bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding the Pursuit of Third-Line Therapies for Overactive Bladder: A Mixed Methods Study
Authors: Gonzalez Javier D. , Martin Leigh , Osmundsen Blake , Garg Bharti , Gregory W. Thomas , Cichowski Sara
Published: March 2024

Importance

Overactive bladder (OAB) affects millions of women in the United States, with negative effects in multiple domains that have an impact on quality of life. Third-line therapies for OAB are as effective or superior to lifestyle/behavior modification and medical management, yet few women access these treatments and often spend more than 36 months to reach these treatments after starting medication. Factors associated with time to reach third-line therapy are not well studied, and little is known about how patients progress through care pathways for OAB.

Objectives

The aim of the study was to determine factors associated with the time spent between second- and third-line therapy for OAB at an academic urogynecology and reconstructive pelvic surgery practice. We sought to identify demographic, treatment, clinical factors, and themes in barriers to receiving treatment for OAB.

Study Design

This was a mixed methods study consisting of a retrospective cohort study followed by qualitative key informant interviews.

Results

Eighty-five total participants were included in the analysis, and 42 (49.5%) spent more than 36 months between initiation of medical management and initial third-line therapy for OAB. No significant (P > 0.05) demographic, clinical, or treatment differences were found between groups. Facilitators and obstacles to receiving third-line therapy were identified among key informants, and a treatment decision framework was developed.

Conclusions

Women often spend more than 36 months to pursue third-line therapy for OAB. Existing objective variables are poor predictors of pursuit of third-line treatment, and leveraging known facilitators and obstacles can be used to develop improved care pathways for OAB.
Dual Incontinence and Risk of Fall: A Retrospective Cohort Study
Authors: Kravitz Elizabeth , Thompson Jacqueline J. , Christiansen Theresa , Arya Lily , Andy Uduak , Kim Edward K.
Published: March 2024

Importance

Although there is a known association between urinary incontinence (UI) and fall risk, it is unclear if having both UI and fecal incontinence, or dual incontinence (DI), increases this risk.

Objective

The objective of our study was to elucidate a relationship between DI and falls.

Study Design

This was a retrospective cohort study at a tertiary academic health system of female patients 65 years and older presenting for a new patient visit to a urogynecology health care professional for UI from 2019 to 2021. Demographic data and responses to intake questionnaires on fall and markers of frailty were extracted. Multivariable logistic regression was performed to identify factors associated with fall adjusting for covariates identified upon univariate comparison.

Results

A total of 2,814 women were included in the analysis; 2,661 patients reported UI alone, and 153 reported DI. A greater proportion of women with DI reported a fall in the past year compared with those with UI alone (22.9% vs 12.2%, P < 0.001). Univariable comparison showed that these 2 groups differed regarding age, body mass index, and estimated median household income. On multivariable logistic regression, DI was significantly associated with falls (adjusted odds ratio 2.56; 95% confidence interval, 1.02–5.46). Other factors independently associated with falls in older women with UI include (adjusted odds ratio, 95% confidence interval): lower income groups (2.35, 1.50–3.67 for $20,000–$40,000, compared with $100,000 and higher-income group), difficulty with activities of daily living (1.60, 1.25–2.13), and unintentional weight loss (1.68, 1.05–2.68).

Conclusion

Patients with DI have a 2-fold higher risk of fall compared with patients with UI alone.
Urinary Sphingosine-1-Phosphate as a Biomarker for Bladder Pain Syndrome
Authors: Eggers Erica , Crouss Tess , Lipetskaia Lioudmila , DiSanto Michael
Published: March 2024

Importance

Sphingosine-1-phosphate (S1P) is a signaling molecule involved in inflammation and bladder contraction.

Objectives

The aims of this case-control pilot study were to compare urinary S1P concentrations in bladder pain syndrome (BPS) participants to controls and determine whether these concentrations correlate with disease severity and duration.

Study Design

Adult females with BPS and controls were enrolled. Bladder pain syndrome participants completed an O’Leary-Sant questionnaire. Information on duration of symptoms and treatment history was obtained. Urinary S1P and creatinine concentrations were determined. Mann-Whitney U tests were used to compare groups, and Spearman correlation was used to test for associations between concentrations and duration and severity of symptoms.

Results

Twenty-five participants were in each group. Median S1P concentration was 1,225 ng/dL in the BPS group and 2,183 ng/dL in the control group, which was significantly different (P < 0.0001). This difference did not persist when normalized to urinary creatinine (P = 0.58). No differences were noted in urinary S1P concentrations between treated and untreated participants (P = 0.53) or with symptom scores of 13 or greater and less than 13 (P = 0.69). Sphingosine-1-phosphate levels did not correlate with O’Leary-Sant scores (P = 0.08) or duration of symptoms (P = 0.67). Results did not change when using S1P concentrations normalized to creatinine.

Conclusions

This study demonstrated successful quantification of human urinary S1P concentrations. A difference in urinary S1P was found between BPS participants and controls but not when normalized to creatinine. While this is the first study to investigate urinary S1P as a biomarker for BPS, results suggest that it may have a potential role as a biomarker requiring further research.
Pain Related to Intradetrusor BotulinumtoxinA: A Randomized Clinical Trial
Authors: Miceli Lia M. , Antosh Danielle D. , Nisar Tariq , Stewart Julie , Rutledge Emily C. , Khavari Rose
Published: March 2024

Importance

OnabotulinumtoxinA (BTX-A) is an effective treatment for overactive bladder (OAB), but few studies have been done to evaluate injection techniques.

