bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and Clinical Risk Factors of Thyroid Cancer in Retrosternal Goiter: A Retrospective Comparative Study with Cervical Multinodular Goiter
Authors: Prete Francesco Paolo , De Luca Giuseppe Massimiliano , Sgaramella Lucia Ilaria , Pasculli Alessandro , Di Meo Giovanna , Testini Carlotta , Puglisi Giuliana Rachele , Rugge Matteo , Gurrado Angela , Testini Mario
Published: January 2025

Background: Surgical intervention in asymptomatic retrosternal goiter (RSG) is debated in the absence of suspicious cytology, while performing fine-needle aspiration (FNA) is challenging in thyroids with mediastinal extension. The rate of unexpected thyroid cancers found at the time of thyroidectomy varies widely, while the notion of increased cancer incidence in RSG with respect to cervical goiters is still controversial. Methods: We retrospectively reviewed 411 patients with a preoperative diagnosis of multinodular goiter (MNG) (114 retrosternal, 297 cervical) who underwent thyroidectomy at an academic endocrine surgery referral center between January 2019 and October 2022. Rates of cancer detected on the final pathology examination, overall and not anticipated by preoperative workup, were compared between cervical MNG (cMNG) and RSG. Results: Patients with RSG were older (58.2% vs. 50.6%; p < 0.001) and more likely to be men (34.2% vs. 23%; p = 0.014). Overall, thyroid cancer was found in 49.5% of cMNG specimens and in 35.1% of RSGs (p = 0.02), and cancer > 1 cm was found in 37.4% of cMNG and 17.4% of RSG (p = 0.003). Prevalence of unexpected thyroid cancer was not significantly different between cMNGs (29.8%) and RSGs (28.8%). Unexpected carcinomas > 1 cm impacted 11% of all RSGs. Conclusions: In this study, the prevalence of unexpected thyroid cancer in RSG was similar to cMNG and significant from a clinical standpoint, with 1 in every 10 RSG diagnosed with differentiated cancer > 1 cm. Findings may be partially attributed to the difficulty in performing FNA in the mediastinum. Surgeons should counsel patients preoperatively regarding the risk of unexpected thyroid cancer to set appropriate expectations of outcome.
Equivalence of Paper and Smartphone Versions of the Beck Depression Inventory-II
Authors: Uchida Hiroyuki , Igusa Takumi , Higashi Yurika , Takeda Minami , Tsuchiya Kenji , Kikuchi Senichiro , Hirao Kazuki
Published: January 2025

Background: The Beck Depression Inventory-II (BDI-II) is a widely used patient-reported outcome (PRO) tool designed to screen for depressive symptoms and assess their severity. In recent years, with advancements in digital technology, the BDI-II has been adapted for use as an electronic PRO (ePRO) tool. However, to the best of our knowledge, the reliability of the smartphone version of the BDI-II has not been thoroughly investigated. This study aimed to assess the equivalence of the traditional paper and smartphone versions of the BDI-II. Methods: This study employed a randomized crossover design with adults (n = 100) from the Gunma Prefecture, Japan. Participants completed both the paper and smartphone versions of the BDI-II at 1-week intervals. The equivalence between the two versions was evaluated using the intraclass correlation coefficient (ICCagreement). Additionally, Cronbach’s alpha and McDonald’s omega were calculated for both versions. Results: The mean age of the participants was 19.78 years (SD = 0.94, 10% male). The ICCagreement between the paper and smartphone versions of the BDI-II was 0.81 (95% CI 0.74–0.87). Cronbach’s alpha was 0.88 (95% CI 0.84–0.91) for the paper version and 0.88 (95% CI 0.84–0.91) for the smartphone version. McDonald’s omega was 0.88 (95% CI 0.81–0.95) for the paper version and 0.89 (95% CI 0.85–0.93) for the smartphone version. Conclusions: The BDI-II is suitable for use in its smartphone version, and the smartphone version of the BDI-II is a valuable addition to the mental healthcare professional’s toolkit.
Subgroup Characteristics of Middle-Aged and Older Women with Chronic Low Back Pain by Multiple Factors: A Hierarchical Cluster Analysis
Authors: Miyachi Ryo , Nishimura Takaaki , Noguchi Masahiro , Goda Akio , Takeda Hiromichi , Takeshima Eisuke , Kanazawa Yuji , Imai Tadashi , Tanaka Wataru
Published: January 2025

Background/Objectives: Chronic low back pain (CLBP) after middle age is a complex multifactorial condition, and subgrouping is recommended to determine effective treatment strategies. Multidimensional data help create new groupings to increase the effectiveness of interventions in middle-aged and older adults with CLBP. This study aimed to investigate the relationship between the factors associated with CLBP after middle age and to create and characterize a new subgroup based on these factors. Methods: A cross-sectional observational study was conducted and included 46 women aged ≥40 years with CLBP who participated in health events. Trunk muscle mass, lumbar movement control ability, autonomic balance, lumbar tenderness threshold, lumbar proprioception, and severity of central sensitization were assessed. Results: Partial correlation analysis revealed a significant negative correlation between lumbar movement control ability and autonomic balance. A significant positive correlation was observed between trunk muscle mass and the lumbar tenderness threshold. Hierarchical clustering analysis identified three subgroups. The cluster 1 participants had low trunk muscle mass, low tenderness threshold, and low severity of central sensitization. The cluster 2 participants had low trunk muscle mass and tenderness threshold and high severity of central sensitization. The cluster 3 participants had high trunk muscle mass and tenderness threshold and were sympathetically predominant. Trunk muscle mass, pressure pain threshold, severity of central sensitization, and autonomic balance were significantly different between the clusters. Conclusions: Three characteristic subgroups were identified. The results contribute to treatment and prevention strategies for middle-aged and older adults with CLBP based on the characteristics of the subgroups rather than a uniform approach.
A Protocol for AI-Powered Tools to Enhance Mobility and Function in Older Adults: An Evidence and Gap Map
Authors: Veras Mirella , Pardo Jordi , Lê Mê-Linh , Jussup Cindy , Tatmatsu-Rocha José Carlos , Welch Vivian
Published: January 2025

