bluuebunny/crossref_metadata_2025 huggingface dataset:
Rethinking Prisoner Reentry
Authors: Goger Annelies , Harding David J. , Henderson Howard
Published: November 2021

With a focus on reentry after prison, we formulate an evidence-supported action plan for enhancing transitions from prison to society that focuses on increasing independence, reducing racial and ethnic disparities, and achieving public safety. Prisoner re-entry is a critical piece of any racial justice agenda as the lack of education or vocational training within carcer institutions impose barriers to job opportunities that, coupled with societal stigmas, often make reintegration extremely challenging. Noting that changes in policies with significant potential to improve reentry outcomes extend beyond federal agencies traditionally involved in the administration of justice, we include ways to reduce reentry barriers such as housing, education, employment, health, and political rights. The paper is divided into short, medium and long-term recommendations. The short-term recommendations pertain to existing funding streams and discretionary authority regarding administrative rules and regulations, funding decisions, and rule enforcement. Medium-term recommendations involve the creation of new legislation, infrastructure, and funding appropriations. In the long-term, recommendations include changes in laws to achieve fundamental re-orientations of existing policy frameworks, and approaches that require substantial new funding appropriations.
Induction motor condition monitoring using infrared thermography imaging and ensemble learning techniques
Authors: Mahami Amine , Rahmoune Chemseddine , Bettahar Toufik , Benazzouz Djamel
Published: November 2021

In this paper, a novel noncontact and nonintrusive framework experimental method is used for the monitoring and the diagnosis of a three phase’s induction motor faults based on an infrared thermography technique (IRT). The basic structure of this work begins with this applying IRT to obtain a thermograph of the considered machine. Then, bag-of-visual-word (BoVW) is used to extract the fault features with Speeded-Up Robust Features (SURF) detector and descriptor from the IRT images. Finally, various faults patterns in the induction motor are automatically identified using an ensemble learning called Extremely Randomized Tree (ERT). The proposed method effectiveness is evaluated based on the experimental IRT images, and the diagnosis results show its capacity and that it can be considered as a powerful diagnostic tool with a high classification accuracy and stability compared to other previously used methods.
Angiogenetic transcriptional profiling reveals potential targets modulated in blood of patients with cardiovascular disorders
Authors: Ukkat Joerg , Rebelo Artur , Trojanowicz Bogusz
Published: November 2021

Objectives

Based on the angiogenetic, transcriptional profile of non-diseased and arteriosclerotic vessels, we aim to identify the leucocytic markers as a potential, minimal invasive tool supporting diagnosis of vascular pathology.

Methods

Transcriptional profiling was performed with Angiogenesis RT2 Profiler PCR (Polymerase Chain Reaction) array on three non-pathological and three arteriosclerotic vessels, followed by immunohistochemical staining. Based on these screening results, selected transcripts were employed for qPCR with specific primers and investigated on the blood RNA (RiboNucleic Acid) obtained from nine healthy controls and 29 patients with cardiovascular disorders. Thereafter, expression of these transcripts was investigated in vitro in human monocytes under calcification-mimicking conditions.

Results and Conclusions

Transcriptional profiling on the vessels revealed that out of 84 targets investigated two were up-regulated more than 100-fold, 18 more than 30 and 15 more than 10, while the most noticeable down-regulation was observed by ephrin-A3 and platelet-derived growth factor alpha (PDGFA) genes. Based on the vessel results, investigations of the selected blood transcripts revealed that thrombospondin 1 (THBS1), thrombospondin 3 (THBS3), transforming growth factor, beta receptor 1 (TGFBR1), platelet-derived growth factor alpha, plasminogen activator, urokinase (PLAU) and platelet/endothelial cell adhesion molecule 1 (PECAM-1) were significantly elevated in cardiovascular blood as compared to corresponding controls. Induction of calcification-related conditions in vitro to human THP-1 monocytes led to noticeable modulation of these transcripts. Taken together, these data demonstrate that leucocytic THBS1, THBS3, TGFBR1, platelet-derived growth factor alpha, PLAU and PECAM-1 have a correlation with cardiovascular disorders and could be used as a supportive tool predicting development of this pathological condition.
Waving away waivers: an obligation to contribute to ‘herd knowledge’ for data linkage research?
Authors: Bradfield Owen M
Published: November 2021

In today’s online data-driven world, people constantly shed data and deposit digital footprints. When individuals access health services, governments and health providers collect and store large volumes of health information about people that can later be retrieved, linked and analysed for research purposes. This can lead to new discoveries in medicine and healthcare. In addition, when securely stored and de-identified, the privacy risks are minimal and manageable. In many jurisdictions, ethics committees routinely waive the requirement for researchers to obtain consent from data subjects before using and linking these datasets in an effort to balance respect for individuals with research efficiency. In this paper, I explore the ethical justification for using routinely collected health data for research without consent. I conclude that, not only is this morally justified but also that data subjects have a moral obligation to contribute their data to such research, which would obviate the need for ethics committees to consider consent waivers. In justifying this argument, I look to the duty of easy rescue, distributive justice and draw analogies with vaccination ethics.
Age-related differences when searching in a real environment: The use of semantic contextual guidance and incidental object encoding
Authors: Ramzaoui Hanane , Faure Sylvane , Spotorno Sara
Published: November 2021

