bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Type D Personality, Role Strain, and Diabetes Distress on Depression in Women With Type 2 Diabetes: A Cross-Sectional Study
Authors: CHEN Shi-Yu , HSU Hui-Chun , HUANG Chiu-Ling , CHEN Yi-Hsuan , WANG Ruey-Hsia
Published: January 2023

Background

Women with diabetes face a significantly elevated risk of developing depression. Clarifying the factors associated with depression is critical to designing more timely interventions for this vulnerable population.

Purpose

This study was developed to examine the impact of Type D personality, diabetes-care-related role strain, and diabetes-related distress on depression in women with Type 2 diabetes.

Methods

A cross-sectional design was used. Convenience sampling was used to recruit 298 women aged 20–64 years who had been diagnosed with Type 2 diabetes for over 6 months from three outpatient endocrine clinics in Taiwan. Demographic and disease characteristics and Type D personality (negative affectivity and social inhibition), diabetes-care-related role strain, and diabetes-related distress and depression status information were collected using self-reported questionnaires and medical records. The important factors of influence on depression were examined using hierarchical multiple regression.

Results

On the basis of the results of the hierarchical multiple regression analysis, age, negative affectivity, diabetes-care-related role strain, and diabetes-related distress were identified as significantly associated with depression, with negative affectivity explaining most (43.4%) of the variance in depression, followed by diabetes-care-related role strain and diabetes-related distress, which respectively explained 3% and 2.5% of the variance.

Conclusions/Implications for Practice

The negative affectivity associated with the Type D personality was shown to be more significantly associated with depression than diabetes-related psychosocial factors such as diabetes-related distress and diabetes-care-related role strain. Timely assessment of negative affectivity and the provision of brief mindfulness intervention to reduce negative affectivity may be useful in preventing depression in women with Type 2 diabetes, whereas addressing diabetes-related distress and diabetes-care-related role strain should not be neglected when providing comprehensive depression-preventing interventions to young women with diabetes.
An Outpatient-Based Training Program Improves Family Caregivers' Preparedness in Caring for Persons With Mild Cognitive Impairment: A Randomized Controlled Trial
Authors: TUNG Yi-En , KUO Li-Min , CHEN Min-Chi , HSU Wen-Chuin , SHYU Yea-Ing Lotus
Published: January 2023

Background

Little is known regarding the effects of training programs on family caregivers of older persons with mild cognitive impairment because of the significant differences in outcome variables measured in the various studies in the literature.

Purpose

This study was designed to examine the effects of an outpatient-based caregiver training program on the preparedness, health-related quality of life, and depressive symptoms of participants responsible for caring for older persons with mild cognitive impairment.

Methods

A randomized clinical trial was implemented. Of the 54 family caregiver participants who provided complete and valid data, 28 and 26 were assigned to the experimental and control groups, respectively. The experimental group participated in a researcher-developed training program that provided information on mild cognitive impairment, strategies for maintaining and promoting cognitive function in persons with mild cognitive impairment, managing their own and their care recipients' healthcare, and managing their own emotional support and stress. Outcomes (caregiver preparedness, health-related quality of life, and depressive symptoms) were assessed before the start of the training program (baseline) and at 1, 3, and 6 months after completion of the program.

Results

After controlling for baseline cognitive function of the care recipients and of caregiver preparedness, the experimental group was shown to be significantly less prepared than the control group at baseline (β = −1.41, p = .031) and better prepared than the control group at all three posttests (group differences: 1.3, 1.53, and 4.24, respectively), with the difference at the third posttest (6 months) reaching statistical significance (p = .008). No impact of the intervention on caregiver depressive symptoms or health-related quality of life was found at posttest.

Conclusions

The training intervention in this study was found to increase the perceived preparedness of the family caregiver participants to handle various aspects of providing care to persons with mild cognitive impairment. However, no changes were found in depressive symptoms or health-related quality of life.
Six-Minute walk distance predicts outcomes in liver transplant candidates
Authors: Cox-Flaherty Katherine , Moutchia Jude , Krowka Michael J. , Al-Naamani Nadine , Fallon Michael B. , DuBrock Hilary , Forde Kimberly A. , Krok Karen , Doyle Margaret F. , Kawut Steven M. , Ventetuolo Corey E.
Published: January 2023

A 6-minute walk test is a simple tool for assessing submaximal exercise capacity. We sought to determine whether a 6-minute walk distance (6MWD) predicts outcomes in patients with cirrhosis. The Pulmonary Vascular Complications of Liver Disease 2 study is a multicenter, prospective cohort study that enrolled adults with portal hypertension during liver transplantation evaluation. We excluded subjects with an incident or prevalent portopulmonary hypertension. The 6-minute walk test was performed using standardized methods. Cox proportional hazards modeling and multivariable linear regression analysis were performed to determine the relationship between baseline 6MWD and outcomes. The study sample included 352 subjects. The mean 6MWD was 391±101 m. For each 50-meter decrease in 6MWD, there was a 25% increase in the risk of death (HR 1.25, 95% CI [1.11, 1.41], p < 0.001) after adjustment for age, gender, body mass index, MELD-Na, and liver transplant as a time-varying covariate. In a multistate model, each 50-meter decrease in 6MWD was associated with an increased risk of death before the liver transplant (p < 0.001) but not after the transplant. 6MWD was similar to MELD-Na in discriminating mortality. Each 50-meter decrease in 6MWD was associated with an increase in all-cause (p < 0.001) and transplant-free hospitalizations (p < 0.001) in multivariable models for time-to-recurrent events. Shorter 6MWD was associated with worse Short Form-36 physical (p < 0.001) and mental component scores (p = 0.05). In conclusion, shorter 6MWD is associated with an increased risk of death, hospitalizations, and worse quality of life in patients evaluated for liver transplantation. The 6-minute walk distance may be a useful adjunct for risk assessment in patients undergoing liver transplant evaluation.
Identifying the Distinct Profiles of Transition Readiness in Chinese Pediatric Cancer Survivors
Authors: Cheng Lei , Mao Xiaorong , Chen Qiurong , Pu Huarong , Yu Ling
Published: January 2023

