bluuebunny/crossref_metadata_2025 huggingface dataset:
Elevated concentrations of amyloid‐β oligomers and their proapoptotic effects on age‐related cataract
Authors: Lin Peimin , Xu Jie , Yang Fan , Li Dan , Zhang Rong , Jiang Yongxiang , Zheng Tianyu
Published: September 2024

Recently, amyloid‐β oligomers (AβOs) have been studied as the primary pathogenic substances in Alzheimer's disease (AD). Our previous study revealed that the Aβ expression level is closely related to ARC progression. Here, we demonstrated that the accumulation of AβOs in the lens epithelium of age‐related cataract (ARC) patients increased during ARC progression and that this alteration was consistent with the changes in mitochondrial function, oxidative stress, and cellular apoptosis. In vitro, human lens epithelial cells (HLECs) treated with AβOs exhibited Ca2+ dyshomeostasis, impaired mitochondrial function, elevated oxidative stress levels, and increased apoptosis. Moreover, the proapoptotic effect of AβOs was alleviated after the uptake of mitochondrial Ca2+ was inhibited. These results establish that AβOs may promote HLEC apoptosis by inducing mitochondrial Ca2+ overload, thus preliminarily revealing the possible association between the accumulation of AβOs and other pathological processes in ARC.
Disruption of HSD17B12 in mouse hepatocytes leads to reduced body weight and defect in the lipid droplet expansion associated with microvesicular steatosis
Authors: Heikelä Hanna , Mairinoja Laura , Ruohonen Suvi T. , Rytkönen Kalle T. , de Brot Simone , Laiho Asta , Koskinen Satu , Suomi Tomi , Elo Laura L. , Strauss Leena , Poutanen Matti
Published: September 2024

The function of hydroxysteroid dehydrogenase 12 (HSD17B12) in lipid metabolism is poorly understood. To study this further, we created mice with hepatocyte‐specific knockout of HSD17B12 (LiB12cKO). From 2 months on, these mice showed significant fat accumulation in their liver. As they aged, they also had a reduced whole‐body fat percentage. Interestingly, the liver fat accumulation did not result in the typical formation of large lipid droplets (LD); instead, small droplets were more prevalent. Thus, LiB12KO liver did not show increased macrovesicular steatosis with the increasing fat content, while microvesicular steatosis was the predominant feature in the liver. This indicates a failure in the LD expansion. This was associated with liver damage, presumably due to lipotoxicity. Notably, the lipidomics data did not support an essential role of HSD17B12 in fatty acid (FA) elongation. However, we did observe a decrease in the quantity of specific lipid species that contain FAs with carbon chain lengths of 18 and 20 atoms, including oleic acid. Of these, phosphatidylcholine and phosphatidylethanolamine have been shown to play a key role in LD formation, and a limited amount of these lipids could be part of the mechanism leading to the dysfunction in LD expansion. The increase in the Cidec expression further supported the deficiency in LD expansion in the LiB12cKO liver. This protein is crucial for the fusion and growth of LDs, along with the downregulation of several members of the major urinary protein family of proteins, which have recently been shown to be altered during endoplasmic reticulum stress.
MicroRNAs in metabolic dysfunction‐associated diseases: Pathogenesis and therapeutic opportunities
Authors: Ma Ningning , Tan Jiaxin , Chen Yingfen , Yang Liu , Li Man , He Yong
Published: September 2024

Metabolic dysfunction‐associated diseases often refer to various diseases caused by metabolic problems such as glucose and lipid metabolism disorders. With the improvement of living standards, the increasing prevalence of metabolic diseases has become a severe public health problem, including metabolic dysfunction‐associated steatotic liver disease (MASLD), alcohol‐related liver disease (ALD), diabetes and obesity. These diseases are both independent and interdependent, with complex and diverse molecular mechanisms. Therefore, it is urgent to explore the molecular mechanisms and find effective therapeutic targets of these diseases. MicroRNAs (miRNAs) have emerged as key regulators of metabolic homoeostasis due to their multitargets and network regulatory properties within the past few decades. In this review, we discussed the latest progress in the roles of miRNA‐mediated regulatory networks in the development and progression of MASLD, ALD, diabetes and obesity.
What Are We Made For? Mobilizing Medical Education Research for Impact
Authors: Sukhera Javeed , Fung Cha-Chi , Teherani Arianne , Wyatt Tasha R. , Schumacher Daniel J. , Leep Hunderfund Andrea N.
Published: September 2024

During the past several decades, medical education research has advanced in many ways. However, the field has struggled somewhat with translating knowledge into practice. The field has tremendous potential to generate insights that may improve educational outcomes, enhance teaching experiences, reduce costs, promote equity, and inform policy. However, the gap between research and practice requires attention and reflection. In this commentary, the authors reflect on ways that medical education researchers can balance relevance and rigor, while discussing a potential path forward. First, medical education research can learn from implementation science, which focuses on adopting and sustaining best practices in real-world settings. Second, gaining a deeper understanding of the complex and dynamic ways that medical education contexts may influence the uptake of research findings into practice would facilitate the translation and mobilization of knowledge into practical settings. Third, moving from unilateral knowledge translation to participatory knowledge mobilization and engaging diverse stakeholders as active participants in the research process can also enhance impact and influence research findings. Overall, for medical education research to effect meaningful change, it must transition from producing generalizable findings to generating context-specific insights and embracing participatory knowledge mobilization. This shift will involve rethinking traditional research approaches and fostering collaboration with knowledge users to cocreate and implement innovative solutions tailored to their unique settings.
More than pacemakers and defibrillators: perioperative management of implantable devices for patient safety
Authors: Harbell Monica W. , Kraus Molly B. , Lopez-Ruiz Andrea , Gerasimov Madina , Maloney Jillian A.
Published: September 2024

Purpose of review

The use of implantable medical devices (IMDs) continues to increase with estimates that 10% of the American population will have an IMD in their lifetime. IMDs require special considerations for management in the perioperative period to ensure optimal patient care and patient safety. This review summarizes the current perioperative considerations for IMDs.

