bluuebunny/crossref_metadata_2025 huggingface dataset:
A biodegradable capacitive-coupling neurostimulator for wireless electroceutical treatment of inflammatory bowel diseases
Authors: Wang Qiong , Yang Ming , Sun Renyuan , Liu Wenliang , Li Wenlong , Xu Baochun , Yang Shiming , Chen Ke , Xiao Jun , Chen Xuyong , Meng Xinyao , Feng Jiexiong , Yu Cunjiang , Luo Zhiqiang
Published: February 2025

Electroceuticals based on peripheral nerve stimulation offer promising treatment for refractory inflammatory diseases such as inflammatory bowel diseases (IBDs). For pediatric IBD (PIBD) patients, wireless, biodegradable miniaturized bioelectronic devices are crucial to prevent neural damage and support neural development during and after therapy. Here we demonstrate a battery-free, miniaturized neurostimulator based on biodegradable materials and capacitive-coupling wireless power transfer. The biodegradable capacitive-coupling (BCC) neurostimulator consists of molybdenum (Mo) electronic components and self-healing biodegradable polyurethane elastomer (SBPUE) encapsulations. The self-healing property of SBPUE enables a stable neural interface. Capacitive coupling wirelessly transfers high-frequency electric fields through a single capacitor between wearable transmitters and implanted BCC neurostimulators. Programmed electrical stimulation of the vagus nerve alleviates PIBD symptoms by restoring CD4
+
T cell balance, enhancing anti-inflammatory effects and suppressing pro-inflammatory effects in the intestines.
TRAF3 is critical for initial T follicular helper cell specification via coordination of the IL-6R/IL-2R–BCL6 signaling nexus
Authors: Shao Peng , Antonetti Regina M. , Arkee Tina , Hornick Emma L. , Xue Hai Hui , Bishop Gail A. , Butler Noah S.
Published: February 2025

CD4
+
T follicular helper (T
FH
) cells are essential for orchestrating robust humoral immunity, yet the signals that initiate T
FH
cell differentiation are not fully understood. We identified that the adapter protein TRAF3 was required for T
FH
cell differentiation and function during systemic inflammatory infections. Loss of CD4
+
T cell–intrinsic TRAF3 impaired chromatin remodeling and transcriptional programming essential for T
FH
cell initiation and instead augmented T
H
1 development and function. TRAF3-deficient CD4
+
T cells exhibited altered interleukin-6 (IL-6) and IL-2 responsiveness, which were coupled to failures in BCL6 expression. Enforced expression of either IL-6 receptor or BCL6 or blockade of IL-2 signaling was sufficient to rescue T
FH
cell differentiation. Human CD4
+
T cells lacking TRAF3 exhibited impaired T
FH
polarization, supporting a conserved mechanism by which TRAF3 regulates CD4
+
T cell fate determination. Thus, TRAF3 functions at the nexus of cytokine, transcriptional, and epigenetic nodes that promote the T
FH
cell specification during infection.
Experimental evolution of
Escherichia coli
on semi-dry silver, copper, stainless steel, and glass surfaces
Authors: Rosenberg Merilin , Park Sandra , Umerov Sigrit , Ivask Angela
Published: February 2025

To study bacterial adaptation to antimicrobial metal surfaces in application-relevant conditions,
Escherichia coli
was exposed to copper and silver surfaces for 30 exposure cycles in low-organic dry or high-organic humid conditions. The evolved populations demonstrated increased metal surface tolerance without concurrent increase in minimal biocidal concentration (MBC) and minimal inhibitory concentration (MIC) values of respective metal ions or selected antibiotics. Mutation analysis did not detect increased mutation accumulation nor mutations in
cop
,
cus
,
cue
,
sil
,
pco
, or general efflux genes known to actively maintain copper/silver homeostasis. Instead, during cyclic exposure, mutations in genes related to cellular barrier functions and sulfur metabolism were enriched, potentially suggesting that reducing bioavailability and passively restricting uptake of the toxic metals rather than active efflux is selected for on copper and silver surfaces. The changes detected in the evolved populations did not indicate an increased risk of antibiotic cross-resistance as a result of copper or silver surface exposure. However, rapid emergence of mutations in
silS
activated the cryptic
sil
efflux locus during silver ion challenge in liquid MBC assay with the evolved populations. The
silS
mutants showed no benefit on copper and silver surfaces but demonstrated decreased sensitivity to ampicillin and ciprofloxacin, as well as copper and silver ions in liquid tests, indicating that efflux might be specific to granting heavy metal tolerance in liquid but not surface exposure format. Our findings highlight the critical importance of appropriate exposure conditions not only in efficacy testing but also in risk assessment of antimicrobial surface applications.