Background

Transition readiness is important for pediatric cancer survivors who need to move from pediatric to adult medical care. However, their transition readiness profiles merit further exploration.

Objectives

The aim of this study was to use a person-centered approach to identify transition readiness profiles of Chinese pediatric cancer survivors aged 12 to 18 years, diagnosed at least 6 months before the study.

Methods

Transition readiness was assessed using the Chinese TRANSITION-Q Scale, and latent class analysis was performed to identify the transition readiness profiles as well as demographic and clinical factors associated with profile classification and to examine how self-efficacy and quality of life may differ between these profiles.

Results

A total of 139 pediatric cancer survivors were included. Three different transition readiness profiles were identified: high transition readiness, medium transition readiness, and low transition readiness. Age, treatment status, and parental working status were significantly associated with the transition readiness profile classifications. Those who were in the low transition readiness profile were likely to have lower self-efficacy and mobility scores than those in the high or medium transition readiness profiles.

Conclusions

Three distinct transition readiness profiles existed in a sample of Chinese pediatric cancer survivors, indicating significant heterogeneity in their transition readiness.

Implications for Practice

Knowledge of transition readiness profiles can assist clinicians in screening pediatric cancer survivors for their profile memberships and provide targeted interventions for those with a low transition profile.
Effects of a Virtual Reality-Based Meditation Intervention on Anxiety and Depression Among Patients With Acute Leukemia During Induction Chemotherapy
Authors: Zhang Bixia , Jin XiaoHuan , Kuang Xiaolin , Shen Biyu , Qiu Dingrong , Peng Jinrui , Chen Erhui , Dai Xiping , Chen Xiaoling , Wong Cho Lee
Published: January 2023

Background

Emerging evidence supports that virtual reality (VR)–based meditation interventions may improve anxiety and depression among patients with cancer. However, empirical studies involving patients with acute leukemia during induction chemotherapy are limited.

Objective

This study aimed to examine the effects of VR-based meditation intervention on alleviating anxiety and depression and improving the quality of life among patients with acute leukemia during induction chemotherapy.

Methods

This randomized controlled trial recruited 63 patients newly diagnosed with acute leukemia. Participants were randomly assigned to an intervention group (received VR-based meditation for 20 min daily for 14 days) and a control group. Anxiety, depression, and quality of life were measured using the State Anxiety Inventory, the Center for Epidemiological Studies Depression Scale, and the Functional Assessment of Cancer Therapy-Leukemia Questionnaire, respectively. All outcomes were measured at baseline and post-intervention.

Results

Compared with patients in the control group, those in the intervention group demonstrated a significantly greater reduction in anxiety (P= .04) and improvement in quality of life (P= .04). However, no significant difference was noted in depression levels between groups (P= .09), although a decreasing trend was observed in the intervention group.

Conclusion

Virtual reality–based meditation intervention effectively alleviated anxiety and improved the quality of life among acute leukemia patients during induction chemotherapy. Future randomized controlled trials with larger sample sizes and longer follow-up periods are warranted.

Implication for Practice

Virtual reality–based meditation can be applied in clinical practice virtually anytime and anywhere to provide a convenient intervention for anxiety reduction for acute leukemia patients during induction chemotherapy.
Perceptions of Authentic Nurse Leader Attributes Among Clinical Nurses and Nurse Leaders
Authors: Giordano-Mulligan Marie , Moran-Peters Judith Ann , Eckardt Sarah
Published: January 2023

OBJECTIVE

This study aimed to develop and validate a tool to measure authentic nurse leadership (ANL) from the perspective of nurse leaders.

BACKGROUND

The COVID-19 pandemic heightened the need for ANL to establish healthy work environments (HWE) that promote positive outcomes.

METHODS

A nonexperimental design and exploratory psychometric analysis developed and validated the Authentic Nurse Leadership Questionnaire for Nurse Leaders (ANLQ-NL) instrument. Relationships were explored between ANLQ-NL and HWE, as measured by the Areas of Worklife Survey (AWS). The Marlowe-Crowne Social Desirability Scale (MC-SDS) was used to measure the nurse leaders' tendency to produce socially desirable responses. The sample consisted of 188 nurse leaders from several US hospitals.

RESULTS

The ANLQ-NL instrument was found to be valid and highly reliable. Each of the constructs aligned with the ANL conceptual framework.

CONCLUSION

The ANL conceptual framework and instruments (ANLQ and ANLQ-NL) can be used for educational programs aimed at developing ANL attributes among nurses.
Retaining the Best
Authors: Sweeney Cynthia Divens , Wiseman Rebecca
Published: January 2023

OBJECTIVE

The purpose of this study was to identify what meaningful recognition is to nurses in a postpandemic healthcare landscape.