Recent findings

This review summarizes perioperative recommendations for spinal cord stimulators, deep brain stimulators, peripheral nerve stimulators, vagus nerve stimulators, muscle stimulators, intrathecal drug delivery systems, implantable infusion pumps, artificial pancreas devices, continuous glucose monitors, and cochlear implants. There are multiple publications and guidelines regarding the perioperative considerations of cardiac implantable electronic devices; thus, this review excludes those devices. This review includes recommendations on management of the device perioperatively, the potential complications, and postoperative care of the device.

There are very few guidelines regarding the perioperative management of IMDs. Given the significant impact that these devices have on patient care and safety, evidence-based guidelines should be established.
Educating for success: ambulatory anesthesia training
Authors: Cormier Nicholas R. , Hyman Jaime B. , O’Rourke Michael
Published: September 2024

Purpose of review

This article explores the unique intersection of the challenges confronting ambulatory anesthesiology education and charts a trajectory forward. The proportion of ambulatory, nonoperating room (NORA), and office-based surgical cases continues to rise; however, the requirements for trainees in these settings have remained static. The rapid evolution of the field combined with a limited workforce also makes continuing education essential, and we discuss the current and future states of ambulatory anesthesia education.

Recent findings

Although numerous resources are available across an array of platforms to foster both trainee education and continuing education for practicing anesthesiologists, there is a paucity of current literature evaluating the impact of new curricula developed specifically for ambulatory, NORA, or office-based anesthesiology (OBA).

We begin with an appraisal of the current state of ambulatory anesthesiology training and evaluate the gap between current graduate medical education and trends in ambulatory surgery. We then develop a vision for an ideal state of future ambulatory education for residents as well as anesthesiologists in practice and highlight the priorities necessary to reach this vision.
The electronic health record: does it enhance or distract from patient safety?
Authors: Tewfik George , Rivoli Steven , Methangkool Emily
Published: September 2024

Purpose of review

The electronic health record (EHR) is an invaluable tool that may be used to improve patient safety. With a variety of different features, such as clinical decision support and computerized physician order entry, it has enabled improvement of patient care throughout medicine. EHR allows for built-in reminders for such items as antibiotic dosing and venous thromboembolism prophylaxis.

Recent findings

In anesthesiology, EHR often improves patient safety by eliminating the need for reliance on manual documentation, by facilitating information transfer and incorporating predictive models for such items as postoperative nausea and vomiting. The use of EHR has been shown to improve patient safety in specific metrics such as using checklists or information transfer amongst clinicians; however, limited data supports that it reduces morbidity and mortality.

There are numerous potential pitfalls associated with EHR use to improve patient safety, as well as great potential for future improvement.
Indications and Long-Term Outcomes of Intercalary Reconstruction Techniques for Diaphyseal Bone Tumors
Authors: Barber Helena F. , Kahan Lindsey G. , McDonald Douglas , English D. Ian
Published: September 2024

Objective:

Intercalary reconstruction after resection of diaphyseal bone tumors allows for adjacent-joint preservation; however, despite implant advancements they continue to experience high failure rates. Free fibular autograft (FFA), allograft interposition, and metallic endoprostheses are used, but there is no consensus on optimal construct.

Methods:

We conducted an IRB-approved retrospective review of patients who underwent intercalary reconstruction for oncologic indications at a single institution (1999 to 2022). Inclusion criteria included intercalary reconstruction with FFA, allograft, or endoprosthesis for oncologic indications and with minimum follow-up of 3 months. Primary outcome was implant survival. Secondary outcomes included complication type, rate, and timing, resection length, distance from articular surface, and failure modes.

Results:

Thirty-five patients met inclusion criteria, 23 men and 12 women. Reconstructive options included: FFA (N=8), endoprosthesis (N=16), and allograft (N=11). Average follow-up was 3.9 years. Average patient age was 41.8 years; FFA patients were younger than endoprosthesis patients (P=0.0002). FFAs were closer to the articular surface than endoprostheses (P=0.0003). Overall implant survival was 36.6% at 21 years; median survival was 2.04 years. Overall complication rate was 65.7%, with no difference between groups. Ten patients (28.5%) ultimately ended with a joint-sacrificing operation.

