bluuebunny/crossref_metadata_2025 huggingface dataset:
Developing Smart Technology for Dementia Care in Transitional Care Units: Barriers to Participant Engagement & Alternative Strategies
Authors: Attef Maryam , Trudel Chantal , Ault Laura , Waldie Piers , Carroll Nadine , Goubran Rafik , Hsu Amy , Jaana Mirou , Sveistrup Heidi , Tan Patrick , Thomas Neil , Wallace Bruce. , Knoefel Frank
Published: September 2024

With an aging population, anticipated increase in dementia cases and the emergence of transitional care units (TCU) serving these individuals, healthcare providers are looking to the future of smart technologies (DementiaTech) to assist in providing care to persons living with dementia (PLWD). Our research aimed to understand how DementiaTech can be effectively implemented and evaluated in a hospital transitional care setting to enhance the quality of life of dementia patients. This paper outlines the challenges we faced in implementing methods to suit the nuances of this context, recovery strategies to adapt the study to probe the research objective, and the results of our adaptations. The study had 2 phases: 1) analyze nighttime workflows in a TCU to implement a sensor-based motion monitoring system that can track patient activity overnight to enhance staff situation awareness (SA) of risk factors related to care; 2) develop a mobile application (app) based on information from patient’s caregivers/family members what they feel is important to know about the daily activity of the patient to involve them in care. During Phase 2, recruiting participants in TCUs presented multifaceted challenges such as staff member turnover, lost participants due to the linear approach of the study and the long lead times with recruitment over time. In response, our team developed alternative methods to explore the research objective which included involving subject matter experts from the steering committee and TCU management to provide their perspectives to develop a preliminary understanding from a clinical perspective. Our results highlight the insights gained from these ‘alternative’ participant groups, followed by a discussion of lessons learned to address engagement challenges. Despite recruitment difficulties, the study provides preliminary insights on developing apps to support caregivers/family members in staying connected to patients in TCUs.
Using Systems Engineering Initiative for Patient Safety (SEIPS) to improve clinician situational awareness for Osteogenesis Imperfecta
Authors: Thompson Sarah A , Orenstein Evan , Kandaswamy Swaminathan
Published: September 2024

Summary:

Osteogenesis Imperfecta (OI), also known as Brittle Bone Disease is a congenital defect. Lack of awareness around a child’s OI condition among caregivers can cause unintended injury during non-OI clinic visits. While Clinical Decision Support (CDS) can help improve situational awareness for clinicians, locally developed CDS in the electronic health record (EHR) often fails to achieve its goals and may even cause further harm and alert fatigue due to mismatches between the design and actual workflows. In this abstract we describe (1) development of an effective CDS through application of the Systems Engineering Initiative for Patient Safety (SEIPS) analysis and (2) potential ways to integrate such research methods in operational context.
Optimizing Health Interventions: A User-Centered Approach to Information Usability
Authors: Nelson Brittany , Petushek Erich
Published: September 2024

Context: Many interventions have been developed to promote healthier lifestyles. However, they fall short of achieving their intended effectiveness. A significant limitation is the lack of a user-centered approach in designing the interventions, decreasing the likelihood of their success. This study directly addresses this limitation by focusing on enhancing the information usability of future educational lifestyle interventions by identifying valuable user insights. Objective: Our primary goal is to identify design features that can be incorporated to increase the usability of lifestyle interventions. Design: Retrospective verbal reports, interviews, and open-ended survey questions were all used to collect user insights on two novel information videos. Insights will help to refine the video interventions and provide insights into design features that could help increase the effectiveness of future educational interventions. Results: Many design recommendations were identified that can help bolster information product usability, including incorporating more data, research, citations, and visual cues to increase the information’s trustworthiness and understandability. Conclusion: Results identify actionable strategies that can be implemented to enhance the usability of future educational interventions, underscoring the crucial role of information usability in optimizing outcomes.
Operationalizing the Connection Between Human Factors Engineering and Patient Safety
Authors: Fuller Helen J.A. , Dietz Aaron S. , Adams Kathleen , Kabel Margo , Arnold Tim
Published: September 2024

There are clear connections between the output of human factors methods and patient safety in the healthcare domain. While human factors techniques generally serve to enhance safety, there are times when these efforts are less well allied or even in opposition. This paper will describe ways in which we have linked safety to usability and added more explicit considerations of patient safety into existing human factors practices. We hope these efforts will encourage acceptance for human factors recommendations and promote buy-in from stakeholders for conducting usability and patient safety work.
Robotics Technology Deployment in Healthcare Environments: A Health System’s Perspective
Authors: Gabet Charlotte , Massing Ethel , Cornet Victor P.
Published: September 2024

Evaluating and deploying robotics technology in hospital environments presents unique operational challenges. In this talk, we describe our experience working with various robotics and non-robotics startups that tested their products at our health system, share strategies aimed at hospitals seeking to evaluate and implement cutting-edge robotics technology, and present suggestions geared towards robotics startups and human factors specialists evaluating robotics technology in hospital environments.
Staying True to Ourselves: Organizational purity at the crossroads of institutional logics and identity work
Authors: Godart Frédéric , Wittman Sarah
Published: September 2024

We build a comprehensive and coherent understanding of organizational purity as an organization’s steadfast adherence to a single institutional logic. This logic becomes the core tenet of its identity, an end in itself rather than a means toward survival. Instead of responding to institutional pressures, pure organizations may self-categorize vis-à-vis a potentially threatening ‘other’ through their own identity work. They mark and pursue their distinction from others, structure themselves to preserve their purity, and favor strategies that express the logic they embody. In so doing they may fail more often than organizations that are more responsive to institutional pressures. When pure organizations enter new institutional fields they can act as change agents, but where their logic dominates, they may block change. Different audiences, in turn, affect the success and survival of pure organizations by conferring authenticity, legitimacy or contempt, depending on their alignment with the pure organization’s logic. Further examining purity will enable organizational theorists to better account for non-rational action and extend work on institutional logics.
Role of the GalNAc-galectin pathway in the healing of premature rupture of membranes
Authors: Chen Jia-Le , Liu Lou , Peng Xin-Rui , Wang Yan , Xiang Xiang , Chen Yu , Xu De-Xiang , Chen Dao-Zhen
Published: September 2024

