bluuebunny/crossref_metadata_2025 huggingface dataset:
Signs of Hemolysis Predict Mortality and Ventilator Associated Pneumonia in Severe Acute Respiratory Distress Syndrome Patients Undergoing Veno-Venous Extracorporeal Membrane Oxygenation
Authors: Rezoagli Emanuele , Bombino Michela , Ware Lorraine B. , Carlesso Eleonora , Rona Roberto , Grasselli Giacomo , Pesenti Antonio , Bellani Giacomo , Foti Giuseppe
Published: July 2024

Cell-free hemoglobin (CFH) is used to detect hemolysis and was recently suggested to trigger acute lung injury. However, its role has not been elucidated in severe acute respiratory distress syndrome (ARDS) patients undergoing extracorporeal membrane oxygenation (ECMO). We investigated the association of carboxyhemoglobin (COHb) and haptoglobin—two indirect markers of hemolysis—with mortality in critically ill patients undergoing veno-venous ECMO (VV-ECMO) with adjusted and longitudinal models (primary aim). Secondary aims included assessment of association between COHb and haptoglobin with the development of ventilator-associated pneumonia (VAP) and with hemodynamics. We retrospectively collected physiological, laboratory biomarkers, and outcome data in 147 patients undergoing VV-ECMO for severe ARDS. Forty-seven patients (32%) died in the intensive care unit (ICU). Average levels of COHb and haptoglobin were higher and lower, respectively, in patients who died. Higher haptoglobin was associated with lower pulmonary (PVR) and systemic vascular resistance, whereas higher COHb was associated with higher PVR. Carboxyhemoglobin was an independent predictor of VAP. Both haptoglobin and COHb independently predicted ICU mortality. In summary, indirect signs of hemolysis including COHb and haptoglobin are associated with modulation of vascular tone, VAP, and ICU mortality in respiratory ECMO. These findings suggest that CFH may be a mechanism of injury in this patient population.
Exam Wrappers in Nursing Education
Authors: Gay Jessica E. , Kuskie Kathryn , Loken Alisha , Klenke-Borgmann Laura
Published: July 2024

Background:

Metacognition can assist students in improving poor examination (exam) performance. An exam wrapper is a metacognitive tool used to assess a student’s thought processes and behavioral patterns during test-taking.

Purpose:

The purpose of this study was to determine the effect of an exam wrapper tool used during one-to-one exam review sessions with faculty on prelicensure nursing students’ subsequent exam performance.

Methods:

Paired t-tests and repeated measures ANOVA were used to compare undergraduate students’ (n = 91) exam scores before and after an exam review session with faculty in which the exam wrapper tool was used.

Results:

Students who completed a one-to-one exam review session with faculty using the exam wrapper showed significant improvement in subsequent exam scores.

Conclusions:

Use of an exam wrapper tool as part of a one-to-one exam review session with faculty is a viable way to leverage metacognition to improve student exam performance.
β-catenin, PAX2, and PTEN Aberrancy Across the Spectrum of Endometrioid Ovarian Lesions
Authors: Del Mundo Maria M. , Aguilar Mitzi , Chen Hao , Niu Shuang , Sahoo Subhransu S. , Roy Sambit , Zheng Wenxin , Lucas Elena , Castrillon Diego H.
Published: July 2024

Endometriosis is a common condition, with the ovary being the most common anatomic site. Endometriosis—particularly in the ovary—is associated with a risk of malignant progression, with a histologic spectrum of lesions from benign to malignant. Recently, a panel of 3 markers consisting of β-catenin, PAX2, and PTEN has been described as a potentially useful diagnostic adjunct in the diagnosis of intrauterine endometrioid neoplasia, where aberrancy for one or more of the markers is strongly associated with neoplasia. Here, we applied the panel to ovarian endometrioid lesions, including endometriosis, endometriosis with flat cytologic atypia, endometrioid borderline tumors, and endometrioid adenocarcinoma (n=85 cases in total). The incidence of aberrancy for the 3 markers increased along this putative neoplastic spectrum, arguing for a role of each of the markers in the neoplastic transformation of ovarian endometriosis. Just 1/32 (3%) of cases of nonatypical endometriosis was marker-aberrant, and this case was aberrant only for PAX2. One of 5 cases (20%) of endometriosis with atypia was marker-aberrant (both PAX2 and PTEN), supporting prior findings that some cases of flat atypia may represent bona fide precursor lesions. Of 19 endometrioid borderline tumors, 10 (53%) were aberrant for one or more markers, with PAX2 being the most frequently aberrant. Of 29 endometrioid adenocarcinomas, 28 (96.6%) were aberrant for at least 1 marker, with PAX2 again the most frequently aberrant. Patterns of aberrancy were well-preserved in areas of nonatypical endometriosis adjacent to borderline tumor or adenocarcinoma, supporting a biological origin in a common marker-aberrant precursor. The findings show that the biomarker panel could be of some diagnostic utility in the characterization of ovarian endometrioid neoplasia, such as in the diagnosis of endometrioid borderline tumor, distinguishing endometrioid from nonendometrioid lesions, or in identifying other types of early precursors at a higher risk of malignant transformation.
The Nature of Adverse Events in Dentistry
Authors: Tokede Bunmi , Yansane Alfa , Walji Muhammad , Rindal D. Brad , Worley Donald , White Joel , Kalenderian Elsbeth
Published: July 2024

Objectives

Learning from clinical data on the subject of safety with regards to patient care in dentistry is still largely in its infancy. Current evidence does not provide epidemiological estimates on adverse events (AEs) associated with dental care. The goal of the dental practice study was to quantify and describe the nature and severity of harm experienced in association with dental care, and to assess for disparities in the prevalence of AEs.