Conclusions:

This study supports the existing literature’s reported high rate of complication and implant failure of intercalary reconstructions. Salvage options are available, including those for secondary joint-sparing operations; however, they often result in a joint-sacrificing endoprosthesis limiting function and longevity. With patients having improved life expectancy for both metastatic and primary bone tumors, implant optimization is critical.
Growth of a Movement Through Spiritual Leadership
Authors: Solari-Twadell P. Ann , McDermott Mary Ann , Schweitzer Roberta , Tippe Carol
Published: September 2024

Faith community nursing often is anchored in a community through local networks that support the development of both the ministry and the faith community nurse. Such local networks are established and sustained through the leadership of faith community nurses (FCNs). A research study interviewed nurses recognized as foundational to the development of FCNs in the United States from 1984 to 2000. The Waterwheel Model of Spiritual Leadership was used as a construct for interviewing 24 FCN leaders discovered through Delphi methodology. An adaptation of Colazzi's method of qualitative analysis was used to analyze data collected in videotaped format. Three predominant themes emerged that may be instrumental to developing future FCN leaders and growth of this specialty nursing practice.
Teaching Application of 3D-printed Models for Nasal Analysis
Authors: Wamkpah Nneoma S. , Cristel Robert T. , O’Connor Zachary , Hanick Andrea , Nguyen Dennis , Chi John J.
Published: September 2024

Background:

A major challenge in learning rhinoplasty is correlating patients’ external and internal nasal structures. We aim to explore the application of three dimensional (3D)-printed models of nasal bony-cartilaginous structures in identifying accurate nasal anatomy.

Methods:

Otolaryngology—head and neck surgery and plastic and reconstructive surgery residents matched patient photograph models, described relative nasal bony-cartilaginous anatomy, completed pre- and postactivity self-evaluations (based on otolaryngology “nasal deformity” milestones including “anatomy,” “function,” “aesthetic,” and “etiology”), and rated the 3D-printed models’ usefulness. Descriptive statistics were measured.

Results:

Thirty-seven residents correctly matched four of six model-photograph pairs and correctly described 15 of 30 anatomic relationships, on average. There was a moderate, statistically significant correlation between postgraduate year and number of correctly matched model-photograph pairs (Spearman rho = 0.58, 95% CI 0.24–0.79) and total items correct (Spearman rho = 0.61, 95% CI 0.28–0.81). Self-ratings on milestones decreased postexercise in all subcategories except “function.” From 0 (low) to 100 (high), learners found the exercise useful (median 85 of 100) with a high recommendation for future use (median 87 of 100).

Conclusions:

Three-dimensional printed models are a valuable tool for understanding nasal anatomy. Continued standardization of designs and assessments of their educational utility will enhance their broader dissemination and implementation.
HKDC1 promotes liver cancer stemness under hypoxia through stabilizing β-catenin
Authors: Fan Li , Tian Cheng , Yang Wentao , Liu Xiaoli , Dhungana Yogesh , Yang Wenjian , Tan Haiyan , Glazer Evan S. , Yu Jiyang , Peng Junmin , Ma Lichun , Ni Min , Zhu Liqin
Published: September 2024

Background and Aims:

Hexokinases (HKs), a group of enzymes catalyzing the first step of glycolysis, have been shown to play important roles in liver metabolism and tumorigenesis. Our recent studies identified hexokinase domain containing 1 (HKDC1) as a top candidate associated with liver cancer metastasis. We aimed to compare its cell-type specificity with other HKs upregulated in liver cancer and investigate the molecular mechanisms underlying its involvement in liver cancer metastasis.

Approach and Results:

We found that, compared to HK1 and HK2, the other 2 commonly upregulated HKs in liver cancer, HKDC1 was most strongly associated with the metastasis potential of tumors and organoids derived from 2 liver cancer mouse models we previously established. RNA in situ hybridization and single-cell RNA-seq analysis revealed that HKDC1 was specifically upregulated in malignant cells in HCC and cholangiocarcinoma patient tumors, whereas HK1 and HK2 were widespread across various tumor microenvironment lineages. An unbiased metabolomic profiling demonstrated that HKDC1 overexpression in HCC cells led to metabolic alterations distinct from those from HK1 and HK2 overexpression, with HKDC1 particularly impacting the tricarboxylic acid cycle. HKDC1 was prometastatic in HCC orthotopic and tail vein injection mouse models. Molecularly, HKDC1 was induced by hypoxia and bound to glycogen synthase kinase 3β to stabilize β-catenin, leading to enhanced stemness of HCC cells.

Conclusions:

Overall, our findings underscore HKDC1 as a prometastatic HK specifically expressed in the malignant compartment of primary liver tumors, thereby providing a mechanistic basis for targeting this enzyme in advanced liver cancer.
Thyroid function and preeclampsia: a two-sample bidirectional Mendelian randomization study
Authors: Li Chu , Sheng Jingjing , Zhang Yawei , Lyu Qiaofei , Yang Liwei , Zhong Zixing
Published: September 2024

Background:

Thyroid dysfunction has been associated with preeclampsia (PE) during pregnancy, but the observational results are conflicting. Our study aims to investigate the causal association and direction between genetically predicted effects of thyroid function on PE and vice versa via two large summary genetic data.

Methods:

We conducted a two-sample bidirectional Mendelian randomization (MR) study using genome-wide association studies (GWAS) summary data from two primarily European cohorts: the ThyroidOmics Consortium and the FinnGen Biobank. We applied the random effects inverse variance weighted (IVW) as our main analysis. MR-Egger and weighted median were used for sensitivity analysis. Statistical analysis was performed using the R program (version 4.3.0) with the two-sample package (version 0.5.6).