Background

Premature rupture of the membranes (PROM) is a key cause of preterm birth and represents a major cause of neonatal mortality and morbidity. Natural products N-acetyl-d-galactosamine (GalNAc), which are basic building blocks of important polysaccharides in biological cells or tissues, such as chitin, glycoproteins, and glycolipids, may improve possible effects of wound healing.

Methods

An in vitro inflammation and oxidative stress model was constructed using tumor necrosis-α (TNF-α) and lipopolysaccharide (LPS) action on WISH cells. Human amniotic epithelial cells (hAECs) were primarily cultured by digestion to construct a wound model. The effects of GalNAc on anti-inflammatory and anti-oxidative stress, migration and proliferation, epithelial-mesenchymal transition (EMT), glycosaminoglycan (GAG)/hyaluronic acid (HA) production, and protein kinase B (Akt) pathway in hAECs and WISH cells were analyzed using the DCFH-DA fluorescent probe, ELISA, CCK-8, scratch, transwell migration, and western blot to determine the mechanism by which GalNAc promotes amniotic wound healing.

Results

GalNAc decreased IL-6 expression in TNF-α-stimulated WISH cells and ROS expression in LPS-stimulated WISH cells (P < 0.05). GalNAc promoted the expression of Gal-1 and Gal-3 with anti-inflammatory and anti-oxidative stress effects. GalNAc promoted the migration of hAECs (50% vs. 80%) and WISH cells through the Akt signaling pathway, EMT reached the point of promoting fetal membrane healing, and GalNAc did not affect the activity of hAECs and WISH cells (P > 0.05). GalNAc upregulated the expression of sGAG in WISH cells (P < 0.05) but did not affect HA levels (P > 0.05).

Conclusions

GalNAc might be a potential target for the prevention and treatment of PROM through the galectin pathway, including (i) inflammation; (ii) epithelial-mesenchymal transition; (iii) proliferation and migration; and (iv) regression, remodeling, and healing.
Gaps in the usage and reporting of multiple imputation for incomplete data: findings from a scoping review of observational studies addressing causal questions
Authors: Mainzer Rheanna M. , Moreno-Betancur Margarita , Nguyen Cattram D. , Simpson Julie A. , Carlin John B. , Lee Katherine J.
Published: September 2024

Background

Missing data are common in observational studies and often occur in several of the variables required when estimating a causal effect, i.e. the exposure, outcome and/or variables used to control for confounding. Analyses involving multiple incomplete variables are not as straightforward as analyses with a single incomplete variable. For example, in the context of multivariable missingness, the standard missing data assumptions (“missing completely at random”, “missing at random” [MAR], “missing not at random”) are difficult to interpret and assess. It is not clear how the complexities that arise due to multivariable missingness are being addressed in practice. The aim of this study was to review how missing data are managed and reported in observational studies that use multiple imputation (MI) for causal effect estimation, with a particular focus on missing data summaries, missing data assumptions, primary and sensitivity analyses, and MI implementation.

Methods

We searched five top general epidemiology journals for observational studies that aimed to answer a causal research question and used MI, published between January 2019 and December 2021. Article screening and data extraction were performed systematically.

Results

Of the 130 studies included in this review, 108 (83%) derived an analysis sample by excluding individuals with missing data in specific variables (e.g., outcome) and 114 (88%) had multivariable missingness within the analysis sample. Forty-four (34%) studies provided a statement about missing data assumptions, 35 of which stated the MAR assumption, but only 11/44 (25%) studies provided a justification for these assumptions. The number of imputations, MI method and MI software were generally well-reported (71%, 75% and 88% of studies, respectively), while aspects of the imputation model specification were not clear for more than half of the studies. A secondary analysis that used a different approach to handle the missing data was conducted in 69/130 (53%) studies. Of these 69 studies, 68 (99%) lacked a clear justification for the secondary analysis.

Conclusion

Effort is needed to clarify the rationale for and improve the reporting of MI for estimation of causal effects from observational data. We encourage greater transparency in making and reporting analytical decisions related to missing data.
Transfusion-related acute lung injury (TRALI) following intravenous immunoglobulin infusion in a rituximab immunosuppressed patient with long-shedding SARS-CoV-2
Authors: Degtiarova Ganna , Conen Anna , Klarer Alexander , Arifi Teuta , Guldimann Gina , Finkener Sebastian , Spirig Andres , Kabitz Hans-Joachim
Published: September 2024

Background

Transfusion-related acute lung injury (TRALI) is a rare life-threatening complication of blood product transfusion. Intravenous immunoglobulin (IVIG)-related TRALI is scarcely reported.

Case presentation

A 63-year-old male patient suffering from multiple sclerosis treated with half-yearly rituximab infusions, was hospitalized due to dry cough, daily fever and shivering for seven days despite antibiotic therapy. Because of the history of COVID-19 one month prior without the symptoms having improved since, persistent bilateral multifocal areas of ground glass opacities in chest computed tomography and positive SARS-CoV-2 PCR from bronchoalveolar lavage with a cycling time of 30.1 COVID-19 due to long-shedding SARS-CoV-2 under immunosuppression with rituximab was diagnosed. He received treatment with nirmatrelvir und ritonavir and because of diagnosed IgG deficiency additionally a single dose of 20 g IVIG. During the IVIG infusion, the patient acutely developed tachycardia, hypotension, fever, chills, and hypoxemic respiratory failure due to pulmonary edema. TRALI was promptly diagnosed, and the patient was transferred to the intensive care unit for non-invasive ventilation for less than 24 h. The patient was discharged home from regular ward 72 h later in a good general condition and no remaining symptoms of TRALI.

