bluuebunny/crossref_metadata_2025 huggingface dataset:
The Collapse of the Versailles System
Authors: Creswell Michael H.
Published: May 2023

Despite the safeguards established at the Paris Peace Conference in 1919, a second World War erupted within a single generation. Many observers believe that had the Allied powers avoided making a few key mistakes, the Versailles System they created could have prevented war from breaking out in 1939. However, no single isolated decision, hasty move, or simple oversight caused the Versailles System to fail and end in a second global cataclysm. The world failed to avert catastrophe mainly because the Versailles System was unenforceable. France recognized this in 1923, and future events would confirm it. In the early 1930s, Germany continued violating the terms of the Versailles Treaty, and those charged with defending the system proved either unable or unwilling to enforce it.
The Memory and Commemoration of War
Authors: Puaca Brian M. , Osa Shizue
Published: May 2023

Memories of World War II have played a critical role in the formation of modern national identities in Europe and East Asia. This essay explores the complicated and often contested memories of World War II in several nations and traces the dramatic evolution of these selective and carefully constructed conceptions of the past in the years since 1945. In its discussion of the interplay between individual, collective, and official memories, the chapter emphasizes the negotiation that takes place among different societal actors, media, and institutions. Furthermore, it underscores the diversity of memory and refutes the notion of any single, uniform European or Asian memory of World War II.
The United Nations and the Grand Alliance
Authors: Woolner David B.
Published: May 2023

This chapter explores the creation of the United Nations and the Grand Alliance during World War II. Technically speaking, both terms refer to the association of nations that was brought together to defeat the Axis. But in practice the two appellations came to embody two distinct entities. The “Grand Alliance,” as coined by Winston Churchill, in essence refers to the military coalition among Great Britain, the United States, and the Soviet Union. The “United Nations” refers to the much broader affiliation of anti-Axis powers represented in the January 1, 1942 Declaration by United Nations, as put forward Franklin Roosevelt. Hence, the two entities represented two separate wartime realities: the concentration and exercise of geo-political power among the Big Three—often guided by the precepts of national interest—versus a more expansive and inclusive interpretation of the exercise of power, based the concept of collective security and international cooperation.
Census Classifications and the Political Construction of Race
Authors: Miyawaki Michael H. , Rodriguez Clara E.
Published: May 2023

When governments attempt statistical representations of their populations, the process is “political to the core.” Political and ideological choices are made, resulting in categories that generally reflect a consensus on who is to be counted, how, and how often. In this chapter, we provide a historical overview of racial and ethnic categories in the U.S. Census, focusing on the classification of five population groups—White people, Black people, American Indians, Asians and Pacific Islanders, and Latinos—and the political factors shaping the ongoing constructions of these groups. Given the political considerations of census categories and question formats, we illustrate that any changes in the classification of populations will remain a political process. We conclude by addressing recent developments in the U.S. Census and raising important questions about future enumeration practices of different population groups, including Latinos and people of Middle Eastern and North African origins.
Cutaneous Adverse Reactions Following Influenza Vaccination in Adults
Authors: Mistry Jenna , Deo Neha , Vance Paul , Alavi Afsaneh
Published: May 2023

OBJECTIVE

To review the literature on cutaneous reactions to the influenza vaccine in adults.

DATA SOURCES

Authors systematically searched three databases: PubMed, MEDLINE, and EMBASE.

STUDY SELECTION

Case reports published between January 1, 1995 and December 31, 2020 that described a cutaneous reaction to any brand of the influenza vaccine in adults were included. Exclusion criteria included having the wrong study design, pediatric cases, publication prior to 1995, and lack of cutaneous reaction to the vaccine.

DATA EXTRACTION

A total of 232 articles were identified. After duplicate removal, title and abstract screening, and full-text screening, 29 studies were included in the final review. Data extracted included patient sex, age, type of influenza vaccine received, time from vaccine administration to cutaneous reaction, duration of cutaneous reaction, description of cutaneous reactions, treatments used, and the outcome (eg, resolution, reoccurrence, complications).

DATA SYNTHESIS

The mean age of participants was 43.7 years (range, 19–82 years), and 60% were women (n = 18). The most frequent cutaneous reaction that occurred following influenza vaccination included erythematous macules/papules/plaques (n = 17 [56.7%]), vasculitic and purpuric rashes (n = 5 [16.7%]), and maculopapular (morbilliform) rashes (n = 3 [10.0%]). All patients received treatment, and 96.7% (n = 29) of the cutaneous manifestations were resolved. Most studies did not report any further complications upon follow-up.