Visual search is a crucial, everyday activity that declines with ageing. Here, referring to the environmental support account, we hypothesised that semantic contextual associations between the target and the neighbouring objects (e.g., a teacup near a tea bag and a spoon), acting as external cues, may counteract this decline. Moreover, when searching for a target, viewers may encode information about the co-present distractor objects, by simply looking at them. In everyday life, where viewers often search for several targets within the same environment, such distractor objects may often become targets of future searches. Thus, we examined whether incidentally fixating a target during previous trials, when it was a distractor, may also modulate the impact of ageing on search performance. We used everyday object arrays on tables in a real room, where healthy young and older adults had to search sequentially for multiple objects across different trials within the same array. We showed that search was quicker (1) in young than older adults; (2) for targets surrounded by semantically associated objects than unassociated objects, but only in older adults; and (3) for incidentally fixated targets than for targets that were not fixated when they were distractors, with no differences between young and older adults. These results suggest that older viewers use both environmental support based on object semantic associations and object information incidentally encoded to enhance efficiency of real-world search, even in relatively simple environments. This reduces, but does not eliminate, search decline related to ageing.
Preoperative abdominal straining in uncomplicated stress urinary incontinence: is there a correlation with voiding dysfunction and de novo overactive bladder after mid-urethral sling procedures?
Authors: Lacovelli Valerio , Serati Maurizio , Bianchi Daniele , Braga Andrea , Turbanti Andrea , Agrò Enrico Finazzi
Published: November 2021

Objectives:

To evaluate the role of preoperative abdominal straining in predicting de novo overactive bladder (OAB) and voiding dysfunction in female patients undergoing suburethral taping by trans-obturator approach (TVT-O) for uncomplicated stress urinary incontinence (SUI).

Methods:

Data from patients who underwent TVT-O surgery for SUI were retrospectively analyzed. Inclusion criteria included: history of pure SUI. Exclusion criteria included previous surgery for urinary incontinence, pelvic radiation, pelvic surgery within the last 3 months, and anterior or apical pelvic organ prolapse (POP) ⩾ +1 cm. Voiding dysfunction has been defined through symptoms and or urodynamics (UDS) signs. Accordingly, patients were divided into group A and group B according to the presence of abdominal straining during UDS. Patients were observed clinically and with UDS at a 3-year follow-up.

Results:

A total of 192 patients underwent TVT-O surgery for uncomplicated SUI. Preoperative abdominal straining was identified in 60/192 patients (Group A: 31.2% vs Group B: 68.8%). Qmax was not different in the two groups (Group A: 19.5 vs Group B: 20.5 mL/s, p = 0.76). Demographics was similar for the two groups regarding age, parity. At 3-year follow-up, voiding dysfunction was reported in Group A: 9 and Group B: 8 patients ( p = 0.056), de novo OAB was significantly reported in Group A: 23 and Group B: 26 patients ( p = 0.007).

Conclusion:

Preoperative abdominal straining was found to be related to a significant incidence of de novo OAB. A significant correlation was not assessed for postoperative voiding dysfunction. Further studies may better define the impact of preoperative abdominal straining.
Identifying the Mechanisms of Rosa Roxburghii Tratt on Treating Gastric Cancer: Combining the Targetable Screening From the Cancer Genome Atlas With Network Pharmacology
Authors: Tang Li , Zhang Shuo , Ji Jia-Cheng , Wang Peng-Jiao , Zhang Min , Feng Pei-Mei , Gao Xiu-Li
Published: November 2021

The Chinese herbal medicine Rosa roxburghii Tratt (RRT) is widely used in the treatment of malignant tumors, including gastric cancer (GC), but its pharmacological mechanism remains unclear. The purpose of this research was to identify the mechanisms of RRT on treating GC by using network pharmacology and molecular docking, combined with the analysis of differential expressed genes in GEO gene chips and TCGA database. We first defined the effective components of RRT and their potential targets for the treatment of GC, and identified core targets according to the topology analysis by constructing a protein-protein interaction network. Furthermore, molecular docking was used to verify the docking between the core active ingredients and the key targets. The results showed that the effect of RRT may be closely associated with multiple signal pathways, including pathways in cancer, phosphatidylinositol 3-kinase-AKT serine/threonine kinase (PI3K-Akt), tumor necrosis factor (TNF), hypoxia-inducible factor 1 (HIF-1), and mitogen-activated protein kinase (MAPK). It is suggested that RRT may play an effect by regulating hypoxia, improving the tumor microenvironment, inhibiting inflammatory reactions and promoting apoptosis. The mechanism of RRT in the treatment of GC is revealed here for the first time based on network pharmacology analysis, which may provide a new direction for further exploration of the mechanisms of RRT in the treatment of GC and a new perspective for research on anti-tumor drugs.
Algorithmic pricing: A concern for platform workers?
Authors: Kloostra Jorn
Published: November 2021