IMPORTANCE

This study examines the evolutionary adaptations of
Escherichia coli
after semi-dry exposure to copper and silver surfaces, leading to an increase in surface tolerance but no increase in mutation accumulation or substantially enhanced metal ion tolerance in standard tests. Notably, enriched mutations indicate a shift toward more energy-passive mechanisms of metal tolerance. Additionally, while enhanced silver efflux was rapidly selected for in a single round of silver exposure in liquid tests and substantially increased copper and silver ion tolerance in conventional test formats, the causal mutations did not improve viability on silver and copper surfaces, underscoring the different fitness scenarios of tolerance mechanisms dependent on exposure conditions. These findings emphasize the need for appropriate exposure conditions in evaluating of both efficacy and the potential risks of using antimicrobial surfaces, as the results from conventional liquid-based tests may not apply in solid contexts.
Intra-serotype variation of
Streptococcus pneumoniae
capsule and its quantification
Authors: Eichner Hannes , Wu Cindy , Cammer Michael , Tran Elizabeth N. H. , Hirst Timothy R. , Paton James C. , Weiser Jeffrey N.
Published: February 2025

Streptococcus pneumoniae
(
Spn
) is a leading respiratory pathogen that depends on a thick layer of capsular polysaccharide (CPS) to evade immune clearance. Disease prevention by CPS-based vaccines is limited because of the species’ high genome plasticity and ability to express over 100 different capsule types (serotypes). Generally, intra-serotype variations in capsulation are overlooked, despite the genetic variability of the bacterium. This oversight may result from a lack of standardized, reliable, and easily available methodology to quantify capsulation. Here, we have modified two methods to analyze the
Spn
capsule: immunoblot quantification of CPS in bacterial lysates and light microscopy to assess capsule thickness. Two assays were used because each measures distinct aspects of capsulation that could be differentially affected by the density of CPS. Quantification of either CPS amount or capsule thickness predicted the effectiveness of immune serum in opsonophagocytic killing assays for isogenic strains. Our standardized approaches both revealed significant differences in both CPS amount and capsule thickness among clinical isolates of the same serotype, challenging the assumption that intra-serotype capsulation is a conserved feature. As expected, these two methods show limited intra-strain correlation between amounts of CPS production and capsule thickness.

IMPORTANCE

Despite the availability of vaccines,
Streptococcus pneumoniae
remains a leading cause of respiratory and invasive diseases. These vaccines target a polysaccharide capsule the bacterium uses to evade the immune system. Variation of the capsule composition subdivides the organism into serotypes and influences its protective potency. Another critical factor affecting this protection is capsule size. It is commonly assumed that
S. pneumoniae
strains of the same serotype produce capsules of consistent size, despite the organism’s heterogeneity. In this study, we challenge this assumption by analyzing clinical isolates of the same serotype. Existing methods were modified to achieve high reproducibility and increase accessibility. Our data reveal significant fluctuations in capsule production within a given serotype. Our findings suggest that
S. pneumoniae
research should consider capsule size, not just its presence and type. The results imply that standardized vaccine efficacy tests may yield variable results depending on the capsule production of target strains.
Two-Photon Ionization of Single Atoms Localized on the Bessel Beam Axis
Authors: Kiselev M. D. , Gryzlova E. V. , Popova M. M. , Grum-Grzhimailo A. N.
Published: February 2025

In the article the effect of twisting of Bessel radiation on two-photon ionization of single atoms localized on the axis of the incident beam is studied. The matrix element of two-photon ionization of this type is obtained for arbitrary polarization and multipolarity of the incident radiation. The differential and integral probability of ionization of an atom over the photoemission angle is analyzed. Illustrative calculations are performed for helium and neon atoms in the simplest case of a circularly polarized field in the electric dipole approximation in the single-active-electron model.
f(Q) gravitational theory and its structure via redshift
Authors: Nashed G. G. L.
Published: February 2025

We introduce a new technique for reformulating the f(Q) gravitational theory based on parameterization of the deceleration parameter or other options. This tool allows us to create modified gravitational scenarios connected to cosmological observations. We examine two models of the deceleration parameter and one model of the effective equation of the state of the universe as discussed in the literature. We utilize the asymptotic behavior of the matter density parameter to further constrain the feasible range of the model parameters. One of the tested models shows how a tiny modification can produce viable cosmic scenarios quantitatively similar to

$$\Lambda $$

Λ

CDM but qualitatively different, whereas the dark energy (DE) sector becomes dynamic and fully explained by modified gravity, not by a cosmological constant.
Primary scintillation yields induced by $$\alpha $$ particles in gas mixtures of Argon/$$\hbox {CF}_4$$ at 9.5 bar
Authors: Amedo P. , Leardini S. , Saá-Hernández A. , González-Díaz D.
Published: February 2025

We report time and band -resolved scintillation from

$$\alpha $$

α

-particles in Ar/

$$\hbox {CF}_4$$

CF
4

mixtures at a pressure of 9.5 bar. Our results show that %-level addition of

$$\hbox {CF}_4$$

CF
4

enables strong wavelength-shifted scintillation in the visible range, with yields at the level of 1000 ph/MeV, scintillation decay times of 9–25 ns and formation times well below 10 ns. Such a performance is a priori sufficient for accurate time-tagging of MeV-particles, without the need to resort to a pure noble gas, thus opening an appealing technological path for next-generation time projection chambers.
Unresolved alterations in bile acid composition and dyslipidemia in maternal and cord blood after UDCA treatment for intrahepatic cholestasis of pregnancy
Authors: Basu Srijani , Običan Sarah , Bertaggia Enrico , Staab Hannah , Izquierdo M. Concepcion , Gyamfi-Bannerman Cynthia , Haeusler Rebecca
Published: February 2025

