bluuebunny/crossref_metadata_2025 huggingface dataset:
Oncology Care in Non-Small Cell Lung Cancer—Personalizing the Treatment Plan
Authors: Vrtis Mary C.
Published: March 2023

With potentially curative targeted and immunotherapies for non-small cell lung cancer, long term survival of at least 5 to 10 years is increasingly possible. A personalized, holistic, and multidisciplinary home healthcare treatment plan can help cancer patients transition from acute to chronic disease management. Factors to be considered include the patient's goals, treatment-related risks, the degree of metastasis, acute symptom management needs, and the desire and ability to participate in the treatment plan. The case history illustrates how genetic sequencing and immunohistochemistry testing guide treatment decisions. Strategies for pharmacological and nonpharmacological management of acute pain related to pathological spinal fractures are discussed. Care coordination that includes the patient, home care nurses and therapists, the oncologist, and the oncology nurse navigator is essential to transition the patient with advanced metastatic cancer to the highest possible functional status and quality of life. Discharge teaching should include early recognition and intervention for adverse effects of medications and signs or symptoms that may signal disease reoccurrence. The use of a written, patient-driven survivorship plan is important to assure diagnostic and treatment information is summarized, follow-up tests and scans are scheduled, and screening tests for other types of cancer are included.
Interrupting Biases in the Experience and Management of Pain Nurses can help address challenges faced by racially and ethnically diverse patients and caregivers.
Authors: Booker Staja Q. , Baker Tamara A. , Epps Fayron , Herr Keela A. , Young Heather M. , Fishman Scott
Published: March 2023

This article is part of a series, Supporting Family Caregivers: No Longer Home Alone, published in collaboration with the AARP Public Policy Institute. Results of focus groups, conducted as part of the AARP Public Policy Institute's No Longer Home Alone video project, supported evidence that family caregivers aren't given the information they need to manage the complex care regimens of family members. This series of articles and accompanying videos aims to help nurses provide caregivers with the tools they need to manage their family member's health care at home.

The articles in this new installment of the series provide practical information nurses can share with family caregivers of persons living with pain. To use this series, nurses should read the articles first, so they understand how best to help family caregivers. Then they can refer caregivers to the informational tear sheet—Information for Family Caregivers—and instructional videos, encouraging them to ask questions. For additional information, see Resources for Nurses. Cite this article as: Booker, S.Q., et al. Interrupting Biases in the Experience and Management of Pain. Am J Nurs 2022; 122(9): 48-54.
Endometrial Carcinomas With Subclonal Loss of Mismatch Repair Proteins
Authors: Mendoza Rachelle P. , Wang Peng , Schulte Jefree J. , Tjota Melissa Y. , Jani Ina , Martinez Anna C. , Haridas Rishikesh , Wanjari Pankhuri , Steinhardt George , Brown Noah , Betz Bryan L. , Chapel David B. , Kertowidjojo Elizabeth , Yamada S.D. , Bennett Jennifer A.
Published: March 2023

Subclonal loss of mismatch repair (MMR) proteins has been described in a small subset of endometrial carcinomas (ECs), but the genomic basis for this phenomenon has received limited attention. Herein, we retrospectively evaluated all ECs with MMR immunohistochemistry (n=285) for subclonal loss, and in those (n=6), performed a detailed clinicopathologic and genomic comparison of the MMR-deficient and MMR-proficient components. Three tumors were FIGO stage IA, and one each stage IB, II, and IIIC2. Patterns of subclonal loss were as follows: (1) 3 FIGO grade 1 endometrioid carcinomas with subclonal MLH1/PMS2, MLH1 promoter hypermethylation, and no MMR gene mutations; (2) POLE-mutated FIGO grade 3 endometrioid carcinoma with subclonal PMS2, and PMS2 and MSH6 mutations limited to the MMR-deficient component; (3) dedifferentiated carcinoma with subclonal MSH2/MSH6, as well as complete loss of MLH1/PMS2, MLH1 promoter hypermethylation, and PMS2 and MSH6 mutations in both components; (4) dedifferentiated carcinoma with subclonal MSH6, and somatic and germline MSH6 mutations in both components, but with a higher allele frequency in MMR-deficient foci. Recurrences occurred in 2 patients, one consisted of the MMR-proficient component from a FIGO 1 endometrioid carcinoma, while the other was from the MSH6-mutated dedifferentiated endometrioid carcinoma. At the last follow-up (median: 44 mo), 4 patients were alive and disease-free and 2 were alive with disease. In summary, subclonal MMR loss reflects subclonal and often complex genomic and epigenetic alterations, which may have therapeutic implications and therefore must be reported when present. In addition, subclonal loss can occur in both POLE-mutated and Lynch syndrome–associated ECs.
Trends in the Provision of Community-Building Activities by Nonprofit Hospitals, 2010-2019
Authors: Singh Simone R. , Cronin Cory , Puro Neeraj , Franz Berkeley
Published: March 2023