Technological developments have been bringing about changes in the field of work since time immemorial. Recently, the emergence of platform work has brought up all kind questions. For instance, in the field of labour law, where the questions seem to focus mostly on the topic legal status of platform workers contract: is the platform worker an employee? At the same time, it is also interesting to examine what it means if it turns out the platform worker is not an employee. In that case, other issues arise, albeit in the area of competition law. In particular, one can think of the consequences of the use of algorithms in determining the tariff of the service. In this article, I examine the consequences competition law has for the platform and individual platform workers. These consequences are nuanced and depend on the specific business model. However, it does not seem to be excluded those involved could face sanctions for a breach of competition law.
Structured patient interview to assess clinical outcomes in complicated urinary tract infections in the APEKS-cUTI study: pilot investigation
Authors: Portsmouth Simon , Echols Roger , Toyoizumi Kiichiro , Tillotson Glenn , Nagata Tsutae Den
Published: November 2021

Background:

The APEKS-cUTI study demonstrated the non-inferiority of cefiderocol to imipenem−cilastatin in the primary endpoint of the composite of clinical and microbiological outcome in patients with complicated urinary tract infections (cUTIs). We piloted a structured patient interview (SPI) to evaluate clinical outcomes based on patient-reported symptoms while conducting this pivotal randomized, double-blind, phase-2 study. The objectives were to assess the value of the SPI, using its performance relative to physician assessment, and also to strengthen the value of patient-reported measures in conducting clinical trials for cUTI treatment.

Methods:

In addition to the protocol-defined clinical and microbiological outcomes, patients randomized in the APEKS-cUTI study were interviewed by the investigator or qualified study personnel at screening/baseline, early assessment (EA), end of treatment (EOT), test of cure (TOC), and follow-up (FUP). The 14-element questionnaire graded cUTI symptoms as absent or present, and if present, as mild, moderate, or severe. Changes in post-baseline symptoms based on patients’ responses were rated by the interviewer. The overall clinical outcome was evaluated based on the responses provided by patients at each time point.

Results:

Among the 371 patients in the modified intention-to-treat population, the rate of SPI completion in each treatment arm exceeded 90% at each time point. SPI-assessed clinical cure rates were 89.7% in the cefiderocol arm and 84.9% in the imipenem–cilastatin arm. There was substantial agreement between SPI evaluation and investigator global assessment of clinical outcome at TOC and FUP, with lower agreement at EA and EOT.

Conclusion:

This analysis suggests that patient-reported symptoms can be effectively captured in hospitalized patients with cUTI in a clinical trial setting. Development of a validated patient-reported outcome for use in such a setting is warranted.

Registration:

NCT02321800 (registered on 22 December 2014).
A Sadness Bias in Political News Sharing? The Role of Discrete Emotions in the Engagement and Dissemination of Political News on Facebook
Authors: de León Ernesto , Trilling Damian
Published: November 2021

In this study, we address the role of emotions in political news sharing on Facebook to better understand the complex relationship between journalism, emotions, and politics. Categorizing Facebook Reactions (particularly, the Sad, Angry, Love, and Wow Reactions) according to the discrete emotions model, we evaluate how positive versus negative political content relates to emotional responses, and how this consequentially influences the degree to which articles are shared across social media in the context of an election. We focus on the landmark 2018 Mexican elections to enable a nuanced conversation on how cues of user emotion predict the far-reaching dissemination of news articles on Facebook during a moment of heightened political attention. Our findings demonstrate a negativity bias in news sharing and engagement, showing an outsized prevalence of anger in response to political news. In addition, we provide evidence of a novel sadness bias in the sharing of political coverage, suggesting that emotions considered as deactivating should be reevaluated in the context of social media.
Anxiety, Depression, and Common Chronic Diseases, and Their Association With Social Determinants in Saudi Primary Care
Authors: Baghdadi Leena R. , Alhassan Mohammed Khalid , Alotaibi Fawaz Hindi , AlSelaim Khalid Badr , Alzahrani Abdulrahman Abdulkhaliq , AlMusaeed Faisal Fahad
Published: November 2021

Introduction:

Patients with chronic diseases can experience psychological conditions, including anxiety and depression. However, the association between chronic diseases and these psychological conditions remains unclear. This study aimed to identify the relationship between anxiety, depression, and common chronic diseases (hypertension, type 2 diabetes, dyslipidemia, and rheumatoid arthritis), and their association with social determinants at an outpatient primary care setting.

Methods:

The validated hospital anxiety and depression scale was administered electronically to eligible participants. For each condition (anxiety and depression), participants were categorized as normal, borderline abnormal, and abnormal, according to their score out of 21 (≤7 = normal, 8-10 = borderline abnormal, ≥11 = abnormal). The scores and numbers of participants in each category were analyzed and compared with their demographic characteristics and chronic diseases for associations and relationships.