Intrahepatic cholestasis of pregnancy (ICP) is characterized by elevated plasma bile acid levels. ICP is linked to adverse metabolic outcomes, including a reported increased risk of gestational diabetes. The standard therapeutic approach for managing ICP is treatment with ursodeoxycholic acid (UDCA) and induction of labor prior to 40 weeks of gestation. To investigate bile acid and metabolic parameters after UDCA treatment, we enrolled 12 ICP patients with singleton pregnancies-half with and half without gestational diabetes-and 7 controls. Our study reveals that after UDCA treatment, notwithstanding a reduction in total bile acid and ALT levels, imbalances persist in the cholic acid (CA) to chenodeoxycholic acid (CDCA) ratio in maternal and cord blood plasma. This indicates a continued dysregulation of bile acid metabolism despite therapeutic intervention. Maternal plasma lipid analysis showed a distinct maternal dyslipidemia pattern among ICP patients, marked by elevated cholesterol levels on VLDL particles and heightened triglyceride concentrations on LDL particles, persisting even after UDCA treatment. Cord plasma lipid profiles in ICP patients exhibited elevated triglyceride and free fatty acid levels alongside a tendency toward increased β-hydroxybutyrate. The changes in lipid metabolism in both maternal and cord blood correlated with the high CA/CDCA ratio, but not total bile acid levels or gestational diabetes status. Understanding the imbalances in maternal and cord bile acid and lipid profiles that persist after standard UDCA therapy provides insights for improving management strategies and mitigating the long-term consequences of ICP.
Understanding Public Knowledge, Attitudes, and Awareness Toward Seizure Episodes Among Residents of Madinah: A Saudi Cross‐Sectional Study
Authors: Almarwani Bayan M. , Alamri Sadin Ayman , Alamri Aseel Ayman , Badawi Ahmad Salim , Khawaji Zakaria Yahya , Akhwan Afnan Mohammad , Garah Basel MohammedBassam , Tawakul Abdullah A.
Published: February 2025

Background: Epilepsy is a prevalent condition that affects a large population. However, a lack of knowledge and misconceptions about seizures can lead to inappropriate reactions and negative attitudes toward people with epilepsy, who are more likely to experience stigma because of their illness. This study explored public knowledge, attitudes, and awareness of epilepsy and seizures among residents of Madinah, Saudi Arabia.

Methods: A descriptive, cross‐sectional study was conducted between September and November 2023 involving 2626 random adult residents of the Madinah Region in Saudi Arabia. Data were collected through an online survey consisting of 27 questions concerning epilepsy.

Results: Regarding participants’ awareness of epilepsy, 92.2% reported having heard or read about it, and 12.8% had attended a course on controlling epileptic seizures. The results showed an acceptable level of understanding about epilepsy. The mean knowledge and attitude scores about epilepsy for the sample were 22 (SD ± 3.2) and 27.1 (SD ± 3.1), respectively, indicating moderate knowledge and positive attitudes toward epilepsy. Among demographic characteristics, knowledge about epilepsy was significantly associated with gender, age, marital status, educational level, occupation, household monthly income, having heard about epilepsy, having a family member diagnosed with epilepsy, and course attendance. However, attitudes toward epilepsy were only significantly associated with gender, having heard about epilepsy, having a family member diagnosed with epilepsy, and course attendance. Similarly, actions toward seizure attacks were significantly associated with all demographic characteristics except education.

Conclusions: The residents of Madinah have generally positive attitudes regarding epilepsy, although their knowledge levels could be enhanced by education. Therefore, more educational awareness campaigns are required to improve public understanding of epilepsy and appropriate actions to take when witnessing a seizure. The results of this study provide a foundation for worldwide comparisons of general levels of knowledge and attitudes concerning epilepsy in Saudi Arabia.
Distributed White Matter Abnormalities in Major Depressive Disorder: A Diffusion Tensor Imaging Combined Support Vector Machine Study
Authors: Li Sen , Xu Yinghong , Cui Jian , Li Kun , Ji Shanling , Shen Hailong , Wan Yu , Dong Chunyu , Zheng Hao , Qiu Wanru , Ping Liangliang , Yu Hao , Zhou Cong
Published: February 2025

Objectives: Existing research by machine learning analysis based on neuroimaging in major depressive disorder (MDD) is limited. This study intends to investigate the integrity of white matter in patients with MDD using diffusion tensor imaging (DTI) combining machine learning approaches and to develop a model to differentiate MDD patients from healthy controls (HCs).

Materials and Methods: Clinical and neuroimaging data were collected from 60 MDD patients and 52 HCs. The tract‐based spatial statistics (TBSS) and automated fiber quantification (AFQ) techniques were employed to analyze DTI data. Differences in diffusion metrics were then used in a support vector machine (SVM) model to determine the most significant features for distinguishing MDD patients from HC.

Results: No significant differences were observed in the TBSS between two groups. The AFQ analysis revealed that MDD patients exhibited reduced axial diffusivity (AD) and fractional anisotropy (FA) in specific segments of nerve fibers. The combined FA + AD model demonstrated better predictive performance with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.833 and a predictive accuracy of up to 85.00%, surpassing models utilizing single FA or AD metrics.

Conclusion: DTI combined with machine learning distinguished MDD patients through specific white matter alterations, underscoring the role of microstructural connectivity in depression pathology.
Association of the Extent of Exposure to Environmental Tobacco Smoke With Exhaled Nitric Oxide and Eosinophils: A Cross‐Sectional Study Based on the NHANES 2007–2012 Database
Authors: Hou Xingfang , Hou Shufen , Hou Chenggong , Chen Xuelian , Tang Yuling
Published: February 2025

Background: Previous studies have demonstrated that exposure to environmental tobacco smoke is associated with a reduction in fractional exhaled nitric oxide (FeNO) levels, elevation in eosinophil (EOS) counts and alterations in airway inflammation patterns, influencing the efficacy of glucocorticoid therapy for TH2 inflammation. No previous study has investigated the association of the extent of exposure to environmental tobacco smoke with FeNO levels. This study aimed to investigate the association of the extent of exposure to environmental tobacco smoke with FeNO level and EOS count.

