bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Non-ablative Medical Therapy on Progression of Hearing Loss in Menière's Disease: A Systematic Review and meta-Analysis
Authors: Thompson-Harvey Adam , Pyle Madeline , Harvey Erin , Harris Michael S.
Published: July 2024

Objective

To systematically review how audiometric data change over time in patients with Menière's disease (MD) undergoing non-ablative medical therapy.

Databases Reviewed

Medline (via PubMed), Scopus, Web of Science, Cumulated Index to Nursing and Allied Health Literature (CINAHL), Google Scholar.

Methods

A systematic review and meta-analysis of the literature was performed. Adult patients undergoing non-ablative medical therapy and reported duration of disease or follow-up were included and pooled estimates of pure-tone average (PTA) were tabulated. Studies were excluded if they did not use established MD, did not have pure-tone average (PTA) audiometric data, underwent ear surgery or ablative therapies, and were systematic reviews or case reports.

Results

Out of 198 articles meeting full eligibility, 13 studies, involving 950 patients with MD, were included in the review and further analyzed. No effect on progression of PTA from initial diagnosis was seen between the different medical therapies within 2 years of non-ablative medical treatment. There was a significant worsening of PTA after 2 year, regardless of treatment used. High levels of heterogeneity among studies were noted up to 6 months from diagnosis (I
2 = 79%), likely reflecting differences in patient characteristics, treatment regimens, and study design. Overall, the risk of bias was low for the majority of included studies.

Conclusions

Patients diagnosed with MD who are undergoing non-ablative medical therapy should be counseled on the likelihood of worsening of hearing loss over the course of the disease despite elected treatment.
Smart solutions in hypertension diagnosis and management: a deep dive into artificial intelligence and modern wearables for blood pressure monitoring
Authors: Juyal Anubhuti , Bisht Shradha , Singh Mamta F.
Published: July 2024

Hypertension, a widespread cardiovascular issue, presents a major global health challenge. Traditional diagnosis and treatment methods involve periodic blood pressure monitoring and prescribing antihypertensive drugs. Smart technology integration in healthcare offers promising results in optimizing the diagnosis and treatment of various conditions. We investigate its role in improving hypertension diagnosis and treatment effectiveness using machine learning algorithms for early and accurate detection. Intelligent models trained on diverse datasets (encompassing physiological parameters, lifestyle factors, and genetic information) to detect subtle hypertension risk patterns. Adaptive algorithms analyze patient-specific data, optimizing treatment plans based on medication responses and lifestyle habits. This personalized approach ensures effective, minimally invasive interventions tailored to each patient. Wearables and smart sensors provide real-time health insights for proactive treatment adjustments and early complication detection.
Novel and complementary treatment approaches in attention-deficit/hyperactivity disorder
Authors: Caterfino Andrew , Krishna Shruthi , Chen Victoria
Published: July 2024

Purpose of review

To provide an updated review of novel and complementary treatment approaches for children and adolescents with attention-deficit/hyperactivity disorder.

Recent findings

The evidence for complementary attention-deficit/hyperactivity disorder treatments is often promising, but limited to small, unblinded studies. Recent evidence from larger, more rigorous studies reveals that most of these treatments have modest efficacy. Omega-3 polyunsaturated fatty acids, saffron, broad spectrum micronutrients, and physical exercise have potential benefits that seem to outweigh known risks. However, neurofeedback, cognitive training, and trigeminal nerve stimulation need further research to determine whether specific sub-groups of children/adolescents with attention-deficit/hyperactivity disorder would benefit long-term with their associated tolerable risks.

There is not sufficient evidence for complementary treatments to be recommended as substitutes for first-line pharmacological and psychosocial treatment options. Nonetheless, some adjuvant therapies to currently recommended attention-deficit/hyperactivity disorder treatments can be safe. Physicians should be familiar with existing and emerging complementary treatments to help guide families.
The Influence of the Extracorporeal Membrane Oxygenation Circuit and Components on Anticoagulation Management: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation CollaborativE Consensus Conference
Authors: Himebauch Adam S. , Priest John R. , Annich Gail M. , McMullan D. Michael , Turner David A. , Muszynski Jennifer A. , Alexander Peta M.A. , Paden Matthew L. , Gehred Alison , Lyman Elizabeth , Said Ahmed S. ,   for the Pediatric Extracorporeal Membrane Oxygenation (ECMO) Anticoagulation CollaborativE (PEACE), in collaboration with the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network, the Pediatric Critical Care Blood Research Network (BloodNet), and the Pediatric ECMO subgroup of PALISI and the Extracorporeal Life Support Organization (PediECMO)
Published: July 2024

OBJECTIVES:

To derive systematic-review informed, modified Delphi consensus regarding the influence of extracorporeal membrane oxygenation (ECMO) circuit components on anticoagulation practices for pediatric ECMO for the Pediatric ECMO Anticoagulation CollaborativE.

DATA SOURCES:

A structured literature search was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021.

STUDY SELECTION:

Management of ECMO anticoagulation in the setting of different ECMO circuit components.