Methods

Through a multistaged sampling procedure, we conducted in-depth retrospective review of patients’ dental and medical records.

Results

We discovered an AE proportion of 1.4% (95% CI, 1.1% to 1.8). At least two-thirds of the detected AEs were preventable. Eight percent of patients who experienced harm due to a dental treatment presented only to their physician and not to the dentist where they originally received care.

Conclusions

Although most studies of AEs have focused on hospital settings, our results show that they also occur in ambulatory care settings. Extrapolating our data, annually, at least 3.3 million Americans experience harm in relation to outpatient dental care, of which over 2 million may be associated with an error.

Practical Implications

Measurement is foundational in enabling learning and improvement. A critical first step in preventing errors and iatrogenic harm in dentistry is to understand how often these safety incidents occur, what type of incidents occur, and what the consequences are in terms of patient suffering, and cost to the healthcare system.
La Crosse virus encephalitis in children
Authors: Ouellette Christopher P.
Published: July 2024

Purpose of review

La Crosse virus encephalitis (LACV-E) is among the most common neuroinvasive arthropod-borne viral infections of childhood in North America. Children are uniquely predisposed to symptomatic disease, whereas symptomatic adult infections remain uncommon. Infection results frequently in neurologic symptomatology including headaches, seizures, and altered mentation, often necessitating hospitalization and significant diagnostic evaluation. The purpose of this review is to provide a contemporary assessment of clinical, laboratory, and neurobehavioral outcomes of children with LACV-E.

Recent findings

Common clinical manifestations at presentation, specifically seizure activity and altered mental status, are independent predictors of disease severity. Epileptiform discharges on electroencephalogram (EEG) during hospitalization may predict long-term epilepsy diagnosis. Lastly, long-term neurologic sequelae from acute infection is persistent and likely under-recognized among children with LACV-E.

As climate change alters the geographic distribution of mosquito borne illnesses, a possibility of regional expansion of La Crosse virus (LACV) endemicity exists. The above data highlight readily identifiable features and testing modalities for clinicians who may encounter this viral infection. Importantly, an emphasis on long term neurobehavioral follow up is necessary to better identify and provide support of affected individuals. Future research in identifying host immune responses to LACV infection, as well as therapeutic options, are needed.
The impact of antioxidant supplements on oocytes and preimplantation embryos of humans and mammals, and their potential application for mitigating the consequences of oxidative stress in vitro: a review
Authors: Guseva Olga , Kan Natalia , Chekmareva Viktoria , Kokorev Daniil , Ilyasov Pavel
Published: July 2024

Nowadays, assisted reproductive technologies are becoming increasingly in demand in people’s lives and activities. One of the most important stages of assisted reproductive technology is the cultivation of oocytes and embryos in vitro. The oxidative stress that arises during such cultivation is a great challenge associated with assisted reproductive technology-related activities. It manifests as an excessive amount of reactive oxygen species, resulting in damage to biomolecules, membranes, and other cell components, which significantly reduces the quality and quantity of oocytes and embryos. One possible solution may be the use of antioxidant supplements of various origins. In this review, we summarize and systematize data related to oxidative stress and the use of antioxidants during the cultivation of human, murine, and farm animal-derived oocytes and embryos. In conclusion, we highlight the need for further research to develop a personalized approach in the field of medical and veterinary-assisted reproductive technologies. One result of this approach may be an increase in the probability of obtaining a healthy fetus with the minimum number of in vitro fertilization attempts.
Prevalence and Influencing Factors of Irritable Bowel Syndrome Among Nurses in China
Authors: Liu Hongyuan , Chen Jie , Li Xiangning , Pang Juan , Gao Yajun , Gao Juan , Yuan Yuan , Yu Xiaoping , Li Yaoyao , Zhang Yu
Published: July 2024

The aims of this study were to investigate the prevalence and influencing factors of irritable bowel syndrome among nurses in order to update the epidemiological data. A questionnaire survey was administered to 1,325 clinical nurses. We used a questionnaire for demographic information, the IBS Severity Scoring System, the IBS Quality of Life questionnaire, the Hospital Anxiety and Depression Scale, the Pittsburgh Sleep Quality Index, and the Maslach Burnout Inventory to conduct our survey. Univariate and multivariate analyses were performed to detect factors influencing irritable bowel syndrome among nurses. The prevalence of irritable bowel syndrome was 13.3%, and the severity of symptoms was mostly moderate. The IBS Quality of Life score was significantly reduced (p < .001). Various foods that caused abdominal pain (egg and dairy products [OR = 4.80], greasy food [OR = 5.80], spicy food [OR = 2.66], raw and cold food [OR = 2.43]), a family history of gastrointestinal diseases (OR = 1.64, 95% CI [1.038, 2.587]), drinking weak green tea (OR = 1.71, 95% CI [1.143, 2.552]), mild depression (OR = 1.78, 95% CI [1.005, 3.156]), and the personal accomplishment dimension of occupational burnout (OR = 2.52, 95% CI [1.039, 6.114]) had important effects on nurses suffering from irritable bowel syndrome. On the contrary, exercising 1–2 hours per week (OR = 0.53, 95% CI [0.327, 0.859]) had a protective effect. The prevalence of irritable bowel syndrome among nurses is relatively high and may be influenced by several factors including genetics, diet, exercise, psychology, and occupational burnout.
Online Educational Module Improves Knowledge of Nurses on Bowel Preparation for Colonoscopy
Authors: Qureshi Ammar , Vestal Crystal C. , Tanare Marie , Ajumobi Adewale B.
Published: July 2024

