bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding lactation policies and resources across a university system: survey and document review
Authors: Ashby Emily L. , Donepudi Sritha , Padilla Heather M.
Published: May 2024

Background

In the U.S., employees often return to work within 8–12 weeks of giving birth, therefore, it is critical that workplaces provide support for employees combining breastfeeding and work. The Affordable Care Act requires any organization with more than 50 employees to provide a space other than a restroom to express breastmilk and a reasonable amount of time during the workday to do so. States and worksites differ in the implementation of ACA requirements and may or may not provide additional support for employees combining breastfeeding and work. The purpose of this study was to conduct an analysis of the policies and resources available at 26 institutions within a state university system to support breastfeeding when employees return to work after giving birth.

Methods

Survey data was collected from Well-being Liaisons in the human resources departments at each institution. In addition, we conducted a document review of policies and online materials at each institution. We used univariate statistics to summarize survey results and an inductive and deductive thematic analysis to analyze institutional resources available on websites and in policies provided by the liaisons.

Results

A total of 18 (65.3%) liaisons participated in the study and revealed an overall lack of familiarity with the policies in place and inconsistencies in the resources offered to breastfeeding employees across the university system. Only half of the participating liaisons reported a formal breastfeeding policy was in place on their campus. From the document review, six major themes were identified: placing the burden on employees, describing pregnancy or postpartum as a “disability,” having a university-specific policy, inclusion of break times for breastfeeding, supervisor responsibility, and information on lactation policies.

Conclusion

The review of each institution’s online resources confirmed the survey findings and highlighted the burden placed on employees to discover the available resources and advocate for their needs. This paper provides insight into how institutions support breastfeeding employees and provides implications on strategies to develop policies at universities to improve breastfeeding access for working parents.
How do labour market conditions explain the development of mental health over the life-course? A conceptual integration of the ecological model with life-course epidemiology in an integrative review of results from the Northern Swedish Cohort
Authors: Hammarström Anne , Westerlund Hugo , Janlert Urban , Virtanen Pekka , Ziaei Shirin , Östergren Per-Olof
Published: May 2024

Background

The aim of this study was to contribute to the theoretical development within the field of labour market effects on mental health during life by integrating Bronfenbrenner’s ecological model with mainly earlier theoretical work on life-course theory.

Methods

An integrative review was performed of all 52 publications about labour market conditions in relation to mental health from the longitudinal Northern Swedish Cohort study. Inductive and deductive qualitative content analysis were performed in relation to Bronfenbrenner’s ecological framework combined with life-course theories.

Results

The following nine themes were identified: 1. Macroeconomic recession impairs mental health among young people. 2. The mental health effects on individuals of youth unemployment seem rather insensitive to recession. 3. Small but consistent negative effect of neighbourhood unemployment and other work-related disadvantaged on individuals’ mental health over life. 4. Youth unemployment becomes embodied as scars of mental ill-health over life. 5. Weak labour market attachment impairs mental health over life. 6. Bidirectional relations between health and weak labour market attachment over life. 7. Macrolevel structures are of importance for how labour market position cause poor health. 8. Unequal gender relations at work impacts negatively on mental health. 9. The agency to improve health over life in dyadic relations. Unemployment in society permeates from the macrolevel into the exolevel, defined by Bronfenbrenner as for example the labour market of parents or partners or the neighbourhood into the settings closest to the individual (the micro- and mesolevel) and affects the relations between the work, family, and leisure spheres of the individual. Neighbourhood unemployment leads to poor health among those who live there, independent of their employment status. Individuals’ exposure to unemployment and temporary employment leads to poorer mental health over the life-course. Temporal dimensions were identified and combined with Bronfenbrenner levels into a contextual life-course model

Conclusion

Combining the ecosocial theory with life-course theories provides a framework for understanding the embodiment of work-related mental health over life. The labour market conditions surrounding the individual are of crucial importance for the embodiment of mental health over life, at the same time as individual agency can be health promoting. Mental health can be improved by societal efforts in regulations of the labour market.
Effectiveness of simulation-based clinical research curriculum for undergraduate medical students - a pre-post intervention study with external control
Authors: Huang Qiao , Yan Si-Yu , Huang Jiao , Guo Yi , Zeng Xian-Tao , Jin Ying-Hui
Published: May 2024

Background

Simulation is widely utilized in medical education. Exploring the effectiveness of high-fidelity simulation of clinical research within medical education may inform its integration into clinical research training curricula, finally cultivating physician-scientist development.

Methods

Standard teaching scripts for both clinical trial and cross-sectional study simulation were designed. We recruited undergraduates majoring in clinical medicine at 3th grade into a pre-post intervention study. Additionally, a cross-sectional survey randomly selected medical undergraduates at 4th or 5th grade, medical students in master and doctor degree as external controls. Self-assessment scores of knowledge and practice were collected using a 5-point Likert scale. Changes in scores were tested by Wilcoxon signed-rank test and group comparisons were conducted by Dunn’s tests with multiple corrections. Multivariable quantile regressions were used to explore factors influencing the changes from baseline.