BACKGROUND

The COVID pandemic has exacerbated the critical need to retain our nursing workforce. Meaningful recognition as a component of a healthy work environment can be a strategy to retain nurses. Identifying what is considered meaningful recognition to nurses will optimize organizational use of it.

METHODS

A descriptive correlational design was used. Members of Sigma Theta Tau in the state of Maryland were asked to respond to an online survey consisting of demographic data and questions exploring meaningful recognition and the healthy work environment using tools with established reliability and validity. Deidentified data from 163 respondents were collected.

RESULTS

Meaningful recognition strategies that meant the most to nurses in this study were: 1) reasonable payment for level of service provided; 2) public recognition within the organization and the profession; and 3) opportunities for professional development. Trends in desired meaningful recognition varied across ethnic/racial and gender groups.

CONCLUSIONS

Meaningful recognition to nurses is as diverse as the nursing population. It is important that instruments be developed to capture the rich cultural and ethnic differences in relation to what is considered meaningful recognition to the nursing workforce. Although pay, public recognition, and opportunities for advancement were seen in this study as important forms of meaningful recognition, a deeper exploration across ethnic, racial, and gender groups is needed. This study underscored that one size of meaningful recognition does not fit all.
A Roadmap to a Comprehensive Evaluation of a Clinical Ladder Program
Authors: Leamon Min , Zedreck-Gonzalez Judith , Coe Paula , Fennimore Laura
Published: January 2023

Clinical ladder programs were designed to support nurse retention and professional development. Hospital systems are vigorously working to recover from the critical staffing shortages exacerbated by the pandemic. The Centers for Disease Control and Prevention framework for program evaluation was utilized to assess a hospital professional nurse clinical ladder. These findings suggest favorable outcomes in commitment to stay and professional development. This evaluation can serve as a potential resource for organizations to evaluate and enhance programs to support nurse retention.
“Could this be cancer?” Addressing diagnostic delay disparities in adolescents and young adults with cancer through targeted awareness and mitigation of barriers to help-seeking behaviors
Authors: Larsen Lorna L. V.
Published: January 2023

Adolescents and young adults (AYAs) with cancer worldwide face unique challenges throughout the course of their disease. Disproportionately long diagnostic delays have been identified as one of the disparities in their care. Decreasing delays in diagnosis requires a multifaceted approach targeting a number of stakeholders including well AYAs and ultimately AYAs with cancer not yet diagnosed. Identifying help-seeking barriers and taking steps to mitigate them has the potential to reduce diagnostic intervals and improve outcomes. AYAs need to understand their cancer risk and early cancer warning signs and be reassured about high cure rates for early cancer. Effective health promotion approaches designed to reach AYAs with symptoms and early detection messages help reduce help-seeking barriers and empower AYAs to ask the question “Could this be cancer?” Upstream cancer awareness and education strategies have the potential to expedite time to diagnosis and treatment, decrease distress, improve patient outcomes, and reduce survivorship disparities.
Concomitant occurrence of acute motor axonal neuropathy in systemic lupus erythematosus
Authors: Lee Mirim , Lee Chang Hee , Ko Jun Young , Kim Aram
Published: January 2023

Few case reports exist on the association of acute motor axonal neuropathy (AMAN), a subtype of the Guillain–Barre syndrome (GBS), with systemic lupus erythematosus (SLE). Standard therapeutic guidelines for concomitant AMAN and SLE in the acute phase are not established, and no studies have reported physical medicine and rehabilitation perspective management in the plateau and recovery phases. A 50-year-old woman with SLE presented with upper- and lower-limb weakness that progressed to an inability to walk. Neurological examination, radiologic evaluation, serologic analysis, and electrodiagnostic study were conducted, and she was diagnosed with AMAN. Subsequently, intravenous immunoglobulin therapy was administered. She complained of residual upper and lower extremity weakness and an inability to walk 3 months after symptom onset. She underwent an intensive inpatient rehabilitation program for 6 weeks, and showed remarkable recovery in muscle strength and functional status (Berg balance scale, modified Barthel index, and GBS disability scale). To our knowledge, this is the first reported case that focused on the functional outcomes after the rehabilitation program in AMAN with a history of SLE. This case report emphasizes the need for rehabilitation intervention for functional recovery in the plateau and recovery phases.
Emerging Challenges to Cellular Therapy of Cancer
Authors: Lulla Premal D. , Brenner Malcolm
Published: January 2023

Cellular immunotherapy of cancer in the form of chimeric antigen receptor–modified T-cell therapy has become a standard treatment for lymphoid and more recently plasma cell malignancies. Although their successes in these cancers represent a breakthrough for adoptive cell therapy, there are several challenges to their continued growth in the field of cancer medicine. In this review, we discuss the progress made thus far toward achieving “off-the-shelf” accessibility of cell therapies that has the potential to greatly offset the costs associated with the current practice of making patient-specific products. We also review the innovations under investigation that attempt to make cellular therapy applicable to solid tumors as well.
Transcription Factors and Cancer
Authors: Shiah Jamie V. , Johnson Daniel E. , Grandis Jennifer R.
Published: January 2023