Results:

The results suggest that genetically predicted hyperthyroidism is causally associated with PE during pregnancy [β = 0.06, 95% confidence interval (CI): 1.01–1.12; P = 0.02], and genetically predicted hypothyroidism is also causally associated with PE during pregnancy (β = 0.11, 95% CI: 1.03–1.21; P = 0.01). These effects were further confirmed with sensitivity analysis. Conversely, preeclampsia is not associated with the risk of thyroid dysfunction in the reverse MR results: thyroid-stimulating hormone (β = 0.00, P = 0.92), free thyroxine (FT4) (β = −0.01, P = 0.56), triiodothyronine (FT3) (β = −0.00, P = 0.72), FT3/FT4 (β = −0.01, P = 0.38), thyroid peroxidase antibodies (β = −0.01, P = 0.64), hyperthyroidism (β = −0.11, P = 0.29) and hypothyroidism (β = 0.04, P = 0.12).

Conclusion:

Our study suggests that hyper-/hypo-thyroidism causally affected preeclampsia, while PE is not causally associated with thyroid dysfunctions.
Quantification of physiological effect of respiration on automated measurement of blood pressure among normotensive adult individuals
Authors: Mondal Soumyajit , Mukherjee Kalarab , Ghosh Ankita , Ahmed Farhad , Ghosh Tandra
Published: September 2024

Background:

Accurate blood pressure measurement necessitates meticulous methodology, as even minor variations like speaking or sitting can impact the readings. Additionally, respiration plays a role in blood pressure, exhibiting a dip during inhalation and a subsequent increase during exhalation. However, the influence of breathing patterns, duration, and rate on blood pressure remains largely unexplored.

Methods:

In this study, we have attempted to quantify the changes in blood pressure and heart rate (HR) of normotensive individuals while performing predefined respiratory patterns – slow, medium, and fast (respiratory rates of 5, 10, and 20/m, respectively). For each respiratory pattern, age-matched and gender-matched (18–40 years) volunteered normotensive individuals were selected as volunteers. Baseline readings were recorded and each volunteer was randomly allotted a respiratory pattern. The volunteers performed the assigned respiratory pattern while the BP and HR were recorded.

Results:

A fall in both SBP and DBP was observed in all three patterns of respiration. There was no inter-pattern difference in the blood pressure change. A novel finding in our study was a trend of respiratory rate and HR – the change in HR linearly increased with a rise in respiratory rate difference. We also proposed a linear regression equation for this increase in HR with the increase in respiratory rate which was statistically significant.

Conclusion:

The findings suggest the decline in blood pressure is independent of the respiratory pattern employed. The study also demonstrates that the HR is a linear function of respiratory rate.
Serum neutrophil gelatinase-associated lipocalin and cystatin C is associated with blood pressure in ex-preterm children and adolescents
Authors: Chainoglou Athanasia , Sarafidis Kosmas , Taparkou Anna , Farmaki Evangelia , Chrysaidou Katerina , Gidaris Dimos , Kollios Konstantinos , Kotsis Vasilios , Stabouli Stella
Published: September 2024

Background:

As preterm birth is a risk factor for hypertension (HTN), biomarkers for early prediction of HTN in childhood is an emerging need. The aims of the study were to evaluate serum biomarkers in ex-preterm children and examine for associations with office peripheral and central SBP (cSBP), ambulatory BP parameters and pulse wave velocity (PWV).

Methods:

This case–control study included children and adolescents born prematurely (ex-preterms) and at full term (controls). All participants underwent office and ambulatory BP monitoring, assessment of cSBP, PWV and serum biomarkers at the same visit. Neutrophil gelatinase-associated lipocalin (NGAL), matrix metalloproteinase-2, metalloproteinase-9 (MMP-2, MMP-9) and Cystatin C (CysC) were measured using ELISA.

Results:

The study population included 52 ex-preterm individuals and 26 controls. Mean age was 10.7 ± 3.6 years. NGAL, MMP-2, MMP-9, and CysC levels were similar between the ex-preterm and the control group. In the ex-preterm group, NGAL is associated with office SBP z score (β = 1.007, 95% CI 1.001–0.014, P = 0.049), CysC with office DBP z score (β = 1.003, 95% CI 1.001–0.005, P = 0.018) and cSBP z score (β = 1.003, 95% CI 1.001–0.005, P = 0.006) independently of age, sex and BMI z score. Among ex-preterm children and adolescents 17% had ambulatory HTN and 31% had white-coat HTN. NGAL levels were higher in ex-preterm children with WCH compared with children with normal BP [57.9 (IQR 50.8) versus 34.6 (IQR 46.2)], P = 0.018].

Conclusion:

WCH is common in ex-preterm children and adolescents and is associated with higher NGAL levels and CysC presents positive association with cSBP. The findings in this study provides preliminary evidence that NGAL and CysC may have a role in predicting the risk of developing hypertension later in life. Further studies are warranted.
Identification of genomic alteration and prognosis using pathomics-based artificial intelligence in oral leukoplakia and head and neck squamous cell carcinoma: a multicenter experimental study
Authors: Cai Xin-Jia , Peng Chao-Ran , Cui Ying-Ying , Li Long , Huang Ming-Wei , Zhang He-Yu , Zhang Jian-Yun , Li Tie-Jun
Published: September 2024

Background:

Loss of chromosome 9p is an important biomarker in the malignant transformation of oral leukoplakia (OLK) to head and neck squamous cell carcinoma (HNSCC), and is associated with the prognosis of HNSCC patients. However, various challenges have prevented 9p loss from being assessed in clinical practice. The objective of this study was to develop a pathomics-based artificial intelligence (AI) model for the rapid and cost-effective prediction of 9p loss (9PLP).

