Published: December 2024

Depressive Störungen gehören zu den häufigsten psychischen Erkrankungen in Deutschland. Trotz umfassender Versorgungsstrukturen gelingt es im deutschen Gesundheitssystem häufig nicht, eine an den Empfehlungen der Nationalen VersorgungsLeitlinie Depression orientierte Behandlung umzusetzen. Auch ist es für Patienten herausfordernd, sich im sektorisierten Versorgungssystem die erforderlichen Therapien selbst zu organisieren, was u. a. mit Unterschieden in Gesundheitswissen, Bildungsstand aber auch impliziten Annahmen von Behandlern zusammenhängen könnte. Diese Aspekte können als Versorgungsungerechtigkeiten verstanden werden. Das DECIDE-Projekt, gefördert durch die Medizininformatikinitiative des BMBF, entwickelt eine digitale Infrastruktur zur Therapiebegleitung bei Depressionen, welche eine App für Patienten und eine Software für Behandler umfasst. Sie soll u. a. eine sektorenübergreifende Falldarstellung, ein digitales Therapiemonitoring, Tele-Bewegungstherapie und einen digitalen Decision Support ermöglichen sowie eine verbessertes Gesundheitswissen der Betroffenen als Basis für partizipative Entscheidungen und Organisation von Therapiemaßnahmen fördern. Anhand einer Weiterentwicklung des Rahmenkonzeptes zur digitalen Versorgungsgerechtigkeit des US-amerikanischen National Institute on Minority Health and Health Disparities diskutieren wir, wie individuelle, interpersonelle, lokal gesellschaftliche und übergreifende gesellschaftliche Faktoren der Versorgungsgerechtigkeit in der DECIDE-Infrastruktur adressiert werden und welche Herausforderungen noch bestehen.
Adhärenz zu E-Tagebuch-Abfragen im Rahmen einer 6-monatigen Studie mit Ecological Momentary Assessment bei Teilnehmern mit Schizophrenie, depressiver Störung und gesunden Kontrollen
Authors: Moldavski Alexander , Benedyk Anastasia , Reichert Markus , Meyer-Lindenberg Andreas , Tost Heike
Published: December 2024

Menschen mit schweren psychiatrischen Erkrankungen (SMI), wie Schizophrenie und schweren Depressionen, haben oft Schwierigkeiten, Zugang zu adäquater Gesundheitsversorgung zu erhalten. Negative Symptome wie Antriebslosigkeit und sozialer Rückzug stellen dabei besondere Herausforderungen dar. Digitale Tools, insbesondere das Ecological Momentary Assessment (EMA), ermöglichen es, durch Smartphone-basierte elektronische Tagebücher (E-Tagebücher) Echtzeitdaten im Alltag der Patienten zu erfassen. In einer prospektiven Studie (INDICATE-N) wurde die Adhärenz zu einem mit täglichen Abfragen E-Tagebuch-Protokoll über 6 Monate bei Patienten mit Schizophrenie (SZ), depressiven Störungen (MDD) und gesunden Kontrollpersonen (HC) untersucht. Es zeigte sich, dass die Adhärenz der Patienten bei etwa 72 % lag, während gesunde Kontrollen eine höhere Adhärenz von etwa 84 % aufwiesen. Interessanterweise war die Teilnahme an den Abfragen unabhängig von der Schwere der Krankheit (gemessen am Clinical Global Impression Scale, CGI), außer bei sehr schwer kranken Patienten, bei denen die Adhärenz etwas geringer war. Diese Ergebnisse zeigen, dass EMA eine praktikable Methode zur Erfassung von Symptomen im Alltag von Patienten mit SMI ist, wobei die kontinuierliche Betreuung und Motivation der Teilnehmer entscheidend für den Erfolg ist.
Palliative Systemtherapie des metastasierten Rektumkarzinoms
Authors: Seufferlein Thomas , Ettrich Thomas Jens
Published: December 2024

Die palliative Behandlung des metastasierten Rektumkarzinoms (mCRC) hat sich in den
letzten Jahren durch neue Behandlungsstrategien wie Induktions- und Erhaltungstherapien, die
Etablierung zielgerichteter Therapien und molekular definierte Therapien in bestimmten
Untergruppen wie MSI-H-Patienten erheblich erweitert. Der folgende Artikel stellt
evidenzbasiert therapeutische Optionen und Behandlungsalgorithmen vor.
Multi-criteria design of multi-energy system for remote area using NSGA-III and fuzzy TOPSIS
Authors: Shakirov Vladislav , Popov Ilya
Published: December 2024

