bluuebunny/crossref_metadata_2025 huggingface dataset:
The Association Between Food Insecurity, Parental Stress, and Child Development
Authors: Belans Rachel , Odom Joanne , Kolm Paul , Rethy Janine A.
Published: August 2024

Background and Objectives:

It is recognized that development in the 0-to-5-year period is predictive of lifelong health and well-being and that early childhood development is influenced by parental mental health. Social stressors such as food insecurity can exacerbate parental mental health issues.

Methods:

To improve understanding of this complex interplay, a primary care pediatric practice designed an innovative meal and grocery delivery program for families experiencing food insecurity with at least one child aged 0-5 years. As part of the program, food insecurity, parental mental health, and child development were assessed.

Results:

Food insecurity was found to be correlated with increased stress in the parent-child system, and increased stress was found to be strongly correlated with delays in early childhood developmental progress.

Conclusions:

These findings suggest that changes in the parent–child relationship resulting from increased parental stress due to food insecurity can play a role in influencing early childhood development.
Spindle Cell Carcinoma of the Ocular Adnexa: A Case Report and Literature Review
Authors: Mason Ryan H. , Chang Kenneth , Nassrallah Georges , Nijhawan Navdeep
Published: August 2024

A 68-year-old woman was seen in oculoplastic consultation with a medial canthal lesion initially diagnosed as an atypical fibroxanthoma. On excisional biopsy, she was found to have a spindle cell carcinoma, which is a rare and reportedly more aggressive form of squamous cell carcinoma. The authors highlight the surgical technique of biopsy and reconstruction, the detailed histologic and immunohistochemical analysis required for accurate diagnosis, considerations for adjuvant treatment, and suggestions for systemic workup and surveillance. This case adds to the small body of available literature on primary spindle cell carcinoma of the ocular surface and ocular adnexa, which the authors have summarized. They hope that as more data become available, there will be clearer diagnostic and treatment algorithms for this uncommon presentation.
Two-year Outcomes of Ultra-low-dose Radiotherapy in the Treatment of Ocular Adnexal B-cell Lymphomas
Authors: Manta Alexandra I. , Schlect David J. , Wang Delia D. , Sullivan Timothy J.
Published: August 2024

Background:

This study focuses on the efficacy and 2-year outcomes of ultra-low-dose radiotherapy (RT) in treating primary and secondary ocular adnexal lymphoma (OAL).

Methods:

A retrospective analysis was conducted on patients with OAL between 2017 and 2022, treated with 4 Gy of RT. The primary and secondary outcomes assessed were response rate, progression-free survival, and lymphoma-related death.

Results:

Twenty-one patients with primary and secondary OAL of diverse, presentations, subtypes, and stages were included. The orbital tumors had an average size of 17 × 16 × 16 mm. Of the 14 primary OAL cases, 3 (14%) had T1N0M0 disease, 8 (38%) T2N0M0, and 3 (14%) T3N0M0 (AJCC 8th edition staging); of the 7 secondary OALs, 4 (19%) were stage IE, 2 (10%) stage IIE, and 1 (5%) stage IIIE (Ann Arbor staging). Ultra-low-dose RT yielded a 95% complete response rate and 100% progression-free survival rates, both locally and systemically at 2 years. Mild dry eyes were reported in 14% of patients as a late treatment toxicity.

Conclusions:

Ultra-low-dose RT emerges as an effective and well-tolerated treatment approach for OAL. Our findings support the use of 4 Gy, showcasing high complete response rates (95%) and durable disease control without significant local relapses over an average follow up of 27 months. Our results align with earlier investigations, validating the curative potential of ultra-low-dose RT and reinforcing the concept of achieving favorable outcomes with minimal intervention. This approach may potentially alleviate the burden of long-term ocular side effects associated with higher radiation doses, enhancing the overall quality of life for OAL patients.
Testosterone and male contraception
Authors: Thirumalai Arthi , Page Stephanie T.
Published: August 2024

Purpose of review

Rates of unintended pregnancy have remained relatively stagnant for many years, despite a broad array of female contraceptive options. Recent restrictions on access to abortion in some countries have increased the urgency for expanding contraceptive options. Increasing data suggest men are keen to utilize novel reversible male contraceptives.

Recent findings

Despite decades of clinical research in male contraception, no reversible hormonal product currently exists. Nestorone/testosterone, among other novel androgens, shows promise to finally move to pivotal Phase 3 studies and introduction to the marketplace.

Hormonal male contraception utilizes androgens or androgen-progestin combinations to exploit negative feedback that regulates the hypothalamic-pituitary-testicular axis. By suppressing release of gonadotropins, these agents markedly decrease endogenous testosterone production, lower intratesticular testosterone and suppress spermatogenesis. The addition of a progestin enhances the degree and speed of sperm suppression. The androgen component preserves a state of symptomatic eugonadism in the male. There is growing demand and acceptance of male contraceptive options in various forms. As these formulations progress through stages of drug development, regulatory oversight and communication with developers around safety and efficacy standards and garnering industry support for advancing the production of male contraceptives will be imperative.
HIV-associated kidney disease: the changing spectrum and treatment priorities
Authors: Wearne Nicola , Davidson Bianca
Published: August 2024

Purpose of review

This review examines the impact of HIV on kidney disease, which remains significant despite advances in antiretroviral therapy (ART). The review is timely due to the shifting epidemiology of kidney disease in people with HIV (PWH), driven by increased ART access, noncommunicable diseases, and region-specific opportunistic infections like tuberculosis.