Results

Seventy-eight undergraduates involved the clinical trial simulation and reported improvement of 1.60 (95% CI, 1.48, 1.80, P < 0.001) in knowledge and 1.82 (95% CI, 1.64, 2.00, P < 0.001) in practice score. 83 undergraduates involved in the observational study simulation and reported improvement of 0.96 (95% CI, 0.79, 1.18, P < 0.001) in knowledge and 1.00 (95% CI, 0.79, 1.21, P < 0.001) in practice. All post-intervention scores were significantly higher than those of the three external control groups, P < 0.001. Higher agreement on the importance of clinical research were correlated with greater improvements in scores. Undergraduates in pre-post study showed high confidence in doing a future clinical research.

Conclusion

Our study provides evidence supporting the integration of simulation into clinical research curriculum for medical students. The importance of clinical research can be emphasized during training to enhance learning effect.
Developing emotional preparedness and mental resilience through high-fidelity simulation: a ‘bridge too far’ for institutions teaching major trauma management and mass-casualty medicine?
Authors: Newton Jon , Smith Andrew D.A.C.
Published: May 2024

Background

Clinical acumen represents only part of being adequately equipped to attend a major incident. The emotive sights, sounds and smells of these dynamic environments are all-encompassing experiences, and responders must also be armed with the emotional preparedness to perform their clinical or managerial duties effectively, as well as the mental resilience to facilitate professional continuance. Despite this, limited training and a sparsity of evidence exists to guide developments within this domain. Historically, major incident training has focused on clinical theory acquisition, but irrespective of how comprehensive the learning materials, they are of little consequence if tandem steps to cultivate mental resilience and emotional preparedness are absent. High-Fidelity Simulation (HFS) has a growing reputation as an effective means of bridging important gaps between theory and practice. This pilot study aimed to measure student’s self-reported perception of their readiness to respond to a major incident following a large-scale HFS.

Methods

Quantitative data was obtained from a sample of 108 students undertaking paramedic science, physician associate studies and adult nursing degree programmes. A bespoke questionnaire was developed to measure self-reported clinical acumen, mental and emotional preparedness.

Results

91% of students agreed the combination of theoretical training and HFS provided made them feel clinically prepared to attend a real major incident; 86% agreed this experience had developed their mental resilience and 90% agreed that they felt emotionally prepared to attend a major incident.

Conclusion

Within this pilot study, the blend of theoretical training and HFS contributed to self-reported clinical acumen, mental and emotional preparation, in learners training to work in disaster environments or emergency medicine settings.
Developing comprehensive woman hand-held case notes to improve quality of antenatal care in low-income settings: participatory approach with maternal health stakeholders in Malawi
Authors: Mndala Leonard , Kondoni Chifundo , Gadama Luis , Bamuya Catherine , Kuyere Annie , Maseko Bertha , Kachale Fannie , Gondwe Mtisunge Joshua , Lissauer David , Nyondo-Mipando Alinane Linda
Published: May 2024

Background

In the quest for quality antenatal care (ANC) and positive pregnancy experience, the value of comprehensive woman hand-held case notes cannot be emphasised enough. However, the woman’s health passport book in Malawi presents gaps which hinder provision of quality care, especially during pregnancy. We aimed to develop a compressive updated woman hand-held case notes tool (health passport book) which reflects WHO 2016 ANC guidelines in Malawi.

Methods

From July 2022 to August 2022, we applied a co-creative participatory approach in 3 workshops with key stakeholders to compare the current ANC tool contents to the WHO 2016 ANC guidelines, decide on key elements to be changed to improve adherence and change in practice, and redesign the woman’s health passport tool to reflect the changes. Within-group discussions led to whole-group discussions and consensus, guided by a modified nominal group technique. Facilitators guided the discussions while ensuring autonomy of the group members in their deliberations. Discussions were recorded and transcribed. Data was analysed through thematic analysis, and reduction and summaries in affinity diagrams. The developed tool was endorsed for implementation within Malawi’s healthcare system by the national safe motherhood technical working group (TWG) in July 2023.

Results

Five themes were identified in the analysis. These were (i) critical components in the current tool missed, (ii) reimagining the current ANC tool, (iii) opportunity for ultrasound scanning conduct and documentation, (iv) anticipated barriers related to implementation of the newly developed tool and (v) cultivating successful implementation. Participants further recommended strengthening of already existing policies and investments in health, strengthening public private partnerships, and continued capacity building of healthcare providers to ensure that their skill sets are up to date.

Conclusion

Achieving goals of quality ANC and universality of healthcare are possible if tools in practice reflect the guidelines set out. Our efforts reflect a pioneering attempt in Malawi to improve women’s hand-held case notes, which we know help in enhancing quality of care and improve overall women’s satisfaction with their healthcare system.
Follow-up after major traumatic injury: a survey of services in Australian and New Zealand public hospitals
Authors: Wake Elizabeth , Ranse Jamie , Campbell Don , Gabbe Belinda , Marshall Andrea P.
Published: May 2024

Background

Increased survival from traumatic injury has led to a higher demand for follow-up care when patients are discharged from hospital. It is currently unclear how follow-up care following major trauma is provided to patients, and how, when, and to whom follow-up services are delivered. The aim of this study was to describe the current follow-up care provided to patients and their families who have experienced major traumatic injury in Australia and New Zealand (ANZ).

Methods

Informed by Donabedian’s ‘Evaluating the Quality of Medical Care’ model and the Institute of Medicine’s Six Domains of Healthcare Quality, a cross-sectional online survey was developed in conjunction with trauma experts. Their responses informed the final survey which was distributed to key personnel in 71 hospitals in Australia and New Zealand that (i) delivered trauma care to patients, (ii) provided data to the Australasian Trauma Registry, or (iii) were a Trauma Centre.

