bluuebunny/crossref_metadata_2025 huggingface dataset:
Aryl hydrocarbon receptor-dependent toxicity by retene requires metabolic competence
Authors: Rude Christian I , Wilson Lindsay B , La Du Jane , Lalli Priscila M , Colby Sean M , Schultz Katherine J , Smith Jordan N , Waters Katrina M , Tanguay Robyn L
Published: August 2024

Polycyclic aromatic hydrocarbons (PAHs) are a class of organic compounds frequently detected in the environment with widely varying toxicities. Many PAHs activate the aryl hydrocarbon receptor (AHR), inducing the expression of a battery of genes, including xenobiotic metabolizing enzymes like cytochrome P450s (CYPs); however, not all PAHs act via this mechanism. We screened several parent and substituted PAHs in in vitro AHR activation assays to classify their unique activity. Retene (1-methyl-7-isopropylphenanthrene) displays Ahr2-dependent teratogenicity in zebrafish, but did not activate human AHR or zebrafish Ahr2, suggesting a retene metabolite activates Ahr2 in zebrafish to induce developmental toxicity. To investigate the role of metabolism in retene toxicity, studies were performed to determine the functional role of cyp1a, cyp1b1, and the microbiome in retene toxicity, identify the zebrafish window of susceptibility, and measure retene uptake, loss, and metabolite formation in vivo. Cyp1a-null fish were generated using CRISPR-Cas9. Cyp1a-null fish showed increased sensitivity to retene toxicity, whereas Cyp1b1-null fish were less susceptible, and microbiome elimination had no significant effect. Zebrafish required exposure to retene between 24 and 48 hours post fertilization (hpf) to exhibit toxicity. After static exposure, retene concentrations in zebrafish embryos increased until 24 hpf, peaked between 24 and 36 hpf, and decreased rapidly thereafter. We detected retene metabolites at 36 and 48 hpf, indicating metabolic onset preceding toxicity. This study highlights the value of combining molecular and systems biology approaches with mechanistic and predictive toxicology to interrogate the role of biotransformation in AHR-dependent toxicity.
Wedelolactone inhibits ferroptosis and alleviates hyperoxia-induced acute lung injury via the Nrf2/HO-1 signaling pathway
Authors: Li Kang , Wang Xiao-Qin , Liao Zhen-Liang , Liu Jun-Ya , Feng Bang-Hai , Ren Ying-Cong , Dai Ni-Nan , Yu Kun , Yu Hong , Chen Hua-Jun , Mei Hong , Qin Song
Published: August 2024

Hyperoxia-induced acute lung injury (HALI) is a complication of oxygen therapy. Ferroptosis is a vital factor in HALI. This paper was anticipated to investigate the underlying mechanism of wedelolactone (WED) on ferroptosis in HALI. The current study used hyperoxia to injure two models, one HALI mouse model and one MLE-12 cell injury model. We found that WED treatment attenuated HALI by decreasing the lung injury score and lung wet/dry (W/D) weight ratio and alleviating pathomorphological changes. Then, the inflammatory reaction and apoptosis in HALI mice and hyperoxia-mediated MLE-12 cells were inhibited by WED treatment. Moreover, WED alleviated ferroptosis with less iron accumulation and reversed expression alterations of ferroptosis markers, including MDA, GSH, GPX4, SLC7A11, FTH1, and TFR1 in hyperoxia-induced MLE-12 cells in vitro and in vivo. Nrf2-KO mice and Nrf2 inhibitor (ML385) decreased WED’s ability to protect against apoptosis, inflammatory response, and ferroptosis in hyperoxia-induced MLE-12 cells. Collectively, our data highlighted the alleviatory role of WED in HALI by activating the Nrf2/HO-1 pathway.
Feature-agnostic metabolomics for determining effective subcytotoxic doses of common pesticides in human cells
Authors: Rivera Emilio S , LeBrun Erick S , Breidenbach Joshua D , Solomon Emilia , Sanders Claire K , Harvey Tara , Tseng Chi Yen , Thornhill M Grace , Blackwell Brett R , McBride Ethan M , Luchini Kes A , Alvarez Marc , Williams Robert F , Norris Jeremy L , Mach Phillip M , Glaros Trevor G
Published: August 2024

Although classical molecular biology assays can provide a measure of cellular response to chemical challenges, they rely on a single biological phenomenon to infer a broader measure of cellular metabolic response. These methods do not always afford the necessary sensitivity to answer questions of subcytotoxic effects, nor do they work for all cell types. Likewise, boutique assays such as cardiomyocyte beat rate may indirectly measure cellular metabolic response, but they too, are limited to measuring a specific biological phenomenon and are often limited to a single cell type. For these reasons, toxicological researchers need new approaches to determine metabolic changes across various doses in differing cell types, especially within the low-dose regime. The data collected herein demonstrate that LC-MS/MS-based untargeted metabolomics with a feature-agnostic view of the data, combined with a suite of statistical methods including an adapted environmental threshold analysis, provides a versatile, robust, and holistic approach to directly monitoring the overall cellular metabolomic response to pesticides. When employing this method in investigating two different cell types, human cardiomyocytes and neurons, this approach revealed separate subcytotoxic metabolomic responses at doses of 0.1 and 1 µM of chlorpyrifos and carbaryl. These findings suggest that this agnostic approach to untargeted metabolomics can provide a new tool for determining effective dose by metabolomics of chemical challenges, such as pesticides, in a direct measurement of metabolomic response that is not cell type-specific or observable using traditional assays.
Characterization of Stemphylium Species Associated with Stemphylium Leaf Spot of Spinach (Spinacia oleracea)
Authors: Spawton Kayla A. , du Toit Lindsey J.
Published: August 2024