The effectiveness of colonoscopy is limited by the adequacy of bowel preparation. Nurses are essential in providing bowel cleansing agents and instructions for hospitalized patients before colonoscopy. This study aims to assess and improve the knowledge of nurses on bowel preparation for inpatient colonoscopy. Participants were asked to complete the survey before and after completing an educational module. The module and survey questions were placed in the NetLearning environment of the hospital intranet. A minimum post-test score of 80% was required to pass the course. A total of 1,107 nurses participated in the survey. Overall, the average score improved from 87% to 93% after the module (p < .0495). Knowledge of the different ways of consuming bowel cleansing agents improved from 54.3% to 83.6% (p = .0001). Only 56.2% of nurses knew how to carry out a split-dose bowel preparation regimen, which increased to 80.1% after the educational module (p = .0001). Nurses’ knowledge about the different ways of consuming bowel cleansing agents before colonoscopy and the split-dose regimen is inadequate. A simple online educational module significantly improved the knowledge of nurses on bowel preparation for colonoscopy.
Incidence of Enteral Nutrition-Related Diarrhea Among Critically Ill Patients in Intensive Care Units
Authors: AlElaimat Manar , Alshraideh Jafar Alasad , Darawad Muhammad W.
Published: July 2024

Enteral nutrition is a common nutritional modality in intensive care units. Despite its valuable benefits, it has many complications among which diarrhea is the most important. However, the incidence of enteral nutrition-related diarrhea is variable in the literature, with no established baseline in Jordan. The aim of this study was to investigate the incidence of enteral nutrition-related diarrhea in intensive care units of a major public hospital in Jordan. A prospective cohort design was adopted over 4 months. Using a consecutive sampling technique, 84 critically ill patients receiving enteral nutrition were recruited. King's Stool Chart was used. The incidence of enteral nutrition-related diarrhea calculated per patient and per feeding day was 63.1% and 13.2%, respectively. Significant positive associations were found between the incidence of diarrhea with feeding days (r = .356, p = .001) and intensive care unit length of stay (r = .254, p = .020). The same was found for the frequency of diarrhea (r = .633, p = .000; r = .439, p = .000, respectively). Conversely, a significant negative association was found between baseline serum albumin and frequency of diarrhea (r = −.250, p = .037). Enteral nutrition-related diarrhea is prevalent in Jordanian intensive care units, but it should not be a barrier to enteral nutrition delivery. It would be beneficial for intensive care unit nurses to improve their nutritional practices by following a nurse-led enteral nutrition protocol to guide the enteral nutrition practices utilizing multidisciplinary approaches.
Disability, Physical Activity, and Their Correlates in Patients With Inflammatory Bowel Disease
Authors: Silva Cândida G. , Santulhão Mariana , Serrado Alícia , Soares Mariana , Morais Nuno
Published: July 2024

Knowledge about disability and physical activity is critical for enhancing self- and clinical management of inflammatory bowel disease, but the interplay between the two is unknown. This study aimed to explore the correlates of disability and physical activity in patients with inflammatory bowel disease. A cross-sectional online survey was conducted in 2019 in Portuguese patients (n = 108) capturing disability, clinical factors including disease status and comorbidities, physical activity habits, and barriers. The magnitude of disability was moderate (mean [95% confidence interval] = 41.85 [38.39, 45.31]). Disease activity and comorbidities were the most important predictors of disability (Model 2, F
(102) = 20.285, p < .001, R
2 = 0.499, R
2
adj = 0.443). About 62% of the participants engaged in moderate (31.5%) to vigorous (30.6%) physical activities. Perceived effort to engage in physical activities was the sole predictor of total weekly physical activity (R
2 = 0.070, R
2
adj = 0.044, p = .006). The amount of disability and physical activity were poorly associated (ρ = −0.144, p = .068). Findings encourage gastroenterology nurses and other healthcare providers involved in the comprehensive care of patients with gastrointestinal disorders to recommend regular physical activity to these patients as part of an overall health enhancement strategy. Disability and back pain should be given further attention.
Continuous Capnography for Early Detection of Respiratory Compromise During Gastroenterological Procedural Sedation and Analgesia
Authors: Tobin Stacey C.
Published: July 2024

Gastroenterology nurses working across a variety of clinical settings are responsible for periprocedural monitoring during moderate to deep procedural sedation and analgesia (PSA) to identify signs of respiratory compromise and intervene to prevent cardiorespiratory events. Pulse oximetry is the standard of care for respiratory monitoring, but it may delay or fail to detect abnormal ventilation during PSA. Continuous capnography, which measures end-tidal CO2 as a marker of alveolar ventilation, has been endorsed by a number of clinical guidelines. Large clinical trials have demonstrated that the addition of continuous capnography to pulse oximetry during PSA for various gastroenterological procedures reduces the incidence of hypoxemia, severe hypoxemia, and apnea. Studies have shown that the cost of adding continuous capnography is offset by the reduction in adverse events and hospital length of stay. In the postanesthesia care unit, continuous capnography is being evaluated for monitoring opioid-induced respiratory depression and to guide artificial airway removal. Studies are also examining the utility of continuous capnography to predict the risk of opioid-induced respiratory depression among patients receiving opioids for primary analgesia. Continuous capnography monitoring has become an essential tool to detect early signs of respiratory compromise in patients receiving PSA during gastroenterological procedures. When combined with pulse oximetry, it can help reduce cardiorespiratory adverse events, improve patient outcomes and safety, and reduce health care costs.
Racial Disparities in Nocturia Persist Regardless of BMI Among American Women
Authors: Napoe Gnankang Sarah , Kermah Dulcie , Mitchell Nia S. , Norris Keith
Published: July 2024

Importance

It is crucial to understand the racial and ethnic disparities that exist in nocturia prevalence to appropriately manage nocturia.