Results

Data were received from 38/71 (53.5%) hospitals. Most were Level 1 trauma centres (n = 23, 60.5%); 76% (n = 16) follow-up services were permanently funded. Follow-up services were led by a range of health professionals with over 60% (n = 19) identifying as trauma specialists. Patient inclusion criteria varied; only one service allowed self-referral (3.3%). Follow-up was within two weeks of acute care discharge in 53% (n = 16) of services. Care activities focused on physical health; psychosocial assessments were the least common. Most services provided care for adults and paediatric trauma (60.5%, n = 23); no service incorporated follow-up for family members. Evaluation of follow-up care was largely as part of a health service initiative; only three sites stated evaluation was specific to trauma follow-up.

Conclusion

Follow-up care is provided by trauma specialists and predominantly focuses on the physical health of the patients affected by major traumatic injury. Variations exist in terms of patient selection, reason for follow-up and care activities delivered with gaps in the provision of psychosocial and family health services identified. Currently, evaluation of trauma follow-up care is limited, indicating a need for further development to ensure that the care delivered is safe, effective and beneficial to patients, families and healthcare organisations.
Association between the triglyceride-glucose index and in-hospital major adverse cardiovascular events in patients with acute coronary syndrome: results from the Improving Care for Cardiovascular Disease in China (CCC)-Acute Coronary Syndrome project
Authors: Wang Wenjie , Yang Jiaxin , Wang Kexin , Niu Jialong , Liu Yixuan , Ge Hailong ,   CCC-ACS Investigators
Published: May 2024

Objective

Although the TyG index is a reliable predictor of insulin resistance (IR) and cardiovascular disease, its effectiveness in predicting major adverse cardiac events in hospitalized acute coronary syndrome (ACS) patients has not been validated in large-scale studies. In this study, we aimed to explore the association between the TyG index and the occurrence of MACEs during hospitalization.

Methods

We recruited ACS patients from the CCC-ACS (Improving Cardiovascular Care in China-ACS) database and calculated the TyG index using the formula ln(fasting triglyceride [mg/dL] × fasting glucose [mg/dL]/2). These patients were classified into four groups based on quartiles of the TyG index. The primary endpoint was the occurrence of MACEs during hospitalization, encompassing all-cause mortality, cardiac arrest, myocardial infarction (MI), and stroke. We performed Cox proportional hazards regression analysis to clarify the correlation between the TyG index and the risk of in-hospital MACEs among patients diagnosed with ACS. Additionally, we explored this relationship across various subgroups.

Results

A total of 101,113 patients were ultimately included, and 2759 in-hospital MACEs were recorded, with 1554 (49.1%) cases of all-cause mortality, 601 (21.8%) cases of cardiac arrest, 251 (9.1%) cases of MI, and 353 (12.8%) cases of stroke. After adjusting for confounders, patients in TyG index quartile groups 3 and 4 showed increased risks of in-hospital MACEs compared to those in quartile group 1 [HR = 1.253, 95% CI 1.121–1.400 and HR = 1.604, 95% CI 1.437–1.791, respectively; p value for trend < 0.001], especially in patients with STEMI or renal insufficiency. Moreover, we found interactions between the TyG index and age, sex, diabetes status, renal insufficiency status, and previous PCI (all p values for interactions < 0.05).

Conclusions

In patients with ACS, the TyG index was an independent predictor of in-hospital MACEs. Special vigilance should be exercised in females, elderly individuals, and patients with renal insufficiency.
Enhancement of vitamin B6 production driven by omics analysis combined with fermentation optimization
Authors: Tian Zhizhong , Liu Linxia , Wu Lijuan , Yang Zixuan , Zhang Yahui , Du Liping , Zhang Dawei
Published: May 2024

Background

Microbial engineering aims to enhance the ability of bacteria to produce valuable products, including vitamin B6 for various applications. Numerous microorganisms naturally produce vitamin B6, yet the metabolic pathways involved are rigorously controlled. This regulation by the accumulation of vitamin B6 poses a challenge in constructing an efficient cell factory.

Results

In this study, we conducted transcriptome and metabolome analyses to investigate the effects of the accumulation of pyridoxine, which is the major commercial form of vitamin B6, on cellular processes in Escherichia coli. Our omics analysis revealed associations between pyridoxine and amino acids, as well as the tricarboxylic acid (TCA) cycle. Based on these findings, we identified potential targets for fermentation optimization, including succinate, amino acids, and the carbon-to-nitrogen (C/N) ratio. Through targeted modifications, we achieved pyridoxine titers of approximately 514 mg/L in shake flasks and 1.95 g/L in fed-batch fermentation.