CONCLUSIONS

Understanding and identifying the relationship between the influenza vaccine and possible cutaneous manifestations can help providers predict and anticipate these adverse effects.
The Development and Feasibility of an Empathy Virtual Reality Scenario in Healthcare Education
Authors: Collier Rosemary , Darling Rosa , Sprague Lori-Marie , Murphy Jamie
Published: May 2023

Technology-enhanced simulations such as virtual reality and computer-based experiences allow students to improve their understanding of patient perspectives and increase empathy for patients. These technologies can be daunting to nursing faculty without robust technology and video development resources. The purpose of this project was to share a guide for creating and implementing a patient-centered immersive virtual reality scenario within a nursing program. The research team developed, filmed, and produced a cost-effective virtual reality simulation scenario for use with smartphones and inexpensive virtual reality headsets, which could be widely disseminated for students to watch in class or online. The virtual reality simulation allowed an immersive first-person view and was well received by both faculty and students. The virtual reality scenario was implemented with ease in classroom, virtual, and laboratory settings. These virtual reality simulations work in the live setting or remotely, and synchronously or asynchronously with minimal equipment, which reduces barriers to access.
Immune Checkpoint Inhibitor-related Pancreatitis: A Case Series, Review of the Literature and an Expert Opinion
Authors: Kramer Sjoerd , van Hee Koen , Blokzijl Hans , van der Heide Frans , Visschedijk Marijn C.
Published: May 2023

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of various malignancies, but are associated with serious adverse events like pancreatitis. Current guidelines are limited to the first step in treating acute ICI-related pancreatitis with steroids but lack treatment advices for steroid dependent pancreatitis. We describe a case series of 3 patients who developed ICI-related pancreatitis with chronic features such as exocrine insufficiency and pancreatic atrophy at imaging. Our first case developed after treatment with pembrolizumab. The pancreatitis responded well after discontinuation of immunotherapy but imaging showed pancreatic atrophy and exocrine pancreatic insufficiency persisted. Cases 2 and 3 developed after treatment with nivolumab. In both, pancreatitis responded well to steroids. However during steroid tapering, pancreatitis recurred and the latter developed exocrine pancreatic insufficiency and pancreatic atrophy at imaging. Our cases demonstrate resemblances with autoimmune pancreatitis based on clinical and imaging findings. In line, both diseases are T-cell mediated and for autoimmune pancreatitis azathioprine is considered as maintenance therapy. Guidelines of other T-cell mediated diseases like ICI-related hepatitis suggest tacrolimus. After adding tacrolimus in case 2 and azathioprine in case 3, steroids could be completely tapered and no new episodes of pancreatitis have occurred. These findings support the idea that the treatment modalities for other T-cell mediated diseases are worthwhile options for steroid dependent ICI-related pancreatitis.
Enhancing Resident Education in Autism Diagnosis: Training on the Screening Tool for Autism in Toddlers
Authors: Belzer Kira , Flake Eric , Kiger Michelle
Published: May 2023

Objective:

Pediatricians feel inadequately prepared to diagnose and manage autism spectrum disorders (ASDs). We developed a curriculum that trains pediatric residents in the Screening Tool for Autism in Toddlers and Young Children (STAT), a tool used to diagnose ASD, and assessed its impact.

Methods:

Pediatric residents completed training in the STAT that included interactive video and practice-based elements. Residents completed pretraining and posttraining surveys assessing comfort with diagnosing and treating ASD, knowledge-based pretests and posttests, posttraining interviews, and follow-up assessments at 6 and 12 months after training.

Results:

Thirty-two residents completed the training. Posttest scores significantly increased [M (SD) 9.8 (2.4) vs 11.7 (2), p < 0.0001]. Knowledge gains were not maintained at 6-month follow-up. Residents reported increased comfort with several ASD management methods and an increased likelihood of using the STAT. More residents reported using the STAT at follow-up: 2 of 29 before training, 5 of 11 at 6 months, and 3 of 13 at 12 months. We identified 4 themes in interview responses: (1) increased sense of empowerment in managing patients with ASD but ongoing reluctance to make a formal diagnosis, (2) logistical barriers affected successful implementation of the STAT, (3) access to developmental pediatricians played an essential role in comfort levels, and (4) the main educational value of the STAT training came from interactive components.

Conclusion:

An ASD curriculum including training in the STAT increased resident knowledge and comfort in diagnosing and managing ASD. Although logistical barriers continue to affect the ability of general pediatricians to diagnose ASD, use of this curriculum has potential to improve long-term outcomes.
Extended Pedicled Perforator Plus Submental Flap for Large Cheek Defect Reconstruction
Authors: Abdelmofeed Ayman M. , Hassan Mohammed Elsayed , Seif Ola , Abdelhalim Mohamed H. , Younes Mohamed T.
Published: May 2023

Background:

The submental flap is an alternative repair technique in the maxillo-facial region when microsurgical reconstruction is not required or is difficult to apply. The purpose of this study was to illustrate the benefits of restoring the cheeks with an extended pedicled submental flap.

Method:

Eight patients aged 58 to 81 years with cheek cancer presented to the surgery department at the Benha University Hospital in Egypt, from May 2019 to October 2021 for the removal of their tumors and reconstruction of the resulting defects, using the extended submental perforator plus pedicled artery flap.

Results:

The average blood loss was 250 cm3 (range: 50–400 cm3). The average operation took 3 hours to complete, including excision and rebuilding (a range of 2.5 to 3.5 hours). The length of the postoperative hospital stay was 2 to 4 days. Fortunately, there was no complete flap loss; nonetheless, distal flap necrosis in one case left a raw area, which was allowed to heal naturally, and hemorrhages in two cases were conservatively handled.