Introduction: Artificial intelligence (AI) is transforming healthcare by enhancing diagnostic accuracy, treatment, and patient monitoring, benefiting older adults by offering personalized care plans. AI-powered tools help manage chronic conditions and maintain independence, making them a valuable asset in addressing aging challenges. Objectives: The objectives are as follows: 1. To identify and describe AI-power-based exercise programs for older adults. 2. To highlight primary evidence gaps in AI interventions for functional improvement and mobility. 3. To evaluate the quality of existing reviews on this topic. Methods: The evidence gap map (EGM) will follow the five-step method, adhering to the Campbell Collaboration guidelines and, if available at the time of reporting, PRISMA-AI standards. Guided by the Metaverse Equitable Rehabilitation Therapy framework, this study will categorize findings across domains like equity, health service integration, interoperability, governance, and humanization. The study will include systematic reviews, randomized controlled trials, and pre-and post-intervention designs. Results will be reported following PRISMA-AI guidelines. We will use AMSTAR-2 Checklist for Analyzing Systematic Reviews on AI Interventions for Improving mobility and function in Older Adults to evaluate the reliability of systematic reviews and focus on internal validity. Conclusions: This comprehensive analysis will act as a critical resource for guiding future research, refining clinical interventions, and influencing policy decisions to enhance AI-driven solutions for aging populations. The EGM aims to bridge existing evidence gaps, fostering a more informed, equitable, and effective approach to AI solutions for older adults.
Loving and Healing a Hurt City: Planning a Green Monterrey Metropolitan Area
Authors: Roggema Rob , Rubio Cisneros Igor Ishi , Junco López Rodrigo , Ramirez Leal Paulina , Ramirez Suarez Marina , Ortiz Díaz Miguel
Published: January 2025

In many conurbations, the pressure on the quality of living increases and affects the most vulnerable human and non-human populations the most. This article describes a proposal for the mapping and design investigation of how a green metropolis can be developed. The approach distinguishes between the landscape producing pain, the ways of healing, and the opportunities to create environments that people can love. This approach reveals concrete and widespread pain in the metropolis, such as impacts on natural landscapes (rivers and mountains), air pollution, ecological degradation, and hydrological disconnections. The strategy to remediate this pain is to uncover hidden and altered creeks and rivers, creating an abundant zone of ecological space around them before human activities and urbanization change the land uses. In addition to this, specific design principles have been developed for hydro-ecological corridors, water retention, green islands, and greenways. Designs for these places can be replicated to support a healing strategy in the Monterrey Metropolitan Area (MMA). Each place creates an environment that the urban residents will appreciate and preserve. The approach to analyzing landscape pain, designing healing strategies, and promoting local places of love can be applied to enhance the quality of life for many urban residents and non-human ecologies in metropolitan areas around the globe.
Determination of Osmotic Flow in Water Transport in an Illitic Clay
Authors: Mánik Marek , Medveď Igor , Keppert Martin , Suchorab Zbigniew , Trník Anton
Published: January 2025

Experimental studies have shown that osmosis could be one of the mechanisms of water transport in porous materials that act, to a certain extent, as semipermeable membranes. In this paper, an experimental apparatus and the corresponding model to measure and determine the osmotic efficiency, σ, of bulk porous materials are described. Both the apparatus and model to interpret water transport in samples are modifications of those of Sherwood and Craster. In addition to σ, the transport parameters of the model include Darcy permeability and water and salt diffusivity. These parameters are used to calculate the ratio of the individual components of the total molar flow. We used the apparatus to measure cylindrical samples made from an illitic clay with a diameter of 45 mm and thickness of 5 mm. The measured transport coefficients were then used to estimate the relative importance of the individual contributions to the total flow of water through the samples. Our results show that the contribution of the osmosis is 82–88%, while the diffusion contributes only 11–13% and the Darcy flow caused by the pressure difference contributes only 1–5%. Even after considering the uncertainties in the measurement of the transport coefficients, which are estimated to be up to 22%, the results show that osmosis makes an important contribution to the total water flow and should not be neglected in general.
Influence of Different Solvents on the Mechanical Properties of Electrospun Scaffolds
Authors: Cicėnas Dovydas , Šešok Andžela
Published: January 2025