Objectives

Nocturia is associated with increased body mass index (BMI) and is most prevalent in Black and Hispanic women, who also have the highest and second highest prevalence of obesity, respectively. We sought to better understand the association of nocturia with BMI category by race and ethnicity in U.S. women.

Study Design

This was a cross-sectional study using publicly available data from the National Health and Nutrition Examination Survey data from 2005 to 2018. We estimated the prevalence of moderate to severe nocturia (defined as 2 or more episodes of nighttime urination) by BMI category within each racial and ethnic (Black, White, Hispanic, and other) group of adult women. Logistic regression was performed to determine the odds ratio of nocturia by race.

Results

The odds of nocturia was 2.25 (2.04–2.49) for Black women, 1.27 (1.15–1.4) for Hispanic women and 0.96 (0.82–1.13) for other women compared to White women. After accounting for BMI, socioeconomic status and comorbidities, the adjusted odds ratio was 1.76 (1.42–2.16) for Black women, 1.1 (.0.88–1.38) for Hispanic women, and 0.81 (0.5–1.29) for other women compared to White women.

Conclusions

Black women were nearly twice as likely to have nocturia than White women. The increased odds of nocturia, while not sustained for Hispanic women, persisted for Black women regardless of socioeconomic status, BMI, and comorbidities. Our study suggests that there are factors other than weight driving the prevalence of nocturia in Black women that require further investigation.
Implementation of a passive bi-articular ankle–knee exoskeleton during maximal squat jumping
Authors: Wade Logan , Lichtwark Glen , Farris Dominic
Published: July 2024

Owing to the unexplored potential to harness knee extension power during jumping, the current study aimed to examine how joint mechanics were altered with a biologically inspired, passive bi-articular ankle–knee exoskeleton, which could potentially facilitate greater jump height by increasing work production about the knee and ankle. Twenty-five participants (16 males and 9 females, 175.2 ± 8.2 cm, 72.9 ± 10.3 kg, 24.0 ± 3.4 years) performed maximal squat jumping with and without the exoskeletal device and we compared jump height, joint moment and joint work of the lower limbs. Despite a low exoskeleton stiffness and therefore a limited capacity to store energy, the bi-articular device resulted in decreased jump height (1.9 ± 3.1 cm,
p
= 0.006), decreased net work about the knee (0.23 J/kg,
p
< 0.001) and no increase in ankle joint work (
p
= 0.207), compared with jumping with no exoskeleton. Based on our findings, to mimic unassisted ankle joint moment profiles, a future bi-articular device would need increased elastic element slack length, greater stiffness and a larger moment arm about the ankle. Future designs could also employ attachment sites that have minimal overlying soft tissue, such as the pelvis, to improve comfort of the device.
Coat colour in marsupials: genetic variants at the
ASIP
locus determine grey and black fur of the brushtail possum
Authors: Bond Donna M. , Veale Andrew , Alexander Alana , Hore Timothy A.
Published: July 2024

The possession of fur or hair is a defining characteristic of mammals and can occur in a variety of colours and patterns. While genetic determinants of coat colour are well described in eutherian ‘placental’ mammals, the other major mammalian infraclass, marsupials, is grossly understudied. The fur of the common brushtail possum (
Trichosurus vulpecula
), an iconic native mammal found throughout Australia and introduced into Aotearoa New Zealand, possesses two main colour morphs: grey and black. To identify genetic variants associated with coat colour, we performed a genome-wide association study (GWAS) with genotype by sequencing (GBS) data. Single nucleotide variants (SNVs) on chromosome 3, close to the
agouti signalling protein
(
ASIP
) gene that controls the temporal and spatial distribution of pigments in eutherian mammals, were identified. Fine-mapping identified a C>T variant at chr3:100483705 that results in a ASIP:p.Arg115Cys missense substitution, and animals homozygous for this variant have black fur. In addition to uncovering the first genetic determinant of coat colour in a natural marsupial population, comparative analysis of
ASIP
in divergent marsupial species identified the dasyurids as having accelerated evolution, reflecting their well described diversity of coat colour and pattern.
Microbial Primer: What is the stringent response and how does it allow bacteria to survive stress?
Authors: Urwin Lucy , Savva Orestis , Corrigan Rebecca M.
Published: July 2024

The stringent response is a conserved bacterial stress response that allows bacteria to alter their activity and survive under nutrient-limiting conditions. Activation of the stringent response is characterized by the production of intracellular signalling molecules, collectively termed (p)ppGpp, which interact with multiple targets inside bacterial cells. Together, these interactions induce a slow growth phenotype to aid bacterial survival by altering the transcriptomic profile of the cell, inhibiting ribosome biosynthesis and targeting enzymes involved in other key metabolic processes.
Reemergence of Oropouche virus between 2023 and 2024 in Brazil
Authors: Scachetti Gabriel C. , Forato Julia , Claro Ingra M. , Hua Xinyi , Salgado Bárbara B. , Vieira Aline , Simeoni Camila L. , Barbosa Aguyda R. C. , Rosa Italo L. , de Souza Gabriela F. , Fernandes Luana C. N. , de Sena Ana Carla H. , Oliveira Stephanne C. , Singh Carolina M. L. , de Lima Shirlene T. , de Jesus Ronaldo , Costa Mariana A. , Kato Rodrigo B. , Rocha Josilene F. , Santos Leandro C. , Rodrigues Janete T. , Cunha Marielton P. , Sabino Ester C. , Faria Nuno R. , Weaver Scott C. , Romano Camila M. , Lalwani Pritesh , Proença-Módena José Luiz , de Souza William M.
Published: July 2024