Conclusions:

For the reconstruction of cheek abnormalities, the submental flap is a viable alternative, particularly in older patients or patients whose overall health has declined and who need less severe therapies and quicker surgery. The submental flap, which conceals the donor site, provides a dependable supply of skin for facial resurfacing with excellent color, shape, and texture matching. The flap is quick, and easy to raise.
Increased Reliability in Medial Canthal Tendon Reposition in Nasoorbitoethmoidal Fractures with Computer-assisted Surgery and Surgical Navigation
Authors: Alamillos Francisco J. , Sanjuan Alba , Centella Inmaculada , Dean Alicia
Published: May 2023

Avulsion of the medial canthal tendon secondary to nasoorbitoethmoidal fractures leads to severe aesthetic and functional impairments. The tendon should be repositioned at the posterior lacrimal crest. Owing to the complexity of nasoorbitoethmoidal fractures, accurate location of this point during surgery can be challenging. With the aid of computer-assisted planning and surgical navigation, the point at which the medial canthal tendon should be repositioned can be easily and precisely located. We have developed an innovative navigation-assisted technique that increases the reliability and safety of internal canthus repositioning. We performed a case series of three consecutive patients who underwent medial canthal tendon repositioning using computer-assisted planning and surgical navigation. We believe that this innovation provides a new and useful application of computer-assisted planning and surgical navigation in craniomaxillofacial surgery.
Cell metabolism-based therapy for liver fibrosis, repair, and hepatocellular carcinoma
Authors: Gilgenkrantz Hélène , Paradis Valérie , Lotersztajn Sophie
Published: May 2023

Progression of chronic liver injury to fibrosis, abnormal liver regeneration, and HCC is driven by a dysregulated dialog between epithelial cells and their microenvironment, in particular immune, fibroblasts, and endothelial cells. There is currently no antifibrogenic therapy, and drug treatment of HCC is limited to tyrosine kinase inhibitors and immunotherapy targeting the tumor microenvironment. Metabolic reprogramming of epithelial and nonparenchymal cells is critical at each stage of disease progression, suggesting that targeting specific metabolic pathways could constitute an interesting therapeutic approach. In this review, we discuss how modulating intrinsic metabolism of key effector liver cells might disrupt the pathogenic sequence from chronic liver injury to fibrosis/cirrhosis, regeneration, and HCC.
A deep-learning radiomics-based lymph node metastasis predictive model for pancreatic cancer: a diagnostic study
Authors: Fu Ningzhen , Fu Wenli , Chen Haoda , Chai Weimin , Qian Xiaohua , Wang Weishen , Jiang Yu , Shen Baiyong
Published: May 2023

Objectives:

Preoperative lymph node (LN) status is essential in formulating the treatment strategy among pancreatic cancer patients. However, it is still challenging to evaluate the preoperative LN status precisely now.

Methods:

A multivariate model was established based on the multiview-guided two-stream convolution network (MTCN) radiomics algorithms, which focused on primary tumor and peri-tumor features. Regarding discriminative ability, survival fitting, and model accuracy, different models were compared.

Results:

Three hundred and sixty-three pancreatic cancer patients were divided in to train and test cohorts by 7:3. The modified MTCN (MTCN+) model was established based on age, CA125, MTCN scores, and radiologist judgement. The MTCN+ model outperformed the MTCN model and the artificial model in discriminative ability and model accuracy. [Train cohort area under curve (AUC): 0.823 vs. 0.793 vs. 0.592; train cohort accuracy (ACC): 76.1 vs. 74.4 vs. 56.7%; test cohort AUC: 0.815 vs. 0.749 vs. 0.640; test cohort ACC: 76.1 vs. 70.6 vs. 63.3%; external validation AUC: 0.854 vs. 0.792 vs. 0.542; external validation ACC: 71.4 vs. 67.9 vs. 53.5%]. The survivorship curves fitted well between actual LN status and predicted LN status regarding disease free survival and overall survival. Nevertheless, the MTCN+ model performed poorly in assessing the LN metastatic burden among the LN positive population. Notably, among the patients with small primary tumors, the MTCN+ model performed steadily as well (AUC: 0.823, ACC: 79.5%).

Conclusions:

A novel MTCN+ preoperative LN status predictive model was established and outperformed the artificial judgement and deep-learning radiomics judgement. Around 40% misdiagnosed patients judged by radiologists could be corrected. And the model could help precisely predict the survival prognosis.
A National, County-Level Evaluation of the Association Between COVID-19 and Sexually Transmitted Infections within the United States in 2020
Authors: Pollack Catherine , Bradburne Jordan , Lee Natalie K. , Manabe Yukari C. , Widdice Lea E. , Gaydos Charlotte A. , Tuddenham Susan A. , Rompalo Anne M. , Jackman Joany , Timm Collin M.
Published: May 2023

Background

Shifts in public health infrastructure to respond to one emerging health threat may have unanticipated consequences for pre-existing diseases. Also, previous research evaluating the impact of COVID-19 on sexually transmitted infections (STIs) has been conducted nationally, with little exploration of the impact on a granular geospatial level. This ecological study seeks to quantify the association between COVID-19 cases or deaths and chlamydia, gonorrhea, and syphilis cases for all United States (US) counties in 2020.

Methods

Separate, adjusted multivariable quasi-Poisson models with robust standard errors modeled the county-level association between 2020 COVID-19 cases and deaths per 100,000 and 2020 chlamydia, gonorrhea, or syphilis cases per 100,000. Models were adjusted for sociodemographic characteristics.