Cancer is defined by the presence of uncontrollable cell growth, whereby improper proliferative signaling has overcome regulation by cellular mechanisms. Transcription factors are uniquely situated at the helm of signaling, merging extracellular stimuli with intracellular responses. Therefore, this class of proteins plays a pivotal role in coordinating the correct gene expression levels for maintaining normal cellular functions. Dysregulation of transcription factor activity unsurprisingly drives tumorigenesis and oncogenic transformation. Although this imparts considerable therapeutic potential to targeting transcription factors, their lack of enzymatic activity renders intervention challenging and has contributed to a sense that transcription factors are “undruggable.” Yet, enduring efforts to elucidate strategies for targeting transcription factors as well as a deeper understanding of their interactions with binding partners have led to advancements that are emerging to counter this narrative. Here, we highlight some of these approaches, focusing primarily on therapeutics that have advanced to the clinic.
Streamlining and Consistency in Surgery: Lean-Six-Sigma to Improve Operating Room Efficiency
Authors: Tanna Neil , Clappier Mona , Barnett Sarah L. , Talamini Mark A. , Coppa Gene F. , Cifu Kelly , Bianculli Andrea R. , Drummond Donna , Bello Stephen , Smith Mark L.
Published: January 2023

Introduction:

Improving peri-operative efficiency helps reduce unnecessary surgical expenditure, increase operating room (OR) throughput, improve patient safety, and enhance staff and patient satisfaction. Lean Six-Sigma (LSS) is a quality improvement model that has been successfully applied to eliminate inefficiencies in the business sector but has not yet been widely adopted in medicine. This study investigates the adaptation of LSS to improve operative efficiency for plastic surgery procedures.

Methods:

The authors followed the Define, Measure, Analyze, Improve, and Control (DMAIC) phases to implement LSS. The key outcome measures gathered were operative times, including the cut-to-close time and the total time the patient spent in the operating room.

Results:

The study included a total of 181 patients who underwent immediate bilateral DIEP flap breast reconstruction between January 2016 and December 2019. The LSS interventions were associated with a decrease in total operative time from 636.36 minutes to 530.35 minutes, and a decrease in the time between incision to closure from 555.16 minutes to 458.85 minutes for a bilateral mastectomy with immediate DIEP flap breast reconstruction.

Conclusion:

This study demonstrates that Lean-Six-Sigma is useful to improve peri-operative efficiency during complex plastic surgery procedures. The workflow of the procedure was improved by determining the optimal spatial positioning and distinct roles for each surgeon and preparing surgeon-specific surgical trays. Two process maps were developed to visualize the positioning of the surgeons during each stage of the procedure and depict the parallel workflow that helped improve intraoperative efficiency.
Early Antiretroviral Therapy Reduces Severity but Does Not Eliminate Neurodevelopmental Compromise in Children With HIV
Authors: Benki-Nugent Sarah , Tamasha Nancy , Mueni Alice , Laboso Tony , Wamalwa Dalton C. , Njuguna Irene , Gómez Laurén , Tapia Kenneth , Bangirana Paul , Maleche-Obimbo Elizabeth , Boivin Michael J. , John-Stewart Grace C.
Published: January 2023

Background:

Early antiretroviral therapy (ART) during infancy reduces cognitive impairment due to HIV, but the extent of benefit is unclear.

Setting:

Children were recruited from hospital and health centers providing HIV care and treatment in Nairobi, Kenya.

Methods:

Cognitive, behavioral, and motor outcomes were assessed in children with HIV and early ART (<1 year), children with HIV and late ART (1.5–6 years), and children HIV–unexposed uninfected (CHUU). Domain z scores and odds neurobehavioral impairment (≤15th percentile in CHUU) were compared in adjusted analyses.

Results:

Children with HIV initiated ART at median ages 0.4 (early ART) and 3.5 years (late ART). Children were assessed at median ages 6.9 (CHUU, N = 61), 6.9 (early ART, N = 54), and 13.5 (late ART; N = 27) years. Children with late ART vs. children with early ART had significantly lower z scores in 7 domains, specifically global cognition, short-term memory, visuospatial processing, learning, nonverbal test performance, executive function, and motor skills (adjusted mean differences, −0.42 to −0.62, P values ≤ 0.05), and had higher odds impairment in 7 domains (adjusted odds ratios [aORs], 2.87 to 16.22, P values ≤ 0.05). Children with early ART vs. CHUU had lower z scores in 5 domains (global cognition, short-term memory, delayed memory, processing speed, and behavioral regulation [adjusted mean differences, −0.32 to −0.88, P values < 0.05]) and higher impairment for 2 domains (short-term memory [aOR, 3.88] and behavioral regulation [aOR 3.46], P values < 0.05). Children with late ART vs. CHUU had lower z scores in 8 domains (adjusted mean differences, −0.57 to −1.05, P values ≤ 0.05), and higher impairment in 7 domains (aORs 1.98 to 2.32, P values ≤ 0.05).