Recent findings

The literature highlights a decline in HIV-associated nephropathy (HIVAN) and a rise in tubulointerstitial diseases and noncommunicable diseases among PWH. Studies from the United States and South Africa report decreased HIVAN prevalence and increased rates of tubulointerstitial diseases linked to tenofovir disoproxil fumarate (TDF) toxicity and tuberculosis (TB). Immune complex glomerulonephritis (ICGN) and diabetic kidney disease (DKD) are also prevalent.

The findings underscore the need for improved diagnostic tools for opportunistic infections, management of ART-related complications, and strategies to address noncommunicable diseases in PWH. There is a need to centralize care to address all health needs simultaneously. Future research should focus on APOL1-targeted therapies and the role of SGLT2 inhibitors in CKD. Enhanced transplantation outcomes and the development of guidelines for managing DKD in PWH are critical for advancing clinical practice and improving patient outcomes.
Serum creatinine and serum cystatin C as an index of muscle mass in adults
Authors: Liu Celina , Levey Andrew S. , Ballew Shoshana H.
Published: August 2024

Purpose of review

Serum creatinine reflects both muscle mass and kidney function. Serum cystatin C has recently been recommended as an additional marker for estimating kidney function, and use of both markers together may provide an index of muscle mass. This review aims to describe the biological basis for and recent research examining the relationship of these markers to muscle mass in a range of adult populations and settings.

Recent findings

This review identified 67 studies, 50 of which had direct measures of muscle mass, and almost all found relationships between serum creatinine and cystatin C and muscle mass and related outcomes. Most studies have been performed in older adults, but similar associations were found in general populations as well as in subgroups with cancer, chronic kidney disease (CKD), and other morbid conditions. Creatinine to cystatin C ratio was the measure examined the most often, but other measures showed similar associations across studies.

Measures of serum creatinine and cystatin C together can be an index of muscle mass. They are simple and reliable measures that can be used in clinical practice and research. Further study is needed to determine actionable threshold values for each measure and clinical utility of testing and intervention.
The Effect of Laughter Yoga Applied to Intensive Care Nurses on Their Perceived Stress, Job Motivation, and Mental Well-being
Authors: Yılmaz Ramazan , Çevik Kaya Kıvan
Published: August 2024

Aim

The aim of this study was to examine the effect of laughter yoga applied to intensive care nurses on perceived stress, job motivation, and mental well-being.

Design

This study was a randomized controlled trial.

Methods

The study was conducted with nurses working at the university hospital's surgical intensive care and anesthesia intensive care units of the third-level intensive care unit in Turkey. Data obtained from 30 participants in the intervention group and 33 participants in the control group were analyzed. The Nurse Introduction Form, Nurse Job Motivation Scale, Perceived Stress Scale, and Warwick-Edinburgh Mental Well-being Scale were used to collect data. Data obtained from the study were evaluated using the SPSS 22.0 package.

Results

It was determined that there was no statistically significant difference in the average scores of the pretest/posttest 1/posttest 2 of the Perceived Stress Scale (13.70 ± 3.33 to 14.57 ± 4.57, P > .05; 13.50 ± 3.15 to 13.48 ± 4.59, P > .05; and 13.56 ± 3.15 to 13.15 ± 3.49, P > .05, respectively) and Work Motivation Scale (59.70 ± 7.58 to 59.69 ± 7.98, P > .05; 60.30 ± 8.07 to 58.48 ± 8.94, P > .05; and 60.56 ± 7.86 to 57.93 ± 9.54, P > .05, respectively) for both the intervention and control groups of nurses. A statistically significant difference was found in the average scores of the Warwick-Edinburgh Mental Well-Being Scale pretest/posttest 1/posttest 2 for the intervention group of nurses (50.90 ± 7.60, 51.50 ± 7.80, and 53.70 ± 7.08, respectively; F = 3.330, P = .043). However, the difference was found to be insignificant in pairwise comparisons in the further analysis (a = b = c). It was determined that there was no statistically significant difference in the average scores of the Warwick-Edinburgh Mental Well-Being Scale pretest/posttest 1/posttest 2 for the control group of nurses (52.21 ± 9.89, 51.93 ± 10.45, and 51.03 ± 9.63, respectively; P > .05).

Conclusions

The application of laughter yoga on intensive care nurses did not result in a significant change in perceived stress levels and work motivation. However, statistically significant differences were observed in the average mental well-being scores among the intervention group.
Early Identification, Intervention, and Prevention of Hospital-Acquired Pressure Injuries Using a Nurse-Driven Pressure Injury Prevention Program
Authors: McCray Sharee , Donaldson Amy
Published: August 2024

Purpose/Objectives

The purpose of this quality improvement project was to reduce the hospital-acquired pressure injury (HAPI) rate to less than 1.177 per 1000 patient-days, increase staff competency and care in pressure injury prevention best practices through implementation of a nurse-driven pressure injury prevention program, to engage patients in pressure injury prevention through implementation of skin rounds, and improve staff adherence to documentation requirements for pressure injury interventions on an amputee/stroke unit.

Description of the Project/Program

HAPIs can lead to negative patient outcomes including pain, infection, extended hospitalization, and morbidity. Using an evidence-based education strategy, the Agency for Healthcare Research and Quality pressure ulcer prevention clinical pathway and skin rounds were implemented. Focused education for nursing, staff competency, daily audits, HAPI rates, and documentation compliance were evaluated pre and post intervention.