Background

Oropouche virus (OROV; speciesOrthobunyavirus oropoucheense) is an arthropod-borne virus that has caused outbreaks of Oropouche fever in Central and South America since the 1950s. This study investigates virological factors contributing to the reemergence of Oropouche fever in Brazil between 2023 and 2024.

Methods

In this study, we combined OROV genomic, molecular, and serological data from Brazil from 1 January 2015 to 29 June 2024, along within vitroandin vivocharacterization. Molecular screening data included 93 patients with febrile illness between January 2023 and February 2024 from the Amazonas State. Genomic data comprised two genomic OROV sequences from patients. Serological data were obtained from neutralizing antibody tests comparing the prototype OROV strain BeAn 19991 and the 2024 epidemic strain. Epidemiological data included aggregated cases reported to the Brazilian Ministry of Health from 1 January 2014 to 29 June 2024.

Findings

In 2024, autochthonous OROV infections were detected in previously non-endemic areas across all five Brazilian regions. Cases were reported in 19 of 27 federal units, with 83.2% (6,895 of 8,284) of infections in Northern Brazil and a nearly 200-fold increase in incidence compared to reported cases over the last decade. We detected OROV RNA in 10.8% (10 of 93) of patients with febrile illness between December 2023 and May 2024 in Amazonas. We demonstrate that the 2023-2024 epidemic was caused by a novel OROV reassortant that replicated approximately 100-fold higher titers in mammalian cells compared to the prototype strain. The 2023-2024 OROV reassortant displayed plaques earlier than the prototype, produced 1.7 times more plaques, and plaque sizes were 2.5 larger compared to the prototype. Furthermore, serum collected in 2016 from previously OROV-infected individuals showed at least a 32-fold reduction in neutralizing capacity against the reassortment strain compared to the prototype.

Interpretation

These findings provide a comprehensive assessment of Oropouche fever in Brazil and contribute to a better understanding of the 2023-2024 OROV reemergence. The recent increased incidence may be related to a higher replication efficiency of a new reassortant virus that also evades previous immunity.
Comprehensive Analysis of Atypical chronic myeloid leukemia (aCML): Epidemiology, Clinical Features, and Survival Outcomes Based on SEER Database Insights
Authors: Wang Fan
Published: July 2024

Background

Atypical Chronic Myeloid Leukemia (aCML) is a rare and aggressive myelodysplastic syndrome/myeloproliferative neoplasm. This study aimed to provide a comprehensive understanding of the epidemiology, clinical characteristics, and survival outcomes of aCML patients.

Methods

The study utilized data from the Surveillance, Epidemiology, and End Results (SEER) database from 2001 to 2020. The age-adjusted incidence rate (AIR) of aCML was calculated, and survival outcomes were analyzed using the Kaplan-Meier method and accelerated failure time (AFT) regression analysis.

Results

The AIR of aCML was found to be 0.024 per 100,000 person-years, with the highest rate observed in 2020. The incidence of aCML increased with age and was higher in males. The study cohort predominantly consisted of elderly White individuals, with an average age at diagnosis of 68.2 ± 15.3 years. The median overall survival (OS) and disease-specific survival (DSS) were 1.4 years and 1.7 years, respectively. Older age was independently associated with worse survival outcomes. Notably, treatment delay and chemotherapy did not significantly impact OS or DSS.

Conclusions

This study provides comprehensive insights into the epidemiology, clinical characteristics, and survival outcomes of aCML, highlighting its rarity, aggressive nature, and poor prognosis. Further research is needed to validate these findings and explore novel therapeutic strategies for improving outcomes in this challenging hematologic malignancy.
Towards Personalized Breast Cancer Risk Management: A Thai Cohort Study on Polygenic Risk Scores
Authors: Nakhonsri Vorthunju , Pithukpakorn Manop , Eu-ahsunthornwattana Jakris , Ngamphiw Chumpol , Wasitthankasem Rujipat , Wilantho Alisa , Wangkumhang Pongsakorn , Boonbangyang Manon , Tongsima Sissades
Published: July 2024