Methods: In this retrospective cohort study, we included 12,766 individuals from the National Health and Nutrition Examination Survey 2007–2012. The extent of exposure to environmental tobacco smoke was assessed by measuring serum cotinine levels. Participants were categorised into quintiles based on their cotinine levels. Logistic regression models were developed to evaluate the association of serum cotinine levels with FeNO levels and EOS count.

Findings: In the unadjusted and adjusted models, the highest quintile of serum cotinine levels (> 105 ng/mL) was significantly negatively associated with FeNO levels. However, low‐to‐moderate quintiles of serum cotinine levels were not significantly associated with FeNO levels. Based on sensitivity analyses, the negative associations between the highest quintile of serum cotinine levels and FeNO levels remained consistent among participants with asthma, chronic bronchitis and respiratory symptoms within 7 days. Increased serum cotinine levels were significantly associated with increased EOS counts, which in turn were significantly associated with increased FeNO levels. EOS significantly mediated 7.59% of cotinine‐associated reductions in FeNO levels.

Conclusions: Our findings indicated that high levels of tobacco smoke exposure are associated with a decrease in FeNO levels and an increase in EOS count. The smoking status should be considered when evaluating type 2 airway inflammation based on FeNO levels and EOS count.
Assessment of Health‐Related Quality of Life Among Palestinian Adolescents With Type 1 Diabetes: A Cross‐Sectional Investigation
Authors: Sadder Farah , Nemer Maysaa
Published: February 2025

Objectives: Type 1 diabetes (T1D) with its worldwide increasing incidence is one of the most serious chronic conditions of adolescence. This study aimed to assess the Palestinian adolescent diabetic patients’ health‐related quality of life (HRQOL) and to identify specific factors that could predict poor quality of life. We also aimed to compare adolescents’ reported HRQOL to proxy reports by their parents.

Methods: A cross‐sectional study was carried out between November 2022 and October 2023 in the six governorates of northern West Bank/Palestine: Jenin, Nablus, Qalqilya, Salfit, Tubas, and Tulkarm. Patients who were diagnosed with T1D for over 6 months from their recruitment, aged between 10 and 18 years, were recruited from diabetes clinics of the Ministry of Health (MOH) and the Palestine Diabetes Institute (PDI). One hundred seventy adolescents and 170 parents (or guardians) completed the Pediatric Quality of Life Inventory (Peds QL) 3.2 Diabetes Module for adolescents and parents, respectively.

Results: An acceptable mean of 70.6 for the total score was reported for the Peds QL 3.2 Diabetes Module. Better scores were reported for the diabetes management summary score compared to the diabetes symptom summary score. Worry and communication were the lowest and highest reported subscores, respectively. Parents reported significantly lower results than adolescents. Income, gender, and hemoglobin A1c (HbA1c) were the main predictors of HRQOL among adolescents with T1D in Palestine.

Conclusions: Future national health strategies should consider income differences and try to overcome health gaps among adolescents with T1D coming from low‐income families. Future research is needed to explore the political and cultural aspects and their effects on HRQOL among diabetic adolescents in Palestine.
Evaluation of the Effect of Severity of Separation Anxiety Disorder on Nicotine Dependence Level
Authors: Bişkiner Enes Berk , Fidanci İzzet , Arz Cemile Esinç , Alici Yilmaz Cansu , Güler Sönmez Tuğba , Kiziltaş Özlem , Aksoy Hilal , Başer Duygu Ayhan
Published: February 2025

Objective: The present study attempts to find the level of association of nicotine dependence with separation anxiety disorder in adults and the interrelationship between these two disorders.

Method: The methodology consisted of 525 individuals aged between 18 and 63 years attending the outpatient clinic of Family Medicine at Hacettepe University. All participants were evaluated in this study with a questionnaire containing all the sociodemographic data, the Fagerström nicotine dependence test (FNBT), and the Separation Anxiety Disorder Severity Scale (SADSS). Data will be processed using the IBM SPSS V23 software package to find the relation between nicotine dependence and separation anxiety.

Results: The analysis also showed that there was no significant statistical relationship between FNBT results and SADSS results, with a correlation of r = 0.037and p = 0.399. In addition, the severity of separation anxiety was found to be higher in females than in males, as identified by the value of p = 0.024. Female participants were more likely to smoke as a way of coping with stress and anxiety compared to male participants. Among males, there was no significant relationship between nicotine dependence and separation anxiety, p = 0.131, suggesting that in males, the nicotine behavior may be influenced more by social and cultural factors.