Outcomes

The HAPI rate reduced from 1.177 to 0.272 per 1000 patient-days. After completion, the unit maintained zero pressure injuries, daily patient care for pressure injuries improved, documentation compliance increased, and staffs’ knowledge and skill set in early identification, intervention, and prevention of pressure injuries heightened.

Conclusion

A nurse-driven pressure injury prevention program was successful in the reduction of the HAPI rate.
Filling Gaps in Practice Leadership
Authors: Negley Kristin D. , Schad Shauna P.
Published: August 2024

Purpose

To create a succession plan for clinical nurse specialist positions across multiple clinical settings.

Description of the Project

Mayo Clinic (Rochester, Minnesota) had multiple clinical nurse specialist position vacancies. However, standard recruitment methods and a collaboration between human resources and nursing managers to expand the applicant pool yielded few applicants. A work group was subsequently commissioned to identify innovative ways to fill the vacant clinical nurse specialist positions. Guiding principles for hiring and implementing the role were developed.

Outcome

During the 4-year project period (2016 through 2019), the time to fill positions decreased from 174 days to 83 days. Nurse managers and clinical nurse specialists reported an increased number of registered nurses seeking information about the profession. Twenty-eight clinical nurse specialist interns, titled clinical resource nurses, were hired, and 14 completed their graduate degree, obtained state licensure, and transitioned to clinical nurse specialist roles. Twelve clinical resource nurses were on schedule to transition to clinical nurse specialist positions, and 2 left their positions.

Conclusion

A succession plan that used clinical nurse specialists to mentor clinical resource nurses to fill gaps in practice priorities while completing graduate education was a successful strategy to fill vacant clinical nurse specialist positions.
Verrucous Carcinoma of the Foot
Authors: Donaldson Elsa K. , Miller Rebecca L.R. , Hayakawa Thomas E.J. , Petropolis Christian J. , Sigurdson Leif , Giuffre Jennifer L.
Published: August 2024

Introduction

Verrucous carcinoma (VC) was first described in 1948 by Dr. Ackerman. It is a low-grade cutaneous squamous carcinoma that usually develops in the oral cavity, the anogenital region, and the plantar surface of the foot. Clinically, there is low suspicion for malignancy given the slow growth of VC lesions and their wart-like appearance. Diagnosis can be difficult because of the benign histological appearance with well-differentiated cells and absence of dysplasia. Surgical excision is the only satisfactory form of treatment for plantar VC; however, this becomes difficult given its benign clinical appearance and the pathologic misinterpretation of the lesion as a benign hyperplasia. While there are case reports and retrospective studies of patients with plantar VC in the literature, we present the largest case series of plantar VC within North America, with recurrence despite negative margins.

Methods

We report on all the plantar VC excised between 2014–2023. We report six cases of VC, their treatment, and their outcomes.

Results

Six patients obtained a diagnosis of plantar VC by incisional biopsy. All patients underwent excision of their lesions and had negative margins reported on the final pathology. All patients developed nonhealing wounds at the site of their lesion excision; therefore, biopsies were performed to confirm a recurrence. All patients had a recurrence of VC at the initial site. All patients underwent re-excision of the lesions. Despite negative margins again on final pathology, all patients had a subsequent second recurrence. Ultimately, all patients underwent an amputation as definitive management. Each patient had an average of 3 operations. There were 4 different surgeons and different pathologists reporting their findings.

Conclusions

Our experience with plantar VC suggests that an aggressive approach to surgical management is needed. Furthermore, management is optimized with the combined expertise of an experienced dermatopathologist and surgeon. Despite negative margins and repeated excisions, VC lesions recur and invade local tissues to the extent that only amputation of the involved foot has resulted in cure.
EXERCISE PRECONDITIONING IMPROVES MESENTERIC LYMPHATIC CONTRACTILITY THROUGH MAM IN RATS FOLLOWING HEMORRHAGIC SHOCK
Authors: Zheng Hai-Ning , Zhang Hong , Wang Jing , Jia Gui-Yan , Zhao Zi-Gang , Niu Chun-Yu
Published: August 2024

Restoration of mesenteric lymphatic microcirculation is crucial for alleviating severe hemorrhagic shock-induced death. Exercise preconditioning (EP) enhances adaptability and resistance to injury and disease. The mitochondria-associated endoplasmic reticulum membrane (MAM) plays a crucial role in the energy and information exchange between the two organelles. Therefore, we hypothesized that EP ameliorates mesenteric lymphatic contractility through MAM in rats following hemorrhagic shock, aiming to confirm that EP enhances resistance to hemorrhagic shock and further popularizes the idea that exercise is beneficial for health. To test this hypothesis, we observed the effects of EP for 4 weeks on survival time and mesenteric lymphatic contractility in conscious rats following hemorrhagic shock and further explored the effects of MAM agonists and inhibitors. The results showed that EP prolonged the survival time and improved the mesenteric lymphatic contractility and reactivity in vivo and in vitro in rats underwent hemorrhagic shock, ameliorated the MAM ultrastructure in lymphatic smooth muscle cells (LSMCs) and reduced the voltage-dependent anion channel 1 (VDAC1, a vital protein of MAM) and IP3R1 expressions in mesenteric lymphatic tissue. Importantly, treatment with 2-APB (IP3R1 inhibitor) or VBIT-12 (VDAC1 inhibitor) prolonged the survival time, improved mesenteric lymphatic contractility in vivo, ameliorated the MAM ultrastructure injury, and decreased the IP3R1 or VDAC1 expressions in LSMCs in rats following hemorrhagic shock. In contrast, the administration of drinking water containing CdCl2 (IP3R1 activator) abolished the beneficial effect of EP on hemorrhagic shock. Taken together, the protective effect of EP on lymphatic contractility following hemorrhagic shock was achieved by improving MAM in LSMCs.
OUTCOMES OF PEDIATRIC FLUID-REFRACTORY SEPTIC SHOCK ACCORDING TO DIFFERENT VASOACTIVE STRATEGIES: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Marchetto Luca , Zanetto Lorenzo , Comoretto Rosanna I. , Padrin Davide , Menon Kusum , Amigoni Angela , Daverio Marco
Published: August 2024