Polygenic Risk Scores (PRS) are now playing an important role in predicting overall risk of breast cancer risk by means of adding contribution factors across independent genetic variants influencing the disease. However, PRS models may work better in some ethnic populations compared to others, thus requiring populaion-specific validation. This study evaluates the performance of 140 previously published PRS models in a Thai population, an underrepresented ethnic group. To rigorously evaluate the performance of 140 breast PRS models, we employed generalized linear models (GLM) combined with a robust evaluation strategy, including Five-fold cross validation and bootstrap analysis in which each model was tested across 1,000 bootstrap iterations to ensure the robustness of our findings and to identify models with consistently strong predictive ability. Among the 140 models evaluated, 38 demonstrated robust predictive ability, identified through > 163 bootstrap iterations (95% CI: 163.88). PGS004688 exhibited the highest performance, achieving an AUROC of 0.5930 (95% CI: 0.5903–0.5957) and a McFadden’s pseudo R2of 0.0146 (95% CI: 0.0139–0.0153). Women in the 90thpercentile of PRS had a 1.83-fold increased risk of breast cancer compared to those within the 30thto 70thpercentiles (95% CI: 1.04–3.18). This study highlights the importance of local validation for PRS models derived from diverse populations, demonstrating their potential for personalized breast cancer risk assessment. Model PGS004688, with its robust performance and significant risk stratification, warrants further investigation for clinical implementation in breast cancer screening and prevention strategies. Our findings emphasize the need for adapting and utilizing PRS in diverse populations to provide more accessible public health solutions.
Detection ofHepatovirus A(HAV) in wastewater indicates widespread national distribution and association with socioeconomic indicators of vulnerability
Authors: Zulli Alessandro , Chan Elana M. G. , Boehm Alexandria B.
Published: July 2024

Wastewater-based epidemiology, which seeks to assess disease occurrence in communities through measurements of infectious disease biomarkers in wastewater, may represent a valuable tool for understanding occurrence of hepatitis A infections in communities. In this study, we measured concentrations ofHepatovirus A(HAV) RNA, in samples from 191 wastewater treatment plants spanning 40 US states and the District of Columbia from September 2023 to June 2024 and compared the measurements with traditional measures of disease occurrence. Nationally, 13.76% of the 21,602 wastewater samples were positive for HAV RNA, and both concentrations and positivity rates were associated with NNDSS hepatitis A case data nationally (Kendall rank correlation coefficient = 0.20, concentrations; and 0.33, positivity rate; both p<0.05). We further demonstrated that higher rates of wastewater HAV detection were positively associated with socioeconomic indicators of vulnerability including homelessness and drug overdose deaths (both p<0.0001). Areas with above average levels of homelessness were 48% more likely to have HAV wastewater detections, while areas with above average levels of drug overdose deaths were 14% more likely to have HAV wastewater detections. Using more granular case data, we present a case study in the state of Maine that reinforces these results and suggests a potential lead time for wastewater over clinical case detection and exposure events. The ability to detect HAV RNA in wastewater before clinical cases emerge could allow public health officials to implement targeted interventions like vaccination campaigns.

Importance

Despite the existence of a highly effective vaccine for Hepatitis A, outbreaks in vulnerable populations remain common. The disease can be asymptomatic or subclinical, and disproportionately impacts populations with inadequate access to healthcare, leading to a severe underestimation of the occurrence of this viral infection. This study investigates the potential for wastewater measurements of biomarkers of the causative agent of hepatitis A (HAV RNA) to provide insights into disease occurrence. Results highlight the potential for wastewater-based epidemiology to be a complementary tool to traditional surveillance for monitoring and controlling HAV transmission.
Time cells emerge early in learning and encode stimulus modality past task requirements
Authors: Bhattacharjee Soumya , Nambisan Hrishikesh , Bhalla Upinder S.
Published: July 2024

Hippocampal neurons represent multiple dimensions of stimulus and behavioural context, including time. It is unclear how soon time-encoding cells emerge during learning, and if they additionally encode context in a manner specific to behavioural paradigm. We investigated simultaneous time and context encoding using 2-photon calcium imaging of mouse hippocampus during a trace eyeblink conditioning (TEC) task with sound and light stimuli. We find that the fraction of time cells is independent of learning and of stimulus modality. Only 13% of cells retain time-encoding on successive days, but persisters remain active within their original stimulus and post-stimulus epochs. Finally, we show that 60% of modality-specific time-encoding cells are active after the stimulus period, but modality-agnostic time cells are rare post-stimulus. Thus, compared to other paradigms, time cells in TEC have distinct learning and turnover properties, and exhibit sustained coding of stimulus modality and time which may subserve associations with subsequent events.
Multivariate, Multi-omic Analysis in 799,429 Individuals Identifies 134 Loci Associated with Somatoform Traits
Authors: Davis Christal N. , Toikumo Sylvanus , Hatoum Alexander S. , Khan Yousef , Pham Benjamin K. , Pakala Shreya R. , Feuer Kyra L. , Gelernter Joel , Sanchez-Roige Sandra , Kember Rachel L. , Kranzler Henry R.
Published: July 2024

Somatoform traits, which manifest as persistent physical symptoms without a clear medical cause, are prevalent and pose challenges to clinical practice. Understanding the genetic basis of these disorders could improve diagnostic and therapeutic approaches. With publicly available summary statistics, we conducted a multivariate genome-wide association study (GWAS) and multi-omic analysis of four somatoform traits—fatigue, irritable bowel syndrome, pain intensity, and health satisfaction—in 799,429 individuals genetically similar to Europeans. Using genomic structural equation modeling, GWAS identified 134 loci significantly associated with a somatoform common factor, including 44 loci not significant in the input GWAS and 8 novel loci for somatoform traits. Gene-property analyses highlighted an enrichment of genes involved in synaptic transmission and enriched gene expression in 12 brain tissues. Six genes, including members of the CD300 family, had putatively causal effects mediated by protein abundance. There was substantial polygenic overlap (76-83%) between the somatoform and externalizing, internalizing, and general psychopathology factors. Somatoform polygenic scores were associated most strongly with obesity, Type 2 diabetes, tobacco use disorder, and mood/anxiety disorders in independent biobanks. Drug repurposing analyses suggested potential therapeutic targets, including MEK inhibitors. Mendelian randomization indicated potentially protective effects of gut microbiota, includingRuminococcus bromii. These biological insights provide promising avenues for treatment development.
Plasma Proteomic Signature of Mucolipidosis Type IV
Authors: Tobin Brendan , Misko Albert , Miller-Browne Victoria , Sangster Madison , Grishchuk Yulia , Wood Levi B.
Published: July 2024