Multi-energy systems (MES) play a key role in solving many significant problems related to economic efficiency, reliability, and impacts on the environment. The multiplicity of goals pursued in the creation of MES gives rise to the problem of multi-criteria choice. The long-life cycle of MES and different development scenarios cause uncertainty in the preferences of decision makers. Focusing on these problems, the article proposes a framework for MES sizing based on multi-criteria optimization and decision-making techniques. Multi-criteria optimization is carried out to find Pareto-optimal MES configurations using the metaheuristic non-dominated sorting genetic algorithm III (NSGA-III). Multi-criteria evaluation of Pareto front alternatives under uncertainty of preferences is performed with fuzzy technique for order of preferences by similarity to ideal solution (TOPSIS). To develop MES that is the most suitable for various scenarios, a new indicator is proposed within the multi-scenario approach, calculated as the geometric mean of fuzzy TOPSIS assessments. The effectiveness of the proposed framework is demonstrated for a remote settlement located on the coast of the Sea of Japan under three scenarios. The geometric mean indicator through the multi-scenario approach identified the MES configuration most suitable for all considered scenarios (levelized cost of energy 0.21 $/kW h (within the interval 0.178–0.275), investment costs 294 289 $(43 573–535 439), CO2 emission 43 008 kg/year (3069–118 542), and unmet load 3262 kW h/year (0–24 044). Furthermore, for the problem being solved, the modified Inverted Generational Distance indicator was used to compare NSGA-III and NSGA-II algorithms. The superiority of NSGA-III over NSGA-II was confirmed (intervals of the indicator estimates are 1874–4040 and 3445–21 521, respectively).
Microstructure and residual stress distribution of dissimilar joints of SS321 to Hastelloy C-276 using CO2 Laser Beam Welding: An experimental validation
Authors: Panchagnula Jayaprakash Sharma , Kunduru Krishnamohan Reddy , Rao K. V. N. V. N. , Vemanaboina Harinadh , Gowd G. Harinath , Paramasivam Prabhu , Bommu Padmaja
Published: December 2024

This study applies a 3D model built for butt dissimilar joints welded using a laser beam. The thermo-mechanical study of SS321 and Hastelloy C-276 uses a volumetric Gaussian heat source model. Ansys parametric design language code is executed in ANSYSTM software for the simulation. Using the CO2 laser beam welding procedure, the simulation’s parameters serve as the experimental input procedures. We employ x-ray diffraction methods to quantify residual stresses in the weldments and evaluate the joint quality. The thermal results show that the fusion zone experiences maximum temperature, and the conduction occurs on the SS321 side. The residual stresses are tension at the fusion zone for simulation and experimentation. The welds exhibited full penetration and a consistent “Y” shape across all samples, indicating good structural integrity without internal defects. The factor of safety from the Finite Element Analysis (FEA) is 1.73, and the experimentation is 2.20. The residual stress varies by 21% from measured and FEA. Studies were carried out to characterize the weldments for their mechanical and metallurgical properties. Tensile tests confirmed that the weld zone’s strength is higher than the parent metals.
Multifunctional III-nitride optoelectronic system on a tiny chip
Authors: Wang Binju , Fu Jianwei , Fu Kang , Ye Ziqi , Wu Wenxuan , Gao Xumin , Yan Jiabin , Wang Yongjin
Published: December 2024

Multi-quantum well (MQW) diodes exhibit simultaneous emission and detection, allowing them to serve as multifunctional devices, including light emitters, receivers, energy transmitters, and information transmitters. Leveraging this capability, we designed a Multifunctional Energy Transfer Information System (METIS) that integrates contactless control, energy harvesting, and information transfer. At the core of this system, the multifunctional energy communication chip operates effectively across a broad range of extreme temperatures and in various solution environments. As the ambient temperature varies from −60 to 120 °C, the peak emission wavelength shifts from 465 to 476 nm, and even with further temperature changes from −70 to 150 °C, the communication function remains stable. Encapsulated for durability, METIS functions reliably in extreme conditions such as ice, water, salt solutions, and other light-transmitting fluids without needing external circuitry. Additionally, we demonstrate passive control of analog switches via MQW diodes. The MQW diodes also enable contactless energy and optical information transfer, ensuring stable and controllable information reconstruction at the receiving end. This approach offers an innovative solution for energy and information transmission in extreme environments.
The transmission modulation effect of patterns on the light extraction of ultraviolet-C light emitting diodes
Authors: Tian Yucheng , Wang Hui , Lu Huimin , Chen Zhizhong , Yu Tongjun
Published: December 2024

The AlGaN-based ultraviolet-C light emitting diodes (UVC LEDs) exhibit low light extraction efficiency (LEE), and patterning substrate surfaces is considered an effective solution. In this work, a simplified model based on the light extraction process of typical flip-chip UVC LEDs is proposed, which accelerates the simulations and illustrates the transmission process of patterned substrates more clearly. It is found that, different from the case in InGaN-based visible LEDs, the patterns on the substrate surfaces of UVC LEDs enhance the LEE by modulating the transmittance. The effects of sub-micron patterns are also studied, and the results suggest that the effects of LEE enhancement from different-scaled patterns vary little, unless the scale is decreased below a certain threshold so that the LEE decreases significantly. The results also show that AlN substrates can exhibit a 33% relative LEE enhancement if properly patterned, in contrast to the 18% enhancement in the case of sapphire. The proposed models and the acquired conclusions should be of help in designing UVC LEDs with high efficiency, especially for those on AlN substrates.
Comparison of IgG serum antibodies, electronic health records and self-report in estimating past infection with Chlamydia trachomatis in a cohort of men who have sex with men
Authors: Waters Mary Bridget , Barbee Lindley A. , Hybiske Kevin , Newman Katherine , Ikeda Ren , LeClair Angela , Golden Matthew R. , Soge Olusegun O. , Manhart Lisa E. , Khosropour Christine M.
Published: December 2024