Conclusion: The results of the present study show that the relationship between nicotine dependence and separation anxiety can be considered from the point of view of gender. Although the relationship between nicotine addiction and anxiety is stronger in females, this relationship is weaker in males. These results indicate that gender differentiation may be performed regarding the treatment of nicotine addiction. Future studies should investigate the interaction of these two diseases in more detail and may help in developing therapeutic measures that are more specific and individualized.
Toxoplasma gondii and Trypanosoma lewisi Infection in Urban Small Mammals From Cotonou, Benin, With Special Emphasis on Coinfection Patterns
Authors: Etougbétché Jonas R. , Houéménou Gualbert , Missihoun Antoine A. , Gauthier Philippe , Dossou Henri-Joël , Galal Lokman , Dalecky Ambroise , Diagne Christophe , Dobigny Gauthier , Mercier Aurélien
Published: February 2025

A growing number of studies has highlighted the importance of coinfections in eco‐evolutionary processes underlying host–parasite interactions and the resulting epidemiology of zoonotic agents. Small mammals, and particularly rodents, are known to be important reservoirs of many zoonotic pathogens, such as Toxoplasma gondii and Trypanosoma lewisi, that are responsible for toxoplasmosis and atypical trypanosomiasis in humans, respectively. Laboratory experiments on rodent models have shown that primary infection with T. lewisi increases the host sensitivity to other parasites, including T. gondii, following an alteration in the immune response. However, data on potential interactions between these parasites in wild small mammals remain scarce. In this study, we determined the T. lewisi prevalence in 553 small mammals from four localities of Cotonou city, Benin. The results were then combined with T. gondii data previously collected for the same individuals in order to investigate the influence of T. lewisi on T. gondii infection, and vice versa, using co‐occurrence tests and generalized linear mixed models (GLMMs). Despite quite high overall prevalence (32.5% and 15.2% for T. lewisi and T. gondii, respectively), we observed a clear and significant segregation between the two parasites. This may be explained by (i) differences in the species‐specific receptivity and/or sensitivity of small mammal host species to infection by these two parasites, with Rattus rattus (Rra), Rattus norvegicus (Rno), and Mastomys natalensis (Mna) being the main hosts of T. lewisi, while Crocidura olivieri (Cro) and Mus musculus domesticus (Mus) were the main hosts for T. gondii; and/or (ii) a possibly high mortality in coinfected animals in the wild. Although dedicated experimental studies are required to confirm this pattern, as they stand, our data fail to support that in nature, the infection of small mammals by one of these two parasites favors widespread infection by the second one.
177Lu-LNC1004 Radioligand Therapy in Patients with End-Stage Metastatic Cancers: A Single-Center, Single-Arm, Phase II Study
Authors: Fu Hao , Huang Jingxiong , Zhao Liang , Chen Yuhang , Xu Weizhi , Cai Jiayu , Yu Lingyu , Pang Yizhen , Guo Wei , Su Bishan , Sun Long , Wu Hua , Zhang Jingjing , Chen Xiaoyuan , Chen Haojun
Published: February 2025

Purpose: Fibroblast activation protein (FAP) is highly expressed in cancer-associated fibroblasts and certain tumor cells, making it a promising therapeutic target for various malignancies. This study evaluated the efficacy and safety of 177Lu-Evans blue-FAP inhibitor (177Lu-EB-FAPI; 177Lu-LNC1004) radioligand therapy (RLT) for treating end-stage metastatic tumors. Patients and Methods: This single-arm, single-center, phase II trial included 28 patients with progressive metastatic malignancies (11 types) and high FAP expression (defined as a maximum standardized uptake value [SUVmax] ≥10 in >50% of tumors) who had exhausted all approved therapies, screened between June 2022 and April 2024. Patients were scheduled to receive four 177Lu-LNC1004 RLT cycles at 3.33 GBq/cycle every 6 weeks. The primary endpoint was post-RLT radiological response. The secondary endpoints were progression-free survival (PFS), overall survival (OS), dosimetry, and safety. Results: Eastern Cooperative Oncology Group scores >2 were observed in 68% of patients. Overall, 63 177Lu-LNC1004 RLT cycles were performed, with 19 (68%) patients undergoing ≥2 cycles. Disease control was achieved in 13 patients [13/28, 46%], with 4 and 9 demonstrating partial response and stable disease, respectively, and associated with improved PFS and OS (P<0.001). The mean absorbed dose in tumors was 4.69±3.83 Gy/GBq (1.18–25.03 Gy/GBq). Treatment-related grade 3/4 hematotoxicity was observed in six patients (21%), with thrombocytopenia, leukopenia, and neutropenia most prevalent. No grade 3/4 hepatotoxicity or nephrotoxicity was observed. Conclusions: FAP-directed RLT using 177Lu-LNC1004 at 3.33 GBq/cycle was well tolerated with an acceptable toxicity profile. Nearly half of patients achieved disease control, which was associated with prolonged PFS and OS.
Data from Expression Patterns of DLL3 across Neuroendocrine and Non-neuroendocrine Neoplasms Reveal Broad Opportunities for Therapeutic Targeting
Authors: Lozada John R. , Elliott Andrew , Evans Mark G. , Wacker James , Storey Kathleen M. , Egusa Emily A. , Zorko Nicholas A. , Kumar Akhilesh , Crymes Anthony , Heath Elisabeth I. , Carneiro Benedito A. , Soares Heloisa P. , Cichocki Frank , Miller Jeffrey S. , Lou Emil , Beltran Himisha , Antonarakis Emmanuel S. , Ryan Charles J. , Hwang Justin H.
Published: February 2025