Stemphylium leaf spot can result in significant losses to spinach seed, processing, and fresh market crops. Stemphylium isolates (n = 1,775) collected from 2000 to 2022 from spinach seed, leaves, and seed crop stem residues were used to assess the diversity of species associated with spinach. Eleven Stemphylium species were identified based on cmdA sequences: S. vesicarium (63.6% of samples), S. beticola (48.9%), S. amaranthi (5.1%), S. eturmiunum (4.5%), S. astragali (4.0%), S. simmonsii (3.4%), and S. lucomagnoense, S. drummondii, S. gracilariae, S. lycopersici, and S. chrysanthemicola (each 0.6 to 1.7%). Only isolates of S. beticola, S. drummondii, and S. vesicarium were pathogenic to spinach. The incidence of spinach seed on which Stemphylium was observed ranged from 2.5 to 73.5% per seed lot, with S. vesicarium and S. beticola predominant. However, only 60.7 and 62.3% of isolates tested for these two species were pathogenic to spinach, respectively. Therefore, the incidence of Stemphylium species on spinach seed may not reflect accurately the risk of a seed lot carrying pathogenic isolates. Fused MAT1-1 and MAT1-2 genes were detected in isolates of S. vesicarium, but only MAT1-1 was detected in S. beticola isolates, which corroborates previous studies that have proposed the two species to be self-fertile. The duration of ascospore dispersal of S. beticola and S. vesicarium from spinach seed crop stem residues in western Washington, the primary region of spinach seed production in the United States, occurred from midwinter to late spring or early fall, potentially serving as inoculum for the next season’s spinach seed crops. Growers should incorporate residues into the soil after harvest to reduce inoculum production of these pathogens on spinach seed crop residues.
Wind-Mediated Dispersal of Beet Leafhoppers and Pine Pollen in Southern Idaho
Authors: Strausbaugh Carl A. , Wenninger Erik J. , Jackson Laurie K. , Vincill Eric
Published: August 2024

The management of beet leafhoppers (BLHs) is important for disease control since BLHs can vector important plant pathogens such as curly top viruses and phytoplasmas in southern Idaho. Historical data for southern Idaho suggests that BLHs need approximately 130 growing degree days (GDDs; 12.8°C base) to initiate dispersal and around 382 GDDs until they reach peak dispersal. A recent study in southern Idaho identified large peak dispersal events of BLHs on 19 May 2020 and 2 June 2021 in Elmore County near Mt. Home, ID. Historically, BLHs have been thought to originate from local areas. However, based on GDDs and dispersal numbers under optimal conditions for Mt. Home, the BLHs likely did not originate from local areas. Data for wind and pine pollen dispersal combined with GDDs for areas known to contain BLHs suggest that the BLHs could have originated outside the local area and possibly up to 142 to 515 km away. At least five conditions appear to be necessary for observation of BLH dispersal into southern Idaho: a wind event must occur (35 km/h average hourly wind speed), dispersal temperature threshold (16 to 18°C) must be met, >130 GDDs must be accumulated to initiate dispersal, daily peak temperatures should reach 24°C, and attractive BLH vegetation such as Russian thistle must be present. Combining wind event forecasts with temperature parameters in the future may make it possible to provide targeted timely insecticide sprays for BLH control.

[Formula: see text] The author(s) have dedicated the work to the public domain under the Creative Commons CC0 “No Rights Reserved” license by waiving all of his or her rights to the work worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law, 2024.
Blocking CTLA‐4 promotes pressure overload‐induced heart failure via activating Th17 cells
Authors: Shang An‐Qi , Yu Chang‐Jiang , Bi Xin , Jiang Wei‐Wei , Zhao Ming‐Luan , Sun Yu , Guan Hong , Zhang Zhi‐Ren
Published: August 2024

Targeting cytotoxic T‐lymphocyte‐associated antigen‐4 (CTLA‐4) with specific antibody offers long‐term benefits for cancer immunotherapy but can cause severe adverse effects in the heart. This study aimed to investigate the role of anti‐CTLA‐4 antibody in pressure overload‐induced cardiac remodeling and dysfunction. Transverse aortic constriction (TAC) was used to induce cardiac hypertrophy and heart failure in mice. Two weeks after the TAC treatment, mice received anti‐CTLA‐4 antibody injection twice a week at a dose of 10 mg/kg body weight. The administration of anti‐CTLA‐4 antibody exacerbated TAC‐induced decline in cardiac function, intensifying myocardial hypertrophy and fibrosis. Further investigation revealed that anti‐CTLA‐4 antibody significantly elevated systemic inflammatory factors levels and facilitated the differentiation of T helper 17 (Th17) cells in the peripheral blood of TAC‐treated mice. Importantly, anti‐CTLA‐4 mediated differentiation of Th17 cells and hypertrophic phenotype in TAC mice were dramatically alleviated by the inhibition of interleukin‐17A (IL‐17A) by an anti‐IL‐17A antibody. Furthermore, the C‐X‐C motif chemokine receptor 4 (CXCR4) antagonist AMD3100, also reversed anti‐CTLA‐4‐mediated cardiotoxicity in TAC mice. Overall, these results suggest that the administration of anti‐CTLA‐4 antibody exacerbates pressure overload‐induced heart failure by activating and promoting the differentiation of Th17 cells. Targeting the CXCR4/Th17/IL‐17A axis could be a potential therapeutic strategy for mitigating immune checkpoint inhibitors‐induced cardiotoxicity.
Activation of the G protein‐coupled sulfakinin receptor inhibits blood meal intake in the mosquito Aedes aegypti
Authors: Jiang Linlong , Xie Xiao Bing , Zhang Lei , Tang Yu , Zhu Xiaojing , Huang Yuqi , Hong Yue , Hansson Bill S. , Cui Zong Jie , Han Qian
Published: August 2024