Results:

We recruited 271 participants (mean age of 51.65 + 11.71 years) attending primary care clinics. Of these patients, 17.7% and 8.9% had borderline abnormal and abnormal depression, respectively, and 10.3% and 8.9% of patients had borderline abnormal anxiety and abnormal anxiety. Common social determinants and lifestyle factors were examined. Age, gender, and sugary drinks’ consumption significantly increased the odds of hypertension and type 2 diabetes; vigorous physical activity 3 times a week, decreased the odds of developing these chronic diseases. Adjusted regression models showed a statistically significant association between the hospital anxiety and depression scale score for borderline and abnormal anxiety and the presence of type 2 diabetes (OR 3.04 [95% CI 1.13, 8.19], P-value = .03 and OR 4.65 [95% CI 1.63,13.22], P-value <.03, respectively) and dyslipidemia (OR 5.93 [95% CI 1.54, 22.86], P-value = .01, and OR 4.70 [95% CI 0.78, 28.35], P-value = .09, respectively). The odds of developing depression were 4 times higher ( P-value .04) in patients with rheumatoid arthritis.

Conclusion:

Among patients attending primary care outpatient clinics, anxiety, and depression were significantly associated with type 2 diabetes and rheumatoid arthritis, respectively. Social determinants and lifestyle factors play a major role in the development of common chronic diseases in Saudi Arabia. Primary care physicians should consider the patients’ psychological status, sociodemographic status, and lifestyle risks during the management of chronic diseases.
Age-Adjusted D-Dimer in the Prediction of Pulmonary Embolism: Systematic Review and Meta-analysis
Authors: Iwuji Kenneth , Almekdash Hasan , Nugent Kenneth M. , Islam Ebtesam , Hyde Briget , Kopel Jonathan , Opiegbe Adaugo , Appiah Duke
Published: November 2021

Background:

Pulmonary embolism (PE), depending on the severity, carries a high mortality and morbidity. Proper evaluation, especially in patients with low probability for PE, is important to avoid unnecessary diagnostic testing.

Objective:

To review the diagnostic utility of conventional versus age-adjusted D-dimer cutoff values in patients 50 years and older with suspected pulmonary embolism.

Methods:

Systematic review with univariant and bivariant meta-analysis.

Data sources:

We searched PubMed, MEDLINE, and EBSCO for studies published before September 20th, 2020. We cross checked the reference list of relevant studies that compares conventional versus age-adjusted D-dimer cutoff values in patients with suspected pulmonary embolism.

Study selection:

We included primary published studies that compared both conventional (500 µg/L) and age-adjusted (age × 10 µg/L) cutoff values in patients with non-high clinical probability for pulmonary embolism.

Results:

Nine cohorts that included 47 720 patients with non-high clinical probability were included in the meta-analysis. Both Age-adjusted D-dimer and conventional D-dimer have high sensitivity. However, conventional D-dimer has higher false positive rate than age-adjusted D-dimer.

Conclusion:

Age-adjusted D-dimer cutoffs combined with low risk clinical probability assessment ruled out PE diagnosis in suspected patients with a decreased rate of false positive tests.
Exploring the Emerging Trends of Spatial Epidemiology: A Scientometric Analysis Based on CiteSpace
Authors: Dai Fuqiang , Liu Hao , Zhang Xia , Li Qing
Published: November 2021

Infectious diseases are common challenges faced by people around the world, which jeopardize public health, as well as human well-being in various aspects of social and economic development. Although much progress has been made in spatial epidemiology, there is still very little scientific understanding of knowledge domain mapping with scientometric analysis. Based on a total of 4,552 literature records collected from the Web of Science Core Collection™, quantitative changes, research frontiers, research hotspots, and collaboration networks were analyzed by CiteSpace. The results show that both total publications and sum of times cited per year exhibit a rapid development trend in recent decades. The USA, England, and France are highly active in the field. The network of documents co-citation analysis is validated with almost same importance of documents, and primary research frontiers are landscape genetics, modeling and spatial analysis, and tropical diseases. The clustering of the keywords co-occurrence analysis network is heterogeneous and highly reliable, and research hotspots are related to phoma stem canker, vector preference, and aerosol chemical component. Scholars in the field of spatial epidemiology are closely connected, and they have been in a stable cooperative network, as well as institutions. Overall, scientometric analysis based on CiteSpace provides a sound tool to better understand the frontiers, hotspots, and emerging trends in the research domain of spatial epidemiology.
The Mediator Role of Sport Competence and Physical Condition in the Motivational Climate and Personal-Social Responsibility in Physical Education
Authors: Ada Elif Nilay , Serin Ali Haydar , Pehlivan Zekai , Çepikkurt Fatma , Ahmad Hasan , Kazak Zişan
Published: November 2021