As part of their annual tax report, nonprofit hospitals are asked to report their community-building activities (CBAs); yet, little is known to date about hospitals' spending on such activities. CBAs are activities that improve community health by addressing the upstream factors and social determinants that impact health. Using data from Internal Revenue Service Form 990 Schedule H, this study used descriptive statistics to examine trends in the provision of CBAs by nonprofit hospitals between 2010 and 2019. While the number of hospitals reporting any CBA spending remained relatively stable at around 60%, the share of total operating expenditures that hospitals contributed to CBAs decreased from 0.04% in 2010 to 0.02% in 2019. Despite the increasing attention paid by policy makers and the public to the contributions that hospitals make to the health of their communities, nonprofit hospitals have not made corresponding efforts to increase their spending on CBAs.
Evaluating Veterans Response Teams and Police Interventions on Veterans' Health Care Utilization
Authors: Tsai Jack , Gonzalez Cecilia , Szymkowiak Dorota , Stewart Katharine , Dillard Dorothy , Whittle Tanya , Woodland Paul
Published: March 2023

This study examined the effects of veteran-specific cooperative police interventions, including a Veterans Response Team (VRT) and broad collaboration between local police departments and a Veterans Affairs (VA) medical center police department (local-VA police [LVP]), on veterans' health care utilization. Data were analyzed on 241 veterans (51 received VRT and 190 received LVP intervention) in Wilmington, Delaware. Nearly all veterans in the sample were enrolled in VA health care at the time of police intervention. Veterans who received VRT or LVP interventions showed similar increases in use of outpatient and inpatient mental health and substance abuse treatment services, rehabilitation services, ancillary care services, homeless programs, and emergency department/urgent care services after 6 months. These findings suggest the importance of relationship building among local police departments, VA Police, and Veterans Justice Outreach to create pathways to care to ensure that veterans are connected to needed VA health care services.
Suspected Nonfatal Cocaine-Involved Overdoses Overall and With Co-involvement of Opioids
Authors: Scholl Lawrence , Liu Stephen , Pickens Cassandra M.
Published: March 2023

Context:

The Centers for Disease Control and Prevention (CDC) developed a syndrome definition for detection of suspected nonfatal cocaine-involved overdoses. The definition can be used to monitor trends and detect anomalies in emergency department (ED) syndromic surveillance data at the national, state, and local levels.

Objective:

This study describes the development of the nonfatal, unintentional/undetermined intent cocaine-involved overdose (UUCOD) definition and analysis of trends over time.

Design/Setting:

CDC developed the UUCOD definition to query ED data in CDC's National Syndromic Surveillance Program (NSSP). Data between 2018 and 2021 were analyzed from 29 states sharing data access in the Drug Overdose Surveillance and Epidemiology (DOSE) System via NSSP. Using Joinpoint regression, trends were analyzed for UUCOD overall, by sex and age group, and for UUCOD co-involving opioids.

Measures:

Time trends between 2018 and 2021 were analyzed by examining average monthly percentage change. Individual trend segments and trend inflection points were analyzed by examining monthly percentage change.

Results:

During 2018-2021, a total of 27 240 UUCOD visits were identified by the syndrome definition. Analyses identified different patterns in trends for males and females, with largely similar trends for persons aged 15 to 44 years and 45 years or older. Analyses also identified seasonal patterns with increases in spring/summer months in UUCOD overall and UUCOD co-involving opioids and declines for both in fall/winter months.

Conclusion:

This UUCOD syndrome definition will be useful for ongoing monitoring of suspected nonfatal overdoses involving cocaine and co-involving cocaine and opioids. Ongoing assessment of cocaine-involved overdose trends might identify anomalies requiring further investigation and inform deployment of resources.
Characterizing the Role of International Graduates of the Epidemic Intelligence Service in Increasing the Epidemiological Capacity and Diversity of the United States Public Health Workforce
Authors: Temate-Tiagueu Yvette , Winquist Andrea , Davis Meagan , Dietz Stephanie , Robinson Byron , Pevzner Eric , Arvelo Wences
Published: March 2023

Context:

A trained and diverse public health workforce is needed to respond to public health threats. The Epidemic Intelligence Service (EIS) is an applied epidemiology training program. Most EIS officers are from the United States, but some are from other countries and bring unique perspectives and skills.

Objectives/Evaluation:

To characterize international officers who participated in the EIS program and describe their employment settings after training completion.

Design:

International officers were people who participated in EIS and who were not US citizens or permanent residents. We analyzed data from EIS's application database during 2009-2017 to describe officers' characteristics. We used data from the Centers for Disease Control and Prevention's (CDC's) workforce database for civil servants and EIS exit surveys to describe jobs taken after program completion.

Main Outcome Measures:

We described the characteristics of the international officers, jobs taken immediately after program completion, and duration of employment at CDC.

Results:

Among 715 officers accepted in EIS classes of 2009-2017, 85 (12%) were international applicants, with citizenships from 40 different countries. Forty (47%) had 1 or more US postgraduate degrees, and 65 (76%) were physicians. Of 78 (92%) international officers with available employment data, 65 (83%) reported taking a job at CDC after program completion. The remaining took a public health job with an international entity (6%), academia (5%), or other jobs (5%). Among 65 international officers who remained working at CDC after graduation, the median employment duration was 5.2 years, including their 2 years in EIS.