Background The best method for measuring a history of Chlamydia trachomatis (CT) infections is unknown. We examined the reliability of three methods as markers of past CT infections: IgG serum antibodies, the electronic health record (EHR) and self-report. Methods This cross-sectional study used data from a cohort study of 122 MSM in King County, Washington, United States. Sera were tested for IgG using the mixed CT peptide enzyme-linked immunosorbent assay (ELISA). Participant data for past CT diagnoses were extracted from the EHR. Self-report of past CT was collected via survey. We calculated positive and negative percent agreements of CT history using total IgG serum antibodies to CT, past EHR diagnosis and self-report of past CT as reference measures when they were compared with one another. Results Of those who were IgG seropositive, only 41.5% had a past diagnosis of CT in their EHRs, but 74.4% self-reported a history of CT. The majority (92.7%) of participants who had a diagnosis of CT in their EHRs reported a past CT infection. Conclusions Self-report in combination with IgG serum antibodies to CT may be a more reliable indicator of past CT than EHRs in settings without comprehensive EHRs.
A multicriteria analysis of meat and milk alternatives from nutritional, health, environmental, and cost perspectives
Authors: Springmann Marco
Published: December 2024

Reducing meat and dairy intake has been identified as a necessary strategy for mitigating the high environmental impacts food systems are currently having on climate change, biodiversity loss associated with land-use changes, and freshwater use. Having a choice of dedicated meat and milk replacements available to consumers can help in the transition toward more plant-based diets, but concerns about nutritional and health impacts and high costs can impede uptake. Here, we conduct a multicriteria assessment of 24 meat and milk alternatives that integrates nutritional, health, environmental, and cost analyses with a focus on high-income countries. Unprocessed plant-based foods such as peas, soybeans, and beans performed best in our assessment across all domains. In comparison, processed plant-based products such as veggie burgers, traditional meat replacements such as tempeh, and plant milks were associated with less climate benefits and greater costs than unprocessed foods but still offered substantial environmental, health, and nutritional benefits compared to animal products. Our findings suggest that a range of food products exist that when replacing meat and dairy in current diets would have multiple benefits, including reductions in nutritional imbalances, dietary risks and mortality, environmental resource use and pollution, and when choosing unprocessed foods over processed ones also diet costs. The findings provide support for public policies and business initiatives aimed at increasing their uptake.
Estimates of optimal supplies of animal-sourced foods differ by food system goal and socioeconomic context
Authors: White Robin R. , Hall Mary Beth
Published: December 2024

Reduced consumption of animal-sourced food (ASF) has been recommended for environmental and human health objectives; however, ASF can be important for food security and diet affordability. We explored country-level relationships among various metrics of food supply, socioeconomic context, food security, diet affordability, and agricultural greenhouse gas emissions (GHGe) to characterize how optimal inclusion ranges for ASF vary with socioeconomic factors and food system goals. Data from 2015 to 2022 for 153 countries were sourced to generate Bayesian Networks representing relationships among the studied food system metrics. Networks were used in simulations to characterize optimal ASF inclusion to achieve environmental, food security, or diet affordability goals based on individual country data. Results are most appropriately interpreted in aggregate rather than as representations of specific countries due in large part to data limitations. Across countries simulated, median total ASF inclusion in the food supply to support food security, GHGe, or affordability objectives was 18.2% ± 12.1%, 11.9% ± 6.8%, and 17.6% ± 8.5%, respectively. Joint optimization for these goals resulted in median ASF inclusion of 15.1% ± 7.2%, with notable regional differences. Although ASF increases were supported in most developing regions, decreases were supported in developed countries. The reported SD in optimal ASF inclusion were considerable, and represented between-country variation. Empirical relationships of food categories to goals consistently favored dairy and egg products over meats. These results support previous literature highlighting the environmental intensity of ASF, but also indicate that moderate ASF supplies contribute to multiple food system goals simultaneously.
C9orf72-linked arginine-rich dipeptide repeats aggravate pathological phase separation of G3BP1
Authors: Van Nerom Margot , Ahmed Junaid , Lazar Tamas , Meszaros Attila , Galand Quentin , De Malsche Wim , Van Lindt Joris , Pancsa Rita , Maes Dominique , Tompa Peter
Published: December 2024

The toxic effects of C9orf72-derived arginine-rich dipeptide repeats (R-DPRs) on cellular stress granules in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia remain unclear at the molecular level. Stress granules are formed through the switch of Ras GTPase-activating protein-binding protein 1 (G3BP1) by RNA from a closed inactive state to an open activated state, driving the formation of the organelle by liquid–liquid phase separation (LLPS). We show that R-DPRs bind G3BP1 a thousand times stronger than RNA and initiate LLPS much more effectively. Their pathogenic effect is underscored by the slow transition of R-DPR–G3BP1 droplets to aggregated, ThS-positive states that can recruit ALS-linked proteins hnRNPA1, hnRNPA2, and TDP-43. Deletion constructs and molecular simulations show that R-DPR binding and LLPS are mediated via the negatively charged intrinsically disordered region 1 (IDR1) of the protein, allosterically regulated by its positively charged IDR3. Bioinformatic analyses point to the strong mechanistic parallels of these effects with the interaction of R-DPRs with nucleolar nucleophosmin 1 (NPM1) and underscore that R-DPRs interact with many other similar nucleolar and stress-granule proteins, extending the underlying mechanism of R-DPR toxicity in cells. Our results also highlight characteristic differences between the two R-DPRs, poly-GR and poly-PR, and suggest that the primary pathological target of poly-GR is not NPM1 in nucleoli, but G3BP1 in stress granules in affected cells.
Prenatal social disadvantage is associated with alterations in functional networks at birth
Authors: Nielsen Ashley N. , Triplett Regina L. , Bernardez Lourdes M. , Tooley Ursula A. , Herzberg Max P. , Lean Rachel E. , Kaplan Sydney , Meyer Dominique , Kenley Jeanette K. , Alexopoulos Dimitrios , Losielle David , Latham Aidan , Smyser Tara A. , Agrawal Arpana , Shimony Josh S. , Jackson Joshua J. , Miller J. Philip , Raichle Marcus E. , Warner Barbara B. , Rogers Cynthia E. , Sylvester Chad M. , Barch Deanna M. , Luby Joan L. , Smyser Christopher D.
Published: December 2024