This study aimed to separately examine the mediator role of two different variables in the relationship between perceived motivational climate and personal-social responsibility in physical education lessons. A total of 406 students ( Mage = 12.91, SD = 1.01), 217 girls ( Mage = 12.88, SD = 1.03) and 189 boys ( Mage = 12.93, SD = 0.99), from the 6th, 7th, and 8th grades attended the study. In the research, the Learning and Performance Orientations in Physical Education Classes Questionnaire, the Personal-Social Responsibility Questionnaire, and Physical Self-Perception Inventory for Children (physical condition and sport competence) were used. To realize the purpose of the research, the measurement models were first tested using the structural equation model; next, multiple regression analysis applications were made. Mediation analysis was carried out separately for the “learning and performance climate dimensions” for the perceived motivational climate questionnaire. For this purpose, the mediating effect of physical condition and sport competence in the relationship between each perceived motivational climate dimension and personal-social responsibility, was examined. In the analyzes, it was found that neither learning nor performance dimensions of perceived motivational climate had any mediating effect on the relationship between personal-social responsibility. However, the perceived learning climate could moderately predict personal-social responsibility whereas the perceived performance climate could not. As a result, it can be said that the most important effect on personal- social responsibility in physical education lessons belongs to “the student learning orientation” factor which belongs only to the perceived learning climate. Since the student’s sport competence or physical condition is not effective in influencing personal-social responsibility, it has become necessary for physical education teachers to make efforts to create a learning-oriented climate that is associated with positive outcomes.
The Effect of Innovation and Participation as Workplace Values on Job Satisfaction and the Mediating Effect of Psychological Ownership
Authors: Aslan Mustafa , Atesoglu Hulya
Published: November 2021

Job satisfaction is an important construct in the organizational behavior domain because it affects several organizational variables, such as performance, organizational citizenship behavior, and organizational commitment. This study investigates the effect of innovation and participation as workplace values on job satisfaction and the mediating role of psychological ownership. Participants ( N = 316) were adults working at different hotels in Antalya, Turkey. The results show innovation and participation as workplace values manifest their effects on job satisfaction through psychological ownership. Moreover, psychological ownership, along with participation, is one of the best estimators of job satisfaction, while participation is the best estimator of psychological ownership among studied variables.
Brotherhood and Hip-Hop: The Case of Chinese Hip-Hop Club Triple H
Authors: Chen Xi , Tong Yazhou , Zhang Jinsheng
Published: November 2021

After hip-hop increased in popularity in Chinese entertainment programs, different perceptions of hip-hop in China reflected a clash of various thinking patterns among audiences, with hip-hop club Triple H on the cusp of controversy. Taking Triple H as a case study, this paper aims to explore how emotional attachments influence the development of Chinese hip-hop clubs in post-subculture. The findings indicated that the brotherhood rooted in hip-hop culture has been reshaped by the hybridity of Chinese hip-hop featuring fraternity mixed with sensitivity, loyalty filled with controversy, and heroism heightened by diversity. This paper argues that the recurring theme of “brotherhood” contributing to the charisma of Chinese hip-hop clubs cannot be partially interpreted as either gangster love or an underground bond, which gives rise to a new approach to the notion of authenticity, with hip-hop interpreted as a distinctive lifestyle.
Objective Assessment System for Hearing Prediction Based on Stimulus-Frequency Otoacoustic Emissions
Authors: Gong Qin , Liu Yin , Xu Runyi , Liang Dong , Peng Zewen , Yang Honghao
Published: November 2021

Stimulus-frequency otoacoustic emissions (SFOAEs) can be useful tools for assessing cochlear function noninvasively. However, there is a lack of reports describing their utility in predicting hearing capabilities. Data for model training were collected from 245 and 839 ears with normal hearing and sensorineural hearing loss, respectively. Based on SFOAEs, this study developed an objective assessment system consisting of three mutually independent modules, with the routine test module and the fast test module used for threshold prediction and the hearing screening module for identifying hearing loss. Results evaluated via cross-validation show that the routine test module and the fast test module predict hearing thresholds with similar performance from 0.5 to 8 kHz, with mean absolute errors of 7.06–11.61 dB for the routine module and of 7.40–12.60 dB for the fast module. However, the fast module involves less test time than is needed in the routine module. The hearing screening module identifies hearing status with a large area under the receiver operating characteristic curve (0.912–0.985), high accuracy (88.4–95.9%), and low false negative rate (2.9–7.0%) at 0.5–8 kHz. The three modules are further validated on unknown data, and the results are similar to those obtained through cross-validation, indicating these modules can be well generalized to new data. Both the routine module and fast module are potential tools for predicting hearing thresholds. However, their prediction performance in ears with hearing loss requires further improvement to facilitate their clinical utility. The hearing screening module shows promise as a clinical tool for identifying hearing loss.
What do Health Workers say About Rural Practice?
Authors: Okyere Eunice , Ward Paul , Marfoh Kissinger , Mwanri Lillian
Published: November 2021

Adequately staffed rural health services improve healthcare delivery and health outcomes, yet this is lacking in rural Ghana. We used a descriptive qualitative design to understand the contextual issues that affect rural practice, in the Upper East Region, Ghana. Sixty-eight in-depth interviews were conducted with healthcare workers and analysed thematically. Four themes were identified: types of postings to rural settings, healthcare workers’ perceptions of their rural postings, perceived enablers and motivators for rural practice, and perceived challenges and barriers to rural practice. While adequate supervision and family proximity are needed to improve the feelings of loneliness, isolation and neglect in rural areas, challenges and barriers such as inadequate security, unstable electricity supply, language barrier, lack of equipment and transport/ambulance have been identified to have negative influence on healthcare workers. The findings highlight the need for healthcare managers to improve fairness and transparency in the posting and reshuffling processes of healthcare workers.
The Interests of Family Medicine Residents in Future Faculty Positions Across the Senior Year
Authors: Weidner Amanda , McGuire Marcia , Stutzman Kim , Glass Justin , Stevens Nancy Gray
Published: November 2021

Background and Objectives

The shortage of residency faculty in the pipeline is a growing concern to meet future workforce needs, though there is little research on attracting residents to be future faculty or what factors would influence their interest in this role. The objectives of this study were: (1) To assess the interest of third year residents (R3s) in faculty positions, and the various factors that might positively or negatively affect this decision; (2) to compare whether this changes across the R3 year; and (3) to compare between chief residents and other R3s.