Results

Every 1,000 additional COVID-19 cases per 100,000 was associated with a 1.80% increase in the average number of chlamydia cases (P < .001) and 5.00% increase in the average number of gonorrhea cases (P < .001). Every 1,000 additional COVID-19 deaths per 100,000 was associated with a 57.9% increase in the average number gonorrhea cases (P < .001) and 74.2% decrease in the average number of syphilis cases (P = .004).

Conclusions

Higher rates of COVID-19 cases and deaths were associated with increased rates of some STIs at the US county-level. The underlying reasons for these associations could not be established by this study. The emergency response to an emerging threat may have unanticipated influence on pre-existing diseases that varies by level of governance.
Qualitative Study on Safe and Effective Handover Information during a Rapid Response Team Encounter
Authors: Greenberg Justin M. , Schmidt Anita , Chang Todd P. , Rake Alyssa
Published: May 2023

Introduction:

A rapid response team (RRT) evaluates and manages patients at risk of clinical deterioration. There is limited literature on the structure of the rapid response encounter from the floor to the intensive care unit team. We aimed to define this encounter and examine provider experiences to elucidate what information healthcare staff need to safely manage patients during an RRT evaluation.

Methods:

This phenomenological qualitative study included 6 focus groups (3 in-person and 3 virtually) organized by provider type (nurses, residents, fellows, attendings), which took place until thematic saturation was reached. Two authors inductively coded transcripts and used a quota sampling strategy to ensure that the focus groups represented key stakeholders. Transcripts were then analyzed to identify themes that providers believe influence the RRT’s quality, efficacy, and efficiency and their ability to manage and treat the acutely decompensating pediatric patient on the floor.

Results:

Transcript coding yielded 38 factors organized into 8 themes. These themes are a summary statement or recap, closed-loop communication, interpersonal communication, preparation, duration, emotional validation, contingency planning, and role definition.

Conclusions:

The principal themes of utmost importance at our institution during an RRT encounter are preparation, a brief and concise handoff from the floor team, and a summary statement from the intensive care unit team with contingency planning at the end of the encounter. Our data suggest that some standardization may be beneficial during the handoff.
Immediate Breast Reconstruction After Neoadjuvant Chemotherapy
Authors: Chi Weiru , Zhang Qi , Li Lun , Chen Ming , Xiu Bingqiu , Yang Benlong , Wu Jiong
Published: May 2023

Background

Breast reconstruction has become an integral component of breast cancer treatment, especially for patients who are unable to undergo breast-conserving surgery after neoadjuvant chemotherapy (NAC). We analyzed factors influencing the type of immediate reconstruction surgery after NAC, as well as the complication rates for each surgery type.

Methods

The study included patients with breast cancer who underwent mastectomy following NAC from 2010 to 2021. Clinicopathological characteristics, unplanned reoperation rates, and the duration of postoperative hospitalization were analyzed in patients undergoing autologous tissue reconstruction (ATR, n = 127), implant-based reconstruction (IBR, n = 60), and combined autologous tissue and implant reconstruction (n = 60).

Results

A total of 1651 patients who received NAC before mastectomy were enrolled. Among them, 247 (15.0%) patients underwent immediate reconstruction (IR), whereas 1404 underwent mastectomy only. Patients in the IR group were younger (P < 0.001), had lower body mass index (P < 0.001), and exhibited earlier clinical (P = 0.003) and nodal (P < 0.001) stage than those in the non-IR group. Patients in the ATR group were older (P < 0.001) and had higher body mass index (P = 0.007), larger tumor size (P = 0.024), and more frequent childbearing history (P = 0.011) than those in the other groups. Complications resulting in unplanned reoperations were more frequent in the IBR group (P = 0.039). The duration of postoperative hospitalization was longest after ATR (P = 0.008).

Conclusions

Age and clinical tumor/nodal stage at presentation are associated with IR for patients undergoing mastectomy after NAC. For patients undergoing IR after NAC, ATR may be safer and more suitable than IBR.
Can Nonalcoholic Steatohepatitis Be Surgically Cured? Liver Histological Comparison after Metabolic Surgery versus Usual Care
Authors: Aminian Ali , Wilson Rickesha , Al-Kurd Abbas , Bena James , Fayazzadeh Hana , Alkhouri Naim , Nissen Steven E. , Dasarathy Srinivasan
Published: May 2023

Objective:

To compare histological outcomes in patients with fibrotic nonalcoholic steatohepatitis (NASH) and obesity after metabolic surgery versus nonsurgical care.

Background:

There are no published data comparing the effects of metabolic surgery versus nonsurgical care on histological progression of NASH.

Methods:

Repeat liver biopsies were performed in patients with BMI >30 kg/m2 at a US health system whose baseline liver biopsy between 2004 and 2016 confirmed a histological diagnosis of NASH including presence of liver fibrosis, but without cirrhosis. Baseline characteristics of liver histology for patients who underwent simultaneous liver biopsy at the time of metabolic surgery were balanced with a nonsurgical control group using overlap weighting methods. The primary composite end point required both resolution of NASH and improvement of at least 1 fibrosis stage in the repeat liver biopsy.