Objective

The primary objective was to evaluate procedural discomfort between 2 commonly used injection techniques for BTX-A.

Study Design

This was a single-blinded, randomized clinical trial of women undergoing injection of 100 U BTX-A for idiopathic OAB. Patients were randomized to 5 mL/5 injection or 10 mL/10 injection groups. Bladder pain was assessed by a validated Numeric Pain Rating Scale. Overactive bladder symptoms were assessed with a standardized questionnaire (Overactive Bladder Questionnaire Short Form). Patient satisfaction, treatment efficacy, and adverse events were assessed at 30 days after procedure.

Results

One hundred eight patients were randomized to 52 in the 5 mL/5 injection arm and 56 in the 10 mL/10 injection arm. Mean procedural pain scores were 3.2 (±2.3) in the 5 mL/5 injection group versus 3.6 (±2.1) in the 10 mL/10 injection group (P = 0.21). No difference was found when categorizing pain scores into ordinal outcomes of low (P = 0.55), medium (P = 0.70), and high (P = 1.0) or a binary outcome of low (P = 0.55) versus medium + high (P = 0.55). Multivariate analyses did not effect statistical significance between the 2 groups for the ordinal outcome (odds ratio = 1.86; 95% confidence interval = 0.77 = 4.52; P = 0.17) or the binary outcome (odds ratio = 1.81; 95% confidence interval = 0.68–4.77; P = 0.28). No difference was observed between overall patient satisfaction, global impression of improvement, Overactive Bladder Questionnaire Short Form scores, or adverse outcomes.

Conclusions

Procedural discomfort related to BTX-A injection for idiopathic OAB was not different between 2 injection protocols. Overall satisfaction was high for both groups, and there was no difference in symptom scores or adverse events.
Impact of resuscitation adjuncts on postintubation hypotension in patients with isolated traumatic brain injury
Authors: Anand Tanya , Hejazi Omar , Conant Madolyn , Joule Dylan , Lundy Megan , Colosimo Christina , Spencer Audrey , Nelson Adam , Magnotti Lou , Joseph Bellal
Published: March 2024

INTRODUCTION

Postintubation hypotension (PIH) is a risk factor of endotracheal intubation (ETI) after injury. For those with traumatic brain injury (TBI), one episode of hypotension can potentiate that injury. This study aimed to identify the resuscitation adjuncts that may decrease the incidence of PIH in this patient population.

METHODS

This is a 4-year (2019–2022) prospective observational study at a level I trauma center. Adult (18 years or older) patients with isolated TBI requiring ETI in the trauma bay were included. Blood pressures were measured 15 minutes preintubation and postintubation. Primary outcome was PIH, defined as a decrease in systolic blood pressure of ≥20% from baseline or to ≤80 mm Hg, or any decrease in mean arterial pressure to ≤60 mm Hg. Multivariable logistic regression was performed to identify the associations of preintubation vasopressor, hypertonic saline (HTS), packed red blood cell, and crystalloids on PIH incidence.

RESULTS

Of the 490 enrolled patients, 16% had mild (head AIS, ≤2), 35% had moderate (head AIS, 3–4), and 49% had severe TBI (head AIS, ≥5). The mean ± SD age was 42 ± 22 years, and 71% were male. The median ISS, head AIS, and Glasgow Coma Scale were 26 (19–38), 4 (3–5), and 6 (3–11), respectively. The mean ± SD systolic blood pressure 15 minutes preintubation and postintubation were 118 ± 46 and 106 ± 45, respectively. Before intubation, 31% received HTS; 10%, vasopressors; 20%, crystalloids; and 14%, at least 1 U of packed red blood cell (median, 2 [1–2] U). Overall, 304 patients (62%) developed PIH. On multivariable regression analysis, preintubation use of vasopressors and HTS was associated with significantly decreased odds of PIH independent of TBI severity, 0.310 (0.102–0.944, p = 0.039) and 0.393 (0.219–0.70, p = 0.002), respectively.

CONCLUSION

Nearly two thirds of isolated TBI patients developed PIH. Preintubation vasopressors and HTS are associated with a decreased incidence of PIH. Such adjuncts should be considered prior to ETI in patients with suspected TBI.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level III.
Locally Advanced Adenocarcinoma of the Esophagus: Is Esophagectomy Associated with Improved Overall Survival?
Authors: Kramer Sarah P , Swanson James , Fernando Mitchel , Park Simon , Verm Raymond , Abdelsattar Zaid , Cohn Tyler , Luchette Fred A , Baker Marshall S
Published: March 2024

BACKGROUND:

Esophagectomy in locally advanced esophageal adenocarcinoma is challenging and carries risk. The value of esophagectomy in locally advanced esophageal adenocarcinoma is not well-defined.

STUDY DESIGN:

The National Cancer Database was used to identify patients with cT4 esophageal adenocarcinoma from 2004 to 2020. Multivariable regression was used to identify factors associated with use of esophagectomy. Cox modeling was used to identify factors associated with all-cause mortality. Patients undergoing esophagectomy were 1:1 propensity score–matched to patients treated nonsurgically. Kaplan–Meier analysis was used to compare 5-year overall survival (OS).