Little is known about the blood‐feeding physiology of arbovirus vector Aedes aegypti although this type of mosquito is known to transmit infectious diseases dengue, Zika, yellow fever, and chikungunya. Blood feeding in the female A. aegypti mosquito is essential for egg maturation and for transmission of disease agents between human subjects. Here, we identify the A. aegypti sulfakinin receptor gene SKR from the A. aegypti genome and show that SKR is expressed at different developmental stages and in varied anatomical localizations in the adult mosquito (at three days after eclosion), with particularly high expression in the CNS. Knockingdown sulfakinin and sulfakinin receptor gene expression in the female A. aegypti results in increased blood meal intake, but microinjection in the thorax of the sulfakinin peptide 1 and 2 both inhibits dose dependently blood meal intake (and delays the time course of blood intake), which is reversible with receptor antagonist. Sulfakinin receptor expressed ectopically in mammalian cells CHO‐K1 responds to sulfakinin stimulation with persistent calcium spikes, blockable with receptor antagonist. These data together suggest that activation of the Gq protein‐coupled (i.e., calcium‐mobilizing) sulfakinin receptor inhibits blood meal intake in female A. aegypti mosquitoes and could serve as a strategic node for the future control of A. aegypti mosquito reproduction/population and disease transmission.
Prediction of Length of Stay After Colorectal Surgery Using Intraoperative Risk Factors
Authors: Huisman Daitlin Esmee , Ingwersen Erik Wouter , Luttikhold Joanna , Slooter Gerrit Dirk , Kazemier Geert , Daams Freek ,   LekCheck Study Group
Published: August 2024

Objective:

The primary objective of this study was to develop a length of stay (LOS) prediction model.

Background:

Predicting the LOS is crucial for patient care, planning, managing expectations, and optimizing hospital resources. Prolonged LOS after colorectal surgery is largely influenced by complications, and an accurate prediction model could significantly benefit patient outcomes and healthcare efficiency.

Methods:

This study included patients who underwent colorectal surgery in 14 different hospitals between January 2016 and December 2020. Two distinct random forest models were developed: one solely based on preoperative variables (preoperative prediction model [PP model]) and the other incorporating both preoperative and intraoperative variables (intraoperative prediction model [IP model]). Both models underwent validation using 10-fold cross-validation. The discriminative power of the model was assessed using the area under the curve (AUC), and calibration was evaluated using a calibration curve. The 2 developed models were compared using DeLong test.

Results:

A total of 2140 patients were included in the analysis. After internal validation, the PP model achieved an AUC of 0.75 (95% confidence interval [CI]: 0.73–0.77), and the IP model achieved an AUC of 0.84 (95% CI: 0.82–0.85). The difference in discrimination between the 2 models was statistically significant (DeLong test, P < 0.001). Both models exhibited good calibration.

Conclusions:

Incorporating intraoperative parameters enhances the accuracy of the predictive model for LOS after colorectal surgery. Improving LOS prediction can assist in managing the increasing number of patients and optimizing the allocation of healthcare resources.
Use of Standardized Nursing Terminologies to Capture Social Determinants of Health Data
Authors: Olsen Jeanette M. , Panasuk Emma J. , Swenson Lily J. , Williams Marty
Published: August 2024

Addressing social determinants of health in nursing care is important for improving health outcomes and reducing health inequities. Using standardized nursing terminologies to capture this information generates sharable data that can be used to achieve these goals and create new knowledge. The purpose of this integrative review was to examine use of standardized nursing terminologies for collecting social determinants of health data in nursing research and practice. The CINAHL, MEDLINE, and Web of Science databases were searched using the terms “social determinants of health” [and] “nursing” [and] “standardized terminology” or names for each of the 12 American Nurses Association–approved terminologies. Limiters included peer-reviewed and English language. After removal of duplicates, 120 articles were found and screened for relevance and quality using a three-step process. This yielded a final sample of seven articles. Article data were extracted and analyzed for themes. In all articles, retrospective, observational, or secondary analysis research designs were used to analyze previously collected data from large, deidentified datasets or research studies. The Omaha System was the only standardized nursing terminology represented in the sample. All operational definitions of social determinants of health included behavioral items. In most studies, a social determinants of health index score was calculated, and data were analyzed using descriptive statistics and visualization methods. Results reported across the articles were diverse; some themes were identified. This review revealed published literature on this topic is limited. More quality improvement and multisite studies that examine the use of standardized nursing terminologies by nurses to collect and use social determinants of health data are needed.
Expanding access to postpartum contraception
Authors: Cooper Michelle , Black Kirsten , Cameron Sharon
Published: August 2024

Purpose of review

Women are particularly vulnerable to unintended pregnancy in the 12 months following a birth. Improving access to postpartum contraception within maternity settings can prevent unintended and closely spaced births, improving the health of mother and child. This review will summarize the recent research in postpartum contraception (PPC), building on existing knowledge and developments in this field.