Methods

Longitudinal survey at two points in time for each of three consecutive cohorts of R3s (2016-2018) from a regional network of family medicine residency programs.

Results

Among the final sample of R3s (176/545, 32% response), nearly half were interested in a residency faculty role. Strong positive influences on interest include the teaching role, advising/mentoring role, range of practice scope, and ability to perform procedures; salary and administrative responsibilities detract from interest. Among the matched sample of 96 R3s who also responded at Time 2 (55% response), non-chief residents had an increase in knowledge of and interest in the faculty role across the R3 year.

Conclusions

Nearly half of senior family medicine residents report positive interest in residency faculty positions and in most components of the role. Mentorship may encourage more residents to consider these positions upon graduation or shortly thereafter. More research on other specialties and with career follow up is recommended.
Can Life Experiences Predict Readiness for Residency? A Family Medicine Residency’s Analysis
Authors: Busha Michael E. , McMillen Brock , Greene Jeffrey , Gibson Kristine , Channell Adam , Ziemkowski Peter
Published: November 2021

BACKGROUND

Program directors for Family Medicine residencies must navigate an increasingly complex recruitment landscape. With increasing United States allopathic and osteopathic graduates and continued high volumes of international graduates, the ability to identify application characteristics that predict quality residents both for filtering applications for interview offers and ranking is vital. Our study concentrates on the predictive value of reported life experiences including volunteerism, work experiences, prior career, research experience, and participation in medical student organizations including student leadership.

METHODS

Through a retrospective cohort study, we extracted the described life experiences from resident application materials. We then obtained initial clinical performance data on the Family Medicine inpatient service during the first six months of residency to determine readiness for residency. This analysis occurred in 2020 and included all matriculants in the graduating classes of 2013 through 2020 for a single residency. Of 110 matriculating residents, data were available for 97(88%).

RESULTS

Applicants with a history of a prior career demonstrated improved overall readiness for residency with competency domain-specific advantages in Interpersonal and Communication Skills and Systems-Based Practice. In contrast, applicants reporting participation in research performed below peers in all competency domains. Applicant reports on volunteerism, work experience, academic productivity and student involvement did not correlate with initial clinical performance.

CONCLUSIONS

Residency directors should recognize applicants with prior careers as likely having strong communications and systems-based practice skills. All other examined experiences should be evaluated within the context of broader applicant assessments including research experience which overall has a potential negative correlation to clinical readiness.
Safety and Effectiveness of Outpatient Total Ankle Arthroplasty
Authors: Kayum Shahin , Kooner Sahil , Khan Ryan M. , Halai Mansur , Awoke Adam , Kanani Asa , Montgomery Spencer , Meldrum Alexander , Daniels Timothy R.
Published: November 2021

Background:

Total ankle arthroplasty (TAA) is a surgical procedure commonly reserved for patients suffering from symptomatic end-stage ankle arthritis. As the number of TAAs increases, so does the associated economic burden. Given these economic constraints, there has been interest in the feasibility of outpatient TAA. The purpose of this study is to evaluate the safety, efficacy, and satisfaction of patients undergoing outpatient TAA.

Methods:

This is a retrospective case series of consecutive patients who underwent outpatient TAA from July 2018 to June 2019. Inclusion criteria included any patient undergoing a primary TAA in the outpatient setting. This was defined as discharge on the same day of surgery or within 12 hours of surgery. All surgeries were completed by a single experienced surgeon through an anterior approach using the Cadence Total Ankle System. Prior to surgery, all patients received a popliteal nerve block. Patients were then discharged home with oral analgesic and a popliteal nerve catheter, which they removed after 48 hours. The primary outcome of interest was postoperative pain control, which was measured using a numeric scale. Secondary outcomes included complication rate, readmission rate, and patient satisfaction. A review of the current literature was then completed to supplement our results.

Results:

In total, 41 patients were included in our analysis. In terms of the primary outcome, the average numeric scale score was 1.98, indicating excellent pain control. Additionally, nearly all 41 patients stated they were very satisfied with their postoperative pain control regimen. In terms of secondary outcomes, the majority of patients stated they were satisfied with discharge on the same day as surgery. There were no readmissions or major complications in our outpatient TAA cohort. When asked if they would recommend the care they experienced to a friend with the same condition, 95% of patients said that they would recommend this care pathway. Our literature review included 5 original studies, which were all retrospective level IV studies. These studies uniformly demonstrated the safety and efficacy of outpatient TAA.