This article investigates the influence of different solvents on the mechanical properties of biocompatible and biodegradable polycaprolactone (PCL) scaffolds. During the research, using electrospinning technology, 27 samples of polycaprolactone nanofibers exposed to different solvents were produced. A tensile test was performed on the produced nanofiber samples, and the nanofiber mechanical properties, yield strength, elastic modulus, and elastic elongation were calculated, and load–displacement and stress–strain dependence diagrams were compared from the obtained results. The strongest nanofiber was singled out, and its mechanical properties were compared with those of biological tissues and its application in tissue engineering. The structure was determined using a scanning electron microscope, and the structures of nanofibers exposed to different solvents were compared. After calculating the influence of different solvents on the mechanical properties of the nanofibers, the strongest structure was identified, PCL and chloroform, which has an elastic modulus of 9.86 MPa and a yield strength of 1.11 ± 0.32 MPa. The type of solvent used in the production of the solution affects the homogeneity of the fibre and the shape of the filaments. In solvents with lower viscosity, the fibre filaments are more homogeneous and more evenly distributed.
Self-Foaming Expanded Ceramsites Prepared from Electrolytic Manganese Residue, Red Mud and Waste Soil
Authors: Yang Zhuowen , Lu Xuesong , Wang Jie , Tan Hongbo
Published: January 2025

In this study, in order to solve the problems of resource utilization of electrolytic manganese residue and the destruction of natural resources by the over-exploitation of raw materials of traditional ceramics, electrolytic manganese residue (EMR), red mud (RM), and waste soil (WS) were used to prepare self-foaming expanded ceramsite (SEC), and different firing temperatures and four groups with different mixing ratios of these three raw materials were considered. Water absorption, porosity, heavy metal ion leaching, and compressive strength in the cylinder of SEC were evaluated. The chemical composition and microscopic morphology of SEC were investigated by XRD and SEM. The mechanism behind the reaction among EMR, RM, and WS and self-foaming was discussed. The results showed that both the temperature and mixing ratio significantly influenced the basic performance of SEC. With the temperature lower than 1200 °C, sphere appearance could be maintained in all of these four groups; however, the density, porosity, and compressive strength in the cylinder seemed unacceptable. When the temperature rose up to 1220 °C, sphere appearance could be only found in the group whose mixing ratio of EMR, RM, and WS was 2:2.5:0.5. Under this condition, the excellent performance of SEC was observed, with a porosity of 46.7%, bulk density of 0.61 g/cm3, and 3 d compressive strength in a cylinder of 26.82 MPa. The mechanism behind the reaction among EMR, RM, and WS could be described: when the temperature is up to 1180 °C, an obvious chemical reaction took place, followed by the liquid phase being produced and the gas released by the decomposition of Fe2O3 in RM and gypsum in EMR. When the temperature is up to 1200 °C, the viscosity of the liquid phase and the rate of gas generation achieved the balance, and the liquid phase encapsulated the gas and anorthite (CaAl2Si2O8) began to grow slowly. As time passed, self-foaming expanded ceramsite was prepared. The results of this study are of great significance in the field of artificial lightweight aggregate and industrial solid waste resource utilization.
Large Improvements in the Thermoelectric Properties of SnSe by Fast Cooling
Authors: Golabek Andrew , Barua Nikhil K. , Niknam Ehsan , Menezes Luke T. , Kleinke Holger
Published: January 2025

As reported during the last five years, SnSe is one of the leading thermoelectric (TE) materials with a very low lattice thermal conductivity. However, its elements are not as heavy as those of classical thermoelectric materials like PbTe or Bi2Te3. Its outstanding TE properties were revealed after repeated purification steps to minimize the amount of oxygen contamination, followed by spark plasma sintering. Recently, we showed that hot-pressing—once optimized—can yield comparable or even better TE performance using the examples of Na- and Cu- as well as Na- and Ag-co-doped SnSe. However, long-term stability remains a challenge during cycling between low and high temperatures. Here, we investigated whether the cooling procedure has a significant impact on the thermoelectric properties of SnSe. We compared cooling of the melt with a 1:1 ratio of Sn:Se from 1273 K down to room temperature in air with quenching in water. As typical for undoped SnSe, both materials were extrinsic p-type semiconductors due to Sn defects. The air-quenched sample exhibited higher thermal conductivity, lower electrical conductivity, and higher Seebeck coefficient, all consistent with a smaller number of defects and thus a smaller number of charge carriers due to the slower cooling procedure. This resulted in a comparatively low peak figure-of-merit value zT of 0.61 at 823 K for the air-quenched sample, compared to the substantially higher peak zT of 1.58 at 813 K for the water-quenched sample.
Synthesis of Nanocrystal-Embedded Bulk Metallic Glass Composites by a Combination of Mechanical Alloying and Vacuum Hot Pressing
Authors: Lee Pee-Yew , Chang Pei-Jung , Chen Chin-Yi , Lin Chung-Kwei
Published: January 2025

Bulk metallic glasses (i.e., BMGs) have attracted a lot of research and development interest due to their unique properties. Embedding BMG composites with nanocrystals can further extend their applications. In this study, Ta-nanocrystal-embedded metallic glass powder was prepared via the mechanical alloying of (Cu60Zr30Ti10)91Ta9 composition for 5 h using starting elemental powders. The structural evolution during the mechanical alloying process was examined using X-ray diffraction, scanning electron microscopy, synchrotron extended X-ray absorption fine structure, transmission electron microscopy, and differential scanning calorimetry. The 5 h as-milled powder was then consolidated into a bulk sample using vacuum hot pressing with an applied pressure of 0.72, 0.96, and 1.20 GPa. The effects of the applied pressure during vacuum hot pressing on the structure of the obtained BMG were investigated. The experimental results show that Ta-nanocrystal-embedded metallic glass composite powder was prepared successfully after 5 h of mechanical alloying. The 5 h as-milled composite powder exhibited a large supercooled region of 43 K between the glass transition temperature of 743 K and the crystallization temperature of 786 K. Using vacuum hot pressing at 753 K for 30 mins with an applied pressure, dense nanocrystal-embedded BMG composites were synthesized. The relative density and the crystallization temperature of the BMG composites increased with increasing applied pressure. The nanocrystal-embedded BMG composites prepared at 753 K for 30 mins with an applied pressure of 1.20 GPa exhibited a relative density of 98.3% and a crystallization temperature of 786 K. These nanocrystals were Ta, Cu51Zr14, and other possible Cu–Zr–Ti alloys (e.g., Cu10Zr7) that were randomly dispersed within the glassy matrix.
Cauchy–Logistic Unit Distribution: Properties and Application in Modeling Data Extremes
Authors: Stojanović Vladica S. , Jovanović Spasojević Tanja , Bojičić Radica , Pažun Brankica , Langović Zlatko
Published: January 2025