Mucolipidosis IV (MLIV) is an autosomal-recessive pediatric disease that leads to motor and cognitive deficits and loss of vision. It is caused by the loss of function of the lysosomal channel transient receptor potential mucolipin-1, TRPML1, and is associated with an early brain phenotype consisting of glial reactivity, hypomyelination, lysosomal abnormalities, and increased cytokine expression. Although the field is approaching the first translationally relevant therapy, we currently lack a molecular signature of disease that can be used to detect therapeutic efficacy. In the current study, we analyzed 7,322 proteins in the plasma proteome and compare protein profiles with clinical measures of disease severity (motor function, muscle tone, and age). To do so, we used aptamer-based protein profiling on plasma isolated from 18 MLIV patients and 37 aged-matched controls from a biorepository. We identified a total of 1,961 differentially expressed proteins between MLIV and control subjects, with functions spanning many major hallmarks of MLIV. Our analysis revealed a decrease in the abundance of neuronal proteins and an increase in muscle proteins, consistent with the neuronal dysfunction and muscle pathology observed in patients. In particular, lower levels of synaptic proteins (e.g., GABARAP) best correlated with disease severity. Next, we compared the plasma proteome of patients to the brain proteome from the mouse model of MLIV and identified shared alterations in 45 proteins. The up-regulated overlapping proteins were largely related to lysosomal function (e.g., ACTN2, GLB1), while the down-regulated proteins were largely related to myelination (e.g. TPPP3, CNTN2). Both signatures are consistent with our understanding of key disease hallmarks: impaired myelination and modified lysosomal function. Collectively, these data indicate that peripheral blood plasma protein signatures mirror changes found in the MLIV brain and suggest candidate markers relevant to MLIV pathology to be validated in future studies.
Dual exposure-by-polygenic score interactions highlight disparities across social groups in the proportion needed to benefit
Authors: Nagpal Sini , Gibson Greg
Published: July 2024

The transferability of polygenic scores across population groups is a major concern with respect to the equitable clinical implementation of genomic medicine. Since genetic associations are identified relative to the population mean, inevitably differences in disease or trait prevalence among social strata influence the relationship between PGS and risk. Here we quantify the magnitude of PGS-by-Exposure (PGSxE) interactions for seven human diseases (coronary artery disease, type 2 diabetes, obesity thresholded to body mass index and to waist-to-hip ratio, inflammatory bowel disease, chronic kidney disease, and asthma) and pairs of 75 exposures in the White-British subset of the UK Biobank study (n=408,801). Across 24,198 PGSxE models, 746 (3.1%) were significant by two criteria, at least three-fold more than expected by chance under each criterion. Predictive accuracy is significantly improved in the high-risk exposures and by including interaction terms with effects as large as those documented for low transferability of PGS across ancestries. The predominant mechanism for PGS×E interactions is shown to be amplification of genetic effects in the presence of adverse exposures such as low polyunsaturated fatty acids, mediators of obesity, and social determinants of ill health. We introduce the notion of the proportion needed to benefit (PNB) which is the cumulative number needed to treat across the range of the PGS and show that typically this is halved in the 70thto 80thpercentile. These findings emphasize how individuals experiencing adverse exposures stand to preferentially benefit from interventions that may reduce risk, and highlight the need for more comprehensive sampling across socioeconomic groups in the performance of genome-wide association studies.
Genetic Overlap Between Inflammatory Bowel Disease and Neurological Disorders: Insights from GWAS and Gene Expression Analysis
Authors: Tripathi Utkarsh , Stern Yam , Dagan Inbal , Nayak Ritu , Romanovsky Eva , Zittan Eran , Stern Shani
Published: July 2024

Inflammatory Bowel Disease (IBD), which includes Crohn’s disease (CD) and Ulcerative Colitis (UC), is a complex and multifactorial condition marked by chronic inflammation of the gastrointestinal tract. This study leverages genome-wide association studies (GWAS) and gene expression data from the Genotype-Tissue Expression (GTEx) project to investigate IBD’s genetic and expression profiles and subtypes. We examined 207 studies related to IBD, 71 specific to CD, and 66 focused on UC, identifying both shared and unique genetic factors among these conditions. GWAS meta-analysis revealed the top IBD-associated genes, which include IL23R, NOD2, ATG16L1, HLA-DRB9, and more. Pathway enrichment analyses identified consistently enriched pathways such as the NF-kappa B signaling pathway, JAK-STAT signaling pathway, and cytokine-cytokine receptor interaction, all of which play critical roles in immune responses and inflammation. Gene Ontology (GO) term analysis highlighted processes like cytokine production, cell activation, and leukocyte activation, reinforcing their involvement in the pathogenesis of IBD. Gene expression analysis showed that genes associated with IBD are expressed not only in the gastrointestinal tract but also in various regions of the brain, suggesting potential links between IBD and neurological functions. Our study further explored the genetic overlap between IBD and several neurological disorders, including schizophrenia, depression, autism spectrum disorder, and attention-deficit/hyperactivity disorder, uncovering a shared genetic architecture. These findings emphasize the systemic nature of IBD and its potential neurological implications, paving the way for targeted therapeutic strategies that address both gastrointestinal and neurological aspects of the disease.
Baseline correlation between pain, range of motion, disability, and health-related quality of life variables in subjects with frozen shoulder: A cross-sectional study
Authors: Poser A , Brindisino F , Feller D , Venturin D
Published: July 2024

Frozen shoulder (FS) is a debilitating condition affecting the glenohumeral joint. As FS frequently manifests as a chronic condition, it intensifies pain and leads to disability and to a deterioration in overall quality of life, affecting physical, behavioral, mental, and social dimensions.