Background: Hemodynamic support using vasoactive agents is a mainstay in the management of patients with pediatric fluid-refractory septic shock (FRSS). However, evidence supporting the appropriate choice of vasoactive agent is limited. This study aimed to perform a systematic review and meta-analysis on the effect of different first-line vasoactive strategies on mortality in pediatric FRSS. Methods: MEDLINE, Embase, Scopus, CINAHL, Web of Science, the Cochrane Library, ClinicalTrials.gov, and the ISRCTN registry were searched up until December 2023. Randomized controlled trials and observational cohort studies reporting vasoactive agent-specific outcomes of children with FRSS were included. Mortality was assessed as primary outcome in studies on patients receiving dopamine, epinephrine, or norepinephrine as first-line. Random-effects meta-analyses were conducted. Prevalence ratio (PR) estimates were calculated between two drugs when was available in the same study. Findings: Of the 26,284 identified articles, 13 were included, for a total of 997 children. Twelve studies included 748 patients receiving a single vasoactive agent. Of these, 361 received dopamine, 271 epinephrine, and 116 norepinephrine. Overall pooled mortality for patients receiving a single vasoactive was 12% (95% CI 6%–21%) of which 11% (95% CI 3%–36%) for patients receiving dopamine, 17% (95% CI 6%–37%) for epinephrine, and 7% (95% CI 1%–48%) for norepinephrine. Four first-line dopamine (176 patients) and first-line epinephrine (142 patients): dopamine showed a tendency toward higher mortality (PR 1.38, 95% CI 0.81–2.38) and a significant higher need for mechanical ventilation (PR 1.12, 95% CI 1.02–1.22). Interpretation: Among children with FRSS receiving a single vasoactive agent, norepinephrine was associated with the lowest mortality rate. Comparing dopamine and epinephrine, patients receiving epinephrine needed less mechanical ventilation and showed a trend for lower mortality rate. Further research is needed to better delineate the first-line vasoactive agent in this population.
USP9X PROMOTES LPS-INDUCED FIBROBLAST CELL APOPTOSIS, INFLAMMATION, AND OXIDATIVE STRESS BY REGULATION OF TBL1XR1 DEUBIQUITINATION
Authors: Yang Juan , Yao Yingying , Fan Shuo , Li Xiaoyan
Published: August 2024

Background: Ubiquitination and deubiquitination are involved in the progression of human diseases, including acute pneumonia. In this study, we aimed to explore the functions of ubiquitin-specific peptidase 9X-linked (USP9X) in lipopolysaccharide (LPS)-treated WI-38 cells. Methods: WI-38 cells were treated with LPS to induce the cellular damage and inflammation. 3-(4, 5-Dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay, and 5-ethynyl-2′-deoxyuridine (EdU) assay were performed to examine the proliferation of LPS-treated WI-38 cells. Flow cytometry analysis was conducted to detect LPS-treated WI-38 cell apoptosis. ELISA kits were utilized to determine the concentrations of inflammatory factors (IL-1β and TNF-α). Superoxide dismutase activity and reactive oxygen species level were examined with related kits. Ubibrowser (http://ubibrowser.bio-it.cn/ubibrowser/), ubiquitination assay, and co-immunoprecipitation assay demonstrated the interaction between USP9X and transducin β-like 1X related protein 1 (TBL1XR1). qRT-PCR assay and western blot assay were manipulated to determine the expression of USP9X and TBL1XR1. TBL1XR1 and USP9X knockdown experiments were conducted to explore their functions on LPS-induced WI-38 cell injury and inflammation. Results: TBL1XR1 expression was upregulated in LPS-treated WI-38 cells. TBL1XR1 knockdown promoted cell proliferation and repressed apoptosis, inflammation, and oxidative stress in LPS-treated WI-38 cells. Moreover, USP9X deubiquitinated TBL1XR1 to regulate TBL1XR1 expression. USP9X knockdown restored the effects of LPS on WI-38 cell proliferation, apoptosis, inflammation, and oxidative stress, but these effects of USP9X knockdown were further abolished by TBL1XR1 overexpression. In addition, USP9X promoted the NF-κB signaling pathway by the deubiquitination of TBL1XR1. Conclusion: USP9X promoted the apoptosis, inflammation, and oxidative stress of LPS-stimulated WI-38 cells through the deubiquitination of TBL1XR1.
Platelet traits and sepsis risk and prognosis: a bidirectional two-sample Mendelian randomization study
Authors: Song Zhonghai , Li Hua , Zhang Jing , Huang Yaomeng , Gao Shichao
Published: August 2024

Background

Sepsis is a critical medical condition characterized by a dysregulated host response to infection. Platelet abnormalities frequently manifest in sepsis patients, but the causal role of platelets in sepsis remains unclear. This study employed a bidirectional two-sample Mendelian randomization (MR) approach to investigate the causal direction between platelets and sepsis.