Conclusions:

The results of our study demonstrate the outpatient TAA is associated with excellent pain control using a multidisciplinary pain approach. The use of standardized outpatient postoperative pathways was effective in preventing readmissions and complications, while still resulting in high patient satisfaction scores. A review of the literature complemented our results, as there are largely no significant differences between outpatient and inpatient TAA. Level of Evidence: Level IV, case series.
Etranacogene dezaparvovec for hemophilia B gene therapy
Authors: Thornburg Courtney D.
Published: November 2021

The treatment landscape for hemophilia has been rapidly changing with introduction of novel therapies. Gene therapy for hemophilia is a promising therapeutic option for sustained endogenous factor production to mitigate the need for prophylactic treatment to prevent spontaneous and traumatic bleeding. Etranacogene dezaparvovec is an investigational factor IX (FIX) gene transfer product that utilizes the adeno-associated virus (AAV) 5 vector with a liver-specific promoter and a hyperactive FIX transgene. Here, the development of etranacogene dezaparvovec and available efficacy and safety data from clinical trials are reviewed. Overall, etranacogene dezaparvovec provides sustained FIX expression for more than 2 years and allows for a bleed and infusion-free life in the majority of patients. Safety, efficacy, and quality-of-life data will inform shared decision-making for patients who are considering gene therapy. Long-term follow-up regarding duration of expression and safety are crucial.
Single-Cell Multiomics Reveals Increased Plasticity, Resistant Populations and Stem-Cell-like Blasts in KMT2A-Rearranged Leukemia
Authors: Chen Changya , Yu Wenbao , Alikarami Fatemeh , Qiu Qi , Chen Chia-hui , Flournoy Jennifer , Gao Peng , Uzun Yasin , Fang Li , Hu Yuxuan , Zhu Qin , Wang Kai , Libbrecht Clara , Felmeister Alex , Rozich Isaiah , Ding Yang-yang , Hunger Stephen P , Wu Hao , Brown Patrick A. , Guest Erin , Barrett David M , Bernt Kathrin M. , Tan Kai
Published: November 2021

KMT2A-rearranged (KMT2A-r) infant ALL is a devastating malignancy with a dismal outcome, and younger age at diagnosis is associated with increased risk of relapse. To discover age-specific differences and critical drivers that mediate poor outcome in KMT2A-r ALL, we subjected KMT2A-r leukemias and normal hematopoietic cells from patients of different ages to single cell multi-omics analyses. We uncovered the following critical new insights: leukemia cells from patients younger than 6 months have significantly increased lineage plasticity. Steroid response pathways are downregulated in the most immature blasts from younger patients. We identify a hematopoietic stem and progenitor-like (HSPC-like) population in the blood of younger patients that contains leukemic blasts and form an immunosuppressive signaling circuit with cytotoxic lymphocytes. These observations offer a compelling explanation for the ability of leukemias in young patients to evade chemotherapy and immune mediated control. Our analysis also revealed pre-existing lymphomyeloid primed progenitors and myeloid blasts at initial diagnosis of B-ALL. Tracking of leukemic clones in two patients whose leukemia underwent a lineage switch documented the evolution of such clones into frank AML. These findings provide critical insights into KMT2A-r ALL and have clinical implications for molecularly targeted and immunotherapy approaches. Beyond infant ALL, our study demonstrates the power of single cell multi-omics to detect tumor intrinsic and extrinsic factors affecting rare but critical subpopulations within a malignant population that ultimately determines patient outcome.

Disclosures

Bernt: Merck: Other: Spouse is an employee of Merck.; Syndax: Research Funding.
ALKBH5 Functions As an Oncogene in Multiple Myeloma
Authors: Qu Jianwei , Hou Yifan , Chen Qingxiao , Chen Jing , LI YI , Zhang Enfan , Gu Huiyao , Xu Ruyi , Liu Yang , He Jingsong , Huang He , Cai Zhen
Published: November 2021

Background: RNA N 6-methyladenosine (m 6A) plays a critical role in regulating gene expression and determining cell fate. The dysregulation of m 6A modulators, including α-ketoglutarate-dependent dioxygenase AlkB homolog 5 (ALKBH5), has been reported to promote tumor development through their enzymatic function. However, the functions of mRNA m 6A and its modulators in multiple myeloma (MM) are largely unknown.

Methods: We queried publicly available MM datasets to study the expression profile of m 6A modulators (METTL3, METTL14, WTAP, FTO, and ALKBH5) in MM and their relationships with clinical outcomes in patients with MM. Both gain- and loss-of-function studies were performed to investigate the role of ALKBH5 in MM. The cell proliferation assay, colony formation assay, Annexin V apoptosis analysis, and 5-ethynyl-2′-deoxyuridine (EdU) assay were performed to evaluate the functions of ALKBH5 in MM in vitro. Human MM cell line xenograft models were constructed to examine the effects of ALKBH5 knockdown or overexpression on MM growth in vivo. The rescue assay using catalytically inactive mutant ALKBH5-H204A was conducted to determine whether demethylation activity was required for the function of ALKBH5 in MM. Then, we performed RNA sequencing and m 6A sequencing to explore the key targets that mediated ALKBH5 function in MM. We investigated the gene regulatory mechanism of ALKBH5 in MM by m 6A immunoprecipitation assay, RNA immunoprecipitation assay, RNA decay assay, dual-luciferase reporter assay, and so forth. Gene set enrichment analysis and Western blotting were employed to determine the downstream signaling pathways regulated by ALKBH5 and the recognized target.