This manuscript deals with a novel two-parameter stochastic distribution, obtained by transforming the Cauchy distribution, using generalized logistic mapping, into a unit interval. In this way, according to the well-known properties of the Cauchy distribution, a unit random variable with significantly accentuated values at the ends of the unit interval is obtained. Therefore, the proposed stochastic distribution, named the Cauchy–logistic unit distribution, represents a stochastic model that may be suitable for modeling phenomena and processes with emphasized extreme values. Key stochastic properties of the CLU distribution are examined, such as moments, entropy, modality, and symmetry conditions. In addition, a quantile-based parameter estimation procedure, an asymptotic analysis of the thus obtained estimators, and their Monte Carlo simulation study are conducted. Finally, the application of the proposed distribution in stochastic modeling of some real-world data with emphasized extreme values is provided.
Prey-Taxis vs. An External Signal: Short-Wave Asymptotic and Stability Analysis
Authors: Morgulis Andrey , Malal Karrar H.
Published: January 2025

We consider two models of the predator–prey community with prey-taxis. Both models take into account the capability of the predators to respond to prey density gradients and also to one more signal, the production of which occurs independently of the community state (such a signal can be due to the spatiotemporal inhomogeneity of the environment arising for natural or artificial reasons). We call such a signal external. The models differ to one another through the description of their responses: the first one employs the Patlak–Keller–Segel law for both responses, and the second one employs Cattaneo’s model of heat transfer for both responses following to Dolak and Hillen. Assuming a short-wave external signal, we construct the complete asymptotic expansions of the short-wave solutions to both models. We use them to examine the effect of the short-wave signal on the formation of spatiotemporal patterns. We do so by comparing the stability of equilibria with no signal to that of the quasi-equilibria forced by the external signal. Such an approach refers back to Kapitza’s theory for an upside-down pendulum. The overall conclusion is that the external signal is likely not capable of creating the instability domain in the parametric space from nothing but it can substantially widen the one that is non-empty with no signal.
Decomposition-Aware Framework for Probabilistic and Flexible Time Series Forecasting in Aerospace Electronic Systems
Authors: Mao Yuanhong , Hu Xin , Xu Yulang , Zhang Yilin , Li Yunan , Lu Zixiang , Miao Qiguang
Published: January 2025

Degradation prediction for aerospace electronic systems plays a crucial role in maintenance work. This paper proposes a concise and efficient framework for multivariate time series forecasting that is capable of handling diverse sequence representations through a Channel-Independent (CI) strategy. This framework integrates a decomposition-aware layer to effectively separate and fuse global trends and local variations and a temporal attention module to capture temporal dependencies dynamically. This design enables the model to process multiple distinct sequences independently while maintaining the flexibility to learn shared patterns across channels. Additionally, the framework incorporates probabilistic distribution forecasting using likelihood functions, addressing the dynamic variations and uncertainty in time series data. The experimental results on multiple real-world datasets validate the framework’s effectiveness, demonstrating its robustness and adaptability in handling diverse sequences across various application scenarios.
High Fixation Failure Rate of Cephalomedullary Nail Fixation in Patients with Low-Energy Basicervical Femoral Fractures: Do We Need Extramedullary Reduction?
Authors: Yon Chang-Jin , Bae Ki-Cheor , Kim Young-Hun , Lee Kyung-Jae
Published: January 2025

Background and Objectives: A basicervical femoral fracture is a relatively uncommon type of proximal femoral fracture. However, as the proportion of proximal femoral fractures rises in conjunction with the aging of society, the absolute number of patients with basicervical femoral fractures is also increasing. Nevertheless, the optimal surgical methods for the treatment of basicervical femoral fractures remain a topic of debate. The aim of this study is to evaluate the failure rates of cephalomedullary nail fixation in basicervical femoral fractures based on reduction types. Methods: A retrospective analysis was conducted on 22 patients (22 hips) with AO/OTA 31-A1.2 hip fractures who had undergone treatment with a cephalomedullary nail (PFNA-II or Gamma-3) between March 2007 and February 2018. They were classified into three groups based on the reduction types: extramedullary (E), anatomical (A), or intramedullary (I). The intramedullary group included cases where the basicervical component was impacted into the medullary canal, while the extramedullary group comprised cases where the component was displaced beyond the medullary canal. The anatomical group consisted of specimens that exhibited complete anatomical reduction. This was determined by both the anteroposterior (AP) view and the lateral view using simple radiographs. Results: There were 13 patients (59.1%) in Group E and 9 patients (40.9%) in Group A. No patients were classified in Group I. Fixation failure occurred in four patients (18.1%, 4/22). In Group E, no patients exhibited fixation failure (0%, 0/13). In contrast, four patients in Group A demonstrated fixation failure (44.4%, 4/9). Group A exhibited a significantly higher incidence of fixation failure (0% vs. 44.4%, p =0.037) compared to Group E. Conclusion: In the treatment of low-energy basicervical femoral fractures with cephalomedullary nails, extramedullary reduction demonstrated a lower rate of fixation failure compared to anatomical reduction in this study. While definitive conclusions regarding its superiority cannot be drawn due to the limited sample size, extramedullary reduction may serve as a promising alternative to reducing the high fixation failure rate associated with this challenging fracture type.
Influence of Extra-Articular Augmentation on Clinical Outcomes and Survival in Patients Undergoing Anterior Cruciate Ligament Reconstruction: A Pseudorandomized Study
Authors: Maestro Antonio , Rodríguez Nicolás , Pipa Iván , Toyos Carmen , Lanuza Lucía , Machado Filipe , Castaño César , Maestro Santiago
Published: January 2025