Childhood exposure to social disadvantage is a major risk factor for psychiatric disorders and poor developmental, educational, and occupational outcomes, presumably because adverse exposures alter the neurodevelopmental processes that contribute to risk trajectories. Yet, given the limited social mobility in the United States and other countries, childhood social disadvantage is frequently preceded by maternal social disadvantage during pregnancy, potentially altering fetal brain development during a period of high neuroplasticity through hormonal, microbiome, epigenetic, and immune factors that cross the placenta and fetal blood–brain barrier. The current study examines prenatal social disadvantage to determine whether these exposures in utero are associated with alterations in functional brain networks as early as birth. As part of the Early Life Adversity and Biological Embedding study, mothers were recruited during pregnancy, prenatal social disadvantage was assessed across trimesters, and their healthy, full-term offspring were imaged using resting-state functional magnetic resonance imaging during the first weeks of life. Multivariate machine learning methods revealed that neonatal functional connectivity (FC) varied as a function of prenatal exposure to social disadvantage (n = 261, R = 0.43, R
2
= 0.18), with validation in an independent sample. Alterations in FC associated with prenatal social disadvantage occurred brain-wide and were most pronounced in association networks (fronto-parietal, ventral attention, dorsal attention) and the somatomotor network. Amygdala FC was altered at birth, with a pattern shared across subcortical structures. These findings provide critical insights into how early in development functional networks begin to diverge in the context of social disadvantage and elucidate the functional networks that are most impacted.
Magnetochrome-catalyzed oxidation of ferrous iron by MamP enables magnetite crystal growth in the magnetotactic bacterium AMB-1
Authors: Amor Matthieu , Chevrier Daniel M. , Siponen Marina I. , Egli Ramon , Scoppola Ernesto , Marcano Lourdes , Li Chenghao , Choueikani Fadi , Faivre Damien
Published: December 2024

Magnetotactic bacteria have evolved the remarkable capacity to biomineralize chains of magnetite [Fe(II)Fe(III)
2
O
4
] nanoparticles that align along the geomagnetic field and optimize their navigation in the environment. Mechanisms enabling magnetite formation require the complex action of numerous proteins for iron acquisition, sequestration in dedicated magnetosome organelles, and precipitation into magnetite. The MamP protein contains c-type cytochromes called magnetochrome domains that are found exclusively in magnetotactic bacteria. Ablation of magnetochromes in MamP prevents bacteria from aligning with external magnetic fields, showing their importance to maintain this biological function. MamP has been proposed, mostly from in vitro experimentations, to regulate iron redox state and maintain an Fe(II)/Fe(III) balance compatible with magnetite formation via the iron oxidase activity of magnetochromes. To test the proposed function for MamP in vivo in the magnetotactic strain
Magnetospirillum magneticum
(AMB)-1, we characterized the iron species in chemical MamP-mediated magnetite syntheses as well as in bacteria unable to produce MamP using a combination of physicochemical methodologies. We show that MamP has no apparent control on the speciation and oxidation state of intracellular iron or on the Fe(II)/Fe(III) balance in magnetite. We propose that MamP promotes magnetite growth by incorporating Fe(III) into preexisting magnetite seeds and that magnetite structure and stoichiometry is maintained by further equilibration with dissolved Fe(II) in magnetosome organelles.
Autonomous phototaxis of hydrogel swimmers
Authors: Cezan S. Doruk , Aggarwal Aaveg , Li Chuang , Yuan Hang , Palmer Liam C. , Olvera de la Cruz Monica , Stupp Samuel I.
Published: December 2024

The design of synthetic soft matter capable of emulating the complex behaviors of living organisms, such as sensing and adapting to their environment, remains an important challenge in developing biomimetic materials. Functionalized hydrogels are ideal candidates for such materials since they are highly responsive to their environment and can be operated in water. In this work, we investigate a hybrid bonding hydrogel composed of peptide amphiphile supramolecular nanofibers covalently attached to a photoresponsive network, in which high-aspect-ratio ferromagnetic nanowires are aligned along the length of the sample, designed to swim under oscillating magnetic fields. This hybrid hydrogel swimmer can autonomously swim toward a light source by utilizing photoinduced interactions between supramolecular and covalent networks reminiscent of phototactic swimming in living systems. Using a combination of experimental techniques and a continuum model incorporating photochemistry, magnetoelasticity, and hydrodynamics, we explain the swimming mechanism and predict phototactic behavior. Our work highlights the potential role of hybrid bonding polymers, which leverage the interplay between supramolecular assemblies and covalent networks. We demonstrate how these polymers can be tailored to react dynamically to their environment, paving the way for developing intelligent and autonomous robotic systems.
Facilitative use of classifiers in heritage Vietnamese
Authors: Nguyen Hoan , Grüter Theres
Published: December 2024