Abstract
Neuroendocrine neoplasms (NEN) encompass a diverse set of malignancies with limited precision therapy options. Recently, therapies targeting DLL3 have shown clinical efficacy in aggressive NENs, including small cell lung cancers and neuroendocrine prostate cancers. Given the continued development and expansion of DLL3-targeted therapies, we sought to characterize the expression of DLL3 and identify its clinical and molecular correlates across diverse neuroendocrine and non-neuroendocrine cancers. Here, we interrogated paired DNA and RNA-sequencing from 1,589 NENs across 29 sites, as well as 203,252 tumors across 47 cancer types. We found that high transcriptomic levels of DLL3 correlated with more aggressive histologic and mutational patterns in NENs, with adverse survival outcomes being reflected in NENs originating from the lung, pancreas, stomach, and small bowel. The heterogeneity in DLL3 expression across NENs was largely explained by site of origin, with lung, prostate, and bladder NENs exhibiting relatively high levels of DLL3, whereas gastroenteropancreatic NENs displayed relatively low expression levels. Although the therapeutic targeting of DLL3 may be less applicable for gastroenteropancreatic NENs, we did find an upregulation of alternative targets such as SEZ6, CELSR3, and SSTR2 in these settings. Lastly, expanding our investigation into non-neuroendocrine cancers, we detected an enrichment of DLL3 in both low-grade and high-grade gliomas, Merkel cell carcinomas, medulloblastomas, and melanomas, with such enrichment being associated with prolonged overall survival in gliomas, but worse overall survival in melanomas. Altogether, we demonstrate that DLL3 represents an attractive target for subsets of neuroendocrine and non-neuroendocrine cancers and uncover opportunities for future therapeutic strategies.
Significance:
DLL3-targeted therapies have recently shown robust clinical efficacy in aggressive neuroendocrine cancers, positioning them to fulfill a great unmet need in these settings. Here, we examine the clinical and biological correlates of DLL3 expression in both neuroendocrine and non-neuroendocrine cancers. Our findings may stimulate the development and application of DLL3-targeted therapies, as well as other precision therapies, in neuroendocrine cancers and beyond.
Gastrointestinal Ultrasound - measurements and normal findings. What do you need to know?
Authors: Möller Kathleen , Fischer Pascal , Gilja Odd Helge , Gottschall Heike , Jenssen Christian , Hollerweger Alois , Lucius Claudia , Meier Jennifer , Rogler Gerhard , Misselwitz Benjamin , Dietrich Christoph F.
Published: February 2025

Background: A standardized examination procedure and correct bowel wall assessment are the prerequisites for correct findings and for distinguishing normal findings from pathological diagnoses. PubMed was searched for the time period from January 01, 1990 – March 29, 2024, using a Boolean search
Summary: The present work provides knowledge and details of the examination of the gastrointestinal tract in transcutaneous ultrasound with examination procedure, transducer selection, transducer guidance, knowledge of the identification of anatomical structures and sonographic assessment. The sonographic reference values for the gastrointestinal tract were researched, compiled, and interpreted. In addition, citations and references of eligible studies were searched to identify further studies for inclusion.
Key Messages: Knowledge of the sonographic appearance of the gastrointestinal tract and the standardized examination of the healthy gastrointestinal tract, including correct measurements, must be trained. Although age, body weight and food ingestion influence the thickness of the intestinal wall, it does not normally exceed 2 mm in the duodenum, jejunum, ileum and colon on US. However, in most clinical studies 3 mm was used as cut-off for pathology. When assessing the appendix, an outer diameter of < 6 mm is considered normal. However, an increase in this diameter may also occur in healthy, asymptomatic people and should be not used as the sole criterion for diagnosing appendicitis. GIUS is now established as valid clinical method to assess patients with digestive diseases. Accordingly, there is a great need for training opportunities and supervision of young doctors who want to enhance their knowledge and skills in GIUS.
Genetic and epigenetic insights into Werner Syndrome
Authors: Paccosi Elena , Guzzon Diletta , Proietti-De-Santis Luca
Published: February 2025

Background:
Werner syndrome is an autosomal recessive disorder characterized by premature aging and cancer predisposition, caused by loss of function mutations in WRN gene. To date, more than 70 different pathogenic variants have been identified across the WRN locus, with an increasing number of newly reported mutations. Even if the clinical phenotypes of WS seem to be indistinguishable among the different WRN mutation types, a certain genotype/phenotype correlation has been identified, especially regarding the predisposition to certain type of malignant disease. Along this line, the knowledge of the genetic aspects related to WRN is a fascinating land still object of intensive studies.

Summary and key messages:
This review discusses both the genetics and epigenetic regulation of WRN gene, with a special focus on the pathogenic variants that have been identified in the WRN locus across different populations. Indeed, we think that investigating these aspects is the basis starting from which is it possible to depict WRN role in aging and cancer development processes, with the final goal of opening new perspectives for future therapeutic strategies directed to the treatment not only of this syndrome, for which, to date, there is no cure, but also of many types of malignant diseases and all those disturbs related to the physiological aging.
РЕАЛЬНЕ ЗАСТОСУВАННЯ ІМЕРСИВНИХ ТЕХНОЛОГІЙ У БІОМЕДИЧНІЙ ОСВІТІ
Authors: Мінцер О. П. , Мохначов С. І. , Ганінець П. П. , Сарканич О. В. , Вембер Є. В.
Published: February 2025