Conclusion:

Early ART in the first year of life attenuates but does not eliminate the neurodevelopmental compromise of HIV.
Causes of Tearing in Patients With Chemotherapy: Meibomian Gland Dysfunction Versus Lacrimal Drainage Obstruction
Authors: Lee Hyunkyu , Yoon Sumin , Baek Sehyun
Published: January 2023

Numerous ocular toxicities that have been associated with the use of chemotherapeutic agents present as problems with the ocular surface, ocular adnexa, and lacrimal system, and many chemotherapeutic agents have tearing as a side effect. In this study, 34 eyes from 17 patients with a mean age of 62.4±14.8 years were analyzed. Chemotherapy was administered for a mean of 13.8±7.6 months. Chemotherapeutic agents of the following types were included: titanium silicate-1 (58.8%), Docetaxel (23.5%), Paclitaxel (11.8%), and 5-fluorouracil (5.9%). Tearing began 9.1 to 10.9 months after chemotherapy treatment. Within 3 months of beginning chemotherapy, tearing occurred in 9 patients (52.9%), and within 6 months, it occurred in 11 patients (64.7%). Mean tear break-up time was 5.4±2.6 sec. Ten eyes (29.4%) had normal fluorescein dye disappearance test findings (within grade 1), and the mean fluorescein dye disappearance test was 1.91±0.87. Among the 34 eyes, 24 (70.6%) had normal puncta and 9 (26.5%) and 1 (2.9%) had stenosis and blockage, respectively. Ten eyes (29.4%) showed total regurgitation, 19 eyes (55.9%) showed partial regurgitation, and 5 eyes (14.7%) showed no regurgitation upon syringing. Four eyes (11.8%) and 30 eyes (88.2%), respectively, showed soft and hard stops upon probing. Dacryoscintigraphy confirmed that 6 eyes (17.6%) were normal, 8 eyes (23.5%) showed post-sac delay or obstruction, and 20 eyes (58.8%) showed pre-sac delay or obstruction. The mean meiboscores for the upper and lower eyelids on LipiView were 2.15±0.86 and 2.53±0.79, respectively. The difference in meiboscores between the upper and lower eyelids was significant (P=0.004). Obstruction of the lacrimal drainage system is a significant contributing factor to tearing in chemotherapy patients. However, reflex tearing because of meibomian gland dysfunction should also be fully considered to effectively manage the tearing because of the high incidence of accompanying meibomian glands loss when the lacrimal drainage system is obstructed.
Diagnostic accuracy of screening tools for pediatric blunt cerebrovascular injury: An ATOMAC multicenter study
Authors: Nickoles Todd A. , Lewit Ruth A. , Notrica David M. , Ryan Mark , Johnson Jeremy , Maxson Robert Todd , Naiditch Jessica A. , Lawson Karla A. , Temkit M'hamed , Padilla Benjamin , Eubanks James W.
Published: January 2023

BACKGROUND

Blunt cerebrovascular injury (BCVI) is rare but significant among children. There are three sets of BCVI screening criteria validated for adults (Denver, Memphis, and Eastern Association for the Surgery of Trauma criteria) and two that have been validated for use in pediatrics (Utah score and McGovern score), all of which were developed using retrospective, single-center data sets. The purpose of this study was to determine the diagnostic accuracy of each set of screening criteria in children using a prospective, multicenter pediatric data set.

METHODS

A prospective, multi-institutional observational study of children younger than 15 years who sustained blunt trauma to the head, face, or neck and presented at one of six level I pediatric trauma centers from 2017 to 2020 was conducted. All patients were screened for BCVI using the Memphis criteria, but criteria for all five were collected for analysis. Patients underwent computed tomography angiography of the head or neck if the Memphis criteria were met at presentation or neurological abnormalities were detected at 2-week follow-up.

RESULTS

A total of 2,284 patients at the 6 trauma centers met the inclusion criteria. After excluding cases with incomplete data, 1,461 cases had computed tomography angiography and/or 2-week clinical follow-up and were analyzed, including 24 cases (1.6%) with BCVI. Sensitivity, specificity, positive predictive value, and negative predictive value for each set of criteria were respectively 75.0, 87.5, 9.1, and 99.5 for Denver; 91.7, 71.1, 5.0, and 99.8 for Memphis; 79.2, 82.7, 7.1, and 99.6 for Eastern Association for the Surgery of Trauma; 45.8, 95.8, 15.5, and 99.1 for Utah; and 75.0, 89.5, 10.7, and 99.5 for McGovern.

CONCLUSION

In this large multicenter pediatric cohort, the Memphis criteria demonstrated the highest sensitivity at 91.7% and would have missed the fewest BCVI, while the Utah score had the highest specificity at 95.8% but would have missed more than half of the injuries. Development of a tool, which narrows the Memphis criteria while maintaining its sensitivity, is needed for application in pediatric patients.

LEVEL OF EVIDENCE

Diagnostic Test/Criteria; Level II.
The Role of AI Model Documentation in Translational Science: A Scoping Review
Authors: Brereton Tracey A. , Malik Momin , Lifson Mark A. , Greenwood Jason D. , Peterson Kevin J. , Overgaard Shauna M.
Published: January 2023

Background

Translation of artificial intelligence/machine learning (AI/ML)-based medical modeling software (MMS) into clinical settings requires rigorous evaluation by interdisciplinary teams and across the AI lifecycle. The fragmented nature of available resources to support MMS documentation limits the transparent reporting of scientific evidence to support MMS, creating barriers and impeding the translation of software from code to bedside.

Objective

The aim of this paper is to scope AI/ML-based MMS documentation practices and define the role of documentation in facilitating safe and ethical MMS translation into clinical workflows.

Methods

A scoping review was conducted in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. MEDLINE (PubMed) was searched using MeSH key concepts of AI/ML, ethical considerations, and explainability to identify publications detailing AI/ML-based MMS documentation, in addition to snowball sampling of selected reference lists. To include the possibility of implicit documentation practices not explicitly labeled as such, we did not use “documentation “ as a key concept but rather as an inclusion criterion. A two-stage screening process (title and abstract screening and full-text review) was conducted by an independent reviewer. A data extraction template was utilized to record publication-related information, barriers to developing ethical and explainable MMS, available standards, regulations, frameworks, or governance strategies related to documentation, and recommendations for documentation for papers that met inclusion criteria.