Conclusion

Our results provide insights into pyridoxine biosynthesis within the cellular metabolic network for the first time. Our comprehensive analysis revealed that the fermentation process resulted in a remarkable final yield of 1.95 g/L pyridoxine, the highest reported yield to date. This work lays a foundation for the green industrial production of vitamin B6 in the future.
Biomimetic bone-periosteum scaffold for spatiotemporal regulated innervated bone regeneration and therapy of osteosarcoma
Authors: Xu Yan , Xu Chao , Song Huan , Feng Xiaobo , Ma Liang , Zhang Xiaoguang , Li Gaocai , Mu Congpu , Tan Lei , Zhang Zhengdong , Liu Zhongyuan , Luo Zhiqiang , Yang Cao
Published: May 2024

The complexity of repairing large segment defects and eradicating residual tumor cell puts the osteosarcoma clinical management challenging. Current biomaterial design often overlooks the crucial role of precisely regulating innervation in bone regeneration. Here, we develop a Germanium Selenium (GeSe) co-doped polylactic acid (PLA) nanofiber membrane-coated tricalcium phosphate bioceramic scaffold (TCP-PLA/GeSe) that mimics the bone-periosteum structure. This biomimetic scaffold offers a dual functionality, combining piezoelectric and photothermal conversion capabilities while remaining biodegradable. When subjected to ultrasound irradiation, the US-electric stimulation of TCP-PLA/GeSe enables spatiotemporal control of neurogenic differentiation. This feature supports early innervation during bone formation, promoting early neurogenic differentiation of Schwann cells (SCs) by increasing intracellular Ca2+ and subsequently activating the PI3K-Akt and Ras signaling pathways. The biomimetic scaffold also demonstrates exceptional osteogenic differentiation potential under ultrasound irradiation. In rabbit model of large segment bone defects, the TCP-PLA/GeSe demonstrates promoted osteogenesis and nerve fibre ingrowth. The combined attributes of high photothermal conversion capacity and the sustained release of anti-tumor selenium from the TCP-PLA/GeSe enable the synergistic eradication of osteosarcoma both in vitro and in vivo. This strategy provides new insights on designing advanced biomaterials of repairing large segment bone defect and osteosarcoma.
Ternary heterostructure-driven photoinduced electron-hole separation enhanced oxidative stress for triple-negative breast cancer therapy
Authors: Dong Shuqing , Huang Yuqi , Yan Hanrong , Tan Huarong , Fan Liying , Chao Minghao , Ren Yiping , Guan Ming , Zhang Jiaxin , Liu Zhao , Gao Fenglei
Published: May 2024

Zinc oxide nanoparticles (ZnO NPs) stand as among the most significant metal oxide nanoparticles in trigger the formation of reactive oxygen species (ROS) and induce apoptosis. Nevertheless, the utilization of ZnO NPs has been limited by the shallowness of short-wavelength light and the constrained production of ROS. To overcome these limitations, a strategy involves achieving a red shift towards the near-infrared (NIR) light spectrum, promoting the separation and restraining the recombination of electron-hole (e−-h+) pairs. Herein, the hybrid plasmonic system Au@ZnO (AZ) with graphene quantum dots (GQDs) doping (AZG) nano heterostructures is rationally designed for optimal NIR-driven cancer treatment. Significantly, a multifold increase in ROS generation can be achieved through the following creative initiatives: (i) plasmonic Au nanorods expands the photocatalytic capabilities of AZG into the NIR domain, offering a foundation for NIR-induced ROS generation for clinical utilization; (ii) elaborate design of mesoporous core-shell AZ structures facilitates the redistribution of electron-hole pairs; (iii) the incorporation GQDs in mesoporous structure could efficiently restrain the recombination of the e−-h+ pairs; (iv) Modification of hyaluronic acid (HA) can enhance CD44 receptor mediated targeted triple-negative breast cancer (TNBC). In addition, the introduced Au NRs present as catalysts for enhancing photothermal therapy (PTT), effectively inducing apoptosis in tumor cells. The resulting HA-modified AZG (AZGH) exhibits efficient hot electron injection and e−-h+ separation, affording unparalleled convenience for ROS production and enabling NIR-induced PDT for the cancer treanment. As a result, our well-designed mesoporous core-shell AZGH hybrid as photosensitizers can exhibit excellent PDT efficacy.
Unveiling heterogeneity in MSCs: exploring marker-based strategies for defining MSC subpopulations
Authors: Chen Si , Liang Bowei , Xu Jianyong
Published: May 2024

Mesenchymal stem/stromal cells (MSCs) represent a heterogeneous cell population distributed throughout various tissues, demonstrating remarkable adaptability to microenvironmental cues and holding immense promise for disease treatment. However, the inherent diversity within MSCs often leads to variability in therapeutic outcomes, posing challenges for clinical applications. To address this heterogeneity, purification of MSC subpopulations through marker-based isolation has emerged as a promising approach to ensure consistent therapeutic efficacy. In this review, we discussed the reported markers of MSCs, encompassing those developed through candidate marker strategies and high-throughput approaches, with the aim of explore viable strategies for addressing the heterogeneity of MSCs and illuminate prospective research directions in this field.
Gynostemma Pentaphyllum ameliorates CCl4-induced liver injury via PDK1/Bcl-2 pathway with comprehensive analysis of network pharmacology and transcriptomics
Authors: Hu Linlan , Zhao Xin , He Xian , Guo Yafei , Cheng Hanxiao , Chen Shaoting , Zhou Guangde , Wang Jiabo , Lu Yawen
Published: May 2024

Background

Gynostemma pentaphyllum (Thunb.) Makino, commonly known as “southern ginseng”, contains high amounts of ginsenoside derivatives and exhibits similar biological activities with Panax ginseng (C. A. MEY) (ginseng), which is usually used as a low-cost alternative to ginseng. G. pentaphyllum has therapeutic effects on liver diseases. However, the mechanisms underlying its hepatoprotective action have not been fully elucidated.