Conclusions:

Most international EIS graduates remain at CDC after program completion, which strengthens the diversity and capacity of CDC's epidemiological workforce. Further evaluations are needed to determine the effects of pulling away crucial talent from other countries needing experienced epidemiologists and to what extent retaining those persons can benefit public health globally.
An Evaluation of the Successes of the NASTAD Minority Leadership Program and Its Implications for Leadership in State Health Departments
Authors: Amutah-Onukagha Ndidiamaka , Gifuni-Koutsouris Jacqueline , Assan Maame Araba , Bryant Cierra , Galvan Rosy
Published: March 2023

Objective:

The Minority Leadership Program (MLP) was developed by the National Alliance of State and Territorial AIDS Directors (NASTAD) to enhance leadership skills among public health professionals of color that work within HIV, viral hepatitis, or drug user health programs in health departments. The goal of the study was to analyze experiences of MLP alumni in their respective health departments, explore opportunities to address cultural issues, and explore leadership opportunities for alumni.

Design:

The research team conducted a mixed-methods approach to this study. It included qualitative data analysis of 2018-2019 MLP applicants (n = 32), online surveys to MLP alumni (n = 51), and key informant interviews with former MLP cohort members (n = 7). Thematic coding was conducted for all qualitative data collection tools using Dedoose.

Setting and Participants:

Study was conducted virtually between September 2020 and March 2021. A total of 90 individuals participated in this evaluation research study. These individuals were former cohort members of MLP by NASTAD.

Intervention:

No health intervention was conducted.

Main Outcome Measure:

Achievement of participant-level experiences after completion of MLP.

Results:

Microaggressions in the workplace, lack of diversity in the workplace, positive experiences participating in the MLP, and networking opportunities were common themes throughout the study. Other themes included challenges and successes experienced after MLP completion, and MLP's contribution to advancing professionally within the health department.

Conclusions:

Overall, participants had positive experiences participating in MLP and spoke highly of the networking opportunities available in the program. Individuals who participated recognized a lack of open dialogue and conversations surrounding racial equity, racial justice, and health equity within their respective departments. The research evaluation team recommends that NASTAD continue collaborating with health departments to address issues on racial equity and social justice with health department staff. Programs such as MLP are critical to diversifying the public health workforce to adequately address issues on health equity.
Rural Public Health Data Challenges During the COVID-19 Pandemic: The Case for Building Better Systems Ahead of a Public Health Crisis
Authors: Bekemeier Betty , Heitkemper Elizabeth , Backonja Uba , Whitman Gregory , Schultz Melinda , Jiang Yufei , Baquero Barbara , Turner Anne M.
Published: March 2023

Context:

Rural public health personnel serve communities that have been particularly susceptible to COVID-19 and yet faced the pandemic with far less well-resourced capacity than their urban counterparts. A critical aspect of addressing local health inequities is access to high-quality population data and the capacity to effectively use data to support decision making. However, much of the data required to investigate inequities are not readily available to rural local health departments and the tools and training to analyze data are often lacking.

Program:

The purpose of our effort was to explore rural data challenges related to COVID-19 and provide recommendations for improving rural data access and capacity ahead of future crises.

Implementation:

We gathered qualitative data in 2 phases, more than 8 months apart, from rural public health practice personnel. Initial data were gathered in October-November 2020 regarding rural public health data needs during the COVID-19 pandemic and then to later identify whether the same findings held true in July 2021 or whether access to and capacity to use data to address the pandemic and related inequities improved as the pandemic progressed.

Evaluation:

In our 4-state exploration focused on access and use of data among rural public health systems to promote health equity in the Northwest United States, we found tremendous and ongoing unmet data needs, challenges with communicating data, and a lack of capacity to meet this public health crisis.

Discussion:

Recommendations for addressing these challenges include increasing dedicated resources specifically to rural public health systems, improving data access and infrastructure, and providing dedicated data-related workforce development.
With or without straps? A pilot study to investigate whether restraint devices affect the wheelchair basketball players' performance
Authors: Macchiarola Dario , Megna Marisa , Quarta Francesco , Bianchi Francesco Paolo , Cipriano Roberta , Andrani Michela , Ricci Vincenzo , Fiore Pietro , Ranieri Maurizio , Farì Giacomo
Published: March 2023

Background:

Wheelchair basketball (WB) represents a great physical activity, rehabilitation, and integration opportunity for people with disability. Straps are wheelchair accessories used to ensure safeness and stability. Nevertheless, some athletes report feeling limited in movements because of these restraint devices. The aim of this study was thus to deepen whether straps could affect performance and cardiorespiratory effort in WB players' athletic gesture and furthermore whether sport performance could be influenced by experience, anthropometric features, or classification score.

Methods:

Ten WB elite athletes were enrolled in this observational cross-sectional study. Speediness, wheelchair maneuverability, and sport-specific skills were evaluated with 3 tests: 20-m straight line test (test 1), figure 8 test (test 2), and figure 8 with ball test (test 3); all tests were performed with and without straps. Cardiorespiratory parameters (blood pressure [BP], heart rate, and oxygen saturation) were registered before and after tests. Anthropometric data, classification score, and practice’s years were collected and compared with test results.

Results:

Performance significantly improved in all tests wearing straps (test 1 P = 0.007, test 2 P = 0.009, and test 3 P = 0.025). No significant variation in cardiorespiratory basic signs emerged before and after the tests, with or without straps (systolic BP P = 0.140, diastolic BP P = 0.564, heart rate P = 0.066, and oxygen saturation P = 0.564). A statistically significant relation between test 1 with straps and classification score (coefficient = −0.25; P = 0.008) and test 3 without straps and classification score (coefficient = 1.00; P = 0.032) was found. No further relations emerged between test results and anthropometric data, classification score, and practice’s years (P > 0.05).