Conclusion

IVIG-related TRALI is a rare but life-threating condition and prompt recognition is lifesaving. Due to an increased use of IVIG not only in long-shedding SARS-CoV-2, an increase of TRALI incidence is expected.
CD25+FOXP3+CD45RA− regulatory T-cell infiltration as a prognostic biomarker for endometrial carcinoma
Authors: Suto Asami , Minaguchi Takeo , Qi Nan , Fujieda Kaoru , Itagaki Hiroya , Tenjimbayashi Yuri , Shikama Ayumi , Tasaka Nobutaka , Akiyama Azusa , Nakao Sari , Nakahashi-Oda Chigusa , Kobayashi Yusuke , Shibuya Akira , Satoh Toyomi
Published: September 2024

Background

Regulatory T (Treg) cells reportedly play crucial roles in tumor angiogenesis as well as antitumor immunity. In order to explore their therapeutic potential, we investigated the precise prognostic impact of Treg markers in endometrial carcinoma.

Methods

We performed multiplexed immunofluorescence and quantitative image analyses of CD25, FOXP3, CTLA4, and CD45RA in tumor specimens from 176 consecutive patients treated at our institution for primary endometrial carcinomas. Bioinformatics analyses were further conducted to corroborate the findings.

Results

High CD25+, FOXP3+, and CD25+FOXP3+CD45RA− stromal cell counts correlated with better overall survival (OS) (p = 0.00019, 0.028 and 0.0012) and MSI-high (p = 0.015, 0.016 and 0.047). High CD45RA+ stromal cell count was associated with superficial myometrial invasion (p = 0.0038). Bioinformatics survival analysis by Kaplan-Meier plotter showed that high CD25, FOXP3, CTLA4, and CD45RA mRNA expressions correlated with better OS (p = 0.046, 0.00042, 0.000044, and 0.0022). Univariate and multivariate analyses with various clinicopathologic prognostic factors indicated that high CD25+ or CD25+FOXP3+CD45RA− stromal cell count was significant and independent for favorable OS (p = 0.0053 and 0.0015). We subsequently analyzed the correlations between the multiplexed immunofluorescence results and treatment-free interval (TFI) after primary chemotherapy in recurrent cases, finding no significant associations. Further analysis revealed that high ratio of CD25+ : CD8+ cell count or CD25+FOXP3+CD45RA− : CD8+ cell count correlated with longer TFI (p = 0.021 and 0.021).

Conclusion

The current observations suggest that the balance between CD25+ or CD25+FOXP3+CD45RA− cells and CD8+ cells, corresponding to promoting or inhibiting effect on tumor angiogenesis, affect tumor chemosensitivity leading to prognostic significance. CD25+FOXP3+CD45RA− effector Treg tumor infiltration may serve as a useful prognostic biomarker and a potential target for immunotherapeutic manipulation of tumor chemosensitivity by novel management for advanced/recurrent endometrial carcinomas.
Tryptophan regulates the expression of IGFBP1 in bovine endometrial epithelial cells in vitro via the TDO2-AHR pathway
Authors: Wang Peng-Chao , Liu Ze-Kun , Li Jia-Rong , Zhao Zi-Hui , Chang Qian-Wen , Guo Xiao-Min , Jin Lin , Hu Yong-Ting , Yang Zhenshan
Published: September 2024

Background

This study aimed to identify the roles of L-tryptophan (Trp) and its rate-limiting enzymes on the receptivity of bovine endometrial epithelial cells. Real-time PCR was conducted to analyze the differential expression of genes between different groups of bovine endometrial epithelial cells. Western blot was performed to detect Cyclooxygenase-2 (COX2) expression after treatment with Trp or kynurenine (the main metabolites of Trp). The kynurenine assay was used to examine if Trp or prostaglandin E2 (PGE2) can increase the production of kynurenine in the bovine endometrial epithelial cells.

Results

Trp significantly stimulates insulin growth factor binding protein 1 (IGFBP1) expression, a common endometrial marker of conceptus elongation and uterus receptivity for ruminants. When bovine endometrial epithelial cells are treated with Trp, tryptophan hydroxylase-1 remains unchanged, but tryptophan 2,3-dioxygenase 2 (TDO2) is significantly increased, suggesting tryptophan is mainly metabolized through the kynurenine pathway. Kynurenine significantly stimulates IGFBP1 expression. Furthermore, Trp and kynurenine significantly increase the expression of aryl hydrocarbon receptor (AHR). CH223191, an AHR inhibitor, abrogates the induction of Trp and kynurenine on IGFBP1. PGE2 significantly induces the expression of TDO2, AHR, and IGFBP1.