RESULTS:

A total of 3,703 patients met inclusion criteria. Of those, 541 (15%) underwent esophagectomy, and 3,162 (85%) did not. Age 65 years or less (adjusted odds ratio [aOR] 1.69, 95% CI 1.33 to 2.14), White race (aOR 2.98, 95% CI 2.24 to 3.96), treatment in academic centers (aOR 1.64, 95% CI 1.33 to 2.02), private insurance (aOR 1.88, 95% CI 1.50 to 2.36), and tumors less than 6 cm (aOR 1.86, 95% CI 1.44 to 2.40) were associated with use of esophagectomy. Government of lack of insurance (hazard ratio [HR] 1.23, 95% CI 1.12 to 1.35), income <$46,000 (HR 1.11, 95% CI 1.03 to 1.20), treatment in nonacademic centers (HR 1.16, 95% CI 1.07 to 1.25), Charlson-Deyo Comorbidity Index 1 or more (HR 1.22, 95% CI 1.12 to 1.32), and tumors 6 cm or more (HR 1.20, 95% CI 1.09 to 1.32) were associated with risk of all-cause mortality. Esophagectomy (HR 0.50, 95% CI 0.44 to 0.56) and systemic therapy (HR 0.40, 95% CI 0.37 to 0.43) were associated with decreased risk of all-cause mortality. Patients undergoing esophagectomy had higher rates of 5-year OS (27.4% vs 13.2%, p < 0.0001) and longer median OS (24.71 vs 10.09 months, p < 0.0001). Among cT4b patients, those who underwent esophagectomy had higher rates of 5-year OS (24.5% vs 12.3%, p < 0.0001) and longer median OS (25.53 vs 11.01 months, p < 0.0001).

CONCLUSIONS:

In cT4 esophageal adenocarcinoma, esophagectomy is associated with improved rates of 5-year OS compared with nonsurgical treatment.
Deep continual multitask out-of-hospital incident severity assessment from changing clinical features
Authors: Ferri Pablo , Sáez Carlos , Félix-De Castro Antonio , Sánchez-Cuesta Purificación , García-Gómez Juan M
Published: March 2024

When developing Machine Learning models to support emergency medical triage, it is important to consider how changes over time in the data can negatively affect the models’ performance. The objective of this study was to assess the effectiveness of novel Deep Continual Learning pipelines in maximizing model performance when input features are subject to change over time, including the emergence of new features and the disappearance of existing ones. The model is designed to identify life-threatening situations, predict its admissible response delay, and determine its institutional jurisdiction. We analyzed a total of 1 414 575 events spanning from 2009 to 2019. Our findings demonstrate important performance improvements, up to 4.9% in life-threatening, 18.5% in response delay and 1.7% in jurisdiction, in absolute F1-score, compared to the current triage protocol, and improvements up to 4.4% in life-threatening and 11% in response delay, in absolute F1-score, respect to non-continual approaches.
A novel scale for assessing caregiving competence in family caregivers of persons with dementia
Authors: Suganuma Ippei , Ogawa Noriyuki , Kamijou Kenji , Nakanishi Aki , Kawasaki Ippei , Itotani Keisuke , Okada Shinichi
Published: March 2024

The aging of family caregivers and the challenges of long-distance caregiving attributed to the increase in the number of elderly individuals living alone have raised concerns about dementia caregiving in Japan. Additionally, with the shifts in family dynamics due to declining birth rates and an extended average lifespan, adapting support strategies for family caregivers is necessary. Thus, it is necessary to measure the caregiving competence of family caregivers early and effectively. However, a comprehensive caregiving competence scale tailored to dementia, including aspects such as caregiving burden, affirmation, and coping, is lacking. Therefore, this study aimed to develop a Caregiving Competence Scale for Dementia (CCSD) for primary family caregivers caring for individuals with dementia. This study focused on primary family caregivers caring for individuals with cognitive impairment and various degrees of dementia. The initial version of the CCSD was developed, and a questionnaire survey was conducted to validate its structural validity and reliability. A total of 150 participants were included in the analysis. The exploratory factor analysis identified five factors with 27 items: Factor 1: “Positive Emotions and Awareness,” Factor 2: “Presence or Absence of Consultation Partners and Family Support,” Factor 3: “Caregiving Burden and Coping Skills,” Factor 4: “Dementia Literacy,” and Factor 5: “Engagement and Emotional Control.” The confirmatory factor analysis revealed a good model fit (comparative fit index = 0.905 and root mean square error of approximation = 0.072). The overall Cronbach’s alpha coefficient for the scale was 0.892. The CCSD, comprising 27 items covering five factors, has been successfully developed as a measurement scale. Measuring caregiving competence contributes to developing targeted support strategies for primary family caregivers and facilitating appropriate interventions.
Objective turning measures improve diagnostic accuracy and relate to real-world mobility/combat readiness in chronic mild traumatic brain injury
Authors: Fino Peter C. , Antonellis Prokopios , Parrington Lucy , Weightman Margaret M. , Dibble Leland E. , Lester Mark E. , Hoppes Carrie W. , King Laurie A.
Published: March 2024

Introduction

Balance and mobility problems are common consequences after mild traumatic brain injury (mTBI). However, turning and non-straight locomotion, which are required for daily living, are rarely assessed in clinical tests of function after mTBI. Therefore, the primary goals of this study were to assess 1) the added value of clinic-based turning task variables, obtained using wearable sensors, over standard general assessments of mobility, and 2) assess the associations between general assessments of mobility, objective variables from clinic-based turning tasks, and ecologically-relevant functional tasks.

Materials and Methods

Fifty-three individuals with mTBI and 57 healthy controls participated across three sites. Participants were tested in a single session that encompassed self-reported questionnaires including demographic information and balance and mobility testing including the use of wearable sensors. Lasso regression models and the area under the receiver-operator characteristic curve (AUC) assessed diagnostic accuracy. Partial correlation coefficients assessed the relationship between each variable with ecologically-relevant functional tasks.