Recent findings

Current models of postpartum contraceptive provision may not adequately meet women's needs. The COVID-19 pandemic led to changes in postpartum contraceptive provision, with an increasing emphasis placed on maternity services. Antenatal contraceptive discussion is associated with increased postpartum contraceptive planning and uptake of methods after birth. Digital health interventions may be a useful tool to support information about contraception. The most effective long-acting reversible contraceptive (LARC) methods, such as the intrauterine device (IUD) and implant, can be challenging to provide in the maternity setting because of availability of trained providers. Postpartum IUD insertion remains relatively under-utilized, despite evidence supporting its safety, efficacy and cost-effectiveness.

Antenatal information needs to be partnered with access to the full range of methods immediately after birth to reduce barriers to PPC uptake. Training and education of maternity providers is central to successful implementation of PPC services.
Unveiling the uncommon: a case report of avascular necrosis in the triquetrum bone without trauma
Authors: Sallameh Jafar , Mansour Majd , Mansour Abdallah N. , Afif Ali , Klayshe Abdalkareem , Shahin Emad
Published: August 2024

Introduction and importance:

Avascular necrosis (AVN) is a rare occurrence in the carpal region, especially in the triquetrum bone, which presents a diagnostic puzzle due to its infrequency and lack of trauma history. This case study explores the signs, diagnosis, and treatment of AVN in a healthy 22-year-old individual, emphasizing the need for early identification using suitable imaging methods.

Case presentation:

A 22-year-old patient complained of persistent wrist pain, specifically on the ulnar side, without any history of injury. Clinical examination revealed tenderness without signs of inflammation, with normal sensation and movement. Initial X-ray results were inconclusive, prompting further investigation with MRI, which showed a decrease in signal intensity in the triquetrum bone, leading to the diagnosis of AVN.

Clinical discussion:

The development of AVN involves compromised blood flow, often due to various factors. While AVN affecting carpal bones is uncommon, the triquetrum bone’s robust blood supply typically protects against such conditions. However, this case highlights an exceptional occurrence. Gelberman’s classification underscores the triquetrum’s vascular nature, explaining why AVN is rare in this bone. MRI plays a crucial role in detecting AVN, especially when symptoms do not align with X-ray findings.

Conclusion:

Avascular necrosis should be considered in carpal bones, even without a history of trauma, with a focus on MRI for early detection. Although AVN of the triquetrum is rare, this case underscores the importance of timely recognition and conservative management. Further research is necessary to establish optimal treatment strategies for this unusual presentation.
Nurse Well-Being and Patient-Specific Outcomes
Authors: Pryor Stacy , Hanson Ardis , Chan Janet , Brunner Hope , Letourneau Rayna , Menon Usha
Published: August 2024

Background:

The health and well-being of the nursing workforce has received recent attention due to nurse attrition and the critical nurse shortages projected across the country. A nurse’s well-being may impact patient outcomes.

Purpose:

The purpose of this scoping review was to assess the association between nurse well-being factors and specific patient outcomes.

Methods:

The preferred reporting items for systematic reviews and meta-analyses (PRISMA) PRISMA Scoping Review protocol and 2020 reporting guidelines were utilized in this review.

Results:

Staffing, environment, physical health, and mental health of nurses were correlated to specific adverse patient outcomes among the 97 articles included in the final review. The majority of the articles reported significant findings.

Conclusions:

Patient outcomes were reviewed as discrete events in the articles examined. With mixed results found on key patient outcomes, future research requires more in-depth investigation into the role nurse well-being has on patient outcomes.
A Case for Open Pedagogy in Nursing Education
Authors: Petrovic Kristin , Perry Beth , Walsh Pamela
Published: August 2024

Background:

Open pedagogy increases access to equitable nursing education with its commitment to the scholarship of “teaching and learning” and critically framed, student-centered, relational, and open knowledge principles.

Purpose:

This study examined the operation of and factors that nurture and challenge the practice of open pedagogy in an undergraduate digital distance nursing education program.

Methods:

An exploratory qualitative methodology was used to examine linkages between open pedagogy and a nursing education program in an open digital distance Canadian university. A critical realist research paradigm provided the framework for the study.

Results:

Our findings shed light on how open pedagogy is practiced in relation to its 5 principles and delve into the major themes of nurse educator agency, course design, and institutional structure.

Conclusions:

The study addresses a dearth in the literature by exploring the potential of open pedagogy to increase access to meaningful and critically framed nursing education.
Qualitative Analysis of an Integrated Curricular Strategy to Develop Health Policy Advocacy
Authors: Cropley Stacey , Hughes Monica , Belcik Kim
Published: August 2024

Background:

Baccalaureate nursing programs have primarily taught policy advocacy using knowledge related to social and health policy and political systems. Creative curricular strategies have not been widely implemented to prepare nursing students to address health policy advocacy.

Purpose:

A qualitative study explored the impact of an innovative intervention to integrate leadership competencies with population health policy advocacy in an undergraduate nursing curriculum.

Method:

The intervention consisted of a 5-part, unfolding assignment across leadership and population health courses. A phenomenological theoretical approach was used to understand and describe students’ perceptions about the intervention and impact on student readiness to engage in health policy advocacy through narrative survey responses.

Results:

Student understanding of policy processes improved postintervention. Students recognized that systems level thinking and developing policy solutions for population health issues were important attainable activities for nurses. This study demonstrates the significance of providing integrated curricula to develop student engagement in policy advocacy.