Results

Of the total 115 papers, 21 (18%) articles met the requirements for inclusion. Data regarding the current state and challenges of AI/ML-based documentation was synthesized and themes including bias, accountability, governance, and interpretability were identified.

Conclusions

Our findings suggest that AI/ML-based MMS documentation practice is siloed across the AI life cycle and there exists a gray area for tracking and reporting of non-regulated MMS. Recommendations from the literature call for proactive evaluation, standards, frameworks, and transparency and traceability requirements to address ethical and explainability barriers, enhance documentation efforts, provide support throughout the AI lifecycle, and promote translation of MMS. If prioritized across multidisciplinary teams and across the AI lifecycle, AI/ML-based MMS documentation may serve as a method of coordinated communication and reporting toward resolution of AI translation barriers related to bias, accountability, governance, and interpretability.
Identification of a mitochondrial targeting sequence in cathepsin D and its localization in mitochondria
Authors: Ikari Naoki , Arakawa Hirofumi
Published: January 2023

Cathepsin D (CTSD) is a major lysosomal protease harboring an N-terminal signal peptide (amino acids 1–20) to enable vesicular transport from endoplasmic reticulum to lysosomes. Here, we report the possibility of a mitochondrial targeting sequence and mitochondrial localization of CTSD in cells. Live-cell imaging analysis with enhanced green fluorescent protein (EGFP)-CTSD indicated that CTSD localizes to mitochondria. CTSD amino acids 21–35 are responsible for its mitochondrial localization, which exhibit typical features of mitochondrial targeting sequences, and are evolutionarily conserved. A proteinase K protection assay and sucrose gradient analysis showed that a small population of endogenous CTSD molecules exists in mitochondria. These results suggest that CTSD is a dual-targeted protein that may localize in both lysosomes and mitochondria.
Nanocrystalline silver layer of knitted polyester outperforms other silver-containing wound dressings in an in vitro wound model
Authors: Hus Jonathan , Frausto Ricardo F. , Grunhut Joel , Hus Nir J.
Published: January 2023

Background

Silver possesses cytotoxic properties against many microorganisms and is regularly used in wound care. Current evidence supporting the use of one type of silver-containing wound dressing (SCWD) is insufficient.

Methods

To examine the ability of selected SCWDs to inhibit the growth of two strains of bacteria (E. coli and S. aureus) commonly found in wounds, an in vitro wound model was used. Bacteria were applied to the surface of nutrient agar and a piece of each SCWD was applied to the bacteria. The plates were incubated at 37°C overnight. The zone of inhibition (ZI) around each SCWD was measured in cm2.

Results

The mean ZI for Acticoat Flex-3 onE. coliwas 1.59 ± 0.15 cm2, which was significantly greater than that observed for Aquacel Ag (p<0.001), Mepilex Ag (p<0.0001), Mepitel Ag (p<0.001), Optifoam (p<0.0001) and Tegaderm Alginate Ag (p<0.01), but statistically indistinguishable from Maxorb II Ag. The mean ZI onS.aureuswas 1.21 ± 0.16 cm2, which was greater than Aquacel Ag (p<0.05), Mepilex (p<0.0001), Optifoam (p<0.0001) and Tegaderm Alginate Ag (p<0.05), but statistically indistinguishable from Maxorb II Ag or Mepitel Ag.

Conclusions

Of the SCWDs tested, Acticoat Flex-3 demonstrated the most robust antimicrobial effect. Herein we show that Acticoat Flex-3 may provide the most wound protection against bacterial infection. In conclusion, these data provide clinicians with additional independent evidence to inform their clinical practice on the use of specific wound dressings.

PRECIS

The antimicrobial properties of Acticoat Flex-3, a dressing composed of nanocrystalline silver layer of knitted polyester, outperformed other silver-containing dressings againstE. coliandS. aureus.
Neurophysiological signatures of cortical micro-architecture
Authors: Shafiei Golia , Fulcher Ben D. , Voytek Bradley , Satterthwaite Theodore D. , Baillet Sylvain , Misic Bratislav
Published: January 2023

Systematic spatial variation in micro-architecture is observed across the cortex. These micro-architectural gradients are reflected in neural activity, which can be captured by neurophysiological time-series. How spontaneous neurophysiological dynamics are organized across the cortex and how they arise from heterogeneous cortical micro-architecture remains unknown. Here we extensively profile regional neurophysiological dynamics across the human brain by estimating over 6 800 timeseries features from the resting state magnetoencephalography (MEG) signal. We then map regional time-series profiles to a comprehensive multi-modal, multi-scale atlas of cortical micro-architecture, including microstructure, metabolism, neurotransmitter receptors, cell types and laminar differentiation. We find that the dominant axis of neurophysiological dynamics reflects characteristics of power spectrum density and linear correlation structure of the signal, emphasizing the importance of conventional features of electromagnetic dynamics while identifying additional informative features that have traditionally received less attention. Moreover, spatial variation in neurophysiological dynamics is colocalized with multiple micro-architectural features, including genomic gradients, intracortical myelin, neurotransmitter receptors and transporters, and oxygen and glucose metabolism. Collectively, this work opens new avenues for studying the anatomical basis of neural activity.
Zika virus dumbbell-1 structure is critical for sfRNA presence and cytopathic effect during infection
Authors: Graham Monica E. , Merrick Camille , Akiyama Benjamin M. , Szucs Matthew , Leach Sarah , Kieft Jeffery S. , Beckham J. David
Published: January 2023