Methods

The protective effects of the ethanolic extract of G. pentaphyllum (GPE) were evaluated using an experimental carbon tetrachloride (CCl4)-induced liver disease model. Potential targets of GPE were predicted using the “Drug-Disease” bioinformatic analysis. Furthermore, comprehensive network pharmacology and transcriptomic approaches were employed to investigate the underlying mechanisms of GPE in the treatment of liver disease.

Results

The pathological examinations showed that GPE significantly alleviated hepatocyte necrosis and liver injury. GPE significantly downregulated Bax and cleaved-PARP expression and upregulated Bcl-2 expression during CCl4-induced hepatocyte apoptosis. We compared the effects of four typical compounds in GPE -a ginsenoside (Rb3) shared by both GPE and ginseng and three unique gypenosides in GPE. Notably, Gypenoside A (GPA), a unique saponin in GPE, markedly reduced hepatocyte apoptosis. In contrast, ginsenoside Rb3 had a weaker effect. Network pharmacology and transcriptomic analyses suggested that this anti-apoptotic effect was achieved by upregulating the PI3K/Akt signaling pathway mediated by PDK1.

Conclusions

These results suggested that G. pentaphyllum had a promising hepatoprotective effect, with its mechanism primarily involving the upregulation of the PDK1/Bcl-2 signaling pathway by GPA, thereby preventing cell apoptosis.

Graphic Abstract
Clinical and genetic analysis of methylmalonic aciduria in 60 patients from Southern China: a single center retrospective study
Authors: Su Ling , Sheng Huiying , Li Xiuzhen , Cai Yanna , Mei Huifen , Cheng Jing , Li Duan , Lu Zhikun , Lin Yunting , Chen Xiaodan , Peng Minzhi , Huang Yonglan , Zhang Wen , Liu Li
Published: May 2024

Background

Methylmalonic aciduria (MMA) is a group of rare genetic metabolic disorders resulting from defects in methylmalonyl coenzyme A mutase (MCM) or intracellular cobalamin (cbl) metabolism. MMA patients show diverse clinical and genetic features across different subtypes and populations.

Methods

We retrospectively recruited 60 MMA patients from a single center and diagnosed them based on their clinical manifestations and biochemical assays. We then performed genetic analysis to confirm the diagnosis and identify the causal variants.

Results

We confirmed the common clinical manifestations of MMA reported previously. We also described four rare MMA cases with unusual symptoms or genetic variants, such as pulmonary hypertension or limb weakness in late-onset patients. We identified 15 MMACHC and 26 MMUT variants in 57 patients, including 6 novel MMUT variants. Two patients had only one MMAA variant each, and one patient had mild MMA due to mitochondrial DNA depletion syndrome caused by a SUCLA2 variant. Among 12 critically ill patients, isolated MMA was associated with higher C3, blood ammonia, and acidosis, while combined MMA was linked to hydrocephalus on skull MRI. MMACHC c.658-660delAAG and MMUT c.1280G > A variants were correlated with more severe phenotypes.

Conclusions

Our study demonstrates the clinical and genotypic heterogeneity of MMA patients and indicates that metabolic screening and genetic analysis are useful tools to identify rare cases.
Detection and characterization of pancreatic and biliary tract cancers using cell-free DNA fragmentomics
Authors: Shi Xiaohan , Guo Shiwei , Duan Qiaonan , Zhang Wei , Gao Suizhi , Jing Wei , Jiang Guojuan , Kong Xiangyu , Li Penghao , Li Yikai , Teng Chuanqi , Xu Xiaoya , Chen Sheng , Nian Baoning , Li Zhikuan , Zhong Chaoliang , Yang Xiaolu , Zhu Guangyu , Du Yiqi , Zhang Dadong , Jin Gang
Published: May 2024

Background

Plasma cell-free DNA (cfDNA) fragmentomics has demonstrated significant differentiation power between cancer patients and healthy individuals, but little is known in pancreatic and biliary tract cancers. The aim of this study is to characterize the cfDNA fragmentomics in biliopancreatic cancers and develop an accurate method for cancer detection.

Methods

One hundred forty-seven patients with biliopancreatic cancers and 71 non-cancer volunteers were enrolled, including 55 patients with cholangiocarcinoma, 30 with gallbladder cancer, and 62 with pancreatic cancer. Low-coverage whole-genome sequencing (median coverage: 2.9 ×) was performed on plasma cfDNA. Three cfDNA fragmentomic features, including fragment size, end motif and nucleosome footprint, were subjected to construct a stacked machine learning model for cancer detection. Integration of carbohydrate antigen 19–9 (CA19-9) was explored to improve model performance.

Results

The stacked model presented robust performance for cancer detection (area under curve (AUC) of 0.978 in the training cohort, and AUC of 0.941 in the validation cohort), and remained consistent even when using extremely low-coverage sequencing depth of 0.5 × (AUC: 0.905). Besides, our method could also help differentiate biliopancreatic cancer subtypes. By integrating the stacked model and CA19-9 to generate the final detection model, a high accuracy in distinguishing biliopancreatic cancers from non-cancer samples with an AUC of 0.995 was achieved.