Materials and methods:

Three hundred thirty-three OLK cases were retrospectively collected with hematoxylin and eosin (H&E)-stained whole slide images and genomic alteration data from multicenter cohorts to develop the genomic alteration prediction AI model. They were divided into a training dataset (n=217), a validation dataset (n=93), and an external testing dataset (n=23). The latest Transformer method and XGBoost algorithm were combined to develop the 9PLP model. The AI model was further applied and validated in two multicenter HNSCC datasets (n=42 and n=365, respectively). Moreover, the combination of 9PLP with clinicopathological parameters was used to develop a nomogram model for assessing HNSCC patient prognosis.

Results:

9PLP could predict chromosome 9p loss rapidly and effectively using both OLK and HNSCC images, with the area under the curve achieving 0.890 and 0.825, respectively. Furthermore, the predictive model showed high accuracy in HNSCC patient prognosis assessment (the area under the curve was 0.739 for 1-year prediction, 0.705 for 3-year prediction, and 0.691 for 5-year prediction).

Conclusion:

To the best of our knowledge, this study developed the first genomic alteration prediction deep learning model in OLK and HNSCC. This novel AI model could predict 9p loss and assess patient prognosis by identifying pathomics features in H&E-stained images with good performance. In the future, the 9PLP model may potentially contribute to better clinical management of OLK and HNSCC.
Utilization of recurrent laryngeal nerve monitoring during thyroid surgery in China: a point prevalence survey (2015–2023)
Authors: Zhao Yishen , Wang Peiyao , Dionigi Gianlorenzo , Kou Jiedong , Li Changlin , Li Fang , Wang Tie , Tian Wen , Jiang Kewei , Wang Ping , Zhang Hao , Sun Hui ,   Chinese Neuromonitoring Study Group (CNMSG)
Published: September 2024

Background:

The survey aimed to elucidate the complete range of national practices, including all technical and non-technical aspects, as well as surgical stratification and maturation, of the use of intraoperative neuromonitoring (IONM) during thyroid surgery in China.

Materials and methods:

Six national questionnaires, developed by the Chinese Neural Monitoring Study Group (CNMSG) between 2015 and 2023, were used to collect and analyze data regarding the clinical application, education, and scientific research related to IONM in Chinese medical institutions.

Results:

Among the surveyed hospitals, 45% reported an average annual surgical volume exceeding 3000 cases, with 82.5% performing more than 80% of the surgeries for malignant thyroid tumors. Additionally, 97.5% of the hospitals reported a less than 3% incidence of postoperative hoarseness with IONM. Statistical analysis from 2011 to 2015 found that the incidence of postoperative hoarseness decreased by 30% in 2013 compared with 2011, when the technology was introduced. Preoperative and postoperative laryngoscopies were routinely performed by 82.5% and 15% of the hospitals, respectively. For 65% of the hospitals, the publication of the Chinese edition of neuromonitoring guidelines in 2013 prompted the utilization of IONM technology. An average annual number of IONM applications exceeding 500 cases (18.5% the average volume) was reported by 80% of the hospitals, while 62.5% reported a cumulative number of applications greater than 5000 cases (47.1% the average cumulative volume). Regarding technical parameters, 75% of the hospitals reported an intraoperative V1 amplitude of greater than 500 µV, and 70% reported an intraoperative loss of signal (LOS) rate of less than 3%. 92.5% of the surveyed hospitals believed that IONM could help identify dissociated nerves, and 95% of the surveyed hospitals believed that IONM could reduce nerve damage. However, 72.5% of the respondents thought that cost was the main limitation. Furthermore, 67.5% of the hospitals reported that half of their thyroid surgical team members were trained in IONM, with 17.5% reporting that all team members were trained. Areas for reinforced training included IONM research methods and directions (72.5%) and analysis and treatment of abnormal EMG signals (72.5%). Research projects related to IONM were conducted by 42.5% of the hospitals, while 52.5% had published papers on neuromonitoring.

Conclusions:

IONM was independently and incrementally associated with the annual surgical volume. This survey emphasized the importance of national collaboration and/or a registry for the uptake, consolidation, and development of CNMSG consensus.
Whole Blood Program: Implementation in a Rural Trauma Center
Authors: Orr Lanny C. , Peterson Alexa L. , Savell Tessa C. , McCotter Elizabeth L. , Palm Craig E. , Arnold Sadie L. , Riha Gordon M. , Thompson Simon J.
Published: September 2024

BACKGROUND:

The balanced transfusion of blood components plays a leading role in traumatic hemostatic resuscitation. Yet, previous whole blood studies have only focused on urban trauma center settings.

OBJECTIVE:

To compare component vs whole blood therapy on wastage rates and mortality in the rural setting.