Zika virus (ZIKV) contains multiple conserved RNA structures in the viral 3’ untranslated region (UTR), including the structure known as dumbbell-1 (DB-1). Previous research has shown that the DB-1 structure is important for flavivirus genome replication and cytopathic effect (CPE). However, the role of the DB structure and the mechanism by which it contributes to viral pathogenesis is not known. Using recently solved flavivirus DB RNA structural data, we designed two DB-1 mutant ZIKV infectious clones termed ZIKV-TL.PK, which disrupts DB-1 tertiary folding and ZIKV-p.2.5’, which alters DB-1 secondary structure formation. In cell culture, we found that viral genome replication of both mutant clones is not significantly affected compared to ZIKV-WT, but viral CPE is considerably decreased. We investigated sub-genomic flaviviral RNA (sfRNA) formation by both DB-1 mutants following A549 infection and found both mutant clones have decreased levels of all sfRNA species compared to ZIKV-WT during infection. To investigate the mechanism of decreased CPE in our DB-1 mutant clones, we assayed ZIKV DB mutant-infected A549 cells for cell viability and caspase activation. We found that cell viability is significantly increased in DB-1 mutant-infected cells compared to ZIKV-WT due to reduced caspase 3 activation. We also show that replication of the ZIKV-P.2.5’ mutant was significantly restricted by type I interferon treatment without altering interferon stimulated gene expression. Using a murine model of ZIKV infection, we show that both ZIKV-DB-1 mutants exhibit reduced morbidity and mortality compared to ZIKV-WT virus due to tissue specific attenuation in ZIKV-DB viral replication in the brain tissue. Overall, our data show that the flavivirus DB-1 RNA structure is important for maintaining sfRNA levels during infection which supports caspase-3 dependent, viral cytopathic effect, type 1 interferon resistance, and viral pathogenesis in a mouse model.
PKM2 diverts glycolytic flux in dependence on mitochondrial one-carbon cycle
Authors: Benzarti Mohaned , Oudin Anais , Viry Elodie , Gargiulo Ernesto , Schmoetten Maryse , Neises Laura , Pulido Coralie , Lorenz Nadia I. , Ronellenfitsch Michael W. , Sumpton David , Warmoes Marc , Jaeger Christian , Lesur Antoine , Moussay Etienne , Paggetti Jerome , Niclou Simone P. , Letellier Elisabeth , Meiser Johannes
Published: January 2023

Throughout the metastatic cascade, cancer cells are faced with harsh metabolic environments and nutritional stresses which apply selection pressure leaving only the most metabolically resilient cells to survive and form metastases. Metabolic characterisation of such cell populationsin vitrois currently challenging. Using galactose as a tool compound to mimic glycolytic limitation within the tumour microenvironment of primary and secondary neoplastic sites, we were able to uncover metabolic flexibility and plasticity of cancer cellsin vitro. In contrast to the established idea that high glycolytic flux and expression of dimeric PKM2 redirects carbons towards anabolic routes such as the pentose phosphate pathway and serine synthesis pathway (SSP), we have discovered by using stable-isotope tracing that also glycolytic limitation results in metabolic rewiring. Surprisingly, despite limited carbon availability and energetic stress, cells induce a near complete block of pyruvate kinase isozyme M2 (PKM2) to divert carbons towards SSP. Simultaneously, TCA cycle flux is sustained and oxygen consumption is increased, both supported by glutamine. Glutamine not only supports TCA cycle flux but also SSP via distinct mechanisms. Due to PKM2 block, malic enzyme exclusively supports TCA cycle flux while mitochondrial phosphoenolpyruvate carboxykinase supports SSP. Moreover, by using genetic modifications of different one-carbon (1C) cycle enzymes, we are able to reverse the PKM2 block suggesting a link between mitochondrial 1C cycle and pyruvate kinase. Thus we show that PKM2 inhibition acts as a branching point to direct glycolytic and glutamine carbons into distinct routes, overall supporting the metabolic plasticity and flexibility of cancer cells.
Formate Promotes Invasion and Metastasis by Activating Fatty Acid Synthesis and Matrix Metalloproteinases
Authors: Delbrouck Catherine , Kiweler Nicole , Pozdeev Vitaly I. , Neises Laura , Oudin Anaïs , Schuster Anne , d’Hérouël Aymeric Fouquier , Shen Ruolin , Halder Rashi , Lesur Antoine , Ogris Christoph , Lorenz Nadia I. , Jaeger Christian , Ronellenfitsch Michael W. , Piraud Marie , Skupin Alexander , Niclou Simone P. , Letellier Elisabeth , Meiser Johannes
Published: January 2023

Metabolic rewiring is essential to enable cancer onset and progression. One important metabolic pathway that is often hijacked by cancer cells is the one-carbon cycle, in which the third carbon of serine is oxidized to formate. We have previously shown that formate production in cancer cells often exceeds the anabolic demand, resulting in formate overflow. Furthermore, we observed that high extracellular formate promotes thein vitroinvasiveness of glioblastoma (GBM) cells. However, additional data supporting thisin vitroobservation and mechanistic details remained elusive so far.