Background and Objectives: Up to 27% of anterior cruciate ligament (ACL) reconstruction cases result in a residual positive pivot shift sign, indicating anteroposterior and rotational instability. This instability can compromise returning to sports and increase the risk of further injuries. The biomechanical role of the anterolateral ligament (ALL) in controlling internal knee rotation is well known. However, there are no clinical trials comparing isolated ACL repairs to those combined with ALL reconstruction. Our objective is to compare the results of these techniques, with a primary focus on assessing knee stability and graft survival, to provide evidence for optimizing surgical approaches, particularly for athletes and physically active individuals. Materials and Methods: An observational study using paired score matching as a method of pseudo-randomization was conducted. Subjects were divided into an ACL group and an ACL+ALL group. Demographic and clinical variables were collected, as well as those related to complications and survival. Results: A total of 236 patients were included, which was reduced to 74 ACL and 37 ACL+ALL after pseudo-randomization, resulting in preoperatively comparable groups. During follow-up, differences in favor of ALL reinforcement were found on the pivot shift test (p = 0.007). No differences were found with regard to the Lachman test (p = 0.201), the International Knee Documentation Committee (IKDC) knee score (p = 0.169), the IKDC subjective score (p = 0.095), intensity of pain (p = 0.928), or complications (p = 0.529). Nor were differences found in the limb symmetry index; the single hop test (p = 0.710); the triple hop test (p = 0.653); the crossover hop test (p = 0.682); the 6 meter timed hop test (p = 0.360); the normalized Y-balance test (YBT) (p = 0.459 anterior; p = 0.898 posterolateral; and p = 0.211 posteromedial directions); or the limb symmetry index of the composite YBT (p = 0.488). There were no differences either with respect to return to sports practice (p = 0.723) or survival (p = 0.798). Conclusions: Patients treated by means of the ACL+ALL technique obtained higher rotational stability, as measured by the pivot shift test, than those subjected to an isolated ACL repair. No differences were found with respect to Lachman test, complications, IKDC, pain, or survival.
Endocrine Adverse Events in Patients Treated with Immune Checkpoint Inhibitors: A Comprehensive Analysis
Authors: Dökmetaş Meriç , Muğlu Harun , Özcan Erkan , Bayram Kuvvet Buket , Helvacı Kaan , Kalacı Ender , Kahraman Seda , Aykan Musa Barış , Çiçin İrfan , Selçukbiricik Fatih , Ölmez Ömer Fatih , Bilici Ahmet
Published: January 2025

Background and Objectives: Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy, but their use is associated with a spectrum of immune-related adverse events (irAEs), including endocrine disorders. This study aims to investigate the incidence, timing, treatment modalities, and impact of ICI-related endocrine side effects in cancer patients. Materials and Methods: This retrospective study analyzed 139 cancer patients treated with ICIs between 2016 and 2022. Data regarding endocrine irAEs, including hypothyroidism, hyperthyroidism, hypophysitis, and diabetes mellitus, were collected. The study examined the timing of irAE onset, management approaches, and the association between irAEs and treatment outcomes. Results: The most common endocrine irAE was hypothyroidism (65.5%), followed by hyperthyroidism (2.3%), hypophysitis (8.6%), and diabetes mellitus (0.7%). These disorders typically emerged within the first six months of ICI therapy. Most cases were managed conservatively or with hormone replacement therapy. Patients who developed endocrine irAEs exhibited a higher objective response rate (ORR) and clinical benefit rate (CBR) compared to those without irAEs. Conclusions: Endocrine dysfunction is a significant toxicity of ICI therapy. Early recognition, prompt diagnosis, and appropriate management are crucial to minimize their impact on patient health and quality of life. This study highlights the potential association between irAEs and improved clinical outcomes. Further research is needed to elucidate the underlying mechanisms and identify predictive biomarkers for irAE development.
Cardiac Hemodynamics, Tissue Oxygenation, and Functional Capacity in Post-COVID-19 Patients
Authors: Nascimento Elizane Poquiviqui do , Nascimento Larissa Fernanda Estevam do , Castro Lhara de Freitas , Barros Vilena Cavalcante de , Bandeira Emily Rachel Pereira , Wanderley e Lima Thiago Bezerra , Otto-Yáñez Matías , Fregonezi Guilherme Augusto de Freitas , Resqueti Vanessa Regiane
Published: January 2025