Results:

133 patients (42 metabolic surgery and 91 nonsurgical controls) had a repeat liver biopsy with a median interval of 2 years. Overlap weighting provided balance for baseline histological disease activity, fibrosis stage, and time interval between liver biopsies. In overlap-weighted patients, 50.1% in the surgical and 12.1% in the nonsurgical group met the primary end point (odds ratio 7.3 [95% CI, 2.8-19.2], P<0.001). NASH resolution and fibrosis improvement occurred in 68.5% and 64.1% of surgical patients, respectively. Surgical and nonsurgical patients who met the primary end point lost more weight than their counterparts who did not meet the primary end point (mean weight loss difference in the surgical group 12.2% [95% CI, 7.3%-17.2%] and in the nonsurgical group 11.6% [95% CI, 6.2%-16.9%]).

Conclusions:

Among patients with fibrotic non-cirrhotic NASH, metabolic surgery resulted in simultaneous NASH resolution and fibrosis improvement in half of patients.
Low to moderate genetic influences on the rapid smell test SCENTinel™
Authors: Hunter Stephanie R. , Lin Cailu , Hannum Mackenzie E. , Bell Katherine , Huang Amy , Joseph Paule V. , Parma Valentina , Dalton Pamela H. , Reed Danielle R.
Published: May 2023

SCENTinel™- a rapid, inexpensive smell test that measures odor detection, intensity, identification, and pleasantness - was developed for population-wide screening of smell function. SCENTinel™was previously found to screen for multiple types of smell disorders. However, the effect of genetic variability on SCENTinel™test performance is unknown, which could affect the test’s validity. This study assessed performance of SCENTinel™in a large group of individuals with a normal sense of smell to determine the test-retest reliability and the heritability of SCENTinel™test performance. One thousand participants (36 [IQR 26-52] years old, 72% female, 80% white) completed a SCENTinel™test at the 2021 and 2022 Twins Days Festivals in Twinsburg, OH, and 118 of those completed a SCENTinel™test on each of the festival’s two days. Participants comprised 55% percent monozygotic twins, 13% dizygotic twins, 0.4% triplets, and 36% singletons. We found that 97% of participants passed the SCENTinel™test. Test-retest reliability ranged from 0.57 to 0.71 for SCENTinel™subtests. Broad-sense heritability, based on 246 monozygotic and 62 dizygotic twin dyads, was low for odor intensity (r=0.03) and moderate for odor pleasantness (r=0.4). Together, this study suggests that SCENTinel™is a reliable smell test with only moderate heritability effects, which further supports its utility for population-wide screening for smell function.
Association of Baseline Cerebrovascular Reactivity and Longitudinal Development of Enlarged Perivascular Spaces in the Basal Ganglia
Authors: Libecap T.J. , Bauer Christopher E. , Zachariou Valentinos , Pappas Colleen A. , Raslau Flavius D. , Liu Peiying , Lu Hanzhang , Gold Brian T.
Published: May 2023

1.

Background

Increasing evidence suggests that enlarged perivascular spaces (ePVS) are associated with cognitive dysfunction in aging. However, the etiology of ePVS remains unknown. Here we tested the possibility that baseline cerebrovascular dysfunction, as measured by an MRI measure of cerebrovascular reactivity (CVR), contributes to the later development of ePVS.

Methods

A total of 79 cognitively normal, older adults (46 women, age range 60-84) were recruited to undergo MRI scanning at baseline and 50 participants returned for a follow-up scan approximately 2.5 years later. ePVS were counted in the basal ganglia, centrum semiovale, midbrain, and hippocampus. CVR, an index of the vasodilatory capacity of cerebral small vessels, was assessed using carbon-dioxide inhalation while acquiring blood oxygen-level dependent (BOLD) MR images.

Results

Low baseline CVR values in the basal ganglia were associated with increased follow-up ePVS counts in the basal ganglia after controlling for age, sex, and baseline ePVS values (coefficient estimate (SE) = -15.87 (3.92), p < 0.001, 95% confidence interval [CI] -23.68 to - 8.05). This effect remained significant after accounting for self-reported risk factors of cerebral small vessel disease (cSVD) (coefficient estimate (SE) = -15.03 (4.00), p < 0.001, CI -23.02 to - 7.05) and neuroimaging markers of cSVD (coefficient estimate (SE) = -13.99 (4.02), p < 0.001, CI -22.03 to -5.95).

Conclusions

Our results demonstrate that low baseline CVR is a risk factor for later development of ePVS. MRI-based CVR may represent a promising biomarker of cSVD.
A reproducibility evaluation of the effects of MRI defacing on brain segmentation
Authors: Gao Chenyu , Landman Bennett A. , Prince Jerry L. , Carass Aaron
Published: May 2023

Purpose

Recent advances in magnetic resonance (MR) scanner quality and the rapidly improving nature of facial recognition software have necessitated the introduction of MR defacing algorithms to protect patient privacy. As a result, there are a number of MR defacing algorithms available to the neuroimaging community, with several appearing in just the last five years. While some qualities of these defacing algorithms, such as patient identifiability, have been explored in previous works, the potential impact of defacing on neuroimage processing has yet to be explored.

Approach

We qualitatively evaluate eight MR defacing algorithms on 179 subjects from the OASIS-3 cohort and the 21 subjects from the Kirby-21 dataset. We also evaluate the effects of defacing on two neuroimaging pipelines— SLANT and FreeSurfer—by comparing the segmentation consistency between the original and defaced images.