Results

Multivariate models revealed high diagnostic accuracy, with an AUC of 0.92, using multiple clinic-based turning variables. The complex turning course (CTC) yielded the highest multivariate AUC (95% CI) of 0.90 (0.84, 0.95) for single task, and the average lap time from the CTC had the highest univariate AUC (95% CI) of 0.70 (0.58, 0.78). Turning variables provided added value, indicated by higher AUCs, over standard general assessments of mobility. Turning variables had strong associations with ecologically-relevant functional tasks and outperformed general assessments of mobility.

Discussion

Clinic-based turning tasks, especially the CTC, have high diagnostic accuracy, strong associations with ecologically-relevant functional tasks, and require relatively short time(s) to complete. Compared to general assessments of mobility, clinic-based turning tasks may be more ecologically-relevant to daily function. Future work should continue to examine the CTC alongside other promising tools for return-to-activity assessments.
Family satisfaction with involvement in decision making in the intensive care unit: A scoping review
Authors: Klaas Ntombifikile , Baliki Onalenna
Published: March 2024

Background

Decision making in the intensive care unit (ICU) is often complex, involving frequent interactions between patients, families, and health care professionals. Family members play an important role as surrogate decision markers because patients admitted in ICU lack decision-making capacity due to their critical state. Lack of regular, timeous, up to date and honest information provided by the ICU healthcare professionals may negatively influence the family members’ decision making ability and overall satisfaction.

Aim

To identify existing literature that describe family satisfaction with involvement in decision making in the intensive care unit.

Methods

A scoping review of literature guided by Arksey and O ‘Malley’s framework was conducted. Literature search was completed using five databases. Primary studies published in English between January 2010 and December 2023 were retrieved and analyzed using thematic analysis.

Results

Of the 152 studies identified during the search, 23 were eligible for inclusion. Most of the studies (n = 19; 83%) focused on family satisfaction with care and decision making and four (n=4; 17%) focused on strategies aimed at enhancing family involvement in decision making. These strategies included: testing the effects of using information booklets, structured attendance of interdisciplinary ward rounds, development and implementation of evidence-based communication algorithm and exploring the culture of interprofessional collaboration. The three themes that emerged from the scoping review were:satisfaction with involvement, communication, and support.

Conclusion

The use of structured communication programs as well as regular, timeous and honest information about the patient’s diagnosis, treatment plan and prognosis are vital measures to enhancing family involvement in decision making.
Preoperative COVID-19 Vaccination is Associated with Decreased Perioperative Mortality after Major Vascular Surgery
Authors: Ratner Molly , Garg Karan , Chang Heepeel , Nigalaye Anjali , Medvedosky Steven , Jacobowitz Glenn , Siracuse Jeffrey J , Patel Virendra , Schermerhorn Marc , DiMaggio Charles , Rockman Caron B
Published: March 2024

Background

The objective of this study was to examine the effect of COVID-19 vaccination on perioperative outcomes after major vascular surgery.

Methods

This is a multicenter retrospective study of patients who underwent major vascular surgery between December 2021 through August 2023. The primary outcome was all-cause mortality within 30 days of index operation or prior to hospital discharge. Multivariable models were used to examine the association between vaccination status and the primary outcome.

Results

Of the total 85,424 patients included, 19161 (22.4%) were unvaccinated. Unvaccinated patients were younger compared to vaccinated patients (mean age 68.44 +/− 10.37 years vs 72.11 +/− 9.20 years, p <.001) and less likely to have comorbid conditions, including hypertension (87.2% vs 89.7%, p <.001), congestive heart failure (14.5% vs 15.9%, p <.001), chronic obstructive pulmonary disease (35.7% vs 36.3, p <.001) and renal failure requiring hemodialysis (1.4% vs 1.7%, p = .005). After risk factor adjustment, vaccination was associated with decreased mortality (OR 0.7, 95% CI 0.62 - 0.81, p <.0001). Stratification by procedure type demonstrated that vaccinated patients had decreased odds of mortality after open AAA (OR 0.6, 95% CI 0.42-0.97, p = 0.03), EVAR (OR 0.6, 95% CI 0.43-0.83, p 0.002), CAS (OR 0.7, 95% CI 0.51-0.88, p = 0.004) and infra-inguinal lower extremity interventions (OR 0.7, 95% CI 0.48-0.96, p = 0.03).

Conclusions

COVID-19 vaccination is associated with reduced perioperative mortality in patients undergoing vascular surgery. This association is most pronounced for patients undergoing aortic aneurysm repair, carotid stenting and infrainguinal bypass.
Factors affecting Cost-Related Medication Non-Adherence among US population with Cardiovascular Risk Factors
Authors: Gandrakota Nikhila , Ramakrishnan Manju , Sudireddy Kavya , Shah Megha K
Published: March 2024

Introduction

In the US, cardiovascular diseases (CVD) are the leading cause of death and disability. Cost-related non-adherence (CRMN) can have serious consequences and worsen CVD outcomes. We examined the relationship between CVD risk factors and CRMN among US adults.

Methods

CDC’s 2019-2021 National Health Interview Survey (NHIS) data was used to examine CRMN among adults, categorized into three groups based on reported risk factors. We used chi-square tests, logistic regression to determine factors associated with CRMN.