Conclusions

The regulation between Trp / kynurenine and PGE2 may be crucial for the receptivity of the bovine uterus.
Berberine and magnolol exert cooperative effects on ulcerative colitis in mice by self-assembling into carrier-free nanostructures
Authors: Xu Yida , Chen Zhejie , Hao Wei , Yang Zhengming , Farag Mohamed , Vong Chi Teng , Wang Yitao , Wang Shengpeng
Published: September 2024

The risk of ulcerative colitis (UC) is increasing worldwide with limited success using classical drugs, which has underscored the development of novel agents. Recently, carrier-free molecular assembly has been proven to be an effective drug delivery system, but it has yet to be examined for UC drug development using phytochemicals. Based on traditional Chinese medicine compatibility and potential medicinal uses, a pair of natural compounds, berberine (BBR) and magnolol (MAG), were found to self-assemble into nanostructures in aqueous solutions. Spectral analysis revealed that the assembly mechanisms of BBR and MAG were mediated through charge interactions and π-π stacking. Pharmacokinetic studies and animal imaging showed that BBR-MAG self-assembly (BM) effectively promoted the oral bioavailability and biodistribution of BBR in the colon. BM exhibited superior effects in regulating inflammatory factors, maintaining colon barrier integrity, and regulating gut microbiota in a dextran sulfate sodium salt-induced colitis mouse model. Additionally, no apparent signs of toxicity were observed, suggesting that BM has a favorable safety profile. This study presents a new strategy for UC management and highlights the cooperative effects of combined phytochemicals.

Graphical Abstract
Mechanical ventilation settings during weaning from venovenous extracorporeal membrane oxygenation
Authors: Passarelli Maria Teresa , Petit Matthieu , Garberi Roberta , Lebreton Guillaume , Luyt Charles Edouard , Pineton De Chambrun Marc , Chommeloux Juliette , Hékimian Guillaume , Rezoagli Emanuele , Foti Giuseppe , Combes Alain , Giani Marco , Schmidt Matthieu
Published: September 2024

Background

The optimal timing of weaning from venovenous extracorporeal membrane oxygenation (VV ECMO) and its modalities have been rarely studied.

Methods

Retrospective, multicenter cohort study over 7 years in two tertiary ICUs, high-volume ECMO centers in France and Italy. Patients with ARDS on ECMO and successfully weaned from VV ECMO were classified based on their mechanical ventilation modality during the sweep gas-off trial (SGOT) with either controlled mechanical ventilation or spontaneous breathing (i.e. pressure support ventilation). The primary endpoint was the time to successful weaning from mechanical ventilation within 90 days post-ECMO weaning.

Results

292 adult patients with severe ARDS were weaned from controlled ventilation, and 101 were on spontaneous breathing during SGOT. The 90-day probability of successful weaning from mechanical ventilation was not significantly different between the two groups (sHR [95% CI], 1.23 [0.84–1.82]). ECMO-related complications were not statistically different between patients receiving these two mechanical ventilation strategies. After adjusting for covariates, older age, higher pre-ECMO sequential organ failure assessment score, pneumothorax, ventilator-associated pneumonia, and renal replacement therapy, but not mechanical ventilation modalities during SGOT, were independently associated with a lower probability of successful weaning from mechanical ventilation after ECMO weaning.

Conclusions

Time to successful weaning from mechanical ventilation within 90 days post-ECMO was not associated with the mechanical ventilation strategy used during SGOT. Further research is needed to assess the optimal ventilation strategy during weaning off VV ECMO and its impact on short- and long-term outcomes.
Updates in Alzheimer's disease: from basic research to diagnosis and therapies
Authors: Liu Enjie , Zhang Yao , Wang Jian-Zhi
Published: September 2024

Alzheimer’s disease (AD) is the most common neurodegenerative disorder, characterized pathologically by extracellular deposition of β-amyloid (Aβ) into senile plaques and intracellular accumulation of hyperphosphorylated tau (pTau) as neurofibrillary tangles. Clinically, AD patients show memory deterioration with varying cognitive dysfunctions. The exact molecular mechanisms underlying AD are still not fully understood, and there are no efficient drugs to stop or reverse the disease progression. In this review, we first provide an update on how the risk factors, including APOE variants, infections and inflammation, contribute to AD; how Aβ and tau become abnormally accumulated and how this accumulation plays a role in AD neurodegeneration. Then we summarize the commonly used experimental models, diagnostic and prediction strategies, and advances in periphery biomarkers from high-risk populations for AD. Finally, we introduce current status of development of disease-modifying drugs, including the newly officially approved Aβ vaccines, as well as novel and promising strategies to target the abnormal pTau. Together, this paper was aimed to update AD research progress from fundamental mechanisms to the clinical diagnosis and therapies.
Global distribution, diversity, and ecological niche of Picozoa, a widespread and enigmatic marine protist lineage
Authors: Huber Paula , De Angelis Daniele , Sarmento Hugo , Metz Sebastian , Giner Caterina R. , Vargas Colomban De , Maiorano Luigi , Massana Ramon , Logares Ramiro
Published: September 2024

Background

The backbone of the eukaryotic tree of life contains taxa only found in molecular surveys, of which we still have a limited understanding. Such is the case of Picozoa, an enigmatic lineage of heterotrophic picoeukaryotes within the supergroup Archaeplastida, which has emerged as a significant component of marine microbial planktonic communities. To enhance our understanding of the diversity, distribution, and ecology of Picozoa, we conduct a comprehensive assessment at different levels, from assemblages to taxa, employing phylogenetic analysis, species distribution modeling, and ecological niche characterization.

Results

Picozoa was among the ten most abundant eukaryotic groups, found almost exclusively in marine environments. The phylum was represented by 179 Picozoa’s OTU (pOTUs) placed in five phylogenetic clades. Picozoa community structure had a clear latitudinal pattern, with polar assemblages tending to cluster separately from non-polar ones. Based on the abundance and occupancy pattern, the pOTUs were classified into four categories: Low-abundant, Widespread, Polar, and Non-polar. We calculated the ecological niche of each of these categories. Notably, pOTUs sharing similar ecological niches were not closely related species, indicating a phylogenetic overdispersion in Picozoa communities. This could be attributed to competitive exclusion and the strong influence of the seasonal amplitude of variations in environmental factors, such as temperature, shaping physiological and ecological traits.