Results: ALKBH5 was overexpressed in MM and associated with a poor prognosis in patients with MM. The increased ALKBH5 expression was required for the survival and growth of MM cells in vitro and in vivo. Mechanistically, m 6A demethylation activity was required for ALKBH5 to exert tumorigenic effects in MM. Tumor necrosis factor (TNF) receptor-associated factor 1 (TRAF1) was identified as a functionally important target of ALKBH5. ALKBH5 regulated TRAF1 expression via affecting mRNA stability of TRAF1 in an m 6A- and YTHDF2-dependent manner. ALKBH5 promoted MM cell growth and survival partly through TRAF1-mediated activation of NF-κB and MAPK signaling pathways.

Conclusion: Our findings showed that ALKBH5 played an oncogenic role in MM and highlighted that ALKBH5 could potentially be a novel therapeutic target in MM.

Disclosures

No relevant conflicts of interest to declare.
Expert-independent classification of mature B-cell neoplasms using standardized flow cytometry: a multicentric study
Authors: Böttcher Sebastian , Engelmann Robby , Grigore Georgiana , Fernandez Paula , Caetano Joana , Flores-Montero Juan , van der Velden Vincent H. J. , Novakova Michaela , Philippé Jan , Ritgen Matthias , Burgos Leire , Lecrevisse Quentin , Lange Sandra , Kalina Tomas , Verde Velasco Javier , Fluxa Rodriguez Rafael , van Dongen Jacques J. M. , Pedreira Carlos E. , Orfao, Alberto
Published: November 2021

Reproducible expert-independent flow-cytometric criteria for the differential diagnoses between mature B-cell neoplasms are lacking. We developed an algorithm-driven classification for these lymphomas by flow cytometry and compared it to the WHO gold standard diagnosis. Overall, 662 samples from 662 patients representing 9 disease categories were analyzed at 9 laboratories using the previously published EuroFlow 5-tube-8-color B-cell chronic lymphoproliferative disease antibody panel. Expression levels of all 26 markers from the panel were plotted by B-cell entity to construct a univariate, fully standardized diagnostic reference library. For multivariate data analysis, we subsequently used canonical correlation analysis of 176 training cases to project the multidimensional space of all 26 immunophenotypic parameters into 36 2-dimensional plots for each possible pairwise differential diagnosis. Diagnostic boundaries were fitted according to the distribution of the immunophenotypes of a given differential diagnosis. A diagnostic algorithm based on these projections was developed and subsequently validated using 486 independent cases. Negative predictive values exceeding 92.1% were observed for all disease categories except for follicular lymphoma. Particularly high positive predictive values were returned in chronic lymphocytic leukemia (99.1%), hairy cell leukemia (97.2%), follicular lymphoma (97.2%), and mantle cell lymphoma (95.4%). Burkitt and CD10+ diffuse large B-cell lymphomas were difficult to distinguish by the algorithm. A similar ambiguity was observed between marginal zone, lymphoplasmacytic, and CD10− diffuse large B-cell lymphomas. The specificity of the approach exceeded 98% for all entities. The univariate immunophenotypic library and the multivariate expert-independent diagnostic algorithm might contribute to increased reproducibility of future diagnostics in mature B-cell neoplasms.
Metabolic profile changes in serum of migraine patients detected using 1H-NMR spectroscopy
Authors: Harder Aster V. E. , Vijfhuizen Lisanne S. , Henneman Peter , Willems van Dijk Ko , van Duijn Cornelia M. , Terwindt Gisela M. , van den Maagdenberg Arn M. J. M.
Published: November 2021

Background

Migraine is a common brain disorder but reliable diagnostic biomarkers in blood are still lacking. Our aim was to identify, using proton nuclear magnetic resonance (1H-NMR) spectroscopy, metabolites in serum that are associated with lifetime and active migraine by comparing metabolic profiles of patients and controls.

Methods

Fasting serum samples from 313 migraine patients and 1512 controls from the Erasmus Rucphen Family (ERF) study were available for 1H-NMR spectroscopy. Data was analysed using elastic net regression analysis.

Results

A total of 100 signals representing 49 different metabolites were detected in 289 cases (of which 150 active migraine patients) and 1360 controls. We were able to identify profiles consisting of 6 metabolites predictive for lifetime migraine status and 22 metabolites predictive for active migraine status. We estimated with subsequent regression models that after correction for age, sex, BMI and smoking, the association with the metabolite profile in active migraine remained. Several of the metabolites in this profile are involved in lipid, glucose and amino acid metabolism.

Conclusion

This study indicates that metabolic profiles, based on serum concentrations of several metabolites, including lipids, amino acids and metabolites of glucose metabolism, can distinguish active migraine patients from controls.