Results

Among 49,464 participants, young, unmarried individuals, females, less educated, and participants from South had higher CRMN than older, married individuals, males, and those with higher education residing in the other regions. Current smokers and those with more CVD risk factors also had a higher CRMN than former smokers and never-smokers. Conversely, those aged 65 or older, with high-income, and excellent self-rated health had lower CRMN than younger participants, low-income families, and those with poor self-health. Public insurance and Medicaid participants had lower CRMN than uninsured (OR 0.13, 95% CI, 0.04-0.45, and OR 0.24, 95% CI, 0.15-0.36). Stratified regression analysis by disease status, i.e., diabetes, hypertension, and hyperlipidemia, revealed participants with high-income had lower odds of CRMN (OR 0.38, 95% CI 0.28-0.50; OR 0.39, 95% CI, 0.28-0.58; OR 0.37, 95% CI 0.27-0.51 respectively) than those with lower incomes.

Conclusion

Adults under 65 with more CVD risk factors are at higher risk of CRMN. Hence, robust prescription drug coverage and targeted interventions are necessary to lower CRMN in those with CVD risk factors.
A novel use of diffusion-weighted whole-body magnetic resonance imaging with background body signal suppression to diagnose infectious aortitis
Authors: Saito Jien , Muto Masahiro , Tada Masafumi , Yokota Isao , Kamiya Shinji , Numata Yukihide , Sasaki Hideki , Hashizume Takuya , Asano Miki , Wakasa Satoru
Published: March 2024

Background

Diffusion-weighted whole-body imaging with background body signal suppression is one of the whole-body magnetic resonance imaging techniques and is effective in diagnosing inflammatory and infectious diseases. We aimed to evaluate the diagnostic performance of this modality in infectious aortitis, which remains unclear.

Methods

The study participants were 32 patients with suspected infectious aortitis who underwent computed tomography and magnetic resonance imaging between September 2020 and November 2022. Sensitivity, specificity, and areas under the curve of each imaging modality were studied using a diagnosis based on a combination of imaging results, clinical symptoms, and laboratory tests. Decision curve analysis was performed to determine the benefit of adding magnetic resonance imaging to computed tomography.

Results

The median age was 74 years, and 23 participants were men. Fifteen patients (47%) were diagnosed with infectious aortitis. Positive findings for infectious aortitis were identified in 19, 18, and 14 patients by computed tomography, diffusion-weighted whole-body imaging, and the combination of both modalities, respectively. Sensitivity, specificity, and area under the curve for correct diagnosis were 93.3%, 70.6%, and 0.82 (95% confidence interval 0.69–0.95), respectively for computed tomography, 93.3%, 76.5%, and 0.85% (95% confidence interval 0.73%–0.97), respectively for diffusion-weighted imaging, and 86.7%, 94.1%, and 0.90 (95% confidence interval 0.80–0.10), respectively for the combination of both modalities. Decision curve analysis reinforced the clinical benefit of combining the two imaging modalities across all ranges of the probability thresholds.

Conclusions

Diffusion-weighted whole-body imaging with background body signal suppression is an effective diagnostic tool for infectious aortitis, especially when combined with computed tomography.

Clinical Perspective

Infectious aortitis is a serious disease that is difficult to accurately diagnose. Although PET-CT is associated with high diagnostic performance, limited access to this modality has encouraged the development of an alternative modality. The whole-body MRI with DWIBS is a more available modality, which is commonly used for cancer diagnosis but is also considered effective in diagnosing infectious diseases. The combination of DWIBS and non-contrast CT yielded a sensitivity of 86.7% (95% CI: 59.5–98.3%), a specificity of 94.1% (95% CI: 71.3–99.9%), and an AUC of 0.90 (95% CI: 0.80–0.10) for the diagnosis of infectious aortitis. DWIBS can be a useful modality as an alternative to PET-CT.
Socio-Economic Factors Associated with Cancer Stigma among Apparently Healthy Women in Semi-urban Nepal
Authors: Paneru Bandana , Karmacharya Aerona , Makaju Soniya , Kafle Diksha , Poudel Lisasha , Mali Sushmita , Timsina Priyanka , Shrestha Namuna , Timalsena Dinesh , Chaudhary Kalpana , Bhandari Niroj , Rai Prasanna , Shakya Sunila , Spiegelman Donna , Sheth Sangini S , Stangl Anne , Eastment McKenna C. , Shrestha Archana
Published: March 2024

Cancer is the primary cause of death globally, and despite the significant advancements in treatment and survival rates, it is still stigmatized in many parts of the world. However, there is limited public health research on cancer stigma among general population (non-patient) women in Nepal. Therefore, this study aims to determine the prevalence of cancer stigma and its associated factors in this group.

Methods

We conducted a cross-sectional study among 426 healthy women aged 30 – 60 years who were residents of Dhulikhel and Banepa in central Nepal. We measured cancer stigma using the Cancer Stigma Scale (CASS). CASS measures cancer stigma in six subdomains (awkwardness, avoidance, severity, personal responsibility, policy opposition, financial discrimination) on a 6-point Likert scale (strongly disagree to agree strongly) with higher mean stigma scores correlating with higher levels of stigma. We used univariable and multivariable linear regression to identify the socio-demographic factors associated with the CASS score.

Results

Overall, the level of cancer stigma was low (mean total stigma score: 2.6 ± 0.6) but still present among participants. Stigma related to personal responsibility had the highest levels (mean stigma score: 3.9 ± 1.3), followed by severity (mean stigma score: 3.2 ± 1.3) and financial discrimination (mean stigma score: 2.9 ± 1.6). There was a significant association of mean CASS score with older age (the mean difference is stigma score: 0.01 points; 95% CI: 0.01-0.02) and lower education (difference -0.02 points; 95% CI: -0.03, -0.003) after adjusting for age, ethnicity, education, marital status, religion, occupation, and parity.