Methods

MR analysis was used to investigate the causal effect of four platelet traits - platelet count (PLT), platelet crit (PCT), mean platelet volume (MPV), and platelet distribution width (PDW)- on sepsis risk and prognosis. Additionally, the study explored the reverse causality, assessing the impact of sepsis on these platelet traits. Genetic variants from large-scale genome-wide association studies (GWAS) served as instrumental variables to infer causality. Sensitivity analyses and heterogeneity tests were conducted to ensure the validity and robustness of the results.

Results

Genetically predicted decreased PCT (OR = 0.938, p = 0.044) and MPV (OR = 0.410, p = 0.006) were associated with an increased risk of sepsis. In the reverse direction, 28-day sepsis mortality was significantly associated with decreased PLT (OR = 0.986, p = 0.034). No significant causal relationships were observed between sepsis and other platelet traits.

Conclusions

This study suggests a causal association between low PCT and MPV levels and increased risk of sepsis. Additionally, sepsis with a poor prognosis was causally linked to decreased PLT. These findings provide novel evidence for the causal relationship between platelet traits and sepsis.
DETECTION AND QUANTIFICATION OF MICROCIRCULATORY DYSFUNCTION IN SEVERE COVID-19 NOT REQUIRING MECHANICAL VENTILATION: A THREE-ARM COHORT STUDY
Authors: Abrard Stanislas , Coquet Thomas , Riou Jérémie , Rineau Emmanuel , Hersant Jeanne , Vincent Antoine , Cordoval Julien , Jacquet-Lagrèze Matthias , Allaouchiche Bernard , Lukaszewicz Anne-Claire , Henni Samir
Published: August 2024

Aim: To identify and describe microcirculatory dysfunction (MD) in severe COVID-19 cases. Methods: This prospective, cohort study evaluated microvascular function in COVID-19 patients with acute respiratory failure not requiring mechanical ventilation and compared it with that of non–COVID-19 intensive care unit (ICU)–matched controls. A validation cohort included healthy, comorbidity-free patients. The primary outcome compared tissue oxygen resaturation slope (rStO2) in COVID-19 patients and non-COVID ICU controls. rStO2 was measured post a 3-min vaso-occlusive test during post-occlusive reactive hyperemia (PORH). Additionally, microvascular reactivity was assessed using perfusion index (PI) during PORH and laser speckle contrast imaging post iontophoresis with acetylcholine (ACH), sodium nitroprusside (SNP), and sublingual microcirculation. Results: Overall, 75 patients (25 per cohort) were included. COVID-19 patients exhibited greater severity than ICU controls, as indicated by their SOFA scores (4.0 [3.0; 4.0] vs. 1.0 [0; 1.0], P < 0.001) and PaO2/FiO2 ratios (113 [82; 150] vs. 443 [348; 533], P < 0.001). No significant difference was observed in rStO2 between the groups. COVID-19 patients showed longer time in reaching peak PI (P = 0.025), reduced vasodilation with ACH and SNP (P = 0.010 and P = 0.018, respectively), and increased microvascular density (P = 0.019) compared to non–COVID-19 ICU controls. Conclusion: We observed evidence of MD in COVID-19 patients through various microcirculatory parameters. This study's reproducible multimodal approach facilitates acute MD detection across multiple clinical applications. Limitations included the observational design, limited statistical power, single-time microvascular measurements, varying illness severity among groups, and possible influences of treatments and vaccinations on MD.
Trial registration
: Clinical-Trials.gov (NCT04773899).
Mobile Phone Apps for Pelvic Floor Disorders
Authors: Kasoff Madison , Alishahian Leael , Gimoto Justin , Steinhart Adi , Grimes Cara L. , Pape Dominique Malacarne
Published: August 2024

Importance

Up to 50% of patients report not readily seeking treatment for pelvic floor disorders (PFDs). The increase in phone applications (apps) for health care information is an opportunity to increase access to care.

Objective

The aim of the study was to systematically evaluate content and function of apps for patients with PFDs.

Study Design

Apps were screened using PFD-related search terms. Included apps were on the Apple store, in English, and targeted patients with PFDs. The primary outcome was app quality based on the APPLICATIONS scoring system (scored 0–16). Secondary outcomes included professional medical involvement, iTunes rating details, the presence of a voiding/bowel diary, tracking of diet, pain/symptoms, exercise, and medication, graphing or social functions, reminders, disease information, and decision support. Data was reported with descriptive statistics (medians (ranges) and n (percentages).

Results

Eight hundred forty apps were identified and 83 were analyzed. The top 3 PFD categories represented were defecatory dysfunction (29), overactive bladder (28), and stress incontinence (27). The median APPLICATIONS score was 7 (3–12). Most apps (78%) were developed without professional medical involvement. Most apps were free, while the remainder ranged from $1.99 to $4.99. No app had all features. Twenty-five apps (30%) included a voiding diary, 33 (40%) had a bowel diary, 27 (33%) included exercise tracking, and 44 (53%) had reminder systems.