Results

Defacing can alter brain segmentation and even lead to catastrophic failures, which are more frequent with some algorithms such asQuickshear,MRI_Deface, andFSL_deface. Compared to FreeSurfer, SLANT is less affected by defacing. On outputs that pass the quality check, the effects of defacing are less pronounced than those of rescanning, as measured by the Dice similarity coefficient.

Conclusions

The effects of defacing are noticeable and should not be disregarded. Extra attention, in particular, should be paid to the possibility of catastrophic failures. It is crucial to adopt a robust defacing algorithm and perform a thorough quality check before releasing defaced datasets. To improve the reliability of analysis in scenarios involving defaced MRIs, it’s encouraged to include multiple brain segmentation pipelines.
Repurposing Non-pharmacological Interventions for Alzheimer’s Diseases through Link Prediction on Biomedical Literature
Authors: Xiao Yongkang , Hou Yu , Zhou Huixue , Diallo Gayo , Fiszman Marcelo , Wolfson Julian , Kilicoglu Halil , Chen You , Su Chang , Xu Hua , Mantyh William G. , Zhang Rui
Published: May 2023

Recently, computational drug repurposing has emerged as a promising method for identifying new pharmaceutical interventions (PI) for Alzheimer’s Disease (AD). Non-pharmaceutical interventions (NPI), such as Vitamin E and Music therapy, have great potential to improve cognitive function and slow the progression of AD, but have largely been unexplored. This study predicts novel NPIs for AD through link prediction on our developed biomedical knowledge graph. We constructed a comprehensive knowledge graph containing AD concepts and various potential interventions, called ADInt, by integrating a dietary supplement domain knowledge graph, SuppKG, with semantic relations from SemMedDB database. Four knowledge graph embedding models (TransE, RotatE, DistMult and ComplEX) and two graph convolutional network models (R-GCN and CompGCN) were compared to learn the representation of ADInt. R-GCN outperformed other models by evaluating on the time slice test set and the clinical trial test set and was used to generate the score tables of the link prediction task. Discovery patterns were applied to generate mechanism pathways for high scoring triples. Our ADInt had 162,213 nodes and 1,017,319 edges. The graph convolutional network model, R-GCN, performed best in both the Time Slicing test set (MR = 7.099, MRR = 0.5007, Hits@1 = 0.4112, Hits@3 = 0.5058, Hits@10 = 0.6804) and the Clinical Trials test set (MR = 1.731, MRR = 0.8582, Hits@1 = 0.7906, Hits@3 = 0.9033, Hits@10 = 0.9848). Among high scoring triples in the link prediction results, we found the plausible mechanism pathways of (Photodynamic therapy, PREVENTS, Alzheimer’s Disease) and (Choerospondias axillaris, PREVENTS, Alzheimer’s Disease) by discovery patterns and discussed them further. In conclusion, we presented a novel methodology to extend an existing knowledge graph and discover NPIs (dietary supplements (DS) and complementary and integrative health (CIH)) for AD. We used discovery patterns to find mechanisms for predicted triples to solve the poor interpretability of artificial neural networks. Our method can potentially be applied to other clinical problems, such as discovering drug adverse reactions and drug-drug interactions.
Correlation between life satisfaction and symptoms of attention deficit hyperactivity disorder (ADHD) in dental students: The mediation of resilience
Authors: Sun Yuwei , Miao Lei , Chen Siying , Piao Zhenya , Tong Chi
Published: May 2023

The aim of the study was to examine the morbidity of Attention Deficit Hyperactivity Disorder (ADHD) symptoms in dental students, explore the correlation between life satisfaction and ADHD symptoms. It also discusses whether resilience mediates the correlation between ADHD symptoms and life satisfaction. Self-report questionnaires consist of the Wender Utah Rating Scale (WURS), the Adult ADHD Self-Report Scale (ASRS), the Satisfaction With Life Scale (SWLS), the Conner-Davidson Resilience Scale (CD-RISC), and sociodemographic characteristics. The analyses with Hierarchical linear regression were operated to investigate the effect of ADHD symptoms on life satisfaction. The study used resampling and asymptotic strategies to discuss the mediation of resilience. 291 dental students became final objects. Twenty students (6.87%) may have ADHD. There were differences in ADHD prevalence among objects of diverse ages and with varying levels of paternal education. The ADHD asymptomatic group had distinctly higher resilience and life satisfaction degrees than the symptomatic group. Inattention and hyperactivity were both correlated negatively with life satisfaction and resilience. Life satisfaction was observably positively associated with resilience. Resilience serves as a mediating role between life satisfaction and the two symptoms of ADHD. Detecting ADHD symptoms earlier is helping improve mental health of future dentists. Resilience intervention programs can enhance life satisfaction of dental students.
The Association of QRS Duration with Risk of Adverse Outcomes in Sex- and Race- Based Subgroups: The Dallas Heart Study
Authors: Kondamudi Nitin , Zeleke Yihun , Rosenblatt Anna , Hu Gene , Grubb Christopher , Link Mark S.
Published: May 2023

Introduction

We explored sex and race differences in the prognostic implications of QRS prolongation among healthy adults.

Methods

Participants from the Dallas Heart Study (DHS) free of cardiovascular (CV) disease who underwent ECG testing and cMRI evaluation were included. Multivariable linear regression was used to examine the cross-sectional association of QRS duration with left ventricular (LV) mass, LV ejection fraction (LVEF), and LV end diastolic volume (LVEDV). Association of QRS duration with risk of MACE was evaluated using Cox models. Interaction testing was performed between QRS duration and sex/race respectively for each outcome of interest. QRS duration was log transformed.