Conclusion:

Nurse educators should explore innovative policy advocacy curricula to prepare baccalaureate graduates to address health equity.
Socioeconomic Disadvantage, Neighborhood Belonging, and Inflammation Among Adolescents
Authors: Chen Michelle A. , Chen Edith , Gallivan Shanti U. , Brody Elizabeth J. , Passarelli Veronica , Miller Gregory E.
Published: August 2024

Objective

Childhood socioeconomic disadvantage is associated with a host of adverse health outcomes across the lifespan. However, there is increasing interest in identifying factors that may promote resilience to disadvantage’s effects on health. One promising candidate in this regard is a sense of neighborhood belonging, which could offset health risks by providing a sense of connection to others, as well as a sense of belonging to a community larger than oneself.

Methods

In a sample of 245 adolescents (age: mean [standard deviation] = 15.98 [0.54] years; sex: 64.1% female; race: 41.6% White, 37.6% Black/African American, 9.8% Other; ethnicity: 68.6% non-Hispanic), we examined neighborhood belonging as a moderator of the relationship between socioeconomic disadvantage (measured on a 0- to 5-point scale, mean [standard deviation] = 1.21 [1.36]) and low-grade inflammation (measured via a composite of circulating inflammatory biomarkers including IL-6, IL-8, IL-10, TNF-α, CRP, and suPAR). Covariates included age, sex, race/ethnicity, and pubertal status.

Results

Neighborhood belonging buffered the relationship between socioeconomic disadvantage and low-grade inflammation, a key mechanistic pathway to multiple chronic diseases. Specifically, there was a positive relationship between socioeconomic disadvantage and low-grade inflammation among individuals with low neighborhood belonging, but not among individuals with high neighborhood belonging.

Conclusions

These findings suggest that neighborhood belonging is one type of social connection factor that can mitigate the relationship between socioeconomic disadvantage and low-grade inflammation in youth.
Consequences of low-level viremia among women with HIV in the United States
Authors: Aldredge Amalia , Mehta C. Christina , Lahiri Cecile D. , Schneider Michael F. , Alcaide Maria L. , Anastos Kathryn , Plankey Michael , French Audrey L. , Floris-Moore Michelle , Tien Phyllis C. , Dionne Jodie , Dehovitz Jack , Collins Lauren F. , Sheth Anandi N.
Published: August 2024

Objective:

Investigate the outcomes of women with HIV (WWH) with low-level viremia (LLV).

Design:

The prevalence of LLV and potential clinical sequelae, such as virologic failure and non-AIDS comorbidity (NACM) development, are poorly characterized among WWH.

Methods:

We analyzed data from the Women's Interagency HIV Study among WWH enrolled from 2003 to 2020 who reported antiretroviral therapy use at least 1 year followed by an HIV-1 viral load less than 200 copies/ml. Consecutive viral load measurements from four semi-annual visits were used to categorize women at baseline as having: virologic suppression (all viral load undetectable), intermittent LLV (iLLV; nonconsecutive detectable viral load up to 199 copies/ml), persistent LLV (pLLV; at least two consecutive detectable viral load up to 199 copies/ml), or virologic failure (any viral load ≥200 copies/ml). Adjusted hazard ratios quantified the association of virologic category with time to incident virologic failure and multimorbidity (≥2 of 5 NACM) over 5-year follow-up.

Results:

Of 1598 WWH, baseline median age was 47 years, 64% were Black, 21% Hispanic, and median CD4+ cell count was 621 cells/μl. After excluding 275 women (17%) who had virologic failure at baseline, 58, 19, and 6% were categorized as having virologic suppression, iLLV, and pLLV, respectively. Compared with WWH with virologic suppression, the adjusted hazard ratio [aHR; 95% confidence interval (CI)] for incident virologic failure was 1.88 (1.44–2.46) and 2.51 (1.66–3.79) for iLLV and pLLV, respectively; and the aHR for incident multimorbidity was 0.81 (0.54–1.21) and 1.54 (0.88–2.71) for iLLV and pLLV, respectively.

Conclusion:

Women with iLLV and pLLV had an increased risk of virologic failure. Women with pLLV had a trend towards increased multimorbidity risk.
Outcomes of Adult Right Graft Living Donor Liver Transplantation Utilizing the Robotic Platform-integrated Real-time Indocyanine Green Fluorescence Cholangiography Compared to the Open Approach
Authors: Raptis Dimitri A. , Vashist Yogesh K. , Kulkarni Rugved , Alabbad Saleh , Elsheikh Yasser , Alnemary Yasir , Malagò Massimo , Broering Dieter C.
Published: August 2024

Objective:

This study aimed to assess short-term biliary outcomes in adult living donor liver transplants using right grafts, comparing robotic surgery with real-time indocyanine green fluorescence cholangiography for optimal hilar plate transection, against the conventional open approach.

Background:

Determining the optimal transection plane through the hilar plate is crucial in donor hepatectomies, impacting outcomes significantly.

Methods:

From 2011 to 2023, a total of 839 right graft living donor hepatectomies were performed, with 414 (49%) performed via the open approach and 425 (51%) utilizing the robotic platform.

Results:

The magnetic resonant cholangiopancreatography predictions correlated moderately with the actual count of graft ducts (r=0.57, P<0.001). Out of all 839 right donor hepatectomies, 321 (44%) were single duct grafts, of which 193/425 (49%) were retrieved with the robotic while 128/414 (38%) were with the open approach (OR: 1.58, 95% CI: 1.16–2.14), P=0.003). Overall, 50 (6%) of the donors developed a biliary complication during their hospital stay, of whom 38 (9%) were grafts retrieved with the open, while 13 (3%) with the robotic approach (OR: 0.31, 95% CI: 0.15–0.61, P<0.001). Similarly, 63 (15%) of the adult recipients developed a biliary complication of any severity when grafts were retrieved with the open approach compared to 35 (8%) with the robotic approach (OR: 0.50, 95% CI: 0.31–0.79), P=0.002).