Conclusions

Most apps had reasonable, but not high, functionality. Current apps provide varying degrees of overall utility, with limited disease information and decision support. Further collaboration with medical providers in app development would support better integration of clinician and patient needs.
Symbol ungrounding: what the successes (and failures) of large language models reveal about human cognition
Authors: Dove Guy
Published: August 2024

Large language models can handle sophisticated natural language processing tasks. This raises the question of how their understanding of semantic meaning compares to that of human beings. Supporters of embodied cognition often point out that because these models are trained solely on text, their representations of semantic content are not grounded in sensorimotor experience. This paper contends that human cognition exhibits capabilities that fit with both the embodied and artificial intelligence approaches. Evidence suggests that semantic memory is partially grounded in sensorimotor systems and dependent on language-specific learning. From this perspective, large language models demonstrate the richness of language as a source of semantic information. They show how our experience with language might scaffold and extend our capacity to make sense of the world. In the context of an embodied mind, language provides access to a valuable form of ungrounded cognition.

This article is part of the theme issue ‘Minds in movement: embodied cognition in the age of artificial intelligence’.
Skill building in freediving as an example of embodied culture
Authors: Downey Greg
Published: August 2024

Skilled activity is a complex mix of automatized action, changed attention patterns, cognitive strategies and physiological adaptations developed within a community of practice. Drawing on physiological and ethnographic research on freediving, this article argues that skill acquisition demonstrates the variety of mechanisms that link biological and cultural processes to produce culturally shaped forms of embodiment. In particular, apneists alter phenotypic expression through patterned practices that canalize development, exaggerating the dive response, developing resistance to elevated carbon dioxide levels (hypercapnia) and accommodating hydrostatic pressure at depth. The community of divers provides technical advice and helps to orient individuals’ motivations. Some biological processes are phenomenologically accessible, but others are sub-aware and must be accessed indirectly through behaviour or altered interactions with the environment. The close analysis of embodied skills like freediving illustrates how phenotypic plasticity is inflected by culturally patterned behaviours. Divers do developmental work on bodily traits like the dive response to achieve more dramatic performance, even if they cannot directly control all elements of the neurological and physiological responses. The example of expert freediving illustrates the imbrication of biology and culture in embodiment.

This article is part of the theme issue ‘Minds in movement: embodied cognition in the age of artificial intelligence’.
Gestures can help children learn mathematics: how researchers can work with teachers to make gesture studies applicable to classrooms
Authors: Seccia Amanda , Goldin-Meadow Susan
Published: August 2024

The gestures we produce serve a variety of functions—they affect our communication, guide our attention and help us think and change the way we think. Gestures can consequently also help us learn, generalize what we learn and retain that knowledge over time. The effects of gesture-based instruction in mathematics have been well studied. However, few of these studies are directly applicable to classroom environments. Here, we review literature that highlights the benefits of producing and observing gestures when teaching and learning mathematics, and we provide suggestions for designing research studies with an eye towards how gestures can feasibly be applied to classroom learning.

This article is part of the theme issue ‘Minds in movement: embodied cognition in the age of artificial intelligence’.
Peripersonal space: why so last-second?
Authors: de Vignemont Frédérique , Farnè Alessandro
Published: August 2024

A vast range of neurophysiological, neuropsychological and behavioural results in monkeys and humans have shown that the immediate surroundings of the body, also known as peripersonal space (PPS), are processed in a unique way. Three roles have been ascribed to PPS mechanisms: to react to threats, to avoid obstacles and to act on objects. However, in many circumstances, one does not wait for objects or agents to enter PPS to plan these behaviours. Typically, one has more chances to survive if one starts running away from the lion when one sees it in the distance than if it is a few steps away. PPS makes sense in shortsighted creatures but we are not such creatures. The crucial question is thus twofold: (i) why are these adaptive processes triggered only at the last second or even milliseconds? And (ii) what is their exact contribution, especially for defensive and navigational behaviours? Here, we propose that PPS mechanisms correspond to a plan B, useful in unpredictable situations or when other anticipatory mechanisms have failed. Furthermore, we argue that there are energetic, cognitive and behavioural costs to PPS mechanisms, which explain why this plan B is triggered only at the last second.

This article is part of the theme issue ‘Minds in movement: embodied cognition in the age of artificial intelligence’.
Disease and ectoparasite management improve nestling golden eagle health and survival: An effective mitigation strategy
Authors: Heath Julie A. , Davis Caitlin M. , Dudek Benjamin M. , McClure Christopher J. W. , Myers Kevin T. , Regnier Emma K. , Rolek Brian W. , Santiago Ashley L.
Published: August 2024