Conclusions:

These findings demonstrated that straps, as well as ensuring safety and preventing injuries, also improve the WB performance, stabilizing the trunk and implementing upper limb skills, without exposing players to excessive cardiorespiratory and biomechanical stresses.
Cultural Adaptation and Validation of the Ostomy Skin Tool to the Brazilian Portuguese
Authors: Nunes Maristela Lopes Gonçalves , Martins Lina , Conceição de Gouveia Santos Vera Lucia
Published: March 2023

PURPOSE:

To adapt the Ostomy Skin Tool (discoloration, erosion, and tissue overgrowth) to the Brazilian culture and to analyze psychometric properties of the adapted version.

DESIGN:

Psychometric (methodologic) evaluation of the instrument.

SUBJECTS AND SETTING:

Three ostomy/enterostomal therapy nurses evaluated the extent and severity of peristomal skin conditions in a sample of 109 adults 18 years or older with peristomal skin complications. These participants were receiving care in an ambulatory care center in outpatient health services in Sao Paulo and Curitiba, Brazil. In addition, interobserver reliability was measured using a group of 129 nurse participants who attended the Brazilian Congress of Stomatherapy held from November 12 to 15, 2017, in Belo Horizonte, a city located in the state of Minas Gerais, Brazil. Nurse participants assessed the descriptions of peristomal skin complications of the Portuguese version, using the same photographs used in the original DET score, purposely placed out of original order.

METHODS:

The study was performed in 2 stages. The instrument was translated into Brazilian Portuguese by 2 bilingual translators, and back-translated into English. The back-translated version was sent to one of the developers of the instrument for additional evaluation. During stage 2, content validity was evaluated by 7 nurses with expertise in ostomy and peristomal skin care. Convergent validity was evaluated by correlating the severity of peristomal skin complications to pain intensity. Discriminant validity was evaluated based on type and time of ostomy creation, presence of retraction, and preoperative stoma site marking. Finally, interrater reliability was evaluated using standardized photograph evaluation reproduced in the same sequence as the original English language version of the instrument, along with paired scores from assessment of adults living with an ostomy generated by an investigator and nurse data collectors.

RESULTS:

The Content Validity Index for the Ostomy Skin Tool was 0.83. Levels of mild agreements were obtained for the nurses' observations in the evaluation of peristomal skin complications using standardized photographs (κ= 0.314). In contrast, moderate to almost perfect agreements were obtained when scores were compared in the clinical setting (κ= 0.48-0.93, according to the domains). Positive correlations between the instrument and pain intensity (r= 0.44;P= .001) indicate convergent validity of the adapted version of the Ostomy Skin Tool. In contrast, analysis of discriminant validity was mixed and definitive conclusions about this form of construct validity cannot be made based on this study.

CONCLUSION:

This study supports convergent validity and interrater reliability of the adapted version of the Ostomy Skin Tool.
Flavobacterium humidisoli sp. nov., isolated from riverside soil
Authors: Ra Jun Sik , Oh Eun Tak , Han Ji-Hye , Kim Seung Bum
Published: March 2023

A novel Gram-stain-negative, yellow-pigmented, non-motile and rod-shaped bacterial strain designated MMS21-Er5T was isolated and subjected to polyphasic taxonomic characterization. MMS21- Er5T could grow at 4–34 °C (optimum, 30 °C), at pH 6–8 (optimum, pH 7) and in the presence of 0–2% NaCl (optimum, 1 %). The results of phylogenetic analysis based on 16S rRNA gene sequences indicated that MMS21- Er5T showed low levels of sequence similarities with other species, as the highest similarity of 97.83 % was observed with

Flavobacterium tyrosinilyticum

THG DN8.8T, then 97.68 % with ‘Flavobacterium ginsengiterrae’ DCY 55 and 97.63 % with

Flavobacterium banpakuense

15F3T, which were well below the suggested cutoff for species distinction. The whole genome sequence of MMS21-Er5T consisted of a single contig of 5.63 Mbp, and the DNA G+C content was 34.06 mol%. The in-silico DNA–DNA hybridization and orthologous average nucleotide identity values were highest with

Flavobacterium tyrosinilyticum

KCTC 42726T (45.7 and 91.92% respectively). The predominant respiratory quinone for the strain was menaquinone-6 (MK-6), the major cellular fatty acid was iso-C15 : 0, and the diagnostic polar lipids were phosphatidylethanolamine and phosphatidyldiethanolamine. The combination of physiological and biochemical tests clearly distinguished the strain from related species of the genus

Flavobacterium

. On the basis of these results, strain MMS21-Er5T evidently represents a novel species of the genus Flavobacterium, for which the name Flavobacterium humidisoli sp. nov. is proposed (type strain=MMS21-Er5T=KCTC 92256T =LMG 32524T).
Epidemiological cluster identification using multiple data sources: an approach using logistic regression
Authors: Susvitasari Kurnia , Tupper Paul F. , Cancino-Muños Irving , Lòpez Mariana G. , Comas Iñaki , Colijn Caroline
Published: March 2023