Conclusions:

The robotic platform with integrated real-time indocyanine green fluorescence cholangiography during right donor hepatectomy offers improved safety for the donor by accurately addressing the right hilar corridor, resulting in fewer graft ducts and fewer complications for the donor and recipient when compared to the standard open approach.
Optimal Treatment Strategies for cT2 Staged Adenocarcinoma of the Esophagus and the Gastroesophageal Junction
Authors: Wirsik Naita M. , Kooij Cezanne D. , Dempster Niall , Crnovrsanin Nerma , Donlon Noel E. , Uzun Eren , Bhanot Kunal , Nienhüser Henrik , Polette Daniela , Kewani Kammy , Grimminger Peter , Reim Daniel , Seyfried Florian , Fuchs Hans F. , Gisbertz Suzanne S. , Germer Christoph-Thomas , Ruurda Jelle P. , Klevebro Fredrik , Schröder Wolfgang , Nilsson Magnus , Reynolds John V. , Van Berge Henegouwen Mark I. , Markar Sheraz , Van Hillegersberg Richard , Schmidt Thomas , Bruns Christiane J.
Published: August 2024

Objective:

To evaluate outcomes after primary surgery (PS) or neoadjuvant treatment followed by surgery (NAT/S) in cT2 staged adenocarcinomas of the esophagus (EAC) and gastroesophageal junction (GEJ), a multinational high-volume center study was undertaken.

Background:

The optimal treatment approach with either NAT/S or PS for clinically staged cT2cNany or cT2N0 EAC and GEJ remains unknown due to the lack of randomized controlled trials.

Methods:

A retrospective analysis of prospectively maintained databases from 10 centers was performed. Between January 2012 and August 2023, 645 patients who fulfilled inclusion criteria of GEJ Siewert type I, II, or EAC with cT2 status at diagnosis underwent PS or NAT/S with curative intent. The primary endpoint was overall survival (OS).

Results:

In the cT2cNany cohort, 192 patients (29.8%) underwent PS and 453 (70.2%) underwent NAT/S. In all cT2cN0 patients (n = 333), NAT/s remained the more frequent treatment (56.2%). Patients undergoing PS were in both cT2 cohorts older (P < 0.001) and had a higher American Society of Anesthesiologists classification (P < 0.05). R0 resection showed no differences between NAT/S and PS in both cT2 cohorts (P > 0.4).

Median OS was 51.0 months in the PS group (95% CI: 31.6–70.4) versus 114.0 months (95% CI: 53.9–174.1) in the NAT/S group (P = 0.003) of cT2cNany patients. For cT2cN0 patients, NAT/S was associated with longer OS (P = 0.002) and disease-free survival (P = 0.001). After propensity score matching of the cT2N0 patients, survival benefit for NAT/S remained (P = 0.004). Histopathology showed that 38.1% of cT2cNany and 34.2% of cT2cN0 patients were understaged.

Conclusions:

Due to the unreliable identification of cT2N0 disease, all patients should be offered a multimodal therapeutic approach.
Machine Learning-Based Algorithm for the Early Prediction of Postoperative Hypocalcemia Risk After Thyroidectomy
Authors: Muller Olivier , Bauvin Pierre , Bacoeur Ophélie , Michailos Théo , Bertoni Maria-Vittoria , Demory Charles , Marciniak Camille , Chetboun Mikael , Baud Grégory , Raffaelli Marco , Caiazzo Robert , Pattou Francois
Published: August 2024

Objective:

We used machine learning to develop and validate a multivariable algorithm allowing the accurate and early prediction of postoperative hypocalcemia risk.

Background:

Postoperative hypocalcemia is frequent after total thyroidectomy. An early and accurate individualized prediction of the risk of hypocalcemia could guide the selective prescription of calcium supplementation only to patients most likely to present with hypocalcemia after total thyroidectomy.

Methods:

This retrospective study enrolled all patients undergoing total thyroidectomy in a single referral center between November 2019 and March 2022 (derivation cohort) and April 2022 and September 2022 (validation cohort). The primary study outcome was postoperative hypocalcemia (serum calcium under 80 mg/L). Exposures were multiple clinical and biological variables prospectively collected and analyzed with various machine learning methods to develop and validate a multivariable prediction algorithm.

Results:

Among 610/118 participants in the derivation/validation cohorts, 100 (16.4%)/26 (22%) presented postoperative hypocalcemia. The most accurate prediction algorithm was obtained with random forest and combined intraoperative parathyroid hormone measurements with 3 clinical variables (age, sex, and body mass index) to calculate a postoperative hypocalcemia risk for each patient. After multiple cross-validation, the area under the receiver operative characteristic curve was 0.902 (0.829–0.970) in the derivation cohort, and 0.928 (95% CI: 0.86; 0.97) in the validation cohort. Postoperative hypocalcemia risk values of 7% (low threshold) and 20% (high threshold) had, respectively, a sensitivity of 92%, a negative likelihood ratio of 0.11, a specificity of 90%, and a positive of 7.6 for the prediction of postoperative hypocalcemia.