Background and Objectives: This study aimed to evaluate and compare the functional capacity of post-COVID-19 patients with a control group and analyze cardiac hemodynamics and muscle tissue oxygenation responses during assessment protocols in both groups. Materials and Methods: A cross-sectional study was conducted involving patients with COVID-19 and a control group who were all aged ≥18 years. Participants underwent two functional capacity tests: the one-minute sit–stand test (1-STS) and the six-minute walk test (6MWT). Cardiac hemodynamic responses were evaluated using impedance during the 1-STS, and tissue perfusion responses in the oxygenation were recorded during and after both tests. The Friedman test was used for within-group and the Mann–Whitney test was used for between-group comparisons. Results: Thirty-six post-COVID-19 patients (median age 36 years, BMI 26.51 kg/m2) and eleven control subjects (median age 25 years, BMI 23.71 kg/m2) were enrolled. The post-COVID-19 group showed a 20% decrease in 6MWT distance (p = 0.0001) and a 28% decrease in 1-STS repetitions (p = 0.01) versus the control group. Cardiac hemodynamic differences were observed in the post-COVID-19 group during the 1-STS, with reductions in the stroke volume index (18%, p = 0.004), cardiac index (21%, p = 0.0009), Contractility Index (78%, p = 0.0001), and Ejection Fraction (29%, p = 0.0003) and increases in Systemic Vascular Resistance (25%, p = 0.03) and the Systemic Vascular Resistance Index (27%, p = 0.0007). Tissue oxygenation during the 6MWT and 1-STS showed no significant differences between groups. Conclusions: The post-COVID-19 subjects exhibited a reduction in functional capacity, changes in hemodynamic responses related to cardiac and systemic vascular resistance, and a similar pattern of muscle oxygen delivery and consumption in both tests
A Study on the Safety and Efficacy of an Innovative Hydrophilic Dialysis Membrane
Authors: Maduell Francisco , Escudero-Saiz Victor Joaquín , Cuadrado-Payán Elena , Rodriguez-Garcia Maria , Gómez Miquel , Rodas Lida María , Fontseré Néstor , Salgado Maria del Carmen , Casals Gregori , Rico Nayra , Broseta José Jesús
Published: January 2025

The dialysis membrane based on a hydrophilic polymer (Hydrolink NV) was designed to enhance the movement of adsorbed water at the blood–membrane interface, aiming to achieve antithrombogenic and antifouling effects. This study aimed to assess the performance and albumin loss of the Hydrolink NV dialyzer in hemodialysis (HD) and post-dilution hemodiafiltration (HDF) with different infusion flows (Qis) and compare it with the hydrophilic FX CorAL dialyzer in post-dilution HDF. A prospective study was carried out in 20 patients. Patients underwent five dialysis sessions with the same routine dialysis parameters: four sessions with the Toraylight NV 2.1 (HD, post-dilution HDF with 50, 75 or auto-substitution Qi) and one with the FX CorAL 800 (post-dilution HDF with auto-substitution Qi). The reduction ratios’ (RRs’) wide range of molecular weight molecules were assessed and the dialysate albumin loss was quantified. The lowest β2-microglobulin, indoxyl-sulfate, and p-cresyl sulfate RR values were observed with the Toraylight NV 2.1 in HD, and they improved progressively with an increased Qi, without differences being observed between the two dialyzers in auto-substitution. A different removal profile was observed in terms of myoglobin, kFLC, prolactin, α1-microglobulin, α1-acid glycoprotein, and λFLC, whose RRs also improved progressively with an increased Qi but were significantly higher with the Toraylight NV than the CorAL in the same convective condition. There were significant differences in the albumin dialysate losses, with the highest value obtained with the Toraylight NV in auto-substitution HDF, with more than 50% of patients surpassing 5 g per session. The Toraylight NV dialyzer has great potential for efficacy but should be used at the optimal convective volume (Qi not exceeding 75 mL/min or FF not exceeding 25%) to avoid excessive albumin loss.
Leadless Pacing: Current Status and Ongoing Developments
Authors: Trohman Richard G.
Published: January 2025

Although significant strides have been made in cardiac pacing, the field is still evolving. While transvenous permanent pacing is highly effective in the management of bradyarrhythmias, it is not risk free and may result in significant morbidity and, rarely, mortality. Transvenous leads are often the weakest link in a pacing system. They may dislodge, fracture, or suffer breaches in their insulation. This review was undertaken to clarify leadless risks, benefits, and alternatives to transvenous cardiac pacing for bradyarrhythmias and heart failure management. In order to clarify the role(s) of leadless pacing, this narrative review was undertaken by searching MEDLINE to identify peer-reviewed clinical trials, randomized controlled trials, meta-analyses, and review articles, as well as other clinically relevant reports and studies. The search was limited to English-language reports published between 1932 and 2024. Leadless pacing was searched using the terms Micra™, Nanostim™, AVEIR™, single-chamber leadless pacemaker, dual-chamber leadless pacemaker, cardiac resynchronization therapy (CRT), cardiac physiological pacing (CPP) and biventricular pacing (BiV). Google and Google Scholar, as well as bibliographies of identified articles were also reviewed for additional references. The advantages and limitations of leadless pacing as well as options that are under investigation are discussed in detail.
Benefits of Immobilized Bacteria in Bioremediation of Sites Contaminated with Toxic Organic Compounds
Authors: Armanu Emanuel Gheorghita , Bertoldi Simone , Chrzanowski Łukasz , Volf Irina , Heipieper Hermann J. , Eberlein Christian
Published: January 2025