Conclusion

While overall cancer stigma was low in Nepal, some subdomains were increased in the general population of women in Nepal. Because stigma may impact engagement in cancer screening efforts, programs should aim to counteract stigma, particularly among older and less educated women.
Maternal Factors Promoting Normal Linear Growth of Children from Impoverished Rwandan Households
Authors: Habimana Jean de Dieu , Korukire Noel , Sara Jewett , Matsiko Eric , Umugwaneza Maryse , Rugema Lawrence , Munyanshongore Cyprien
Published: March 2024

Background

Linear growth faltering continues to be a pervasive public health concern, considering its persistent prevalence and repercussions. This study aimed to investigate potential maternal factors promoting normal linear growth among children from impoverished Rwandan households.

Methods

A structured questionnaire was used to collect data from 807 mother-child dyads selected using a multi-stage cluster sampling procedure. The main outcome variable was height-for-age Z-scores. The main predictors were the mother has income-generating activity, maternal education, maternal depression, household decision-making (HHDM), number of ANC visits, use of family planning method, family planning types, and mode of delivery. The potential confounding variables were child age, both parents working, good handwashing practice, owning a vegetable garden, and the total number of livestock. Univariate analysis was used to establish means, frequencies, and percentages; the Kruskal-Wallis, Mann-Whitney U, and Spearman Rank Correlation tests were used for bivariate analysis and robust linear regression for multivariable analysis.

Results

Maternal factors promoting normal linear growth of children were the presence of the mother’s income-generating activity (ꞵ=0.640 [0.0269−1.253], p-value=0.041), mother’s involvement in household decision-making (ꞵ=0.147 [0.080− 0.214], p-value<0.001), and higher frequency of ANC consultations (ꞵ=0.189 [0.025− 0.354], p-value=0.024). Additionally, a combination of household decision-making with ANC visit numbers predicted an increase in child linear growth (ꞵ=0.032 [0.019− 0.045], p-value<0.001).

Conclusion

Maternal factors such as maternal income-generating activity, maternal involvement in household decision-making, and increased number of ANC visits were found to promote normal child linear growth and can provide valuable information for shaping interventions and policies aimed at promoting child growth in the Rwandan community.
Computational analysis of SOD1-G93A mouse muscle biomarkers for comprehensive assessment of ALS progression
Authors: Gómez-Gálvez Pedro , Navarro Victoria , Castro Ana M. , Paradas Carmen , Escudero Luis M.
Published: March 2024

Aims

To identify potential image biomarkers of neuromuscular disease by analysing morphological and network-derived features in skeletal muscle biopsies from a murine model of amyotrophic lateral sclerosis (ALS), the SOD1G93Amouse, and wild-type (WT) controls at distinct stages of disease progression.

Methods

Using the NDICIA computational framework, we quantitatively evaluated histological differences between skeletal muscle biopsies from SOD1G93Aand WT mice. The process involved the selection of a subset of features revealing these differences. A subset of discriminative features was selected to characterise these differences, and their temporal dynamics were assessed across disease stages.

Results

Our findings demonstrated that muscle pathology in the mutant model evolves from early alterations in muscle fibre arrangement, detectable at the presymptomatic stage through graph theory features, to the subsequent development of the typical morphological pattern of neurogenic atrophy at more advanced disease stages.

Conclusions

Our assay identifies a neurogenic signature in mutant muscle biopsies, even when the disease was phenotypically imperceptible.

KEY POINTS

-

NDICIA analysis detected differences between SOD1G93Aand WT muscles at presymptomatic stage through the analysis of graph theory features.

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Our computational tool identified different neurogenic-like traits in the ALS mouse model at all analysed stages of disease progression.

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Differences between SOD1G93Aand WT muscle images became more pronounced as the disease advanced.

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The integration of UMAP into the upgraded NDICIA framework was validated as a robust alternative to PCA.

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Muscle fibre characteristics in SOD1WTclosely resembled those of WT mice.
A novel regulatory pathway recognizes and degrades transcripts with long 3′ untranslated regions
Authors: Daly Ciarán W.P. , Kristjánsdóttir Katla , West Jessica D. , Vu Luyen Tien , Fogarty Elizabeth A. , Geissler Rene , McDermott Ciara , Venkataramany Akila , Grimson Andrew
Published: March 2024

Quantitative control of gene expression is fundamental to cellular function, and post transcriptional regulation is a consequential, additional layer of control over protein output. Within mammalian mRNAs, the 3′ untranslated region (3′UTR) acts as a hub of regulatory control, typically mediated by regulatory sequence elements within the 3′UTR. We have found that expression from transcripts with long 3′UTRs is strongly repressed compared to those with short 3′UTRs, and this phenomenon appears to be independent of sequence elements within the 3′UTR. The repression increases with 3′UTR length and is substantial; reporters with 2,000 nucleotide long 3′UTRs are repressed >10 fold compared to 400 nucleotide 3′UTRs. Conversely, increasing the length of the coding region has no effect on expression, demonstrating that it is 3′UTR length, not transcript length, that elicits repression. Reporters with different length 3′UTRs show no difference in transcription rates nor translation efficiency but have clear differences in mRNA half lives and nucleocytoplasmic distribution, indicating repression of long 3′UTR transcripts is mediated by accelerated RNA decay. However, this transcript degradation does not involve the nonsense mediated decay (NMD) pathway nor other canonical RNA decay pathways. In order to identify trans factors involved in 3′UTR length mediated decay, we quantified the differences in proteins bound to reporters with long and short 3′UTRs, and identified over 100 differentially associated factors. Knockdowns of two differentially associating proteins, the mRNA nuclear export factors DDX39B and ZC3H11A, indicate they play a role in repression of mRNAs with long 3′UTRs. This study establishes a novel length dependent regulatory feature of 3′UTRs, which potentially regulates many genes.
Individual trajectories for recovery of neocortical activity in disorders of consciousness
Authors: Tewarie Prejaas K.B. , Abeysuriya Romesh , Panda Rajanikant , Nùñez Pablo , Vitello Marie M. , van der Lande Glenn , Gosseries Olivia , Thibaut Aurore , Laureys Steven , Deco Gustavo , Annen Jitka
Published: March 2024