Recent research has highlighted the value of investigating the online language processing of heritage speakers
(HS) as a means of accessing their implicit language knowledge (Montrul, 2023). While
studies have shown that Spanish and Polish HS use grammatical gender cues to predict upcoming nouns (Fuchs, 2022a, 2022b), less is known about Vietnamese HS’ use
of prenominal classifiers (e.g., con for animate objects, cái for inanimate objects) to
facilitate their processing (but see Ito et al., 2024). This study examined if and how
home-country raised and heritage speakers of Vietnamese in the U.S. use classifiers to facilitate the processing of upcoming
nouns, and whether heritage language proficiency is a modulating factor. Forty-one adult native speakers of Vietnamese (18
home-country raised, 23 HS) completed a visual-world eye-tracking experiment, an offline cloze test to assess knowledge of
classifier–noun pairings, and a Vietnamese listening proficiency test. The results indicate that despite more variable knowledge
of classifier–noun pairings and generally slower lexical access, HS use classifiers as a semantically informative cue during
real-time comprehension, albeit to a somewhat lesser extent than their home-country raised peers. Increased proficiency in the
heritage language, whether measured objectively or self-rated, was not found to enhance engagement in prediction.
The N-periodic wave solutions to the

N
=
1

supersymmetric Sawada–Kotera–Ramani equation
Authors: Xin 辛 Pengcheng 鹏程 , Zhao 赵 Zhonglong 忠龙 , Wang 王 Yu 宇
Published: December 2024

The N-periodic wave solvability problem for the

N
=
1

supersymmetric Sawada–Kotera–Ramani equation is considered by combining the Hirota’s bilinear method and the super Riemann theta function. The constraint equations and unknown parameters are redefined, and the numerical calculation process of the N-periodic wave solutions is derived. It has been verified that under certain conditions, the asymptotic relations between N-periodic wave solutions and N-soliton solutions can be established. Some numerical solutions of three-periodic wave are presented. Under the influence of the Grassmann variable, the three-periodic wave solutions will generate an influence band in the middle region, and the amplitude becomes bigger as the distance from the influence band increases.
Development of immunocompetent full thickness skin tissue constructs to model skin fibrosis for high-throughput drug screening
Authors: Lim Yi Wei , Quinn Russell , Bharti Kapil , Ferrer Marc , Zarkoob Hoda , Song Min Jae
Published: December 2024

The lack of the immune component in most of the engineered skin models remains a challenge to study the interplay between different immune and non-immune cell types of the skin. Immunocompetent human in vitro skin models offer potential advantages in recapitulating in vivo like behavior which can serve to accelerate translational research and therapeutics development for skin diseases. Here we describe a three-dimensional human full-thickness skin (FTS) equivalent incorporating polarized M1 and M2 macrophages from human peripheral CD14+ monocytes. This macrophage-incorporated FTS model demonstrates discernible immune responses with physiologically relevant cytokine production and macrophage plasticity under homeostatic and lipopolysaccharide stimulation conditions. M2-incorporated FTS recapitulates skin fibrosis phenotypes with transforming growth factor-β1 treatment as reflected by significant collagen deposition and myofibroblast expression, demonstrating a M2 potentiation effect. In conclusion, we successfully biofabricated an immunocompetent FTS with functional macrophages in a high-throughput (HT) amenable format. This model is the first step towards a HT-assay platform to develop new therapeutics for skin diseases.
Engineering pore-enriched and pre-vascularized volumetric constructs for enhanced blood glucose regulation in type 1 diabetes therapy
Authors: Kim Jaewook , Shim In Kyong , Lee Yu Na , Kim Myungji , Hwang Dong Gyu , Kim Jihwan , Jo Yeonggwon , Chae Suhun , Kim Jisoo , Kim Song Cheol , Cho Dong-Woo , Jang Jinah
Published: December 2024

Managing type 1 diabetes mellitus (T1DM) presents significant challenges because of the complexity of replicating the microenvironment of pancreatic islets and ensuring the long-term viability and function of transplanted insulin-producing cells (IPCs). This study developed a functional approach that utilizes 3D bioprinting technology to create pore-enriched and pre-vascularized tissue constructs incorporating a pancreatic tissue-derived decellularized extracellular matrix and human-induced pluripotent stem cells (hiPSCs) aimed at enhancing blood glucose regulation in T1DM. We designed a volumetric 3D pancreatic tissue construct that supported the engraftment, survival, and insulin-producing functionality of hiPSC-derived IPCs. The construct’s porosity was optimized to enhance IPC delivery efficiency. Additionally, human umbilical vein endothelial cells co-cultured with IPCs in a patterned structure facilitated pre-vascularization, improving construct integration with host tissues and accelerating revascularization post-transplantation. Our results demonstrate high cell viability and sustained insulin production in diabetic rodent models, indicating the constructs’ effectiveness in regulating blood glucose levels over an extended period. The findings of this study not only underscore the potential of 3D bioprinting for creating functional tissue constructs for T1DM treatment but also offer efficient cell delivery techniques applicable to other areas of regenerative medicine.
Artesunate remarkably alleviates interstitial cystitis/bladder pain syndrome in a murine model: Novel molecular signature deciphered by bulk tissue and single‐cell transcriptomic analysis
Authors: Wu Yanyuan , Shi Bowen , He Yedie , Wang Song , Zhou Jiatong , Qi Jun , Ding Jie , Wang Zongping
Published: December 2024