Results

The study included 2,785 participants. Longer QRS duration was associated with higher LV mass, lower LVEF, and higher LVEDV, independent of CV risk factors ([β: 0.21, P<0.001], [β: - 0.13, P<0.001], [β: 0.22, P<0.001] respectively). Men with longer QRS duration were more likely to have higher LV mass and higher LVEDV compared to women (P-int=0.012, P-int=0.01, respectively). Black participants with longer QRS duration were more likely to have higher LV mass as compared to White participants (P-int<0.001). In Cox analysis, QRS prolongation was associated with higher risk of MACE in women (HR = 6.66 [95% CI: 2.32, 19.1]) but not men. This association was attenuated after adjustment for CV risk factors, with a trend toward significance (HR = 2.45 [95% CI: 0.94, 6.39]). Longer QRS duration was not associated with risk of MACE in Black or White participants in the adjusted models. No interaction between sex/race and QRS duration for risk of MACE was observed.

Discussion

In healthy adults, QRS duration is differentially associated with abnormalities in LV structure and function. These findings inform the use of QRS duration in identifying subgroups at risk for CV disease, and caution against using QRS duration cut offs uniformly for clinical decision making.

What is known?

QRS prolongation in healthy adults is associated with higher risk of death, cardiovascular disease, and left ventricular hypertrophy.

What the study adds?

QRS prolongation may reflect a higher degree of underlying LV hypertrophy in Blacks compared to Whites. Longer QRS interval may reflect higher risk of adverse cardiac events, driven by prevalent cardiovascular risk factors.

Graphic Abstract

Risk of underlying left ventricular hypertrophy in demographic groups based on QRS prolongation
Genomic and transcriptomic analysis revealed new insights into the influence of key T6SS geneshcpandvgrGon drug resistance and interbacterial competition inKlebsiella pneumoniae
Authors: Li Wanzhen , Huang Xiaolan , Li Dan , Liu Xiaofen , Jiang Xiaoying , Bian Xingchen , Li Xin , Zhang Jing
Published: May 2023

Type VI secretion systems (T6SSs) act as a molecular weapon in interbacterial competition and play an important role in cell-cell interactions. Different species of bacteria use their T6SSs to perform a variety of functions according to ecological niche. Therefore, it is necessary to better understand the T6SS potential ofKlebsiella pneumoniae(K. pneumoniae), a common clinical opportunistic pathogen. Here, we conducted a genomic analysis on the evolution, T6SS, virulence and antimicrobial resistance of 65K. pneumoniaein patients with different infections. And we combined transcriptome analysis after knockout of key gene in T6SS of this species. Results showed that genes encoding a T6SS were present in allK. pneumoniaein this study, and there was no correlation was found between T6SS cluster and carbapenem resistance and virulence genes. Differentially expressed genes (DEGs) including 1298 co-upregulated and 1714 co-downregulated were identified afterhcporvgrGdeletion. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis have demonstrated common changes in quorum sensing, propionate metabolism and other pathways. And we found that the deletion ofhcporvgrGgenes up-regulated of beta-lactam (blaKPC-2) and other resistance genes. Interbacterial competition experiments showed thathcpandvgrGare essential genes for competitive ability of ST11K. pneumoniae. Taken together, the entire study provides further insight into the investigation of T6SS inK. pneumoniaethrough genomic and transcriptomic analysis.

Importance

Gram-negative bacteria use T6SS to deliver toxin effectors to interact with neighboring cells for niche advantage.K. pneumoniaeis an opportunistic nosocomial pathogen that often carriers multiple cope T6SSs, but the function of its T6SS has not yet elucidated. Here, we performed a genomic analysis of 65 clinicalK. pneumoniaestrains, in order to explore the relationship between T6SS and virulence and resistance genes. We also study the repertoire after knockout of key gene in T6SS of this species by transcriptomics. It was suggested that T6SS is associated with drug resistance, and its key geneshcpandvgrGare critical for the interspecies competition ofK. pneumoniae.
Oncogenic reactivation of young L1s is a hallmark of colon cancer
Authors: Neu Devin , Hung Stevephen , Bartels Cynthia F. , Faber Zachary J. , Lovrenert Katreya , Pontius W. Dean , Morgan Laura , Chakraborty Maharshi , Liao Will , Chin Diana , Hong Ellen S. , Gray Jeremy , Moreno Victor , Kalady Matthew , Peters Ulrike , Gryder Berkley , Sallari Richard C. , Scacheri Peter C.
Published: May 2023