Conclusions

Overall, this work advances our understanding of uncharted protists’ evolutionary dynamics and ecological strategies. Our results highlight the importance of understanding the species-level ecology of marine heteroflagellates like Picozoa. The observed phylogenetic overdispersion challenges the concept of phylogenetic niche conservatism in protist communities, suggesting that closely related species do not necessarily share similar ecological niches.
Infiltrating treg reprogramming in the tumor immune microenvironment and its optimization for immunotherapy
Authors: Zhou Zhaokai , Xu Jiaxin , Liu Shutong , Lv Yingying , Zhang Ruiqi , Zhou Xing , Zhang Yuyuan , Weng Siyuan , Xu Hui , Ba Yuhao , Zuo Anning , Han Xinwei , Liu Zaoqu
Published: September 2024

Immunotherapy has shown promising anti-tumor effects across various tumors, yet it encounters challenges from the inhibitory tumor immune microenvironment (TIME). Infiltrating regulatory T cells (Tregs) are important contributors to immunosuppressive TIME, limiting tumor immunosurveillance and blocking effective anti-tumor immune responses. Although depletion or inhibition of systemic Tregs enhances the anti-tumor immunity, autoimmune sequelae have diminished expectations for the approach. Herein, we summarize emerging strategies, specifically targeting tumor-infiltrating (TI)-Tregs, that elevate the capacity of organisms to resist tumors by reprogramming their phenotype. The regulatory mechanisms of Treg reprogramming are also discussed as well as how this knowledge could be utilized to develop novel and effective cancer immunotherapies.
Unraveling the impact of hyperleptinemia on female reproduction: insights from transgenic pig model
Authors: Jamal Muhammad Ameen , Cheng Yixiao , Jiao Deling , Cheng Wen , Zou Di , Wang Xia , Wei Taiyun , Guo Jianxiong , Xu Kaixiang , Zhao Heng , Pu Shaoxia , Yang Chang , Qing Yubo , Jia Baoyu , Li Honghui , Zhao Rusong , Zhao Hong-Ye , Wei Hong-Jiang
Published: September 2024

Background

Infertility is a growing global health concern affecting millions of couples worldwide. Among several factors, an extreme body weight adversely affects reproductive functions. Leptin is a well-known adipokine that serves as an endocrine signal between adiposity and fertility. However, the exact mechanisms underlying the effects of high leptin level on female reproduction remain unclear.

Methods

Transgenic pigs overexpressing leptin (♀) were produced by backcrossing and screened for leptin overexpression. The growth curve, fat deposition, reproductive performance, apoptosis, serum hormones and cholesterol production, RNA sequencing, and single-nucleus RNA sequencing (snRNA-seq) of the leptin-overexpressing pigs and wild-type group were evaluated.

Results

Transgenic pigs overexpressing leptin (♀) were obtained, which exhibited significantly reduced body weight, body size, and back fat thickness. These pigs manifested a late onset of puberty (330 ± 54.3 vs. 155 ± 14.7 days), irregular estrous behavior characterized by increased inter-estrous interval (29.2 ± 0 vs. 21.3 ± 0.7 days), and more number of matings until pregnancy (at least 3 times). This reproductive impairment in leptin pigs was related to hormonal imbalances characterized by increased levels of FSH, LH, prolactin, E2, P4, and TSH, altered steroidogenesis such as increased levels of serum cholesterol esters along with steroidogenic markers (StAR, CYP19A), and ovarian dysfunctions manifested by neutrophilic infiltration and low expression of caspase-3 positive cells in the ovaries. Moreover, bulk RNA sequencing of the ovaries also revealed neutrophilic infiltration followed by upregulation of inflammation-related genes. Furthermore, snRNA-seq reflected that leptin overexpression triggered immune response, suppressed follicle development and luteinization, resulting in metabolic dysfunction and hormone imbalance in the ovary.

Conclusions

Low body weight in leptin overexpressing pigs adversely affects the reproductive performance, causing delayed puberty, irregular estrous cycles, and reduced breeding efficiency. This is linked to metabolic imbalances, an increased immune response, and altered ovarian functions. This study provides a theoretical basis for the complex mechanisms underlying leptin, and infertility by employing leptin-overexpressing female pigs.
Transjugular antegrade transvenous obliteration, with and without portal decompression, for management of rectal variceal hemorrhage
Authors: Li Gabriel E. , Chick Jeffrey Forris Beecham , Monroe Eric J. , Abad-Santos Matthew , Hua Ethan W. , Shin David S.
Published: September 2024

Purpose

To report antegrade transvenous obliteration, with or without concurrent portosystemic shunt creation, for the treatment of hemorrhagic rectal varices.

Materials and methods

Eight patients, including five (62.5%) females and three (37.5%) males, with mean age of 55.8 ± 13.8 years (range: 30–70 years), underwent transjugular-approach antegrade transvenous obliteration of rectal varices, with or without portosystemic shunt creation. Demographic data, procedural details, technical success of variceal obliteration, clinical success, adverse events, and follow-up outcomes were retrospectively recorded. Clinical success was defined as resolution of rectal hemorrhage.

Results

Portal venous access was achieved via a transjugular intrahepatic approach in all patients. The inferior mesenteric vein was selected, and foamy sclerosant (1:2:3 mixture by volume of ethiodized oil: sodium tetradecyl sulfate: air) was injected into the rectal varices with antegrade balloon occlusion in seven (87.5%) and without balloon occlusion in one (12.5%). Five of eight (62.5%) patients underwent concomitant transjugular intrahepatic portosystemic shunt (TIPS) creation (mean diameter 8.4 ± 0.9-mm) immediately following transvenous obliteration. Technical success of variceal obliteration was achieved in all patients. There were no immediate post-procedural adverse events. There were no reported occurrences of rectal ischemia, perforation, or stricture following obliteration. Two (40%) of the patients who underwent concomitant TIPS creation developed hepatic encephalopathy within 30 days of the procedure, which was medically managed. Clinical resolution of hemorrhage was achieved in all patients with no recurrent rectal variceal hemorrhage during mean follow-up of 666 ± 396 days (range: 14 − 1,224 days).