Interstitial cystitis/bladder pain syndrome is a chronic pain syndrome of elusive etiology, accompanied by lower urinary tract symptoms. Over the past decades, many studies have been carried out for exploration of more effective therapies against IC/BPS. However, the results have been inconsistent, probably due to the multifactorial nature of IC/BPS. We establish a model of IC/BPS in mice by combining protamine sulfate /lipopolysaccharide and phenylephrine. Typical histological changes and symptoms were observed. We then explored the effectiveness of artesunate (ART), which has been reported to alleviate autoimmune diseases. Phenotypic tests demonstrated a significant reduction in symptoms. Histological staining showed pathological improvement. WGCNA identified three gene modules specifically related to IC/BPS, and six genes were identified as hub genes. CIBERSORT analysis showed that the activated NK cells seem to be decreased in IC modeling group and partially restored in IC + ART group, whereas the resting NK cells showed the opposite trend. Single‐cell transcriptomic analysis elaborated on the changing trends of subgroups of infiltrated immune cells, including T cells, NK cells, and dendritic cells. Our study represents our effort in establishing a reliable and reproducible IC/BPS murine model, and the first study using scRNA‐seq in exploring the immune microenvironment of the IC/BPS murine model, and the possible molecular mechanisms of ART treatment in IC/BPS. Further studies are needed to confirm the effect of ART in IC/BPS patients.
Glucagon-like peptide-1 receptor agonists in peri-operative care
Authors: Paggers Larissa , Mesotten Dieter , Stragier Hendrik
Published: December 2024

With the growing use of glucagon-like-peptide-1 (GLP-1) receptor (GLP-1R) agonists as anti-obesity medication it is becoming increasingly important to examine its consequences in the peri-operative period. GLP-1R agonists are known for their effects of glucose-lowering and gastroparesis the latter causing some safety concerns regarding induction of anaesthesia, more specifically the risk of pulmonary aspiration. This article gathers the available evidence on this subject in addition to the already established guidelines. Current evidence makes us assume there is indeed an increased level of gastroparesis, but there are no studies to date with evidential confirmation of a presumed elevated risk of pulmonary aspiration. Future perspectives should focus on the actual risk of pulmonary aspiration and the possible implementation of ultrasound in the preoperative assessment.
One Concentration Does Not Fit All: It is Time to Personalize the Therapeutic Range of Infliximab in Crohn Disease
Authors: Franck Bénédicte , Tron Camille , Verdier Marie-Clémence , Bellissant Eric , Peaucelle Anne-Sophie , Roblin Xavier , Lemaitre Florian , Bouguen Guillaume
Published: December 2024

Background:

Therapeutic drug monitoring of infliximab is commonly performed based on trough concentration. However, doses and dosing intervals may be adapted to patient outcomes, and this trough concentration target may correspond to a large range of exposures in terms of the area under the concentration–time curve (AUC). The objectives of this study were to assess the real-life exposure to intravenous infliximab in patients with Crohn disease in remission at year 1 and to assess the evolution of exposure in patients who switched to subcutaneous infliximab.

Methods:

The authors conducted a retrospective observational pharmacokinetic study in patients with Crohn disease who had available infliximab concentrations during intravenous and subcutaneous infliximab maintenance therapy as per the standard of care. Infliximab exposure parameters (AUCs and trough concentrations, C0) were compared for different dosing regimens of intravenous infliximab before (intravenous) and after (subcutaneous) the switch.

Results:

A total of 113 patients had 383 intravenous infliximab concentrations. Dosing intervals ranged from 4 to 12 weeks. The median/range/CV% C0, AUC0-t, and AUC0–8weeks were 5.3 mcg/mL [<LLoQ-49.6]/71.6%, 37,792 mcg.h/mL [4971–116,366]/33.1%, and 41,582 mcg.h/mL [7953–232,048]/43.9%, respectively. Forty-one patients had available paired C0 after both intravenous and subcutaneous administration. A poor correlation was found between preswitch intravenous infliximab C0 and postswitch subcutaneous infliximab C0.

Conclusions:

In this study, the authors suggested that in patients treated with IV IFX, different targets of C0 should be proposed according to treatment schemes and that AUC0-t might be a relevant determinant of clinical remission. Moreover, exposure did not remain stable throughout the switch from IV to SC IFX in any patient. These variations may depend on the intravenous dosing interval before switching.
Perceived Social Support Mediates the Relationship Between Benefit Finding and Depressive Symptoms Among Young and Middle-Aged Stroke Survivors and Their Spouse Caregivers
Authors: Liu Ya-ting , Zhang Si-xun , Xiang Dan-dan , Ge Song , Liu Zhi-wei , Fan Bao-yu , Zhang Zhen-xiang , Li Xin , Mei Yong-xia
Published: December 2024

Background

Existing literature indicates that benefit finding and social support play protective roles against depressive symptoms. However, there is a lack of understanding regarding the interplay between benefit finding, social support, and depressive symptoms within the dyadic context of stroke survivor-spousal caregiver relationships.

Objective

The objective of this study is to investigate the relationships among benefit finding, social support, and depressive symptoms in young and middle-aged stroke survivors and their spouse caregivers. In addition, the mediating role of social support in the association between benefit finding and depressive symptoms is explored.