Although bioremediation is considered the most environmentally friendly and sustainable technique for remediating contaminated soil and water, it is most effective when combined with physicochemical methods, which allow for the preliminary removal of large quantities of pollutants. This allows microorganisms to efficiently eliminate the remaining contaminants. In addition to requiring the necessary genes and degradation pathways for specific substrates, as well as tolerance to adverse environmental conditions, microorganisms may perform below expectations. One typical reason for this is the high toxicity of xenobiotics present in large concentrations, stemming from the vulnerability of bacteria introduced to a contaminated site. This is especially true for planktonic bacteria, whereas bacteria within biofilms or microcolonies have significant advantages over their planktonic counterparts. A physical matrix is essential for the formation, maintenance, and survival of bacterial biofilms. By providing such a matrix for bacterial immobilization, the formation of biofilms can be facilitated and accelerated. Therefore, bioremediation combined with bacterial immobilization offers a comprehensive solution for environmental cleanup by harnessing the specialized metabolic activities of microorganisms while ensuring their retention and efficacy at target sites. In many cases, such bioremediation can also eliminate the need for physicochemical methods that are otherwise required to initially reduce contaminant concentrations. Then, it will be possible to use microorganisms for the remediation of higher concentrations of xenobiotics, significantly reducing costs while maintaining a rapid rate of remediation processes. This review explores the benefits of bacterial immobilization, highlighting materials and processes for developing an optimal immobilization matrix. It focuses on the following four key areas: (i) the types of organic pollutants impacting environmental and human health, (ii) the bacterial strains used in bioremediation processes, (iii) the types and benefits of immobilization, and (iv) the immobilization of bacterial cells on various carriers for targeted pollutant degradation.
The Response Regulator OmpR Negatively Controls the Expression of Genes Implicated in Tilimycin and Tilivalline Cytotoxin Production in Klebsiella oxytoca
Authors: Varela-Nájera Ramón G. , De la Cruz Miguel A. , Soria-Bustos Jorge , González-Horta Carmen , Delgado-Gardea Ma Carmen E. , Yáñez-Santos Jorge A. , Cedillo María L. , Hirakawa Hidetada , Fox James G. , Sánchez-Ramírez Blanca , Ares Miguel A.
Published: January 2025

Klebsiella oxytoca toxigenic strains represent a critical health threat, mainly due to their link to antibiotic-associated hemorrhagic colitis. This serious condition results from the bacteria’s ability to produce tilimycin and tilivalline cytotoxins. Our research highlights the pivotal role of OmpR, a key regulator within the EnvZ/OmpR two-component system, in controlling the virulence factors associated with K. oxytoca. Our findings strongly indicate that OmpR is a repressor of the aroX and npsA genes, the first genes of aroX and NRPS operons, respectively, which are indispensable for producing these enterotoxins. Notably, in the absence of OmpR, we observe a significant increase in cytotoxic effects on Caco-2 cells. These observations identify OmpR as a crucial negative transcription regulator for both operons, effectively managing the release of these cytotoxins. This research deepens our understanding of the mechanisms of toxigenic K. oxytoca and opens promising avenues for targeting OmpR for new therapeutic interventions. By focusing on this innovative approach, we can develop more effective solutions to combat this pressing health challenge, ultimately improving patient outcomes against this pathogen.
Characterization and Probiotic Potential of Levilactobacillus brevis DPL5: A Novel Strain Isolated from Human Breast Milk with Antimicrobial Properties Against Biofilm-Forming Staphylococcus aureus
Authors: Iliev Ivan , Yahubyan Galina , Apostolova-Kuzova Elena , Gozmanova Mariyana , Mollova Daniela , Iliev Iliya , Ilieva Lena , Marhova Mariana , Gochev Velizar , Baev Vesselin
Published: January 2025

Lactobacillus is a key genus of probiotics commonly utilized for the treatment of oral infections The primary aim of our research was to investigate the probiotic potential of the newly isolated Levilactobacillus brevis DPL5 strain from human breast milk, focusing on its ability to combat biofilm-forming pathogens such as Staphylococcus aureus. Employing in vitro approaches, we demonstrate L. brevis DPL5′s ability to endure at pH 3 with survival rates above 30%, and withstand the osmotic stress often found during industrial processes like fermentation and freeze drying, retaining over 90% viability. The lyophilized cell-free supernatant of L. brevis DPL5 had a significant antagonistic effect against biofilm-producing nasal strains of Staphylococcus aureus, and it completely eradicated biofilms at subinhibitory concentrations of 20 mg·mL−1. Higher concentrations of 69 mg·mL−1 were found to have a 99% bactericidal effect, based on the conducted probability analysis, indicating the production of bactericidal bioactive extracellular compounds capable of disrupting the biofilm formation of pathogens like S. aureus. Furthermore, genome-wide sequencing and analysis of L. brevis DPL5 with cutting-edge Nanopore technology has uncovered over 50 genes linked to probiotic activity, supporting its ability to adapt and thrive in the harsh gut environment. The genome also contains multiple biosynthetic gene clusters such as lanthipeptide class IV, Type III polyketide synthase (T3PKS), and ribosomally synthesized, and post-translationally modified peptides (RiPP-like compounds), all of which are associated with antibacterial properties. Our study paves the way for the further exploration of DPL5, setting the stage for innovative, nature-inspired solutions to combat stubborn bacterial infections.
Usefulness of a TDM-Guided Approach for Optimizing Teicoplanin Exposure in the Treatment of Secondary Bloodstream Infections Caused by Glycopeptide-Susceptible Enterococcus faecium
Authors: Gatti Milo , Rinaldi Matteo , Giannella Maddalena , Viale Pierluigi , Pea Federico
Published: January 2025