Розглянуто питання розроблення, застосування та перспектив імерсивних технологій в охороні здоров’я та біомедичній освіті. Проаналізовано можливості застосування імерсивних технологій у біомедичній освіті, їх переваги та обмеження, а також перспективи подальшого розвитку. Імерсивні технології уже сьогодні є перспективним інструментом для біомедичної практики та освіти. Однак поточні дослідження для здобувачів медичної освіти занадто багато зосереджуються на питаннях, пов’язаних із хірургією та анатомією. Технологія занурення широко прийнята та використовується як у біомедичній практиці, так і в освіті для зменшення існуючих недоліків. Інтерактивна технологія може створити освітній процес, орієнтований на здобувачів (студентів), дозволяючи їм отримати інтерактивний і персоналізований практичний досвід, використовуючи можливість перекладу та портативність пристроїв VR/AR/MR/XR. Відповідно до результатів метааналізів запровадження технології занурення в освітньому процесі може суттєво підвищити показники здатності здобувачів освіти, зокрема студентів і аспірантів, виконувати медичні процедури. З огляду на ці переваги, важливо розглянути можливість широкого впровадження технології занурення в біомедичну практику та освіту.
Neurovascular Decoupling Is Associated With Lobar Intracerebral Hemorrhages and White Matter Hyperintensities
Authors: van Dijk Suzanne E. , Drenth Nadieh , Hafkemeijer Anne , Labadie Gerda , Witjes‐Ané Marie‐Noëlle W. , Baas Frank , Vreijling Jeroen P. , Blauw Gerard J. , Rombouts Serge A. R. B. , van der Grond Jeroen , van Rooden Sanneke
Published: February 2025

Background

Neurovascular coupling is a fundamental aspect of brain function by regulating cerebral blood flow in response to regional neuronal activity. Increasing evidence suggest neurovascular decoupling occurs early in the progression of Alzheimer disease (AD), potentially reflecting early vascular damage. Therefore, understanding the relationship between neurovascular coupling and established vascular risk factors for AD is essential to gain deeper insights into the vascular mechanisms underlying AD.

Methods

This cross‐sectional observational study investigated the association between neurovascular coupling and vascular risk factors for AD, specifically small vessel disease magnetic resonance imaging markers, cardiovascular risk factors, and the apolipoprotein E genotype. The cohort included 119 participants diagnosed with subjective cognitive impairment, mild cognitive impairment, and AD‐related dementia, as well as individuals without cognitive complaints. Neurovascular coupling was measured by blood‐oxygen‐level‐dependent functional magnetic resonance imaging amplitude in response to visual stimulation.

Results

Our findings revealed that decreased neurovascular coupling is linked to structural brain changes typically seen in small vessel disease; specifically we found an association between neurovascular coupling and white matter hyperintensities load (
β
=−0.199,
P
=0.030) and presence of lobar intracerebral hemorrhage (
β
=−0.228,
P
=0.011).

Conclusions

This raises the suggestion that a decreased neurovascular coupling in the disease process of AD is related to comorbid small vessel disease.
Oestrous cycle synchronization protocols in rats using cloprostenol and progesterone injections
Authors: Potapova Sophia , Stratilov Viktor , Vetrovoy Oleg , Safarova Diana , Tyulkova Ekaterina
Published: February 2025

This study investigated the effectiveness of combining cloprostenol (Cl) and progesterone (Pg) injections for oestrous synchronization in female rats. A comprehensive series of experiments was conducted to explore the impact of hormonal injections on subsequent reproductive behaviour. The study involved dividing rats into distinct groups, with each group subjected to specific injections of either Cl, Pg, or their combinations. We observed a 100% conception efficiency within the first day after the last Cl injection in the Cl + Pg + Cl group. This finding underscores the remarkable effectiveness of the employed protocol, resulting in a rapid initiation of pregnancy in a substantial number of female rats on the same day.
Intermittent Thermal Extraction Optimization in Geothermal Heating Systems: A Case Study of Pei County, Jiangsu Province, China
Authors: Lei Zhihong , Zhang Qing , Lin Xingjie , Li Yunfeng
Published: February 2025

Geothermal heating is gaining attention as a low-carbon energy solution with potential for sustainable systems. This article investigates the feasibility of utilizing medium to deep geothermal energy for heating in southern China, particularly in Anguo Town, Pei County, Jiangsu Province. Using TOUGH2 software, we developed a dual-vertical-well geothermal extraction model to simulate various operational scenarios and identify effective heating strategies. Our findings show that the extraction and injection processes enhance groundwater convection, overshadowing the natural flow effects. The reservoir's pressure dynamics allow it to self-regulate, returning to equilibrium after each injection-extraction cycle, while the temperature field can experience thermal breakthroughs due to cooling over time. Key factors influencing outcomes included the injection fluid rate, which greatly impacted produced water temperature and its fluctuations, while the height difference between wells and well spacing primarily affected long-term changes in production temperature. The optimized parameters for the geothermal system in Anguo Town were identified as an injection flow rate of qinj  = 50 kg/s, a well spacing of d = 400 m, and a perforation section height difference of Δh = 168.8 m. Under these conditions, the geothermal system can operate continuously over 50 extraction cycles, providing stable heat supply ranging from 4567.5 to 7492.2 kW each cycle. This research provides valuable insights for effectively harnessing medium to deep geothermal resources for supply heating in southern China, contributing to a more sustainable energy landscape.
Exploring the Influences of Sleep Disturbances in Mothers of School-Aged Children With Developmental Disabilities
Authors: Lee Jiwon , Hobbs Gerald , Spratling Regena
Published: February 2025

Background:

Although sleep is a modifiable health behavior linked to health and daytime functioning, studies have limited exploration of how mother and child-related factors interplay with mothers’ sleep disturbance in mothers of children with developmental disabilities.