Conclusion

Transvenous obliteration, with or without concurrent TIPS creation, is feasible with promising results for the management of rectal variceal hemorrhage.
Understanding the role of bats as fungal vectors in the environment
Authors: Liu Xiang-Fu , Karunarathna Samantha Chandranath , Tibpromma Saowaluck , Chethana K. W. Thilini , Hyde Kevin D. , Elgorban Abdallah M. , Suwannarach Nakarin , Kumla Jaturong , Mortimer Peter E. , Hughes Alice C.
Published: September 2024

Bats (Chiroptera), the second largest group of mammals, are known for their unique immune system and their ability to act as vectors for various zoonoses. Bats also act as important carriers of fungi, which include plant, animal, and human pathogens. Their roosting areas, foraging behaviors, and even migration routes make bats ideal vectors for fungi. We isolated 75 culturable fungal species from bats in Yunnan Province, China, with 36 species representing known pathogens of plants, animals, and humans, while 39 species are non-pathogenic fungi. Among these species, 77% (58 species) belonged to Ascomycota, 9% (seven species) belonged to Basidiomycota, and 13% (10 species) belonged to Mucoromycota. Even though several taxonomic studies on fungi associated with bats have been published, studies exploring the role of bats as fungal vectors are lacking. This study discusses the fungi host-specific traits and pathogenicity and the impact and ecological significance of bats as fungal vectors.
Metabolomics-based biomarkers of probiotic efficacy in toxicological settings
Authors: Emegano Declan Ikechukwu , Battal Dilek , Kocadal Kumsal
Published: September 2024

Background

Metabolomics is the study of metabolites in cells, tissues, live organisms, and biological fluids to elucidate their composition and possible roles. Metabolomics and its biomarkers have emerged as a powerful tool for evaluating the efficacy of probiotics in various pathological conditions, including toxicological settings. This review explores the use of metabolomics-based markers to assess the safety and efficacy of probiotics in toxicological settings.

Result

This review aims to determine biomarkers for measuring the effectiveness of probiotic therapies in toxicological contexts based on exposure, effects, susceptibility, prognostic, and therapeutic biomarkers. In this study, 1979 articles were systematically searched in PubMed (PM), Scopus (Sc), Google Scholar (GS), and Web of Science (WOS) between the years 2013 and 2023 inclusive using keywords, inclusion, and exclusion criteria. The result showed that 1439 human samples were used from 2013 to 2023 publications with the UK having the highest number of publications, data, and sample types in 2023. Again, the result showed most of the publications are on susceptibility-based biomarkers.

Conclusion

Metabolomics-based biomarkers may provide insight into metabolism-related alterations related to probiotic therapies while clarifying their biological mechanisms, especially in toxicology enabling specific probiotic therapy.
Early Circulating Tumor DNA Shedding Kinetics for Prediction of Platinum Sensitivity in Patients With Small Cell Lung Cancer
Authors: Murciano-Goroff Yonina R. , Hui Angela B.-Y. , Araujo Filho Jose A. , Hamilton Emily G. , Chabon Jacob J. , Moding Everett J. , Bonilla Rene F. , Lebow Emily S. , Gomez Daniel , Rimner Andreas , Ginsberg Michelle S. , Offin Michael , Kundra Ritika , Allaj Viola , Norton Larry , Reis-Filho Jorge S. , Razavi Pedram , Drilon Alexander , Jones David R. , Isbell James M. , Lai W. Victoria , Rudin Charles M. , Alizadeh Ash A. , Li Bob T. , Diehn Maximilian
Published: September 2024

PURPOSE

Small cell lung cancer (SCLC) is characterized by rapid progression after platinum resistance. Circulating tumor (ctDNA) dynamics early in treatment may help determine platinum sensitivity.

MATERIALS AND METHODS

Serial plasma samples were collected from patients receiving platinum-based chemotherapy for SCLC on the first 3 days of cycle one and on the first days of subsequent cycles with paired samples collected both before and again after infusions. Tumor-informed plasma analysis was carried out using CAncer Personalized Profiling by deep Sequencing (CAPP-Seq). The mean variant allele frequency (VAF) of all pretreatment mutations was tracked in subsequent blood draws and correlated with radiologic response.

RESULTS

ctDNA kinetics were assessed in 122 samples from 21 patients. Pretreatment VAF did not differ significantly between patients who did and did not respond to chemotherapy (mean 22.5% v 4.6%, P = .17). A slight increase in ctDNA on cycle 1, day 1 immediately post-treatment was seen in six of the seven patients with available draws (fold change from baseline: 1.01-1.44), half of whom achieved a response. All patients who responded had a >2-fold decrease in mean VAF on cycle 2 day 1 (C2D1). Progression-free survival (PFS) and overall survival (OS) were significantly longer in patients with a >2-fold decrease in mean VAF after one treatment cycle (6.8 v 2.6 months, log-rank P = .0004 and 21.7 v 6.4 months, log rank P = .04, respectively).