In the present study, we now demonstrate that inhibition of formate overflow results in a decreased invasiveness of GBM cellsex vivoandin vivo. Additionally, we observed that exposure to exogeneous formate can induce a transiently stable pro-invasive phenotype that results in increased metastasis formationin vivo. All in all, these results suggest that a local formate increase within the tumor microenvironment may be one factor that can promote cancer cell motility and dissemination.

Mechanistically, we uncover a previously undescribed interplay where formate acts as a trigger to alter fatty acid metabolism and matrix metalloproteinase (MMP) activity which in turn impacts cancer cell invasiveness. We thus highlight the role of formate as a pro-invasive metabolite. Gaining a deeper understanding of formate overflow and how it promotes invasion in cancer, may open new therapeutic opportunities to prevent cancer cell dissmination.
In silico Antibody-Peptide Epitope prediction for Personalized cancer therapy
Authors: Jacobs Ivan , Ming Lim Chwee , Mong Jamie , Emmanoil Maragkoudakis , Malik Nishant
Published: January 2023

The human leukocyte antigen (HLA) system is a complex of genes on chromosome 6 in humans that encodes cell-surface proteins responsible for regulating the immune system. Viral peptides presented to cancer cell surfaces by the HLA trigger the immune system to kill the cells, creating Antibody-peptide epitopes (APE). This study proposes an in-silico approach to identify patient-specific APEs by applying complex networks diagnostics on a novel multiplex data structure as input for a deep learning model. The proposed analytical model identifies patient and tumor-specific APEs with as few as 20 labeled data points. Additionally, the proposed data structure employs complex network theory and other statistical approaches that can better explain and reduce the black box effect of deep learning. The proposed approach achieves an F1-score of 80% and 93% on patients one and two respectively and above 90% on tumor-specific tasks. Additionally, it minimizes the required training time and the number of parameters.
Combined KRASG12Cand SOS1 inhibition enhances and extends the anti-tumor response in KRASG12C-driven cancers by addressing intrinsic and acquired resistance
Authors: Thatikonda Venu , Lu Hengyu , Jurado Sabine , Kostyrko Kaja , Bristow Christopher A. , Bosch Karin , Feng Ningping , Gao Sisi , Gerlach Daniel , Gmachl Michael , Lieb Simone , Jeschko Astrid , Machado Annette A. , Marszalek Ethan D. , Mahendra Mikhila , Jaeger Philipp A. , Sorokin Alexey , Strauss Sandra , Trapani Francesca , Kopetz Scott , Vellano Christopher P. , Petronczki Mark , Kraut Norbert , Heffernan Timothy P. , Marszalek Joseph R. , Pearson Mark , Waizenegger Irene , Hofmann Marco H.
Published: January 2023

Efforts to improve the anti-tumor response to KRASG12Ctargeted therapy have benefited from leveraging combination approaches. Here, we compare the anti-tumor response induced by the SOS1-KRAS interaction inhibitor, BI-3406, combined with a KRASG12Cinhibitor (KRASG12Ci) to those induced by KRASG12Ci alone or combined with SHP2 or EGFR inhibitors. In lung cancer and colorectal cancer (CRC) models, BI-3406 plus KRASG12Ci induces an anti-tumor response stronger than that observed with KRASG12Ci alone and comparable to those by the other combinations. This enhanced anti-tumor response is associated with a stronger and extended suppression of RAS-MAPK signaling. Importantly, BI-3406 plus KRASG12Ci treatment delays the emergence of acquired adagrasib resistance in both CRC and lung cancer models and is associated with re-establishment of anti-proliferative activity in KRASG12Ci-resistant CRC models. Our findings position KRASG12Cplus SOS1 inhibition therapy as a promising strategy for treating both KRASG12C-mutated tumors as well as for addressing acquired resistance to KRASG12Ci.
BRWD1 orchestrates chromatin topology by converting static to dynamic cohesin complexes
Authors: Mandal Malay , Maienschein-Cline Mark , Hu Yeguang , Mohsin Azam , Veselits Margaret L. , Wright Nathaniel E. , Okoreeh Michael K. , me Yoon Young , Veselits Jacob , Georgopoulos Katia , Clark Marcus R.
Published: January 2023

Lymphocyte development consists of sequential and mutually exclusive cell states of proliferative selection and antigen receptor gene recombination1. Transitions between each state require large, coordinated changes in epigenetic landscapes and transcriptional programs2,3. How this occurs remains unclear. Herein, we demonstrate that in small pre-B cells, the lineage and stagespecific epigenetic reader Bromodomain and WD Repeating Containing Protein 1 (BRWD1)2,4reorders three-dimensional chromatin topology to affect transition between proliferative and gene recombination molecular programs. BRWD1 regulated the switch between poised and active enhancers interacting with promoters and coordinated this withIgklocus contraction. BRWD1 did so by converting chromatin-bound static cohesin to dynamic complexes competent to mediate long-range looping. Remarkably, ATP depletion recapitulated cohesin distributions observed inBrwd1-/-cells. Therefore, in small pre-B cells, cohesin conversion is the main energetic mechanism dictating where dynamic looping occurs in the genome. Our findings provide a new mechanism of cohesin regulation and reveal how cohesin function can be dictated by lineage contextual mechanisms to facilitate specific cell fate transitions.