In the management of infectious disease outbreaks, grouping cases into clusters and understanding their underlying epidemiology are fundamental tasks. In genomic epidemiology, clusters are typically identified either using pathogen sequences alone or with sequences in combination with epidemiological data such as location and time of collection. However, it may not be feasible to culture and sequence all pathogen isolates, so sequence data may not be available for all cases. This presents challenges for identifying clusters and understanding epidemiology, because these cases may be important for transmission. Demographic, clinical and location data are likely to be available for unsequenced cases, and comprise partial information about their clustering. Here, we use statistical modelling to assign unsequenced cases to clusters already identified by genomic methods, assuming that a more direct method of linking individuals, such as contact tracing, is not available. We build our model on pairwise similarity between cases to predict whether cases cluster together, in contrast to using individual case data to predict the cases’ clusters. We then develop methods that allow us to determine whether a pair of unsequenced cases are likely to cluster together, to group them into their most probable clusters, to identify which are most likely to be members of a specific (known) cluster, and to estimate the true size of a known cluster given a set of unsequenced cases. We apply our method to tuberculosis data from Valencia, Spain. Among other applications, we find that clustering can be predicted successfully using spatial distance between cases and whether nationality is the same. We can identify the correct cluster for an unsequenced case, among 38 possible clusters, with an accuracy of approximately 35 %, higher than both direct multinomial regression (17 %) and random selection (< 5 %).
GEO Data Sets Analysis On Mechanism of Action of IFNβ-1a Treatment in Multiple Sclerosis
Authors: Ho Adam
Published: March 2023

Multiple Sclerosis (MS) is an autoimmune disease that affects millions of people worldwide and causes symptoms such as dysarthria, ataxia, and nystagmus. MS is known to be characterized by an autoimmune attack by the immune system on the myelin sheath of neurons, causing inflammation and scarring (sclerosis). In the status quo, MS is treated or alleviated by disease-modifying therapies, including beta interferons (IFNβ) and monoclonal antibodies. Yet, the mechanism of action (MOA) of IFNβ is not fully understood, and only a limited proportion of patients respond to IFNβ treatment. Mononuclear cells from therapy-naïve MS patients, IFN-β-1a-treated MS patients after 12 months from three databases on GEO are analysed to examine RNA changes that characterize both the disease and its treatment. 28 differentially expressed genes (DEGs) are identified in all three of the databases and passed the cut-off criteria. Using the 28 DEGs, we performed DAVID and PANTHER analysis, revealing that the biological process “immune response”, “defence against virus”, and “regulation of viral genome replication” are enriched. A protein interaction network for the DEGs was constructed and a protein module was identified and analysed with PANTHER, revealing “interleukin-27-mediated signalling pathway”, “regulation of ribonuclease activity”, “regulation of type III interferon production”, “cellular response to exogenous double-stranded RNA (dsRNA)”, and “ISG15-protein conjugation are enriched for >100 folds. Cytoscape analysis further identified the hub genes IFI44L, IFI44, and STAT1 and they may be important mediators in the therapeutic effect of IFNβ treatment and warrant further study. Overall, the findings of the present study provide insights into the MOA of IFNβ-1a and provide greater confidence on which genes are differentially expressed in MS before and after IFNβ-1a treatment. The results also are additional evidence for the role of viral infection in MS, a topic that is gaining interest in the MS research community.
Uptake of intramuscular vitamin K administration after birth and maternal and infant demographic variables: a national cohort study
Authors: Brunton S , Fenton L , Hardelid P , Williams TC
Published: March 2023

A long-acting monoclonal antibody against Respiratory Syncytial Virus (RSV), given as a one-off injection shortly after birth, is likely to be introduced soon. We hypothesised that carer acceptance of intra-muscular (IM) vitamin K, another injection given shortly after birth, might serve as a proxy indicator of likely acceptance of any such anti-RSV intervention, given previous associations described between IM vitamin K acceptance and subsequent non-immunisation. Using a national dataset of all postnatal health visitor visits in Scotland from 2018-2021 we explored demographic variables associated with non-acceptance of IM vitamin after birth. We found that in the time period 2019-2021 over 95.5% of carers were documented as consenting to this intervention, with only 1.1% requesting oral vitamin K and 0.9% refusing vitamin K altogether. Infant ethnicity, use of English as a first language at home, socio-economic position and maternal age were not associated with reduced uptake of IM vitamin K. We therefore did not identify any groups that might require increased engagement prior to the roll-out of a long-acting monoclonal antibody for RSV.
Differential effects of frailty on biventricular function and prognosis analysis in senile patients
Authors: Jing Jiang , Baojun Yang , Zhao Zhiying , Dili Xie , Yunhe Zhang , Rong Yu , Jing Jin
Published: March 2023

Objective

To investigate the differential effects of frailty on biventricular function in senile patients and analyse the prognosis of different combinations of clinical status.