METHODS:

This study was a nonrandomized, retrospective, observational, single-center study on a cold-stored whole blood program implementation for adult massive transfusions from 2020 to 2022 at a Level II trauma center. Trauma registry data determined the facility’s whole blood needs and facilitated sustainable blood supplies. Whole blood use protocols were established, and utilization and laboratory compliance for incompatible ABO antibody hemolysis was monitored and reviewed monthly at stakeholder and trauma services meetings.

RESULTS:

From 2018 to 2019, the facility initiated component therapy massive transfusions every 9 days (n = 41). Therefore, four units of low-titer, O-positive whole blood delivered fortnightly was determined to provide patient coverage and minimize wastage. Across the study time frame (2020–2022), there were n = 68 hemodynamically unstable patients, consisting of those receiving whole blood, n = 37, and patients receiving component therapy, n = 31. Mortality rates were significantly lower (p = .030) in the whole blood population (n = 3, 8%) compared to those solely receiving component therapy (n = 9, 29%). Wastage rates were constantly evaluated; in 2021, 43.4% was not utilized, and in 2022, this was reduced to 38.7%. Anecdotally, nurses appreciated the ease of administration and documentation of transfusing whole blood, as it negated ratio compliance.

CONCLUSION:

This evidence-based whole blood program provides vital care to severely injured trauma patients in a vast, rural region.
Caring for Persons with Alzheimer's Disease during a Pandemic
Authors: Kokoszka Lori , Pariseault Christine , Pariseault Christine A. , Hunter Devon
Published: September 2024

The population experiencing Alzheimer's disease (AD) and their caregivers have been tremendously impacted by the global COVID-19 pandemic. Outpatient services became less accessible during the pandemic lockdown which caused increased caregiver burden more than usual. Further examination discovered that caregivers were unable to properly take care of themselves because of the need to provide around-the-clock care to loved ones, who pre-pandemic were able to receive supplemental caregiving services. The purpose of this integrative review was to provide a synthesis of information regarding caregiver experiences, during a time of limited resources, such as with the COVID-19 global pandemic. A comprehensive search of the literature databases Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Medline was completed yielding qualitative and mixed-methods studies. The literature search yielded 14 articles which met the criteria. Three themes emerged during this review. They include: Deprivation of self-care and social connectedness, Fragmented care and resources, and Improved policy development. Multiple gaps in caregiver needs have been identified throughout the literature. Outpatient services, home health aides, and respite care remain necessary elements of care for those with AD and for the relief of the caregiver. Forward planning should include government policies to support caregiving of those with AD, especially in the light of service restrictions or unavailable services.
The Effect of Treatment Adherence on Health Status of Outpatients with Chronic Obstructive Pulmonary Disease
Authors: Trieu Nguyen Thi Thu , Upvall Michele , Hoai Nguyen Thi Yen , Thuy Pham Thi , Long Tran Van , Phuong Nguyen Thi Anh
Published: September 2024

Adherence to COPD treatment plays a crucial role in patient health outcomes. Understanding the correlation between treatment adherence and health status is vital for clinicians to develop effective disease management strategies. This study aimed to examine treatment adherence and its impact on the health status of COPD patients, specifically focusing on the effects of adhering to inhaled medications and breathing exercises. A cross-sectional study involving 420 outpatients diagnosed with COPD was conducted. The study encompassed administering questionnaires, observing patient breathing exercises, and measuring ventilatory function. Results showed that only 36.9% of participants adhered to treatment, with 44.7% following inhaler protocols and 36.9% regularly engaging in breathing exercises. The patients who were non-adherent exhibited a 0.3-fold increase in disease severity compared to the adherent group (p = .002). These findings suggest that consistent adherence to treatment, including inhaled medications and breathing exercises, may positively affect health status by reducing disease severity and airway obstruction in COPD patients. To address this, we recommend that home care clinicians implement a post-discharge assessment and intervention program. This program should focus on educating patients about the importance of treatment adherence and promoting behaviors that reinforce adherence to prescribed therapies.
A study of attention allocation mode in clinical decision-making in nurses with different professional titles: An eye-tracking experiment
Authors: Hou Chenxin , Jin Xiaoyan , Xu Weiran , Zhang Jianxia , Ma Li , Guo Jinyu , Shang Shaomei
Published: September 2024

Objective:

The aim of this experiment was to investigate the way in which attention is allocated in the clinical decision-making process of nurses of different professional ranks and titles and associated factors.

Methods:

Seventy-six subjects from the emergency departments of 3 hospitals in Beijing were recruited in this experiment using the convenience sampling method, including 28 junior nurses, 24 senior nurses, and 24 supervisor nurses. Subjects were required to complete clinical decision tasks, and data on subjects’ visual behavior were recorded and analyzed using a Tobii Pro eye-tracker during the decision-making process.

Results:

Nurses with high professional titles had a higher correct response rate in the nursing diagnosis and ranking of nursing diagnoses part (P < 0.05), and it was found that nurses with high professional titles would pay attention to pathophysiological mechanisms of illness earlier when making decisions (F = 3.808, P = 0.024). The heat maps showed differences in the attention allocation modes of nurses with different titles during the decision-making process.