Conclusions

Our model demonstrated ultrasensitivity of plasma cfDNA fragementomics in detecting biliopancreatic cancers, fulfilling the unmet accuracy of widely-used serum biomarker CA19-9, and provided an affordable way for accurate noninvasive biliopancreatic cancer screening in clinical practice.
Effects of mechanical ventilation on the interstitial extracellular matrix in healthy lungs and lungs affected by acute respiratory distress syndrome: a narrative review
Authors: Al-Husinat Lou’i , Azzam Saif , Al Sharie Sarah , Al Sharie Ahmed H. , Battaglini Denise , Robba Chiara , Marini John J. , Thornton Lauren T. , Cruz Fernanda F. , Silva Pedro L. , Rocco Patricia R. M.
Published: May 2024

Background

Mechanical ventilation, a lifesaving intervention in critical care, can lead to damage in the extracellular matrix (ECM), triggering inflammation and ventilator-induced lung injury (VILI), particularly in conditions such as acute respiratory distress syndrome (ARDS). This review discusses the detailed structure of the ECM in healthy and ARDS-affected lungs under mechanical ventilation, aiming to bridge the gap between experimental insights and clinical practice by offering a thorough understanding of lung ECM organization and the dynamics of its alteration during mechanical ventilation.

Main text

Focusing on the clinical implications, we explore the potential of precise interventions targeting the ECM and cellular signaling pathways to mitigate lung damage, reduce inflammation, and ultimately improve outcomes for critically ill patients. By analyzing a range of experimental studies and clinical papers, particular attention is paid to the roles of matrix metalloproteinases (MMPs), integrins, and other molecules in ECM damage and VILI. This synthesis not only sheds light on the structural changes induced by mechanical stress but also underscores the importance of cellular responses such as inflammation, fibrosis, and excessive activation of MMPs.

Conclusions

This review emphasizes the significance of mechanical cues transduced by integrins and their impact on cellular behavior during ventilation, offering insights into the complex interactions between mechanical ventilation, ECM damage, and cellular signaling. By understanding these mechanisms, healthcare professionals in critical care can anticipate the consequences of mechanical ventilation and use targeted strategies to prevent or minimize ECM damage, ultimately leading to better patient management and outcomes in critical care settings.
Isolation, characterization and functional analysis of a bacteriophage targeting Culex pipiens pallens resistance-associated Aeromonas hydrophila
Authors: Li Jinze , Du Jiajia , Ding Guangshuo , Zhang Wenxing , Zhou Yinghui , Xu Yidan , Zhou Dan , Sun Yan , Liu Xiaoqiu , Shen Bo
Published: May 2024

Background

Culex pipiens pallens is a well-known mosquito vector for several diseases. Deltamethrin, a commonly used pyrethroid insecticide, has been frequently applied to manage adult Cx. pipiens pallens. However, mosquitoes can develop resistance to these insecticides as a result of insecticide misuse and, therefore, it is crucial to identify novel methods to control insecticide resistance. The relationship between commensal bacteria and vector resistance has been recently recognized. Bacteriophages (= phages) are effective tools by which to control insect commensal bacteria, but there have as yet been no studies using phages on adult mosquitoes. In this study, we isolated an Aeromonas phage vB AhM-LH that specifically targets resistance-associated symbiotic bacteria in mosquitoes. We investigated the impact of Aeromonas phage vB AhM-LH in an abundance of Aeromonas hydrophila in the gut of Cx. pipiens pallens and its effect on the status of deltamethrin resistance.

Methods

Phages were isolated on double-layer agar plates and their biological properties analyzed. Phage morphology was observed by transmission electron microscopy (TEM) after negative staining. The phage was then introduced into the mosquito intestines via oral feeding. The inhibitory effect of Aeromonas phage vB AhM-LH on Aeromonas hydrophila in mosquito intestines was assessed through quantitative real-time PCR analysis. Deltamethrin resistance of mosquitoes was assessed using WHO bottle bioassays.

Results

An Aeromonas phage vB AhM-LH was isolated from sewage and identified as belonging to the Myoviridae family in the order Caudovirales using TEM. Based on biological characteristics analysis and in vitro antibacterial experiments, Aeromonas phage vB AhM-LH was observed to exhibit excellent stability and effective bactericidal activity. Sequencing revealed that the Aeromonas phage vB AhM-LH genome comprises 43,663 bp (51.6% CG content) with 81 predicted open reading frames. No integrase-related gene was detected in the vB AH-LH genome, which marked it as a potential biological antibacterial. Finally, we found that Aeromonas phage vB AhM-LH could significantly reduce deltamethrin resistance in Cx. pipiens pallens, in both the laboratory and field settings, by decreasing the abundance of Aeromonas hydrophila in their midgut.

Conclusions

Our findings demonstrate that Aeromonas phage vB AhM-LH could effectively modulate commensal bacteria Aeromonas hydrophila in adult mosquitoes, thus representing a promising strategy to mitigate mosquito vector resistance.

Graphical Abstract
Evaluation of the vector competence for Batai virus of native Culex and exotic Aedes species in Central Europe
Authors: Heitmann Anna , Wehmeyer Magdalena Laura , Lühken Renke , Kliemke Konstantin , Jöst Hanna , Becker Norbert , Helms Michelle , Schmidt-Chanasit Jonas , Jansen Stephanie
Published: May 2024

Background

Batai virus (BATV) is a zoonotic arbovirus of veterinary importance. A high seroprevalence in cows, sheep and goats and infection in different mosquito species has been observed in Central Europe. Therefore, we studied indigenous as well as exotic species of the genera Culex and Aedes for BATV vector competence at different fluctuating temperature profiles.