Conclusions:

Using machine learning, we developed and validated a simple multivariable model that allowed the accurate prediction of postoperative hypocalcemia. The resulting algorithm could be used at the point of care to guide clinical management after total thyroidectomy.
Active head movements contribute to spatial updating across gaze shifts
Authors: Bayer Manuel , Zimmermann Eckart
Published: August 2024

Keeping visual space constant across movements of the eye and head is a not yet fully understood feature of perception. To understand the mechanisms that update the internal coordinates of space, research has mostly focused on eye movements. However, in natural vision, head movements are an integral part of gaze shifts that enlarge the field of vision. Here, we directly compared spatial updating for eye and head movements. In a virtual reality environment, participants had to localize the position of a stimulus across the execution of a gaze shift. We found that performing head movements increased the accuracy of spatial localization. By manipulating the speed of the visual scene displacement that a head movement produced, we found that spatial updating takes into account the sensorimotor contingencies of vision. When we presented gaze-contingent visual motion, subjects overestimated the position of stimuli presented across gaze shifts. The overestimation decreased if subjects were allowed to perform eye movements during the head movement. We conclude that head movements contribute to stabilizing visual space across gaze shifts and that contingencies of head movements, rather than being cancelled, facilitate the updating.
Do large language models have a legal duty to tell the truth?
Authors: Wachter Sandra , Mittelstadt Brent , Russell Chris
Published: August 2024

Careless speech is a new type of harm created by large language models (LLM) that poses cumulative, long-term risks to science, education and shared social truth in democratic societies. LLMs produce responses that are plausible, helpful and confident, but that contain factual inaccuracies, misleading references and biased information. These subtle mistruths are poised to cumulatively degrade and homogenize knowledge over time. This article examines the existence and feasibility of a legal duty for LLM providers to create models that ‘tell the truth’. We argue that LLM providers should be required to mitigate careless speech and better align their models with truth through open, democratic processes. We define careless speech against ‘ground truth’ in LLMs and related risks including hallucinations, misinformation and disinformation. We assess the existence of truth-related obligations in EU human rights law and the Artificial Intelligence Act, Digital Services Act, Product Liability Directive and Artificial Intelligence Liability Directive. Current frameworks contain limited, sector-specific truth duties. Drawing on duties in science and academia, education, archives and libraries, and a German case in which Google was held liable for defamation caused by autocomplete, we propose a pathway to create a legal truth duty for providers of narrow- and general-purpose LLMs.
Simulation studies of social systems: telling the story based on provenance patterns
Authors: Wilsdorf Pia , Reinhardt Oliver , Prike Toby , Hinsch Martin , Bijak Jakub , Uhrmacher Adelinde M.
Published: August 2024

Social simulation studies are complex. They typically combine various data sources and hypotheses about the system’s mechanisms that are integrated by intertwined processes of model building, simulation experiment execution and analysis. Various documentation approaches exist to increase the transparency and traceability of complex social simulation studies. Provenance standards enable the formalization of information on sources and activities, which contribute to the generation of an entity, in a queryable and computationally accessible manner. Provenance patterns can be defined as constraints on the relationships between specific types of activities and entities of a simulation study. In this paper, we refine the provenance pattern-based approach to address specific challenges of social agent-based simulation studies. Specifically, we focus on the activities and entities involved in collecting and analysing primary data about human decisions, and the collection and quality assessment of secondary data. We illustrate the potential of this approach by applying it to central activities and results of an agent-based simulation project and by presenting its implementation in a web-based tool.
Inbreeding avoidance, competition and natal dispersal in a pair-living, genetically monogamous mammal, Azara’s owl monkey (
Aotus azarae
)
Authors: Corley Margaret , Garcia de la Chica Alba , van der Heide Griëtte , Rotundo Marcelo , Caccone Adalgisa , Fernandez-Duque Eduardo
Published: August 2024

Natal dispersal is an important life-history stage influencing individual fitness, social dynamics of groups and population structure. Understanding factors influencing dispersal is essential for evaluating explanations for the evolution and maintenance of social organization, including parental care and mating systems. The social and mating systems of Azara’s owl monkeys (
Aotus azarae
) are infrequent among mammals; these primates are pair-living, serially and genetically monogamous and both sexes directly care for offspring. To evaluate the role that competition and inbreeding avoidance play in shaping dispersal patterns, we used 25 years of demographic and genetic data to examine how variation in timing of natal dispersal is related to social (adult replacements, step-parents, births and group size) and ecological factors (seasonal abundance of resources) in a wild population of
A. azarae
in Formosa, Argentina. We found that all males and females dispersed from their natal groups, but subadults delayed dispersal when a step-parent of the opposite sex joined the group, indicating that they may perceive these step-parents as potential mates. Dispersal was more probable when resource conditions were better, regardless of age. Overall, agonistic conflict over food and potential mates with adults in the natal group, as well as inbreeding avoidance, contribute to regulating dispersal.
Behaviour of dissolved inorganic salts in the cooling water of a nuclear power plant open recirculation system and formation of water discharge
Authors: Biedunkova Olha , Kuznietsov Pavlo , Gandziura Volodymyr
Published: August 2024

The main problem in the operation of nuclear power plants (NPPs) is the scale formation of mineral impurities in an open recirculating system (ORS). The discharge of water from an ORS into natural water bodies can alter the chemical equilibrium of wastewater components, necessitating continuous monitoring. The purpose of this study was to analyse the behaviour of dissolved inorganic salts (DIS) in water within an ORS during water treatment, using the Rivne Nuclear Power Plant (RNPP) as a case study. Moreover, the analysis impact of their discharge with return water in the Styr River. The DIS concentration has a significant impact on the efficiency of the system and the environmental of an ORS power plant. Altogether, each of the DIS components was analysed separately using the standard measurement methods, statistical methods of data processing and correlation analysis. In addition, the annual discharge of the DIS components was calculated, and the amount of discharge was assessed for compliance with the maximum discharge limit. Thus, the impact of the formation of DIS and the variations in their concentration levels upon the discharge of wastewater into a natural water body were examined.
C. perfringens enterotoxin-claudin pore complex: Models for structure, mechanism of pore assembly and cation permeability
Authors: Nagarajan Santhosh Kumar , Weber Joy , Roderer Daniel , Piontek Jörg
Published: August 2024