Changes in the distribution and behavior of pathogens and parasites associated with climate change are creating emerging threats for wildlife. These threats have created an urgent need for conservation strategies to manage wildlife. Conservation strategies could provide reliable and cost-effective compensatory mitigation options for protected species affected by renewable energy production, such as golden eagles (Aquila chrysaetos). We used nest camera data to assess survival and cause of death for golden eagle nestlings in southern Idaho, USA. Together, poultry bugs (Haematosiphon inodorus), a blood-sucking ectoparasite that lives in golden eagle nests, and trichomonosis, a fatal disease that is transmitted through the consumption of rock pigeons (Columba livia) caused ~ 27% of nestlings to die per year. From 2022-2023, we treated trichomonosis-infected nestlings with an anti-protozoan drug and developed a protocol for reducing poultry bug densities in eagle nests, then we projected the effects of disease and parasite treatments on population growth using simulation models. We collected pre-treatment information on nestling health and survival, and then, after young fledged, we applied 1 of 3 experimental parasite treatments to eagle nests: permethrin and diatomaceous earth, diatomaceous earth only, or water - a control, and measured effects on eagle health and survival the following year. Ten eagle nestlings with trichomonosis, that otherwise would have died, were successfully treated and lived to fledge from the nest. The permethrin and diatomaceous earth treatment significantly reduced poultry bug densities in eagle nests in the subsequent breeding season and created measurable improvements to nestling health and survival. Nestlings had significantly higher hematocrit, female nestlings had higher mass, and, on average, more nestlings (0.70) successfully survived to fledge compared with control- and diatomaceous earth-treated nests. Further, treatment of disease and parasites was projected to increase population growth rates by 4% and 8%, respectively. In total, we estimate saving 17.5 nestlings, which equates to 10.2 adult eagles, through disease and parasite treatments in two years. In areas with dense concentrations of poultry bugs or where eagles consume rock pigeons, disease and parasite treatments could be an effective compensatory mitigation option or management tool with population-level impacts on eagle populations.
Boundary conditions for synaptic homeodynamics during the sleep-wake cycle
Authors: Kinoshita Fukuaki L. , Yamada Rikuhiro G. , Ode Koji L. , Ueda Hiroki R.
Published: August 2024

Understanding synaptic dynamics during the sleep-wake cycle is crucial yet remains controversial. The synaptic homeostasis hypothesis (SHY) suggests synaptic depression during non-rapid eye movement (NREM) sleep, while other studies report synaptic potentiation or synaptic changes during NREM sleep depending on activities in wakefulness. To find boundary conditions between these contradictory observations, we focused on learning rules and firing patterns that contribute to the synaptic dynamics. Using computational models, we found that under Hebbian and spike-timing dependent plasticity (STDP), wake-like firing patterns decrease synaptic weights, while sleep-like patterns strengthen synaptic weights. We refer to this tendency as Wake Inhibition and Sleep Excitation (WISE). Conversely, under Anti-Hebbian and Anti-STDP, synaptic depression during NREM sleep was observed, aligning with the conventional synaptic homeostasis hypothesis. Moreover, synaptic changes depended on firing rate differences between NREM sleep and wakefulness. We provide a unified framework that could explain synaptic homeodynamics under the sleep-wake cycle.
SUV39H1 Preserves Cancer Stem Cell Chromatin State and Properties in Glioblastoma
Authors: Li Chunying , Xie Qiqi , Ghosh Sugata , Cao Bihui , Du Yuanning , Vo Giau Van , Huang Timothy Y. , Spruck Charles , Wang Y. Alan , Nephew Kenneth P. , Shen Jia
Published: August 2024

Of the more than 100 types of brain cancer, glioblastoma (GBM) is the deadliest. As GBM stem cells (GSCs) are considered to be responsible for therapeutic resistance and tumor recurrence, effective targeting and elimination of GSCs could hold promise for preventing GBM recurrence and achieving potential cures. We show here thatSUV39H1, which encodes a histone-3, lysine-9 methyltransferase, plays a critical role in GSC maintenance and GBM progression. Upregulation of SUV39H1 was observed in GBM samples compared to normal brain tissues, and knockdown of SUV39H1 in patient-derived GSCs impaired their proliferation and stemness. Single-cell RNA-seq analysis demonstrated restricted expression of SUV39H1 is in GSCs relative to non-stem GBM cells, likely due to super-enhancer-mediated transcriptional activation, while whole cell RNA-seq analysis revealed that SUV39H1 regulates G2/M cell cycle progression, stem cell maintenance, and cell death pathways in GSCs. By integrating the RNA-seq data with ATAC-seq (assay for transposase-accessible chromatin followed by sequencing), we further demonstrated altered chromatin accessibility in key genes associated with these pathways following SUV39H1 knockdown. Treatment with chaetocin, a SUV39H1 inhibitor, mimicked the functional effects of SUV39H1 knockdown in GSCs and sensitized GSCs to the GBM chemotherapy drug temozolomide. Furthermore, targeting SUV39H1 in vivo using a patient-derived xenograft model for GBM inhibited GSC-driven tumor formation. This is the first report demonstrating a critical role for SUV39H1 in GSC maintenance. SUV39H1-mediated targeting of GSCs could enhance the efficacy of existing chemotherapy, presenting a promising strategy for improving GBM treatment and patient outcomes.

Highlights

SUV39H1 is upregulated in GBM, especially GSCs

Targeting SUV39H1 disrupts GSC maintenance and sensitizes GSCs to TMZ

Targeting SUV39H1 alters chromatin accessibility at cell cycle and stemness genes

Targeting SUV39H1 suppresses GSC-driven tumors in a patient-derived xenograft model
De-biased sparse canonical correlation for identifying cancer-related trans-regulated genes
Authors: Huey Nathan , Dutta Diptavo , Laha Nilanjana
Published: August 2024