The evolution from disturbed brain activity to physiological brain rhythms can precede recovery in patients with disorders of consciousness (DoC). Accordingly, intriguing questions arise: What are the pathophysiological factors responsible for disrupted brain rhythms in patients with DoC, and are there potential pathways for individual patients with DoC to return to normal brain rhythms? We addressed these questions at the individual subject level using biophysical simulations based on electroencephalography (EEG). The main findings are that unconscious patients exhibit a loss of excitatory corticothalamic synaptic strength. Synaptic plasticity in this excitatory corticothalamic circuitry fosters physiological brain rhythms in the selection of patients with DoC. The extent to which this occurred was correlated with cerebral glucose uptake. The current findings emphasize the importance of excitatory thalamocortical activity in reestablishing normal brain rhythms after brain injury and show that biophysical modelling of the corticothalamic circuitry could help select patients that might be potentially receptive to treatment and undergo plasticity.
Strategic use of male alternative reproductive tactics in cooperatively breeding banded mongoose groups
Authors: Birch Graham , Nichols Hazel J. , Mwanguhya Francis , Blount Jonathan D. , Cant Michael A.
Published: March 2024

Alternative reproductive tactics (ARTs) allow smaller or less competitive individuals to reproduce by avoiding direct fights through sneaky strategies. Within cooperatively breeding groups ARTs are rarely reported, potentially due to difficulties observing male reproductive behaviour in the wild, or reproductive suppression by fellow group members. In societies where all mating opportunities cannot be monopolised by one male, young males could use sneaky tactics as a ‘stepping-stone’ to gain limited reproductive success while they grow in resource holding potential (RHP). Using 20 years of pedigree, weight, group demography, and behavioural data, we investigated the use of sneaky ‘pesterer’ ARTs in wild banded mongooses. Instead of a ‘stepping stone’, pestering tactics were typically a rare back-up used by males displaced from mate guarding tactics by higher RHP rivals. Additionally, pesterers have lower siring success compared to mate guards, despite similar weight loss costs, which may explain why most males settle for reproductive inactivity rather than use pestering tactics. However, pestering allows younger males to gain access to older, higher fecundity females in the group and may even facilitate inbreeding avoidance. Overall, ARTs provide a viable option for reproductive fitness for some males that lose out on reproductive positions in highly male-skewed groups.
The Pannexin-1 N-terminal Helix Gates a Switch between Ion Conductance and Anandamide Transport
Authors: Anderson Connor L. , Weilinger Nicolas L. , Visser Frank , Nielsen Allison C. , Boyce Andrew K.J. , Thompson Roger J.
Published: March 2024

Anandamide is an endovanilloid and endocannabinoid with ligand activity at transient receptor potential vanilloid 1 channels and cannabinoid receptors, respectively. We have reported that block of Pannexin-1 channels in the CA1 hippocampus can increase concentrations of anandamide and induce presynaptic plasticity. It is not known how an ion channel can contribute to clearance of a lipid-derived signalling molecule. Here, we use electrophysiology and imaging of uptake of fluorescent anandamide to determine the structure-function relationship between the ion conduction and anandamide trasporter activities of pannexin-1. Expression of rat, mouse or human pannexin-1 in HEK cells caused a time dependent increase in anandamide uptake by all three orthologs. However, human pannexin-1 had reduced ion conduction. Low concentrations of anandamide augmented uptake of its fluorescent derivative, whereas higher concentrations competed, suggesting that anadamide may facilitate its own transport. Deletion of the N-terminal helix of pannexin-1 and the channel blocker, probenecid, blocked ion conduction but enhanced anandamide transport. In contrast, mutation of pore facing isoleucine 41 caused a gain of function in ion conduction with loss of anandamide transport. We conclude that the pannexin-1 channel is a dual ion channel / anandamide transporter and that these properties are gated by the channels N-terminal helix and likely linked to its presence or absence within the pore lining region.
Time-resolved oxidative signal convergence across the algae–embryophyte divide
Authors: Rieseberg Tim P. , Dadras Armin , Darienko Tatyana , Post Sina , Herrfurth Cornelia , Fürst-Jansen Janine M. R. , Hohnhorst Nils , Petroll Romy , Rensing Stefan A. , Pröschold Thomas , de Vries Sophie , Irisarri Iker , Feussner Ivo , de Vries Jan
Published: March 2024

The earliest land plants faced a significant challenge in adapting to environmental stressors. Stress on land is unique in its dynamics, entailing swift and drastic changes in light and temperature. While we know that land plants share with their closest streptophyte algal relatives key components of the genetic makeup for dynamic stress responses, their concerted action is little understood. Here, we combined time-course stress profiling using photophysiology, transcriptomics on 2.7 Tbp of data, and metabolite profiling analyses on more than 270 distinct samples, to study stress kinetics across three 600-million-year-divergent streptophytes. Through co-expression analysis and Granger causal inference we predict a gene regulatory network that retraces a web of ancient signal convergence at ethylene signaling components, osmosensors, and chains of major kinases. These kinase hubs already integrated diverse environmental inputs since before the dawn of plants on land.
Reproducible generation of human liver organoids (HLOs) on a pillar plate platformviamicroarray 3D bioprinting
Authors: Shrestha Sunil , Lekkala Vinod Kumar Reddy , Acharya Prabha , Kang Soo-Yeon , Vanga Manav Goud , Lee Moo-Yeal
Published: March 2024