Conclusions:

Lower-titled nurses focused more on the symptoms and signs section when making clinical decisions and paid less attention to the auxiliary examination results section, demonstrating a poorer level of active attention. Nurses with higher titles were relatively more comprehensive in their distribution of attention to patient disease information when making decisions and paid attention to the information in the patient’s auxiliary examination section earlier.
Alar base symmetry in orthognathic surgery: Patients with unilateral cleft
Authors: Fukuyama Sotatsu , Saito Takafumi , Lo Lun-Jou
Published: September 2024

Background:

Patients with unilateral cleft lip and palate (UCLP) could present with a notable nasal deformity with alar base retrusion, which should be considered when planning orthognathic surgery (OGS).

Methods:

This retrospective study included 84 patients with Class III malocclusion. Cone beam computed tomographic data were used for the investigation. 42 patients had complete UCLP, and the other 42 did not have a cleft. All the patients underwent preoperative virtual surgical planning. Preoperative and postoperative images were used to measure anteroposterior changes in the bone and soft tissue at the alar bases.

Results:

In the UCLP group, varying degrees of alar base discrepancies were observed before surgery. In the piriform region of the cleft side, the bone was retruded in 32 cases, but the soft tissue was thicker in 38 cases, and the mean skin surface was anterior in 28 cases. After surgery, the bone discrepancy was not significantly changed (p = 0.288), however, the skin surface symmetry was improved (p = 0.013). Relating to the bone advancement, the ratio of soft tissue change was smaller on the cleft side than the noncleft side (0.56 ± 0.30 vs. 0.77 ± 0.33, p < 0.001). In the control group, a consistent ratio change was observed on both sides (0.76 ± 0.19 vs. 0.79 ± 0.27, p = 0.544).

Conclusions:

This study revealed improved alar base symmetry in patients with UCLP after OGS. The soft tissue change ratios were different across the cleft, which should be considered during treatment planning.
Education for people with serious chronic respiratory diseases and their informal caregivers: how to address challenges that impact learning
Authors: Muijsenberg Anouk J.L. , Houben-Wilke Sarah , Spruit Martijn A. , Janssen Daisy J.A.
Published: September 2024

Purpose of review

Shared decision making is crucial in palliative care for people with serious chronic respiratory diseases and their informal caregivers. Patient education is a critical component in this process, as it provides patients and their informal caregivers the necessary knowledge for informed decisions regarding symptom management, coping with breathlessness, and advance care planning. However, education does not automatically lead to acquiring knowledge. This review describes challenges for education for people with serious chronic respiratory diseases and their informal caregivers and describes how learner-centered education can address these.

Recent findings

People with serious chronic respiratory diseases and their informal caregivers face diverse information needs and learning challenges, with low health literacy and cognitive problems being common. Healthcare professionals can facilitate learner-centered education by enhancing motivation for knowledge acquisition by meeting information needs and learning preferences of patients and their informal caregivers, and by ensuring that information is understandable and readable for those with low health literacy and cognitive problems. E-health applications may serve as valuable tools in this process.

Learner-centered education may enhance knowledge acquisition in people with serious chronic respiratory diseases and their informal caregivers aiming to gain control over symptoms and optimize shared decision making and advance care planning.
Enterotoxigenic Escherichia coli in Blantyre, Malawi
Authors: Ashton Philip , Katuah Zefaniah Joel , Botomani Arnold , Kutambe Belson M. , Cunliffe Nigel A. , von Mentzer Astrid , Msefula Chisomo , Jere Khuzwayo C.
Published: September 2024

We announce the deposition of the first two enterotoxigenic Escherichia coli (ETEC) genomes from Malawi. They were isolated from the faeces of asymptomatically infected children obtained in 2014. Both genomes encode the porcine variant of the heat labile toxin and no known ETEC colonisation factors.
Identifying deleterious noncoding variation through gain and loss of CTCF binding activity
Authors: Tubbs Colby , Benton Mary Lauren , McArthur Evonne , Capra John A. , Ruderfer Douglas M.
Published: September 2024

Noncoding single nucleotide variants are the predominant class of genetic variation in whole genome sequencing and are key drivers of phenotypic variation. However, their functional annotation remains challenging. To address this, we develop a hypothesis-driven functional annotation scheme for CTCF binding sites given CTCF’s critical roles in gene regulation and extensive profiling in regulatory datasets. We synthesize CTCF’s binding patterns at 1,063,879 genomic loci across 214 biological contexts into a summary metric, which we refer to as binding activity. We find that binding activity is significantly enriched for both conserved nucleotides (Pearson R = 0.31, p < 2.2 x 10-16) and sequences that contain high-quality CTCF binding motifs (Pearson R = 0.63, p = 2.9 x 10-12). We then integrate binding activity with high confidence change in precision weight matrix scores. By applying this framework to 1,253,330 SNVs in gnomAD, we explore signatures of selection acting against the disruption of CTCF binding. We find a strong, positive relationship between the mutability adjusted proportion of singletons (MAPS) metric and the loss of CTCF binding at loci with highin vitroactivity (Pearson R = 0.67, p = 1.5 x 10-14). To contextualize these findings, we apply MAPS to other functional classes of variation and find that a subset of 198,149 loss of CTCF binding variants are observed as infrequently as missense variants. This work implicates these thousands of rare, noncoding variants that disrupt CTCF binding for further functional studies while providing a blueprint for the interpretable annotation of noncoding variants.
Machine Learning Driven Optimization for High Precision Cellular Droplet Bioprinting
Authors: Shin Jaemyung , Kang Minseok , Hyun Kinam , Li Zhangkang , Kumar Hitendra , Kim Kangsoo , Park Simon S. , Kim Keekyoung
Published: September 2024