Methods and Results

Patients aged ≥80 years with at least one basic disease causing heart failure were included and divided into three groups according to frailty score. Basic data, ultrasound data, and follow-up data were collected and analyses of differences between groups and survival were performed. The proportion of patients with right heart failure in the frailty group was significantly higher than that in the others. A total of 33 (15.1%) patients died within a year, 162 (74%) were readmitted within 1 year, and 84 (38.4%) were admitted for heart failure within 1 year. The frailty group with right heart failure had the highest rate of all cause and heart failure-related readmission. Frailty significantly increased the risk of 1-year all-cause mortality, all-cause readmission, and heart failure-related readmission. Right heart failure significantly increased the 1-year all-cause readmission and heart failure-related readmission rates. After adjusting for the interaction of factors, only frailty had a significant effect on the three prognostic events.

Conclusions

Right heart failure is more likely to be associated with frailty in senile patients. One-year all-cause mortality, all-cause readmission, and heart failure-related readmission rates were significantly increased in frail patients with right heart failure.

Frailty was a significant predictor of all-cause death, all-cause readmission, and heart failure-related readmission.
Ventricular Dyssynchrony Late after the Fontan Operation is Associated with Decreased Survival and the Presence of Arrhythmias
Authors: Gearhart Addison , Bassi Sunakshi , Rathod Rahul H. , Beroukhim Rebecca S. , Lipsitz Stuart , Gold Maxwell P. , Harrild David M. , Dionne Audrey , Ghelani Sunil J.
Published: March 2023

Background

Ventricular dyssynchrony and its relationship to clinical outcomes is not well characterized in patients following Fontan palliation.

Methods

Single-center retrospective analysis of cardiac magnetic resonance (CMR) imaging of patients with a Fontan circulation and age-matched healthy comparison cohort as controls. Feature tracking was performed on all slices of a ventricular short-axis cine stack. Circumferential and radial strain, strain rate, and displacement were measured; and multiple dyssynchrony metrics were calculated based on timing of these measurements (including standard deviation of time-to-peak, maximum opposing wall delay, and maximum base-to-apex delay). Primary endpoint was a composite measure including time to death or heart transplant listing (D/HTx); secondary outcomes were the presence of atrial or ventricular arrhythmias.

Results

A total of 503 cases (15y; IQR 10, 21) and 42 controls (16y; IQR 11, 20) were analyzed. Compared to controls, Fontan patients had increased dyssynchrony metrics, longer QRS duration, larger ventricular volumes, and worse systolic function. Dyssynchrony metrics were higher in patients with right ventricular (RV) or mixed morphology compared to those with LV morphology. At median follow-up of 4.3 years, 11% had D/HTx, 7% ventricular arrhythmia, and 38% atrial arrhythmia. Multiple risk factors for D/HTx were identified, including RV morphology, ventricular dilation, dysfunction, QRS prolongation, and dyssynchrony. Ventricular dilation and RV morphology were independently associated with D/HTx; ventricular dilation and global circumferential strain were independently associated with ventricular and atrial arrhythmias.

Conclusions

Mechanical dyssynchrony is highly prevalent in functional single ventricles palliated to the Fontan circulation and is more pronounced in hearts with RV or mixed ventricular morphology compared to those with LV morphology. Dyssynchrony is associated with death or need for heart transplantation and cardiac arrhythmias. These data add to the growing understanding regarding factors that can be used to risk-stratify patients with the Fontan circulation.
Elevated symptoms of depression and anxiety among family members of critically ill COVID-19 patients - An observational study of five cohorts across four countries
Authors: Lovik Anikó , González-Hijón Juan , Hoffart Asle , Fawns-Ritchie Chloe , Magnúsdóttir Ingibjörg , Lu Li , Unnarsdóttir Anna Bára , Kähler Anna K. , Campbell Archie , Hauksdóttir Arna , Chourpiliadis Charilaos , McCartney Daniel L. , Thordardóttir Edda Björk , Joyce Emily E. , Frans Emma M. , Jakobsdóttir Jóhanna , Trogstad Lill , Andreassen Ole A. , Magnus Per , Johnson Sverre Urnes , Sullivan Patrick F. , Aspelund Thor , Porteous David J. , Ask Helga , Ebrahimi Omid V. , Valdimarsdóttir Unnur Anna , Fang Fang
Published: March 2023

Background

Little is known regarding the mental health impact of having a significant person (family member and/or close friend) with COVID-19 of different severity.

Methods

The study included five prospective cohorts from four countries (Iceland, Norway, Sweden, and the UK) with self-reported data on COVID-19 and symptoms of depression and anxiety during March 2020-March 2022. We calculated the prevalence ratio (PR) of depression and anxiety in relation to having a significant person with COVID-19 and performed a longitudinal analysis in the Swedish cohort to describe the temporal patterns of the results.

Results

162,237 and 168,783 individuals were included in the analysis of depression and anxiety, respectively, of whom 24,718 and 27,003 reported a significant person with COVID-19. Overall, the PR was 1.07 (95% CI: 1.05-1.10) for depression and 1.08 (95% CI: 1.03-1.13) for anxiety among significant others of COVID-19 patients. The respective PRs for depression and anxiety were 1.04 (95% CI: 1.01-1.07) and 1.03 (95% CI: 0.98-1.07) if the significant person was never hospitalized, 1.15 (95% CI: 1.08-1.23) and 1.24 (95% CI: 1.14-1.34) if the patient was hospitalized, 1.42 (95% CI: 1.27-1.57) and 1.45 (95% CI: 1.31-1.60) if admitted to the ICU, and 1.34 (95% CI: 1.22-1.46) and 1.36 (95% CI: 1.22-1.51) if the significant person died. Individuals of hospitalized, ICU admitted, or deceased patients showed higher prevalence of depression and anxiety during the entire 12 months after the COVID-19 diagnosis of the significant person.