While the impact of pain on disability is widely acknowledged, recent literature highlights a growing body of evidence indicating the correlation between pain and health-related, social, and mental distress and unfavorable outcomes in patients with FS.

Up to day, the need for pain to be avoided or alleviated as much as possible has been challenged, with a paradigm shift from traditional biomedical models of pain towards a biopsychosocial model of pain disorders. Research has further shown that psychological factors might affect the function and quality of life in patients with pain and can modulate the individuals’ pain experience and therefore may play a role in the development and/or maintenance of chronic pain states.

As the current healthcare pathway for subjects suffering from FS often inadequately addresses these healthcare needs, and professionals tend to predominantly concentrate on biological and clinical symptoms, theaimof this study will be to explore correlations among Patient-Reported Outcome Measures (PROMs) for pain, and disability, health-related domains, and ROM measurements in individuals with FS during their initial physiotherapy consultation
Cost-effectiveness of the Strategies for Surveillance of Antimicrobial-resistant Gonorrhea in the US: a Modelling Study
Authors: Prakhova Sofya
Published: July 2024

Background

The Gonococcal Isolate Surveillance Project (GISP) is a sentinel surveillance system to monitor the spread of antimicrobial-resistant (AMR) gonorrhea. Under GISP surveillance strategy, urethral isolates are utilized for monitoring the spread of the resistance and the obtained estimates are used for informing the gonorrhea treatment guidelines. In 2017, the enhanced Gonococcal Isolate Surveillance Project (eGISP) was established which also includes the non-urethral isolates. Using eGISP estimates for informing the gonorrhea treatment guidelines is an alternative surveillance strategy that can be used.

Methods

We utilized our previously developed continuous-time agent-based model of gonorrhea transmission among the US men who have sex with men (MSM) population and calculated the total number of discounted quality-adjusted life years (QALYs) and total discounted costs over 25 years under GISP and eGISP surveillance strategy. We also evaluated cost-effectiveness of both surveillance strategies.

Results

Under GISP surveillance strategy, $2.9M (95% uncertainty interval: $23,131, $9.4M) were saved and 31.3 (0, 134.9) QALYs were gained in the simulated cohort of 10,000 US MSM over 25 years compared to no surveillance. Performing eGISP surveillance strategy instead would result in additional $57,449 (−$100,914, $221,663) saved and 0.59 (−0.79, 2.5) QALYs gained.

Conclusion

The current GISP surveillance strategy significantly reduces the costs and increases the health benefits compared to no surveillance. However, switching from the current strategy to eGISP strategy is cost saving and should be considered in order to improve the population health and reduce the financial burden of gonorrhea.
Hot Spring Residency and Disease Association: a Crossover Gene-Environment Interaction (GxE) Study in Taiwan
Authors: Wu Hsin-Yu , Chang Kao-Jung , Chiu Wei , Wang Ching-Yun , Hsu Yu-Tien , Wen Yuan-Chih , Chiang Pin-Hsuan , Chen Yu-Hsiang , Dai He-Jhen , Lu Chia-Hsin , Chen Yi-Cheng , Tsai Han-Ying , Chen Yu-Chun , Hsu Chih-Hung , Hsieh Ai-Ru , Chiou Shih-Hwa , Yang Yi-Ping , Hsu Chih-Chien
Published: July 2024

Background

The advent of genetic biobanking has powered gene-environment interaction (GxE) studies in various disease contexts. Therefore, we aimed to discover novel GxE effects that address hot spring residency as a risk to inconspicuous disease association.

Methods

A complete genetic and demographic registry comprising 129,451 individuals was obtained from Taiwan Biobank (TWB). Geographical disease prevalence was analyzed to identify putative disease association with hot-spring residency, multivariable regression and logistic regression were rechecked to exclude socioeconomic confounders in geographical-disease association. Genome-wide association study (GWAS), gene ontology (GO), and protein-protein interaction (PPI) analysis identified predisposing genetic factors among hotspring-associated diseases. Lastly, a polygenic risk score (PRS) model was formulated to stratify environmental susceptibility in accord to their genetic predisposition.

Results

After socioeconomic covariate adjustment, prevalence of dry eye disease (DED) and valvular heart disease (VHD) was significantly associated with hot spring distribution. Through single nucleotide polymorphisms (SNPs) discovery and subsequent PPI pathway aggregation, CDKL2 and BMPR2 kinase pathways were significantly enriched in hot-spring specific DED and VHD functional SNPs. Notably, PRS predicted disease well in hot spring regions (PRSDED: AUC=0.9168; PRSVHDAUC=0.8163). Hot spring and discovered SNPs contributed to crossover GxE effect on both DED (relative risk (RR)G+E-=0.99; RRG+E+=0.35; RRG+E+=2.04) and VHD (RRG+E-=0.99; RRG+E+=0.49; RRG+E+=2.01).

Conclusion

We identified hot-spring exposure as a modifiable risk in the PRS predicted GxE context of DED and VHD.

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