Objective:

We aimed to explore the nature of sleep disturbances, their impact on health and daytime functioning, and strategies used to promote restful sleep in mothers of children with developmental disabilities.

Methods:

Using a qualitative descriptive approach, 13 mothers of school-aged children (6-12 years) with developmental disabilities who reported poor sleep quality completed semi-structured interviews. Interviews were transcribed, followed by thematic analysis.

Results:

Four themes were revealed: (1) I haven’t slept well in years; (2) My child doesn’t sleep well; (3) Being a mother of a child with a special need; and (4) Different strategies used to sleep better. Mothers reported chronic sleep disturbances that often started with the birth of their children and the negative effect of sleep disturbance on their health and daytime functioning. Mothers attributed their children with developmental disabilities’ sleep problems and chronic stress associated with daily caregiving as reasons for their sleep disturbances. Mothers tried various sleep-promoting activities to improve their sleep; they remained frustrated with not having consistent solutions and desired to learn specific strategies to manage sleep for themselves and their children.

Conclusion:

Our findings highlight the need to develop sleep health interventions, including strategies to reduce mothers’ stress and manage their children with developmental disabilities’ sleep problems, which may improve sleep and prevent adverse health outcomes.
Advances in sporadic brain arteriovenous malformations: Novel genetic insights, innovative animal models, and emerging therapeutic approaches
Authors: Ueki Yasuhito , Naylor Ryan M , Ghozy Sherief A , Thirupathi Kasthuri , Rinaldo Lorenzo , Kallmes David F , Kadirvel Ramanathan
Published: February 2025

Brain arteriovenous malformations (bAVMs) are a notable cause of intracranial hemorrhage, strongly associated with severe morbidity and mortality. Contemporary treatment options include surgery, stereotactic radiosurgery, and endovascular embolization, each of which has limitations. Hence, development of pharmacological interventions is urgently needed. The recent discovery of the presence of activating Kirsten rat sarcoma ( KRAS) viral oncogene homologue mutations in most sporadic bAVMs has opened the door for a more comprehensive understanding of the pathogenesis of bAVMs and has pointed to entirely novel possible therapeutic targets. Herein, we review the status quo of genetics, animal models, and therapeutic approaches in bAVMs.
The Safety and Tolerability of High Dose Intravenous Push Levetiracetam
Authors: Brandes Melissa , Flack Tara , Hays William B.
Published: February 2025

Objective: Levetiracetam (LEV) is a guideline-recommended antiepileptic that has been shown to be effective in the termination of status epilepticus. Traditionally, LEV is diluted in 100 mL of compatible fluid and administered as an intravenous (IV) piggyback over 15-60 minutes. Recent data supports the administration of LEV as an undiluted IV push. However, there is limited literature supporting the safety and tolerability of undiluted IV push administration of high dose LEV (2500 mg to 4500 mg). The purpose of this study was to further investigate safety and tolerability of IV push levetiracetam at doses 2500 mg and greater. Methods: A retrospective chart review was conducted to evaluate adverse drug reactions following IV push administration of levetiracetam at a dose of 2500 mg or greater between the dates 8/5/2021 to 6/30/2022. During chart review, each patient was evaluated for any adverse events that occurred utilizing provider documentation, significant event forms, and/or allergy list documentation following administration of IV push LEV. Results: Throughout the study period, 340 doses of LEV 2500 mg and greater were evaluated. Most common total dose was 3000 mg and weight-based dose was 50-59.99 mg/kg. 119 doses of 4000 mg or greater were evaluated. 338/340 (99.4%) doses were considered to be well-tolerated. One patient experienced erythema at the injection site and another patient was noted to have nystagmus. Significance: This study adds to the body of literature that rapid administration of undiluted LEV, including doses of 2500 mg to 4500 mg is safe and tolerable.
P/CVE-as-counterinsurgency: Police violence and police reform in Kenya’s counterterrorism agenda
Authors: Mesok Elizabeth , Schildknecht Darja
Published: February 2025

This article considers the calls for police reform and the continuation of police brutality to be twinning modes of policing within Kenya’s broader counterterrorism and preventing and countering violent extremism (P/CVE) architecture. Rather than seeing ongoing police brutality as a failure of, or at odds with, calls for police reform, we argue that what appears to be a paradox is actually indicative of a dialectic central to civil counterinsurgency – a dialectic comprising what we call ‘coercive compliance’ and ‘abject coercion’. Based on extensive field research in Kenya, this article centers the institution of the police as an integral mode of P/CVE-as-counterinsurgency to analyze various manifestations of police power, including international compliance vis-a-vis police reform, police brutality, and community engagement. We further theorize P/CVE-as-counterinsurgency in conversation with Kenya’s colonial history, arguing that police violence is neither new nor unique to today’s counterterrorism regime. Rather, we argue that contemporary policing in Kenya contains sediment of racialized counterinsurgency tactics that were critical to colonial rule in the mid-20th century. In conclusion, we offer reflections on other security contexts where the dialectic of coercive compliance and abject coercion might serve as a useful analytic.