Methods

A total of 203 pairs of stroke survivor-spouse caregiver were included in the study. Depressive symptoms, social support, and benefit finding were measured using the Patient Health Questionnaire-9, the Perceived Social Support Scale, the Benefit Finding Scale, and the Caregiver Benefit Finding Scale. The Actor-Partner Interdependence Mediation Model was used to assess direct and indirect effect.

Results

The findings revealed a significant negative association between higher levels of benefit finding and lower depressive symptoms in both stroke survivors (actor effect, −0.126) and spousal caregivers (partner effect, −0.044). Perceived social support emerged as a significant mediator in the relationship between benefit finding and depressive symptoms in spousal caregivers (indirect effect, −0.024). Furthermore, spousal caregivers' perceived social support served as a mediating variable between caregiver benefit finding and depressive symptoms in stroke survivors (indirect effect, −0.023).

Conclusion

The study underscores the interdependence between stroke survivors and spousal caregivers, highlighting the mutual influence they have on each other. Consequently, targeted interventions addressing both members of the dyad, with a focus on enhancing benefit finding and social support, could prove beneficial in ameliorating depressive symptoms in stroke survivor-spousal caregiver.
Efficacy and Safety of Dose Increase From 40 mg/d to 80 mg/d of Lurasidone in Patients With Schizophrenia
Authors: Takeuchi Hiroyoshi , Uchida Hiroyuki
Published: December 2024

Objectives

The primary objective of this study was to evaluate the efficacy and safety of increasing the dose of lurasidone from 40 mg/d to 80 mg/d in patients with schizophrenia.

Methods

This post hoc analysis focused on patients who completed a 6-week double-blind, placebo-controlled trial of lurasidone and transitioned to a subsequent 12-week open-label extension trial. Patients initially assigned to lurasidone (40 mg/d) or placebo during the double-blind trial (DBT-LUR group or DBT-PLA group, respectively) received lurasidone (40 mg/d) during the extension. Clinicians could increase the dose to 80 mg/d based on clinical judgment. The efficacy outcomes included the change in the Positive and Negative Syndrome Scale (PANSS) total score from the start to the end of the lurasidone (80 mg/d) treatment period. Safety outcome was the rate of newly emergent adverse events.

Results

Of 287 patients in the intention-to-treat population, 153 received an increased dose of lurasidone from 40 mg/d to 80 mg/d. Significant reductions in the PANSS total scores were observed in both groups (all P values, ≤0.001). Additionally, 35.9% of the DBT-LUR group and 40.0% of the DBT-PLA group achieved a ≥20% reduction in the PANSS total score. New adverse events emerged in 47.4% of the DBT-LUR group and 48.0% of the DBT-PLA group during the lurasidone (80 mg/d) treatment period.

Conclusions

Increasing the dose of lurasidone from 40 mg/d to 80 mg/d may be effective and well tolerated in patients with schizophrenia. Because of the lack of a control group and blinding, the results should be interpreted with caution.
The impact of lymph node involvement on adjuvant chemotherapy and survival in patients with resected invasive intraductal papillary mucinous neoplasm: a propensity score matching study based on SEER database and external validation
Authors: Gan Wei , Pu Ning , Han Jiande , Yin Hanlin , Chen Qiangda , Zhang Lei , Wu Wenchuan , Xu Huaxiang , Shi Chenye , He Junyi , Jin Yun , Lou Wenhui , Wang Wenquan , Liu Liang
Published: December 2024

Background:

Limited knowledge and guidelines exist for invasive intraductal papillary mucinous neoplasm (IPMN). This study aims to explore the significance of lymph node involvement on adjuvant chemotherapy (ACT) for invasive IPMN.

Materials and Methods:

Patients diagnosed with invasive IPMN were selected from both the SEER database and our hospital. Kaplan-Meier analysis, Cox proportional hazards model, and propensity score matching (PSM) were employed in this study.

Results:

In the SEER group, multivariate analysis involving 775 patients revealed that several factors including age, tumor differentiation, AJCC-T staging, N staging, and TNM stage significantly influenced overall survival (OS) and cancer-specific survival (CSS). Turning to the Zhongshan Hospital group (ZS group), which had 94 recruited patients, multivariate analysis for OS, CSS, and recurrence-free survival (RFS) showed that AJCC N staging emerged as the most significant risk factor, with HR values of 4.664, 4.955, and 3.175, respectively. In subgroup analysis, ACT provided survival advantages for patients with positive lymph node metastasis (LNM). In a PSM analysis focused on patients with positive LNM, the comparison revealed that ACT emerged as a critical factor influencing both OS and CSS (both p<0.005). Especially, these patients younger than 60 year old, or those with AJCC-T2-N+ staging were found to get apparently benefit from ACT as revealed by our subgroup interaction analysis.

Conclusion:

LNM plays a pivotal role in the management of invasive IPMN patients underwent surgery, and ACT might be a beneficial therapeutic option for individuals concurrent with LNM, particularly among those younger than 60 year old, or with AJCC-T2-N+ staging.
Fast score is associated with patient-reported outcomes in patients with metabolic dysfunction-associated steatotic liver disease
Authors: Hashida Ryuki , Kawaguchi Takumi , Nakano Dan , Tsutsumi Tsubasa , Kawaguchi Machiko , Takahashi Hirokazu , Tajima Hiroshi , Matsuse Hiroo , Golabi Pegah , Gerber Lynn H. , Younossi Zobair M. , Hiraoka Koji
Published: December 2024

Backgrounds

People with metabolic dysfunction-associated steatotic liver disease (MASLD) frequently report fatigue. This symptom is associated with hepatic inflammation and fibrosis. FibroScan-aspartate aminotransferase (FAST) score is a noninvasive measurement tool that can be used to assess the severity of MASLD. We aimed to investigate the independent factors associated with patient-reported outcomes (PROs) including fatigue, and their FAST scores.