CONCLUSION

A >2-fold decrease in ctDNA concentration was observed by C2D1 in all patients who were sensitive to platinum-based therapy and was associated with longer PFS and OS.
Liposomal Formulations of Anti-Alzheimer Drugs and siRNA for Nose-to-Brain Delivery: Design, Safety and Efficacy In Vitro
Authors: Lee David , Shen Andrew M , Garbuzenko Olga B , Minko Tamara
Published: September 2024

β-site amyloid precursor protein cleaving enzyme (BACE1) represents a key target for Alzheimer’s disease (AD) therapy because it is essential for producing the toxic amyloid β (Aβ) peptide that plays a crucial role in the disease’s development. BACE1 inhibitors are a promising approach to reducing Aβ levels in the brain and preventing AD progression. However, systemic delivery of such inhibitors to the brain demonstrates limited efficacy because of the presence of the blood-brain barrier (BBB). Nose-to-brain (NtB) delivery has the potential to overcome this obstacle. Liposomal drug delivery systems offer several advantages over traditional methods for delivering drugs and nucleic acids from the nose to the brain. The current study aims to prepare, characterize, and evaluate in vitro liposomal forms of donepezil, memantine, BACE-1 siRNA, and their combination for possible treatment of AD via NtB delivery. All the liposomal formulations were prepared using the rotary evaporation method. Their cellular internalization, cytotoxicity, and the suppression of beta-amyloid plaque and other pro-inflammatory cytokine expressions were studied. The Calu-3 Transwell model was used as an in vitro system for mimicking the anatomical and physiological conditions of the nasal epithelium and studying the suitability of the proposed formulations for possible NtB delivery. The investigation results show that liposomes provided the effective intracellular delivery of therapeutics, the potential to overcome tight junctions in BBB, reduced beta-amyloid plaque accumulation and pro-inflammatory cytokine expression, supporting the therapeutic potential of our approach.

Graphical Abstract
Evaluation of the Noninvasive Estimated Continuous Cardiac Output System for Pediatric Patients: A Prospective Observational Study
Authors: Taniguchi Tomoya , Fujii Tasuku , Takakura Masashi , Nishiwaki Kimitoshi
Published: September 2024

BACKGROUND:

The estimated continuous cardiac output (esCCO) system is a hemodynamic monitor that uses electrocardiograms and pulse oximeter waves to noninvasively estimate cardiac output. The coefficients for esCCO measurement have been established for adult patients, but the appropriate coefficients for pediatric patients are unclear. Therefore, this study determined esCCO coefficients for pediatric patients and validated the accuracy and tracking ability of a modified esCCO system.

METHODS:

An initial study compared cardiac output measurements using transthoracic echocardiography and esCCO in 60 pediatric patients aged <15 years who underwent elective noncardiac surgery. Consequently, the coefficients for the esCCO measurements were redefined for pediatric patients. The main study compared cardiac output measurements between transthoracic echocardiography and modified esCCO in 80 pediatric patients. Measurements were performed pre- and postoperatively, and the accuracy and trending ability of the cardiac output measurements were evaluated using Bland-Altman analysis and a polar plot.

RESULTS:

The correlation coefficients between the modified esCCO and transthoracic echocardiography were 0.96 and 0.98 in the pre- and postoperative measurements, respectively. In Bland-Altman analysis, the bias (standard deviation [SD]), 95% limits of agreement, and percentage error were 0.03 (0.28), −0.53 to 0.60, and 18% in the preoperative measurement, and −0.04 (0.19), –0.42 to 0.35, and 15% in the postoperative measurement, respectively. The polar plot showed that the cardiac output changes were well tracked, with an angular bias (SD) of 2.9° (6.0°) and radial 95% limits of agreement ranging from −9.2° to 14.9°.

CONCLUSIONS:

Cardiac output measurement by esCCO with modified coefficients for pediatric patients showed high accuracy and tracking ability compared with cardiac output measurement by transthoracic echocardiography. This noninvasive cardiac output measurement could benefit perioperative hemodynamic monitoring in children.
“You Go First, You Kaza!”: Using Casting and Intertextuality to Rewrite Myth in the Miniseries Eagles
Authors: Inbar Anat Sella
Published: September 2024

This article demonstrates how layers of meanings accumulated in an actor's persona can influence the readings of other, newer performances by the same actor, thus creating new and sometimes subversive meanings in those performances and enabling a radical rereading of past texts, and even related historical events and myth, in light of the new ones. Specifically, the article explores the meanings associated with the public image of Yehoram Gaon, a well-known Israeli actor and singer, and analyzes his performance and role in the award-winning 2010 Israeli television miniseries Eagles (Hebrew, Nevelot; slang, “bastards”). In an interpretive intertextual reading, it reveals how one of Gaon's famous embodiments, the fictional character of Kazablan, is reincarnated in the text. Kazablan has become a symbol of ethnic discrimination in Jewish-Israeli society because of his Mizrahi descent (Mizrahim are Jews originating in Asian and African countries). Moreover, Gaon is also well-known for his cinematic career where he portrayed iconic war heroes, including in one of Israel's most successful feature films, Operation Thunderbolt (1977), which helped shape a national myth. Casting him as a sort of runaway killer in a series that challenges national myth is therefore a charged stand. The article suggests that this hinted presence of characters from previous roles, carried into the miniseries text through casting and embodiment, allows for a new reading of main Israeli canonical texts, and for a new perspective on myth and historical events.
When the Adaptation Reveals the Original: Comparative Analysis of Series and National Ethos
Authors: Hanhart-Marmor Yona
Published: September 2024

This article compares the Israeli series BeTipul and its French adaptation En thérapie to show that while the changes that were made in the adaptation were minimal, analyzing them proves to be a powerful tool for understanding the national ethos of both Israeli and French societies. The anchoring of the French protagonists in the longue durée—through cultural references, evocation of the psychoanalytic tradition, and grounding in Jewish history—contrasts with the acute presentism that characterizes the Israeli version. The adaptation thus proves to be a gateway to understanding the culture that produced the original. In this way, this case study contributes to the study of the international circulation of television productions and to the analysis of the tension between international homogenization and local specificities.
Türkiye’de Bir İdeoloji Olarak Cumhuriyet
Authors: Ertugay Fatih
Published: September 2024