To assess the clinical usefulness of teicoplanin optimized by means of a therapeutic drug monitoring (TDM)-guided approach for treating secondary bloodstream infections (BSIs) caused by Enterococcus faecium. Hospitalized patients having in the period 1 March 2021–31 October 2024 a documented BSI caused by glycopeptide-susceptible Enterococcus faecium being treated with teicoplanin as definitive targeted therapy optimized by means of a real-time TDM-guided expert clinical pharmacological advice (ECPA) program were retrospectively included. Teicoplanin trough concentrations (Cmin) ranging from 20 to 30 mg/L were defined as the desired target of efficacy based on international guidelines. Univariate analysis was performed for assessing variables potentially associated with microbiological failure (defined as persistence at the infection site of the index Enterococcus faecium strain after more than 7 days from starting treatment as documented by follow-up blood cultures). Overall, 67 patients (median age 70 years; male 55.2%) were included. Catheter-related BSIs (50.7%) and intrabdominal/biliary tract (29.9%) infections were the main sources of Enterococcus faecium BSI. The desired target of teicoplanin Cmin was attained in 62.7% of patients at the first TDM assessment and significantly increased to 85.1% (p = 0.003) at subsequent TDM-guided ECPA instances during the overall treatment course. Microbiological eradication was obtained in 95% of cases (63/67). In the univariate analysis, failing effective source control was the only variable associated with an increased risk of microbiological failure (75.0% vs. 12.7%; p = 0.01). Targeted TDM-guided teicoplanin therapy, coupled with effective source control of the primary infection site by granting microbiological eradication in the vast majority of cases, may be considered a reasonable strategy for managing glycopeptide-susceptible Enterococcus faecium secondary BSIs.
Changes in RNA Splicing: A New Paradigm of Transcriptional Responses to Probiotic Action in the Mammalian Brain
Authors: Yue Xiaojie , Zhu Lei , Zhang Zhigang
Published: January 2025

Elucidating the gene regulatory mechanisms underlying the gut–brain axis is critical for uncovering novel gut–brain interaction pathways and developing therapeutic strategies for gut bacteria-associated neurological disorders. Most studies have primarily investigated how gut bacteria modulate host epigenetics and gene expression; their impact on host alternative splicing, particularly in the brain, remains largely unexplored. Here, we investigated the effects of the gut-associated probiotic Lacidofil® on alternative splicing across 10 regions of the rat brain using published RNA-sequencing data. The Lacidofil® altogether altered 2941 differential splicing events, predominantly, skipped exon (SE) and mutually exclusive exon (MXE) events. Protein–protein interactions and a KEGG analysis of differentially spliced genes (DSGs) revealed consistent enrichment in the spliceosome and vesicle transport complexes, as well as in pathways related to neurodegenerative diseases, synaptic function and plasticity, and substance addiction across brain regions. Using the PsyGeNET platform, we found that DSGs from the locus coeruleus (LConly), medial preoptic area (mPOA), and ventral dentate gyrus (venDG) were enriched in depression-associated or schizophrenia-associated genes. Notably, we highlight the App gene, where Lacidofil® precisely regulated the splicing of two exons causally involved in amyloid β protein-based neurodegenerative diseases. Although the splicing factors exhibited both splicing plasticity and expression plasticity in response to Lacidofil®, the overlap between DSGs and differentially expressed genes (DEGs) in most brain regions was rather low. Our study provides novel mechanistic insight into how gut probiotics might influence brain function through the modulation of RNA splicing.
Fecal Microbiome and Metabolomic Profiles of Mixed-Fed Infants Are More Similar to Formula-Fed than Breastfed Infants
Authors: Wang Mei , Valizadegan Negin , Fields Christopher J. , Donovan Sharon M.
Published: January 2025

Many infants consume both human milk and infant formula (mixed-fed); however, few studies have investigated how mixed feeding affects the gut microbiome composition and metabolic profiles compared to exclusive breastfeeding or formula feeding. Herein, how delivery mode and early nutrition affect the microbiome and metabolome of 6-week-old infants in the STRONG Kids2 cohort was investigated. Fecal samples were collected from exclusively breastfed (BF; n = 25), formula-fed (FF; n = 25) or mixed-fed (MF; n = 25) participants. Within each feeding group, infants were either delivered vaginally (VD; n = 13) or by Cesarean section (CS; n = 12). Feeding mode affects the fecal microbiome diversity, composition, and functional potential, as well as metabolomic profiles regardless of delivery mode. Alpha and beta diversity of MF differed from that of BF (p < 0.05) but were comparable to FF infants. Functional analyses have shown 117 potential metabolic pathways differed between BF and FF, 112 between BF and MF, and 8 between MF and FF infants (p < 0.05, q < 0.10). Fecal metabolomic profiles of MF and FF clustered together and separated from BF infants. In total, 543 metabolites differed between BF and FF, 517 between BF and MF, and 3 between MF and FF (p < 0.05, q < 0.10). Delivery mode affected overall microbial composition (p = 0.022) at the genus level and 24 potential functional pathways, with 16 pathways being higher in VD than CS infants (p < 0.05, q < 0.10). Metabolomic analysis identified 47 differential metabolites between CS and VD, with 39 being lower in CS than VD (p < 0.05, q < 0.10). In summary, fecal microbiota composition and function and metabolite profiles of 6-week-old MF infants are closer to FF than BF infants.