The pore-formingClostridium perfringensenterotoxin (CPE), a common cause of foodborne diseases, facilitates Ca2+influx in enterocytes, leading to cell damage. Upon binding to certain claudins (e.g. claudin-4), CPE forms oligomeric pores in the cell membrane. While the CPE-claudin interaction mechanism is well known, the structure and assembly of the pore complex remain elusive. Here, using AlphaFold2 complex prediction, structure alignment, and molecular dynamics simulations, we generated models of pre-pore and pore states of the CPE-claudin-4 complex sequentially addressing CPE-claudin, CPE-CPE, and claudin-claudin interactions, along with CPE conformational changes. The CPE pore is a hexameric variation of the typically heptameric pore stem and cap architecture of aerolysin-like β-barrel pore-forming toxins (β-PFT). The pore is lined with three hexa-glutamate rings, which differs from other β-PFTs and confers CPE-specific cation selectivity of the pore. Additionally, the pore center is indicated to be anchored by a dodecameric claudin ring formed by a cis-interaction variant of an interface found in claudin-based tight junction strands. Mutation of an interfacial residue inhibited CPE-mediated cell damagein vitro. We propose that this claudin ring constitutes an anchor for a twisting mechanism that drives extension and membrane insertion of the CPE β-hairpins. Our pore model agrees with previous key experimental data providing insights into the structural mechanisms of CPE-mediated cytotoxic cation influx.
Multiplex genome editing eliminates the Warburg Effect without impacting growth rate in mammalian cells
Authors: Hefzi Hooman , Martínez-Monge Iván , Marin de Mas Igor , Cowie Nicholas Luke , Toledo Alejandro Gomez , Noh Soo Min , Karottki Karen Julie la Cour , Decker Marianne , Arnsdorf Johnny , Camacho-Zaragoza Jose Manuel , Kol Stefan , Schoffelen Sanne , Pristovšek Nuša , Hansen Anders Holmgaard , Miguez Antonio A. , Bjorn Sara Petersen , Brøndum Karen Kathrine , Javidi Elham Maria , Jensen Kristian Lund , Stangl Laura , Kreidl Emanuel , Kallehauge Thomas Beuchert , Ley Daniel , Ménard Patrice , Petersen Helle Munck , Sukhova Zulfiya , Bauer Anton , Casanova Emilio , Barron Niall , Malmström Johan , Nielsen Lars K. , Lee Gyun Min , Kildegaard Helene Faustrup , Voldborg Bjørn G. , Lewis Nathan E.
Published: August 2024

The Warburg effect is ubiquitous in proliferative mammalian cells, including cancer cells, but poses challenges for biopharmaceutical production, as lactate accumulation inhibits cell growth and protein production. Previous efforts to eliminate lactate production via knockout have failed in mammalian bioprocessing since lactate dehydrogenase has proven essential. However, here we eliminated the Warburg effect in Chinese hamster ovary (CHO) and HEK293 cells by simultaneously knocking out lactate dehydrogenase and regulators involved in a negative feedback loop that typically inhibits pyruvate conversion to acetyl-CoA. In contrast to long-standing assumptions about the role of aerobic glycolysis, Warburg-null cells maintain wildtype growth rate while producing negligible lactate. Further characterization of Warburg-null CHO cells showed a compensatory increase in oxygen consumption, a near total reliance on oxidative metabolism, and higher cell densities in fed-batch cell culture. These cells remained amenable for production of diverse biotherapeutic proteins, reaching industrially relevant titers and maintaining product glycosylation. Thus, the ability to eliminate the Warburg effect is an important development for biotherapeutic production and provides a tool for investigating a near-universal metabolic phenomenon.
SleepSatelightFTC: A Lightweight and Interpretable Deep Learning Model for Single-Channel EEG-Based Sleep Stage Classification
Authors: Ito Aozora , Tanaka Toshihisa
Published: August 2024

Sleep scoring by experts is necessary for diagnosing sleep disorders. To this end, electroencephalography (EEG) is an essential physiological examination. As manual sleep scoring based on EEG signals is time-consuming and labor-intensive, an automated method is highly desired. One promising automation technology is deep learning, which has performed well or better than experts in sleep scoring. However, deep learning lacks adequate interpretability, which is crucial for ensuring safety and accountability, especially for complex inference processes. We propose SleepSatelightFTC, a lightweight model that achieves comparable performance to state-of-the-art models with only one-third of their parameters. Based on the rules for sleep scoring, self-attention is applied to each of the time- and frequency-domain inputs, a raw EEG signal and its amplitude spectrum. The simple method of continuously connecting the intermediate outputs of the epoch-wise model has resulted in a highly lightweight architecture. On the Sleep- EDF-78 dataset, our model achieves an accuracy of 84.8% and a kappa coefficient of 0.787 while requiring significantly fewer parameters (0.47x10^6) compared to existing models (1.3--4.54x10^6). The visualization of feature importance obtained from self-attention confirms that the proposed model learns representative waveform features, including K-complexes and sleep spindles.