Methods

Field caught Culex pipiens biotype pipiens, Culex torrentium, Aedes albopictus and Aedes japonicus japonicus from Germany and Aedes aegypti laboratory colony were infected with BATV strain 53.3 using artificial blood meals. Engorged mosquitoes were kept under four (Culex species) or three (Aedes species) fluctuating temperature profiles (18 ± 5 °C, 21 ± 5 °C, 24 ± 5 °C, 27 ± 5 °C) at a humidity of 70% and a dark/light rhythm of 12:12 for 14 days. Transmission was measured by testing the saliva obtained by forced salivation assay for viable BATV particles. Infection rates were analysed by testing whole mosquitoes for BATV RNA by quantitative reverse transcription PCR.

Results

No transmission was detected for Ae. aegypti, Ae. albopictus or Ae. japonicus japonicus. Infection was observed for Cx. p. pipiens, but only in the three conditions with the highest temperatures (21 ± 5 °C, 24 ± 5 °C, 27 ± 5 °C). In Cx. torrentium infection was measured at all tested temperatures with higher infection rates compared with Cx. p. pipiens. Transmission was only detected for Cx. torrentium exclusively at the highest temperature of 27 ± 5 °C.

Conclusions

Within the tested mosquito species, only Cx. torrentium seems to be able to transmit BATV if the climatic conditions are feasible.

Graphical Abstract
Concepts of lines of therapy in cancer treatment: findings from an expert interview-based study
Authors: Falchetto Lisa , Bender Bernd , Erhard Ian , Zeiner Kim N. , Stratmann Jan A. , Koll Florestan J. , Wagner Sebastian , Reiser Marcel , Gasimli Khayal , Stehle Angelika , Voss Martin , Ballo Olivier , Vehreschild Jörg Janne , Maier Daniel
Published: May 2024

Objective

The concept of lines of therapy (LOT) in cancer treatment is often considered for decision making in tumor boards and clinical management, but lacks a common definition across medical specialties. The complexity and heterogeneity of malignancies and treatment modalities contribute to an inconsistent understanding of LOT among physicians. This study assesses the heterogeneity of understandings of the LOT concept, its major dimensions, and criteria from the perspective of physicians of different specialties with an oncological focus in Germany. Semi-structured expert interviews with nine physicians were conducted and evaluated using qualitative content analysis.

Results

Most interviewees agreed that there is no single definition for LOT and found it difficult to explicate their understanding. A majority of experts stated that they had already encountered misunderstandings with colleagues regarding LOT and that they had problems with deciphering LOT from the medical records of their patients. Disagreement emerged about the roles of the following within the LOT concept: maintenance therapy, treatment intention, different therapy modalities, changing pharmaceutical agents, and therapy breaks. Respondents predominantly considered the same criteria as decisive for the definition of LOT as for a change in LOT (e.g., the occurrence of a progression event or tumor recurrence).
Progresses in overcoming the limitations of in vitro erythropoiesis using human induced pluripotent stem cells
Authors: Ju Hyeonwoo , Sohn Yeowon , Nam Yoojun , Rim Yeri Alice
Published: May 2024

Researchers have attempted to generate transfusable oxygen carriers to mitigate RBC supply shortages. In vitro generation of RBCs using stem cells such as hematopoietic stem and progenitor cells (HSPCs), embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs) has shown promise. Specifically, the limited supplies of HSPCs and ethical issues with ESCs make iPSCs the most promising candidate for in vitro RBC generation. However, researchers have encountered some major challenges when using iPSCs to produce transfusable RBC products, such as enucleation and RBC maturation. In addition, it has proven difficult to manufacture these products on a large scale. In this review, we provide a brief overview of erythropoiesis and examine endeavors to recapitulate erythropoiesis in vitro using various cell sources. Furthermore, we explore the current obstacles and potential solutions aimed at enabling the large-scale production of transfusable RBCs in vitro.
Sex-specific impacts of prenatal bisphenol A exposure on genes associated with cortical development, social behaviors, and autism in the offspring’s prefrontal cortex
Authors: Kanlayaprasit Songphon , Saeliw Thanit , Thongkorn Surangrat , Panjabud Pawinee , Kasitipradit Kasidit , Lertpeerapan Pattanachat , Songsritaya Kwanjira , Yuwattana Wasana , Jantheang Thanawin , Jindatip Depicha , Hu Valerie W. , Kikkawa Takako , Osumi Noriko , Sarachana Tewarit
Published: May 2024

Background

Recent studies have shown that prenatal BPA exposure altered the transcriptome profiles of autism-related genes in the offspring’s hippocampus, disrupting hippocampal neuritogenesis and causing male-specific deficits in learning. However, the sex differences in the effects of prenatal BPA exposure on the developing prefrontal cortex, which is another brain region highly implicated in autism spectrum disorder (ASD), have not been investigated.

Methods

We obtained transcriptome data from RNA sequencing analysis of the prefrontal cortex of male and female rat pups prenatally exposed to BPA or control and reanalyzed. BPA-responsive genes associated with cortical development and social behaviors were selected for confirmation by qRT-PCR analysis. Neuritogenesis of primary cells from the prefrontal cortex of pups prenatally exposed to BPA or control was examined. The social behaviors of the pups were assessed using the two-trial and three-chamber tests. The male-specific impact of the downregulation of a selected BPA-responsive gene (i.e., Sema5a) on cortical development in vivo was interrogated using siRNA-mediated knockdown by an in utero electroporation technique.