Human liver organoids (HLOs) hold significant potential for recapitulating the architecture and function of liver tissues in vivo. However, conventional culture methods of HLOs, forming Matrigel domes in 6-/24-well plates, have technical limitations such as high cost and low throughput in organoid-based assays for predictive assessment of compounds in clinical and pharmacological lab settings. To address these issues, we have developed a unique microarray 3D bioprinting protocol of progenitor cells in biomimetic hydrogels on a pillar plate with sidewalls and slits, coupled with a clear bottom, 384-deep well plate for scale-up production of HLOs. Microarray 3D bioprinting, a droplet-based printing technology, was used to generate a large number of small organoids on the pillar plate for predictive hepatotoxicity assays. Foregut cells, differentiated from human iPSCs, were mixed with Matrigel and then printed on the pillar plate rapidly and uniformly, resulting in coefficient of variation (CV) values in the range of 15 - 18%, without any detrimental effect on cell viability. Despite utilizing 10 – 50-fold smaller cell culture volume compared to their counterparts in Matrigel domes in 6-/24-well plates, HLOs differentiated on the pillar plate exhibited similar morphology and superior function, potentially due to rapid diffusion of nutrients and oxygen at the small scale. Day 25 HLOs were robust and functional on the pillar plate in terms of their viability, albumin secretion, CYP3A4 activity, and drug toxicity testing, all with low CV values. From three independent trials of in situ assessment, the IC50 values calculated for sorafenib and tamoxifen were 6.2 ± 1.6 µM and 25.4 ± 8.3 µM, respectively. Therefore, our unique 3D bioprinting and miniature organoid culture on the pillar plate could be used for scale-up, reproducible generation of HLOs with minimal manual intervention for high-throughput assessment of compound hepatotoxicity.
Environmental DNA as a complementary tool for biodiversity monitoring: A multi-technique and multi-trophic approach to investigate cetacean distribution and feeding ecology
Authors: Afonso Luis , Costa Joana , Correia Ana Mafalda , Valente Raul , Lopes Eva , Tomasino Maria Paola , Gil Ágatha , Oliveira-Rodrigues Cláudia , Sousa-Pinto Isabel , López Alfredo , Magalhães Catarina
Published: March 2024

The use of environmental DNA (eDNA) to assess the presence of biological communities has emerged as a promising monitoring tool in the marine conservation landscape. Moreover, advances in Next-Generation Sequencing techniques, such as DNA metabarcoding, enable multi-species detection in mixed samples, allowing the study of complex ecosystems such as oceanic ones. We aimed at using these molecular-based techniques to characterise cetacean communities, as well as potential prey in the northern coast of Mainland Portugal. During seasonal campaigns, we collected seawater samples, along with visual records of cetacean occurrence. The eDNA extracted from 64 environmental samples was sequenced in an Illumina platform, with universal primers targeting marine vertebrates. Five cetacean species were identified by molecular detection: common dolphin (Delphinus delphis), bottlenose dolphin (Tursiops truncatus), Risso’s dolphin (Grampus griseus), harbour porpoise (Phocoena phocoena) and fin whale (Balaenoptera physalus). Overall, except for the fin whale (not sighted during the campaigns), this cetacean community composition was similar to that obtained through visual monitoring, and the complementary results suggest their presence in the region all year round. In addition, the positive molecular detections of B. physalus are of special relevance since there are no visual records reported in the area. The detection of multiple known preys of the identified dolphins indicates they use these coastal areas for feeding purposes. While this methodological approach remains in a development stage, the present work highlights the benefits of using eDNA to study marine communities, with specific applications for research on cetacean distribution and feeding ecology, ultimately serving as the baseline of a methodological approach for biodiversity monitoring and marine conservation.
Whole-body simulation of realistic fruit fly locomotion with deep reinforcement learning
Authors: Vaxenburg Roman , Siwanowicz Igor , Merel Josh , Robie Alice A. , Morrow Carmen , Novati Guido , Stefanidi Zinovia , Both Gert-Jan , Card Gwyneth M. , Reiser Michael B. , Botvinick Matthew M. , Branson Kristin M. , Tassa Yuval , Turaga Srinivas C.
Published: March 2024

The body of an animal influences how the nervous system produces behavior. Therefore, detailed modeling of the neural control of sensorimotor behavior requires a detailed model of the body. Here we contribute an anatomically-detailed biomechanical whole-body model of the fruit flyDrosophila melanogasterin the MuJoCo physics engine. Our model is general-purpose, enabling the simulation of diverse fly behaviors, both on land and in the air. We demonstrate the generality of our model by simulating realistic locomotion, both flight and walking. To support these behaviors, we have extended MuJoCo with phenomenological models of fluid forces and adhesion forces. Through data-driven end-to-end reinforcement learning, we demonstrate that these advances enable the training of neural network controllers capable of realistic locomotion along complex trajectories based on high-level steering control signals. We demonstrate the use of visual sensors and the re-use of a pre-trained general-purpose flight controller by training the model to perform visually guided flight tasks. Our project is an open-source platform for modeling neural control of sensorimotor behavior in an embodied context.