Conclusions

Close friends and family members of critically ill COVID-19 patients show elevated prevalence of depression and anxiety throughout the first year after the diagnosis.
CBD lengthens sleep, shortens ripples and leads to intact simple but worse cumulative memory
Authors: Samanta Anumita , Aleman-Zapata Adrian , Agarwal Kopal , Özsezer Pelin , Alonso Alejandra , van der Meij Jacqueline , Rayan Abdelrahman , Navarro-Lobato Irene , Genzel Lisa
Published: March 2023

Cannabidiol (CBD) is on the rise as over-the-counter medication to treat sleep disturbances, anxiety, pain and epilepsy due to its action on the excitatory/inhibitory balance in the brain. However, it remains unclear if CBD also leads to adverse effects via changes of sleep macro- and microarchitecture. To investigate the effect of CBD on sleep and sleep-related memory consolidation, we performed two experiments using the Object Space Task testing both simple and cumulative memory in rats. We show that oral CBD administration extended the sleep period but changed the properties of NonREM sleep oscillations (delta, spindle, ripples). Specifically, CBD also led to less long (>100ms) ripples and consequently worse cumulative memory consolidation. In contrast, simple memories were not affected. In sum, we can confirm the beneficial effect of CBD on sleep, however, this comes with changes in NonREM oscillations that negatively impact memory consolidation.
Mice with renal-specific alterations of stem cell-associated signaling develop symptoms of chronic kidney disease but surprisingly no tumors
Authors: Myszczyszyn Adam , Popp Oliver , Kunz Severine , Sporbert Anje , Jung Simone , Penning Louis C. , Fendler Annika , Mertins Philipp , Birchmeier Walter
Published: March 2023

Previously, we found that Wnt and Notch signaling govern stem cells of clear cell kidney cancer (ccRCC) in patients. To mimic stem cell responses in the normal kidney in vitro in a marker-unbiased fashion, we have established organoids from total single adult mouse kidney epithelial cells in Matrigel and serum-free conditions. Deep proteomic and phosphoproteomic analyses revealed that the organoids resembled renewal of adult kidney tubular epithelia, since organoid cells displayed activity of Wnt and Notch signaling, long-term proliferation and expression of markers of proximal and distal nephron lineages. In our wish to model stem cell-derived human ccRCC, we have generated two types of genetic double kidney mutants in mice: Wnt-β-catenin-GOF together with Notch-GOF and Wnt-β-catenin-GOF together with a most common alteration in ccRCC, Vhl-LOF. An inducible Pax8-rtTA-LC1-Cre was used to drive recombination specifically in adult kidney epithelial cells. We confirmed mutagenesis of β-catenin, Notch and Vhl alleles on DNA, protein and mRNA target gene levels. Surprisingly, we observed symptoms of chronic kidney disease (CKD) in mutant mice, but no increased proliferation and tumorigenesis. Thus, the responses of kidney stem cells in the organoid and genetic systems produced different phenotypes, i.e. enhanced renewal versus CKD.
Living Photovoltaics based on Recombinant Expression of MtrA Decaheme in Photosynthetic Bacteria
Authors: Reggente Melania , Schurgers Nils , Mouhib Mohammed , Politi Sara , Antonucci Alessandra , Boghossian Ardemis A.
Published: March 2023

At the center of microbial bioelectricity applications lies the critical need to express foreign heme proteins that are capable of redirecting the electron flux of the cell’s metabolism. This study presents bioengineeredSynechocystissp. PCC 6803 cells capable of increased electrogenicity through the introduction of a genetic construct for cytochrome expression. We could demonstrate the functional expression of the periplasmic MtrA decaheme c-type cytochrome fromShewanella oneidensis, a dissimilatory metal-reducing exoelectrogen, insideSynechocystis. Protein expression was verified through western-blotting and immunostaining, and oxygen evolution, optical density, and absorption measurements confirm sustained cell activity and viability under the tested expression conditions. Furthermore, the bioengineered cells show enhanced mediated exoelectrogenicity, as confirmed through a colorimetric iron assay and electrochemical measurements. Compared to wildtype cells on graphite electrodes, the bioengineered cells show a 2-fold increase in light-dependent, extracellular electron transfer, achieving photocurrent densities of 4 μA/cm2under white light illumination of ∼500 μmol m-2s-1. The increased capacitance obtained under illumination and suppressed photocurrents in the presence of the photosynthetic inhibitor, 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) suggest increased extraction of photosynthetically derived electrons from the recombinant cells. The improved bioelectricity transport across the outer membranes, as achieved through the heterologous heme expression inside cyanobacteria, presents new opportunities for re-wiring the metabolisms of light-harvesting microbes.
Adulis and the transshipment of baboons during classical antiquity
Authors: Grathwol Franziska , Roos Christian , Zinner Dietmar , Hume Benjamin , Porcier Stéphanie M. , Berthet Didier , Cuisin Jacques , Merker Stefan , Ottoni Claudio , Van Neer Wim , Dominy Nathaniel J. , Kopp Gisela H.
Published: March 2023