Türkiye’de 29 Ekim 1923’te yeni devletin siyasal sistemi ile ilgili önemli bir karar verilerek Cumhurî yönetim biçimine geçilmiştir. Bu sadece bir siyasal sistem değişikliği olarak tezahür etmemiş aynı zamanda topyekûn bir siyasal ve toplumsal anlayış değişikliğine tekabül eden bir adım olmuştur. Cumhuriyet fikri ve olgusu zamanla farklı bileşenlerin de etkisi ile kendisini bir siyasal felsefe, daha yerinde bir ifadeyle bir ideoloji olarak da var etmiştir. Çalışma temel olarak Türkiye’de Cumhuriyet ve cumhuriyetçiliğin bir ideolojiye dönüşmüş olduğunu iddia etmektedir. Bu ideoloji, cumhuriyetçilik fikrinden esinlendiği/etkilendiği kadar, zamanla onu aşan hatta onun içermediği değer, kavram ve anlayışları da bünyesine eklemiştir. Böylece Cumhuriyetçilik eklektik, nevi şahsına münhasır; bu muhtevasıyla kimi arızalarla malûl bir düşünce ve yaklaşım biçimi halini almıştır. Çalışma bir siyasal sistem ve siyasal felsefe olan cumhuriyetçilik ile Türkiye bağlamında belirli toplum kesimleri açısından bir ideolojiye dönüşen cumhuriyetçilik arasındaki ilişkiyi/ilişkisizliği incelemeyi amaçlamaktır. Bu analizin önceliklerinden birisi de söz konusu ilişki/ilişkisizliğin Türkiye siyasal pratiğinde ne tür handikaplar ve sorunlar üretmiş olduğu, halen de üretebilecek olması sorunsalını irdelemektir.
Border natures
Authors: Λεβίδης Στέφανος
Published: September 2024

Η διατριβή διερευνά κριτικά τις περίπλοκες εμπλοκές της πολιτικής βίας και των περιβαλλοντικών διαδικασιών που έχουν ως αποτέλεσμα την κατασκευή των λεγόμενων «φυσικών» συνόρων: εθνικά σύνορα όπου η φύση θεωρείται ότι οριοθετεί και οχυρώνει το έθνος-κράτος. Λαμβάνοντας τα σύνορα της Ελλάδας ως μελέτη περίπτωσης, η διατριβή επιδιώκει να καταδείξει ότι, σε αντίθεση με τις αντιλήψεις περί φυσικών συνόρων ως χώρων που λειτουργούν χωρίς ανθρώπινη παρέμβαση, η υλικότητά τους και οι φυσικές διεργασίες στην πραγματικότητα υβριδοποιούνται και σμιλεύονται από το έθνος κράτος με σκοπό να επιελούν συγκεκριμένα θανατηφόρα καθήκοντα αποτροπής, αποκλεισμού και διαγραφής πληθυσμών. Το Μέρος Ι (Ghost Habitats) διερευνά την ορεινή, τριμερή συνοριακή περιοχή των Πρεσπών μεταξύ Ελλάδας, Βόρειας Μακεδονίας και Αλβανίας, για να εξετάσει πώς η οριοθέτηση και η επιβολή των συνόρων αναδιαμορφώνει τα περιφερειακά οικοσυστήματα για να τα μετατρέψει σε «άγρια». Σύνορα που υπόκεινται σε διαφορετικές έννομες τάξεις από την υπόλοιπη κυρίαρχη επικράτεια. Το Μέρος II (Anáchoma), που ερευνήθηκε από κοινού με τον συνάδελφο Ifor Duncan, θεωρεί τον ποταμό Έβρο μεταξύ Ελλάδας, Τουρκίας και Βουλγαρίας ως συσκευή συνοριακής βίας και συσκότισης, καθώς και ως φορέα που καταγράφει, αποθηκεύει και περιοδικά αποκαλύπτει αυτή η βία μέσω εποχιακών αλλαγών στον υδρολογικό της κύκλο. Το Μέρος ΙΙΙ (Grey Rocks, Black Waves) εξετάζει το αρχιπελαγικό σύνορο του Αιγαίου μεταξύ Ελλάδας και Τουρκίας, για να συζητήσει τον τρόπο με τον οποίο η γεωγραφικά και ιστορικά πυκνή υλικότητά του επιστρατεύεται ως αμυντική υποδομή ενάντια στη σύγχρονη μετανάστευση στη θάλασσα. Ενσωματώνοντας μια μεθοδολογία που δανείζεται από διαφορετικούς κλάδους όπως η εγκληματολογία, ο κινηματογράφος, η αρχαιολογία, η βοτανική και η ωκεανογραφία, η διατριβή αμφισβητεί τις κοινές κατανοήσεις των εδαφικών ορίων ως γραμμές που απλώς γράφονται σε φυσικά σκηνικά, για να συμπεριλάβουν κριτικά τους πολλαπλούς ανθρώπινους φορείς και τον τρόπο που αυτοί χρησιμοποιούν περιβαλλοντικές διαδικασίες για το έργο της συνοριακής οχύρωσης. Για να περιγράψει αυτά τα υβριδικά οριακά περιβάλλοντα, και τις σύνθετες αιτιώδεις σχέσεις που δημιουργούν, η διατριβή εισάγει τη λειτουργική έννοια της «συνοριακής φύσης»: ένα περίπλοκο σχεσιακό σύνολο αποτελούμενο απο φυσικές διαδικασίες, τον ίδιο τον χώρο του συνόρου, τεχνολογίες επιτήρησης, νομοθεσίες, καθώς και μορφές ζωής πέρα απο το ανθρώπινο - ποτάμια, κύματα και βουνά.