Summary

In cancer multi-omic studies, identifying the effects of somatic copy number aberrations (CNA) on physically distal gene expressions (trans-associations) can potentially uncover genes critical for cancer pathogenesis. Sparse canonical correlation analysis (SCCA) has emerged as a promising method for identifying associations in high-dimensional settings, owing to its ability to aggregate weaker associations and its improved interpretability. Traditional SCCA lacks hypothesis testing capabilities, which are critical for controlling false discoveries. This limitation has recently been addressed through a bias correction technique that enables calibrated hypothesis testing. In this article, we leverage the theoretical advancements in de-biased SCCA to present a computationally efficient pipeline for multi-omics analysis. This pipeline identifies and tests associations between multi-omics data modalities in biomedical settings, such as the trans-effects of CNA on gene expression. We propose a detailed algorithm to choose the tuning parameters of de-biased SCCA. Applying this pipeline to data on estrogen receptor (ER)-associated CNAs and 10,756 gene expressions from 1,904 breast cancer patients in the METABRIC study, we identified 456 CNAs trans-associated with 256 genes. Among these, 5 genes were identified only through de-biased SCCA and not by the standard pairwise regression approach. Downstream analysis with the 256 genes revealed that these genes were overrepresented in pathways relevant to breast cancer.
Mutualisms within light microhabitats drive sensory convergence in a mimetic butterfly community
Authors: Wainwright J. Benito , Loupasaki Theodora , Ramírez Francisco , Penry Williams Iestyn L. , England Sam J. , Barker Annalie , Meier Joana I. , How Martin J. , Roberts Nicholas W. , Troscianko Jolyon , Montgomery Stephen H.
Published: August 2024

Niche partitioning within variable habitats can expose species to distinct sensory information. Vision is the primary sensory modality used by many animals to interact with their habitat. However, within diurnal terrestrial ecosystems, little is known if, and how, variation in light environments impact species assemblages and visual system evolution. By studying a diverse, sympatric community of mimetic butterflies, we demonstrate that forest architecture creates a mosaic of light microhabitats that drive adaptive sensory convergence and divergence in both peripheral and central sensory systems. Our study provides insights into the dynamic response of visual systems when confronted with similar ecological challenges, and illustrates the wide-reaching consequences of interspecific mutualisms, such as mimicry, on organismal evolution.
Oncolytic vaccinia virus as a precision cancer vaccine platform
Authors: Komant Shae J , Wang Jun Li , Favis Nicole , Alex Cyril , Evans David H , Noyce Ryan S , Baldwin Troy A
Published: August 2024

Oncolytic viruses (OVs) are a unique immunotherapeutic tool as they possess the ability to selectively replicate in and kill tumor cells while also having the potential to induce potent anti-tumor immune responses. Further, the use of OVs as payload delivery systems to the tumor offers a precision approach to enhancing immune responses generated during OV therapy through the viral expression of immune stimulating molecules in the tumor. Notably, Vaccinia virus (VACV) is a strong oncolytic candidate due to its ability to infect a wide range of cancer cells, and a genome capable of harbouring large inserts of exogenous DNA. Peptide-Major Histocompatibility Complexes (pMHC-I) are vital components of the immune recognition of tumors, leading to the activation of antigen specific T cells and targeted killing of cells. Here, we examined the use of an oncolytic VACV (VACVΔ4x) expressing a single chain trimer (SCT) pMHC-I complex (VACVΔ4x-SCT) encoding a tumor associated or specific antigen. VACVΔ4x-SCT treatment was investigated in two immunologically cold tumor models, B16F10 melanoma and EMT6 breast cancer. VACV expression of tumor specific SCTs lead to drastic differences in tumor growth between the two models, where enhanced tumor clearance was observed in the EMT6 model. Tumor antigen specific CD8+ T cells were isolated from both tumor and spleen following VACV-SCT treatment, indicating the ability to induce targeted tumor specific responses with viral therapy. Initial tumor clearance was also observed to be protective in the EMT6 model, leading to tumor rejection upon subsequent challenge. Overall, we demonstrate the ability to generate a personalized cancer vaccine capable of inducing system recognition and elimination of tumor cells, validating VACV as a potential vaccine platform.
Dialogues in colour and behaviour - Integration of complex signalling traits and physiology
Authors: Patro Subhasmita , Saravanan Thejaswini , Parag Ayush , Thaker Maria
Published: August 2024

Animal communication can be complex, often involving multiple static and dynamic traits. The extent to which these traits are correlated can elucidate their function as either redundant or multiple messages. Using the agamid lizard,Psammophilus dorsalis, as a model system we examined patterns of trait expression and the role of steroid hormones in mediating these traits during social interactions. We staged male-male interactions in the lab and measured the repertoire of display behaviour and colours, which change dynamically in the visible and ultraviolet ranges in different body regions. Additionally, we measured testosterone and corticosterone levels before and after the social trials.

Our results show that within behaviour and colour trait categories, components were strongly correlated within individuals, suggesting either a shared physiological pathway or redundant information content. However, across trait categories, correlation patterns varied. The chromatic contrast of the (yellow) dorsal region of lizards was correlated with both body size and level of aggression, whereas the size of UV patches was correlated with body size only. We also found a negative association between baseline corticosterone levels, body size and dorsal yellow chromatic contrast, suggesting a mechanistic link between these traits. However, social interaction induced testosterone and corticosterone levels were uncorrelated with the expression of the dynamic behavioural and colour displays during the social interactions itself. Notably, the intensity of colour and behavioural displays of males were matched by their opponents. Overall, our results suggest that multiple signalling traits can ensure both redundancy as well as provide multiple messages to receivers, thus improving the robustness of information transfer, particularly during competitions which have high fitness consequences.