Transposable elements become increasingly active in both cancerous and aging cells, driven by loss of DNA methylation as cells divide. Here we leverage the epigenomes of colon cancers with matched adjacent tissue, in addition to non-cancerous normals and cell line models, to assess the role of transposable elements as drivers or passengers in cancer development. Using the baseline of activity from normal and adjacent tissue, we show that the youngest subfamilies of the LINE1 (L1) family exhibit a degree of activity and recurrence across patients that goes beyond what is expected from hypomethylation and cell division, suggesting an additional mechanism of oncogenic reactivation. We characterize this mechanism and find that the loss of the tumor suppressor PLZF drives young L1 reactivation in a cell-division-independent manner. PLZF de-repression exposes abundant motifs for tumor core factors in the L1 5’UTR. Active young L1s act as oncogenic enhancers, interacting with oncogenes via gained chromatin loops. We uncover oncogenic L1 reactivation as a hallmark of colon cancer, where young L1s activate universally in our cohort at high levels of recurrence, act as enhancers to oncogenes, and become wired into the core regulatory circuitry of colon cancer.
Computational modeling of methylation impact of AML drivers reveals new pathways and refines AML risk-stratification
Authors: Gurun Burcu , Tyner Jeffrey W. , Demir Emek , Druker Brian J. , Spellman Paul T.
Published: May 2023

Decades before its clinical onset, epigenetic changes start to accumulate in the progenitor cells of Acute Myelogenous Leukemia (AML). Delineating these changes can improve risk-stratification for patients and shed insights into AML etiology, dynamics and mechanisms. Towards this goal, we extracted “epigenetic signatures” through two parallel machine learning approaches: a supervised regression model using frequently mutated genes as labels and an unsupervised topic modeling approach to factorize covarying epigenetic changes into a small number of “topics”. First, we created regression models forDNMT3AandTET2, the two most frequently mutated epigenetic drivers in AML. Our model differentiated wild-type vs. mutant genotypes based on their downstream epigenetic impacts with very high accuracy: AUROC 0.9 and 0.8, respectively. Methylation loci frequently selected by the models recapitulated known downstream pathways and identified several novel recurrent targets. Second, we used topic modeling to systematically factorize the high dimensional methylation profiles to a latent space of 15 topics. We annotated identified topics with biological and clinical features such as mutation status, prior malignancy and ELN criteria. Topic modeling successfully deconvoluted the combined effects of multiple upstream epigenetic drivers into individual topics including relatively infrequent cytogenetic events, improving the methylation-based subtyping of AML. Furthermore, they revealed complimentary and synergistic interactions between drivers, grouped them based on the similarity of their downstream methylation impact and linked them to prognostic criteria. Our models identify new signatures and methylation pathways, refine risk-stratification and inform detection and drug response studies for AML patients.

KEY POINTS

Supervised and unsupervised models reveal new methylation pathways of AML driver events and validate previously known associations.

IndividualDNMT3AandTET2signatures are accurate and robust, despite the complex genetic and epigenetic make-up of samples at diagnosis.

Unsupervised topic modeling factorizes covarying methylation changes and isolates methylation signatures caused by rare mutations.

Topic modeling reveals a group of mutations with similar downstream methylation impacts and mapped to adverse-risk class by ELN.

Topic modeling uncovers methylation signatures of infrequent cytogenetic events, significantly improving methylation-based subtyping.

Our models can be leveraged to build predictive models for AML-risk.

Our models show that cytogenetic events, such as t(15;17) have widespreadtransdownstream methylation impacts.
The stool microbiome in patients with psoriatic arthritis is altered but, unlike the skin microbiome, does not change following treatment: evidence for an underlying inflammatory drive from the intestine
Authors: Castelino Madhura , Ijaz Umer Z , Tutino Mauro , MacDonald Elizabeth , Fragoulis George E. , Ho Pauline , Mewar Devesh , Chelliah Gladston , McBain Andrew , O’Neill Catherine , Siebert Stefan , Barton Anne , Milling Simon
Published: May 2023

Objectives

There is growing recognition that interactions between bacteria and the immune response may contribute to inflammation in psoriatic arthritis (PsA). To identify how the skin and stool microbiota may contribute to pathogenesis, we analysed the microbiota and immunophenotype of patients with PsA before and after therapy.

Methods

We examined the phenotype of PBMCs as well as skin and stool microbiota from 22 healthy volunteers, 7 PsA patients receiving methotrexate, and 23 PsA patients treated with biologic DMARDs. Samples for microbiome analysis were collected before therapy and after 3-6 months. First, we identified differences in the skin and stool microbiota between PsA patients and health volunteers. We then assessed changes in the microbiome occurring after treatment.

Results

As hypothesised, treatment responses were reflected by changes in both the skin microbiota and in the immunophenotype. However, in the stool samples, dysbiosis persisted after therapy. This dysbiosis was associated with changes in the peripheral blood immunophenotype. Correlation analysis enabled identification not only of specific microbial taxa (Clostridial species) that contributed to the persistent dysbiosis, but also of interactions between taxa and the immune response.

Conclusions

These analyses indicate that specific Clostridial species contribute to persistent gut dysbiosis in PsA, and their prevalence is associated with specific immunological changes that are not altered by treatment. Thus, an underlying inflammatory response in the intestine appears to contribute to the pathogenesis of PsA.

Key Messages

What is already known about this subject?

Intestinal bacterial populations are altered in people with inflammatory diseases, including psoriatic arthritis (PsA).

Interactions between bacteria and the immune system may contribute to the pathogenesis of inflammatory diseases.

What does this study add?

While skin bacteria in patients with PsA revert towards normal after treatment, stool bacteria remain different from healthy individuals.

Specific bacterial types are correlated with specific changes in the immune system in PsA.

How might this impact on clinical practice or future developments?

Identification of the bacteria that drive persistent underlying changes in the immune response may enable these to be targeted.