Results

Genes disrupted by prenatal BPA exposure were associated with ASD and showed sex-specific dysregulation. Sema5a and Slc9a9, which were involved in neuritogenesis and social behaviors, were downregulated only in males, while Anxa2 and Junb, which were also linked to neuritogenesis and social behaviors, were suppressed only in females. Neuritogenesis was increased in males and showed a strong inverse correlation with Sema5a and Slc9a9 expression levels, whereas, in the females, neuritogenesis was decreased and correlated with Anxa2 and Junb levels. The siRNA-mediated knockdown of Sema5a in males also impaired cortical development in utero. Consistent with Anxa2 and Junb downregulations, deficits in social novelty were observed only in female offspring but not in males.

Conclusion

This is the first study to show that prenatal BPA exposure dysregulated the expression of ASD-related genes and functions, including cortical neuritogenesis and development and social behaviors, in a sex-dependent manner. Our findings suggest that, besides the hippocampus, BPA could also exert its adverse effects through sex-specific molecular mechanisms in the offspring’s prefrontal cortex, which in turn would lead to sex differences in ASD-related neuropathology and clinical manifestations, which deserves further investigation.
Prevalence of SARS-CoV-2 antibodies and associated factors in the adult population of Belgium: a general population cohort study between March 2021 and April 2022
Authors: Van der Heyden Johan , Leclercq Victoria , Duysburgh Els , Cornelissen Laura , Desombere Isabelle , Roukaerts Inge , Gisle Lydia
Published: May 2024

Background

This study assessed seroprevalence trends of SARS-CoV-2 antibodies in the Belgian adult population between March 2021 and April 2022, and explored factors associated with seropositivity and seroreversion among the vaccinated and unvaccinated population.

Methods

A prospective longitudinal surveillance study was conducted within a random sample of the general population (18 + years) in Belgium, selected from the national register through a multistage sampling design. Participants provided a saliva sample and completed a survey questionnaire on three occasions: at baseline and in two follow-up waves. Outcome variables included (1) seropositivity, defined as the presence of SARS-CoV-2 antibodies, assessed with a semi-quantitative measure of anti-RBD (Receptor Binding Domain) IgG ELISA and (2) seroreversion, defined as passing from a positive to a negative antibody test between two measurements. Trends in SARS-CoV-2 antibody prevalence were assessed using binary logistic regression with contrasts applying post-stratification. Potential determinants of seropositivity were assessed through multilevel logistic regressions.

Results

In total 6,178 valid observations were obtained from 2,768 individuals. SARS-CoV-2 antibody prevalence increased from 25.1% in the beginning of the study period to 92.3% at the end. Among the vaccinated population, factors significantly associated with higher seropositivity rates were being younger, having a bachelor diploma, living with others, having had a vaccine in the last 3 months and having received a nucleic-acid vaccine or a combination. Lower seropositivity rates were observed among vaccinated people with a neurological disease and transplant patients. Factors significantly associated with higher seropositivity rates among the unvaccinated population were having non-O blood type and being non-smoker. Among vaccinated people, the seroreversion rate was much lower (0.3%) in those who had received their latest vaccine in the last 3 months compared to those who had received their latest vaccine more than 3 months ago (2.7%) (OR 0.13; 95%CI 0.04–0.42).

Conclusions

The rapid increase in antibody seropositivity in the general adult population in Belgium during the study period was driven by the vaccination campaign which ran at full speed during this period. Among vaccinated people, seropositivity varied in function of the time since last vaccine, the type of vaccine, sociodemographic features and health status.
Comparison of angiographic change in side-branch ostium after drug-coated balloon vs. drug-eluting stent vs. medication for the treatment of de novo coronary bifurcation lesions
Authors: Her Ae-Young , Kim Bitna , Kim Sunwon , Kim Yong Hoon , Scheller Bruno , Shin Eun-Seok
Published: May 2024

Objectives

Data on side-branch (SB) ostial effect after drug-coated balloon (DCB) treatment in the context of de novo coronary bifurcation lesions are limited. We aimed to investigate the angiographic outcomes of SB ostium after DCB treatment compared with drug-eluting stents (DESs) implantation in the main vessel (MV) or optimal medical therapy (OMT) for the treatment of de novo coronary bifurcation lesions.

Methods

Serial angiographic changes in the SB ostium were compared between DCB, DES, and medication alone for MV treatment. Δ value was calculated by subtracting the follow-up value from the pre-procedure value.

Results

A total of 132 bifurcation lesions were included for analysis (44 lesions in DCB group; 38 lesions in DES group; 50 lesions in OMT group). The minimal lumen diameter (MLD) of SB ostium showed an increase at follow-up in the DCB group, whereas a decrease was observed in both the DES and OMT groups (ΔMLD: −0.16 ± 0.45 mm for DCB group vs. 0.50 ± 0.52 mm for DES group vs. 0.08 ± 0.38 mm for OMT group, p < 0.001). The diameter stenosis (DS) of SB ostium showed a marked decrease at follow-up in the DCB group, in contrast to an increase observed in both the DES and OMT groups (ΔDS: 8.01 ± 18.96% for DCB group vs. −18.68 ± 18.60% for DES group vs. −2.05 ± 14.58% for OMT group, p < 0.001).

Conclusions

In de novo coronary bifurcation lesions, DCB treatment on the MV demonstrated favorable angiographic outcomes in the SB ostium at 6–9 month follow-up compared to DES implantation or OMT.