Methods

We enrolled 116 patients with MASLD. PROs were assessed by the Chronic Liver Disease Questionnaire for nonalcoholic fatty liver disease (CLDQ-NAFLD), which consists of six domains including fatigue. Each domain score that was less than 6 was classified into the impairment group. A cutoff value of 0.67 in the FAST score was used to categorize a high or low FAST score. Independent factors associated with impaired PROs and fatigue were analyzed using logistic regression analysis and a graphical model.

Results

For factor total, in the logistic regression analysis, the high FAST score was only identified as a negative independent factor for impaired total CLDQ-NAFLD (odds ratio: 5.9, 95% confidence interval: 1.11–31.20, P = 0.034). The graphical model revealed that FAST score, BMI, and age directly interact with impaired total CLDQ-NAFLD. For fatigue, there was no statistically significant factor in the logistic regression analysis. The graphical model revealed that the FAST score, BMI, estimated glomerular filtration rate, and age directly interact with fatigue.

Conclusion

We found that the FAST score directly interacted with total CLDQ-NAFLD and the domain of fatigue. The FAST score may be a useful tool to assess impaired CLDQ-NAFLD.
The effect of catecholamine versus non-catecholamine vasopressors on renal function and recovery in vasodilatory shock: A systematic review of preclinical and clinical studies
Authors: Vernon-Elliot Jake , Goradia Shruti , Bellomo Rinaldo , Lankadeva Yugeesh R. , Burrell Louise M. , See Emily J.
Published: December 2024

Background: Acute kidney injury (AKI) is a common complication of vasodilatory shock. AKI is associated with an increased risk of death, prolonged hospital stays, and subsequent transition to chronic kidney disease. Catecholamines have historically been used as the first-line vasopressors for vasodilatory shock; however, they may adversely affect renal function and recovery.

Objectives: To compare the effects of catecholamine and non-catecholamine vasopressors on AKI risk and recovery in preclinical and clinical studies of vasodilatory shock.

Methods: Medline, Embase, and Cochrane Central Register of Controlled Trials were systematically searched to identify studies reporting renal outcomes associated with catecholamine (norepinephrine, epinephrine, metaraminol, phenylephrine, dopamine) and non-catecholamine vasopressors (vasopressin, angiotensin II), in preclinical models or adult cohorts of vasodilatory shock. Two independent reviewers screened studies and extracted data using a prespecified form for qualitative synthesis and risk of bias assessment.

Results: Of 3,504 citations, 90 studies were eligible for inclusion: 41 preclinical studies, 17 non-randomized clinical studies, 28 randomized clinical studies, and 4 post-hoc analyses. Risk of bias was generally low in preclinical studies and low to moderate in clinical studies. In preclinical studies, catecholamine vasopressors exacerbated medullary hypoxia and intrarenal inflammation compared to non-catecholamine vasopressors. In clinical studies, catecholamines were associated with higher serum creatinine, lower urine output, and increased requirements for renal replacement therapy (RRT) compared to non-catecholamine vasopressors. In patients on high dose catecholamines, adjunctive angiotensin II was associated with improved RRT liberation.

Conclusions: Preclinical and clinical studies suggest that non-catecholamine vasopressors may confer renal benefits compared to catecholamine vasopressors. These hypothesis-generating observations suggest the need for comparative studies focused on renal outcomes.

Systematic Review Registration: PROSPERO 2024 CRD42024527773
Baicalin alleviates LPS-induced cytotoxicity in acute lung injury through mediating METTL14/SOX6 axis
Authors: Chen Yuexuan , Gu Yuhai , Gao Zhihan
Published: December 2024

Background

Baicalin (C21H18O11) is a flavonoid component extracted from scutellaria baicalensis with biological activity in various types of diseases, including acute lung injury (ALI). The relevant mechanism behind baicalin in ALI needs further investigation.

Methods

ALI model in vitro was established by lipopolysaccharide (LPS) in WI-38 cells (lung fibroblast). Cell growth was determined via MTT assay and EdU assay. Apoptosis was assessed using flow cytometry, caspase 3 assay and TUNEL assay. Oxidative indicators and inflammatory cytokines were detected by commercial kits. Interaction between methyltransferase-like 14 (METTL14) and SRY-Box Transcription Factor 6 (SOX6) was studied using Methylated RNA Immunoprecipitation (MeRIP) and dual-luciferase reporter assay. RT-qPCR and western blot were applied for examining gene levels.

Results

Baicalin enhanced cell growth and reduced apoptosis, oxidative stress, inflammation after ALI was induced by LPS. Downregulation of SOX6 weakened LPS-induced cytotoxicity in WI-38 cells. Baicalin prevented from LPS-induced lung cell injury via reducing SOX6 expression. SOX6 expression was stabilized by METTL14 through its methylation modification. METTL14/SOX6 axis was related to the regulation of baicalin in LPS-treated WI-38 cells.

Conclusion

Therefore, baicalin played an important role to inhibit LPS-induced cytotoxicity in vitro via METTL14-mediated methylation of SOX6.