Controlled volume microliter cell-laden droplet bioprinting is important for precise biologics deposition, reliably replicating 3D microtissue environments for building cell aggregates or organoids. To achieve this, we propose an innovative machine-learning approach to predict cell-laden droplet volumes according to input parameters. We developed a novel bioprinting platform capable of collecting high-throughput droplet images and generating an extensive dataset for training machine learning and deep learning algorithms. Our research compared the performance of three machine learning and two deep learning algorithms that predict droplet volume based on numerous bioprinting parameters. By adjusting bioink viscosity, nozzle size, printing time, printing pressure, and cell concentration as input parameters, we precisely could control droplet sizes, ranging from 0.1 µL to 50 µL in volume. We utilized a hydrogel precursor composed of 5% gelatin methacrylate and a mixture of 0.5% and 1% alginate, respectively. Additionally, we optimized the cell bioprinting process using green fluorescent protein-tagged 3T3 fibroblast cells. These models demonstrated superior predictive accuracy and revealed the interrelationships among parameters while taking minimal time for training and testing. This method promises to advance the mass production of organoids and microtissues with precise volume control for various biomedical applications.
Interference with Systemic Negative Feedback Regulation as a Potential Mechanism for Nonmonotonic Dose-Responses of Endocrine-Disrupting Chemicals
Authors: Shi Zhenzhen , Xiao Shuo , Zhang Qiang
Published: September 2024

Background

Endocrine-disrupting chemicals (EDCs) often exhibit nonmonotonic doseresponse (NMDR) relationships, posing significant challenges to health risk assessment and regulations. Several molecular mechanisms operating locally in cells have been proposed, including opposing actions via different receptors, mixed-ligand heterodimer formation, and receptor downregulation. Systemic negative feedback regulation of hormone homeostasis, which is a common feature of many endocrine systems, has also been invoked as a mechanism; however, whether and how exactly such global feedback structure may underpin NMDRs is poorly understood.

Objectives

We hypothesize that an EDC may compete with the endogenous hormone for receptors (i) at the central site to interfere with the feedback regulation thus altering the physiological hormone level, and (ii) at the peripheral site to disrupt the hormone action; this dual-action may oppose each other, producing nonmonotonic endocrine effects. The objective here is to explore – through computational modeling – how NMDRs may arise through this potential mechanism and the relevant biological variabilities that enable susceptibility to nonmonotonic effects.

Methods

We constructed a dynamical model of a generic hypothalamic-pituitary-endocrine (HPE) axis with negative feedback regulation between a pituitary hormone and a terminal effector hormone (EH). The effects of model parameters, including receptor binding affinities and efficacies, on NMDR were examined for EDC agonists and antagonists. Monte Carlo human population simulations were then conducted to systemically explore biological parameter conditions that engender NMDR.

Results

When an EDC interferes sufficiently with the central feedback action of EH, the net endocrine effect at the peripheral target site can be opposite to what is expected of an agonist or antagonist at low concentrations. J/U or Bell-shaped NMDRs arise when the EDC has differential binding affinities and/or efficacies, relative to EH, for the peripheral and central receptors. Quantitative relationships between these biological variabilities and associated distributions were discovered, which can distinguish J/U and Bell-shaped NMDRs from monotonic responses.

Conclusions

The ubiquitous negative feedback regulation in endocrine systems can act as a universal mechanism for counterintuitive and nonmonotonic effects of EDCs. Depending on key receptor kinetic and signaling properties of EDCs and endogenous hormones, some individuals may be more susceptible to these complex endocrine effects.
Projection Statistics – ProST: Online statistical assessment of group separation in data projection analysis
Authors: Salem Danny , Surendra Anuradha , McDowell Graeme SV , Čuperlović-Culf Miroslava
Published: September 2024

Motivation

Unsupervised data projection for the determination of trends in the data, visualization of multidimensional data in a reduced dimension space or feature space reduction through combination of data is a major step in data mining. Methods such as Principal Component Analysis or t-Distribution Stochastic Neighbor Embedding are regularly used as one of the first steps in computational biology or omics investigation. However, the significance of the separation of sample groups by these methods generally relies on visual assessment. User-friendly application for different projection methods, each focusing on distinct data properties, are needed as well as a rigorous method for statistical determination of the significance of separation of groups of interest in each dataset.

Results

We present Projection STatistics (ProST), a user-friendly solution for data projection analysis providing three unsupervised (PCA, t-SNE and UMAP) and one supervised (LDA) approach. For each method we are including a novel statistical investigation of the significance of group separation with Mann-Whitney U-rank or t-test analysis as well as necessary preprocessing steps. ProST provides an unbiased, objective application of the determination of the significance of the separation of measurement groups through either linear or manifold projection analysis with methods ranging from a focus on the separation of points based on major variances or on point proximities based on distance.

Availability

The ProST software application is freely available athttps://complimet.ca/shiny/ProST/with source code provided onhttps://github.com/complimet/prost.

Contact

danny.salem@nrc-cnrc.gc.caorMiroslava.cuperlovic-culf@nrc-cnrc.gc.ca

Supplementary information

Supplementary help pages are provided athttps://complimet.ca/shiny/ProST/.