Adulis, located on the Red Sea coast in present-day Eritrea, was a bustling trading centre between the first and seventh centuries CE. Several classical geographers––Agatharchides of Cnidus, Pliny the Elder, Strabo––noted the value of Adulis to Greco-Roman Egypt, particularly as an emporium for living animals, including baboons (Papiospp.). Though fragmentary, these accounts predict the Adulite origins of mummified baboons in Ptolemaic catacombs, while inviting questions on the geoprovenance of older (Late Period) baboons recovered from Gabbanat el-Qurud (“Valley of the Monkeys”), Egypt. Dated to ca. 800–540 BCE, these animals could extend the antiquity of Egyptian-Adulite trade by as much as five centuries. To explore this possibility, we analysed complete mitochondrial genomes from a mummified baboon from Gabbanat el-Qurud and 14 museum specimens with known provenance together with published georeferenced mitochondrial sequence data. Phylogenetic assignment connects the mummified baboon to modern populations ofPapio hamadryasin Eritrea and eastern Sudan. This result, assuming geographical stability of phylogenetic clades, suggests that present-day Eritrea, and by extension Adulis, was a source of baboons for Late Period Egyptians. It also establishes geographic continuity with baboons from the fabled Land of Punt (Dominy et al., 2020), giving weight to speculation that Punt and Adulis were essentially the same trading centres separated by a thousand years of history.
Cancer associated fibroblasts serve as an ovarian cancer stem cell niche through noncanonical Wnt5a signaling
Authors: Fang Yiming , Xiao Xue , Wang Ji , Dasari Subramanyam , Pepin David , Nephew Kenneth P. , Zamarin Dmitriy , Mitra Anirban K.
Published: March 2023

Frequent relapse and chemoresistance cause poor outcome in ovarian cancer (OC) and cancer stem cells (CSCs) are important contributors. While most studies focus exclusively on CSCs, the role of the microenvironment in providing optimal conditions to maintain their tumor-initiating potential remains poorly understood. Cancer associated fibroblasts (CAFs) are a major constituent of the OC tumor microenvironment and we show that CAFs and CSCs are enriched following chemotherapy in patient tumors. CAFs significantly increased OC cell resistance to carboplatin. Using heterotypic CAF-OC cocultures andin vivolimiting dilution assay, we confirmed that the CAFs act by enriching the CSC population. CAFs were found to increase the symmetric division of CSCs as well as the dedifferentiation of bulk OC cells into CSCs. The effect of CAFs was limited to OC cells in their immediate neighborhood, which could be prevented by inhibiting Wnt. Analysis of single cell RNA-seq data from OC patients revealed that Wnt5a as the highest expressed Wnt in CAFs and that certain subpopulations of CAFs express higher levels of Wnt5a. We found that Wnt5a from CAFs activated a noncanonical Wnt signaling pathway involving the ROR2/PKC/CERB1 axis in the neighboring CSCs. While canonical Wnt signaling was predominant in interactions between cancer cells in patients, non-canonical Wnt pathway was activated by CAF-OC crosstalk. Treatment with a Wnt5a inhibitor sensitized tumors to carboplatinin vivo. Together, our findings demonstrate a novel mechanism of CSC maintenance by signals from the microenvironmental CAFs, which can be targeted to treat OC chemoresistance and relapse.

Statement of significance

CAFs serve as CSC niche through a Wnt5a mediated noncanonical Wnt signaling. Disease relapse and development of chemoresistance is a major problem in OC, which can be potentially addressed by targeting Wnt5a.
A New Behavioral Paradigm for Frustrative Non-reward Reveals a Global Change in Brain Networks by Frustration
Authors: Naik Aijaz Ahmad , Ma Xiaoyu , Munyeshyaka Maxime , Leibenluft Ellen , Li Zheng
Published: March 2023

Background

Irritability, defined as proneness to anger, can reach a pathological extent. It is a defining symptom of Disruptive Mood Dysregulation Disorder (DMDD) and one of the most common reasons youth presents for psychiatric evaluation and care. Aberrant responses to frustrative non-reward (FNR, the response to omission of expected reward) are central to the pathophysiology of irritability. FNR is a translational construct to study irritability across species. The development of preclinical FNR models would advance mechanistic studies of the important and relatively understudied clinical phenomenon of irritability.

Methods

We used FNR as a conceptual framework to develop a novel mouse behavioral paradigm named Alternate Poking Reward Omission (APRO). After APRO, mice were examined with a battery of behavioral tests and processed for whole brain c-Fos imaging. FNR increases locomotion and aggression in mice regardless of sex. These behavioral changes resemble the symptoms observed in youth with severe irritability. There is no change in anxiety-like, depression-like, or non-aggressive social behaviors. FNR increases c-Fos+ neurons in 13 subregions of thalamus, iso-cortex and hippocampus including the prelimbic, ACC, hippocampus, dorsal thalamus, cuneiform nucleus, pons, and pallidum areas. FNR also shifts the brain network towards a more global processing mode.

Conclusion

Our novel FNR paradigm produces a frustration effect and alters brain processing in ways resembling the symptoms and brain network reconfiguration observed in youth with severe irritability. The novel behavioral paradigm and identified brain regions lay the groundwork for further mechanistic studies of frustration and irritability in rodents.