DATA EXTRACTION:

Two authors reviewed all citations independently, with a third independent reviewer resolving conflicts. Twenty-nine references were used for data extraction and informed recommendations, evidence-based consensus statements, and good practice statements. Evidence tables were constructed using a standardized data extraction form.

DATA SYNTHESIS:

Risk of bias was assessed using the Quality in Prognosis Studies tool. The evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation system. Forty-eight experts met over 2 years to develop evidence-based recommendations and, when evidence was lacking, expert-based consensus statements or good practice statements for the influence of ECMO circuit and components on anticoagulation management. A web-based modified Delphi process was used to build consensus via the Research And Development/University of California Appropriateness Method. Consensus was defined as greater than 80% agreement. One good practice statement, 2 weak recommendations, and 2 consensus statements are presented.

CONCLUSIONS:

The incorporation of new component technologies into clinical practice has outpaced clinical investigations of anticoagulation strategies for pediatric ECMO. Future investigations should leverage academic and industrial collaborations, translational platforms, and modern biostatistical methods to improve patient outcomes.
Mixed Gestational Trophoblastic Tumors—Challenging Clinicopathological Presentations
Authors: Niu Na , Buza Natalia , Hui Pei
Published: July 2024

Mixed gestational trophoblastic tumors are exceptionally rare and have variable clinicopathological presentations. We report 3 such tumors with different combinations of choriocarcinoma (CC), placental site trophoblastic tumor (PSTT), and epithelioid trophoblastic tumor (ETT). The patients’ age ranged from 38 to 44 years. Mixed trophoblastic tumor was not considered at the initial diagnosis and all 3 tumors were proven of gestational origin by DNA genotyping. Patient #1 presented with serum human chorionic gonadotropin (hCG) of 97 mIU/mL and a 5.6-cm cervical mass that was initially interpreted as PSTT on biopsy. Hysterectomy revealed a mixed PSTT (60%) and ETT (40%) with extrauterine metastases of only the ETT component. The tumor recurred 15 months after a multiagent chemotherapy and was tested positive for programmed death-ligand 1. The patient received immune checkpoint inhibitor therapy and remained disease-free after 24 months. Patient #2 presented with vaginal bleeding and serum hCG of 46,458 mIU/mL. An endometrial biopsy was interpreted as CC. Recurrence developed in the uterus and lung after methotrexate-based chemotherapy. A mixed CC and ETT were eventually diagnosed upon consultation review. Patient #3 presented with a complete hydatidiform mole and serum hCG of 744,828 mIU/mL. Three months after methotrexate, followed by actinomycin D therapy, a uterine mass was found. Hysterectomy revealed a mixed CC and PSTT. In conclusion, the rarity, elusive presentation, and wide range of histology make the diagnosis of mixed trophoblastic tumors highly challenging. The clinical management and prognosis are dictated by each component of the tumor. CC component must be considered when the patient presents with a high serum hCG level.
Prevalence of Occult Ovarian Cancer and Metastatic Breast Cancer in Ovarian Ablation Specimens of Patients With Hormone Receptor-Positive Breast Cancer: Implications for Tissue Sampling Strategies, Early Ovarian Cancer Detection and Resource Utilization
Authors: Walia Anjali , Ladwig Nicholas R. , Mak Julie S. , Rabban Joseph T.
Published: July 2024

Bilateral oophorectomy is one method of hormone suppression for premenopausal patients with hormone receptor-positive breast cancer. Such specimens could, in theory, harbor occult early ovarian cancer and/or metastatic breast cancer but guidelines for tissue sampling for pathologic examination remain to be addressed. Therefore, we evaluated oophorectomy specimens from 166 patients who underwent ovarian ablation for hormone receptor-positive breast cancer. Results of germline genetic testing were documented by the surgeon in only 31.3% of the pathology specimen requisition forms, whereas that information was available for 81.3% of patients elsewhere in the electronic medical records. All but 5.2% tested negative for a hereditary ovarian cancer gene pathogenic variant before oophorectomy. Complete tissue sampling was performed in 77.1% of the cases and representative sampling in the remainder. No cases of ovarian cancer were observed. Ovarian metastasis of breast cancer was identified in 9.6% of patients, all of whom were already known to have advanced-stage disease. The number of tissue cassettes per ovary required for complete tissue submission was on average three times higher than that for representative tissue sampling (P < 0.01) and ranged up to 20 cassettes per ovary when multiple follicle cysts were present. We propose that guidelines for tissue sampling in this context be defined by a combination of hereditary risk and macroscopic examination; representative sampling is reasonable for macroscopically normal ovaries in hormone receptor-positive breast cancer patients whose germline genetic testing is negative. Positive genetic test results merit complete tissue submission even if macroscopically normal. This strategy balances the goals of early ovarian cancer detection and optimal resource utilization. However, it depends on clear documentation of genetic test results. Our study demonstrates that many opportunities remain to close gaps in the communication of genetic test results by clinicians submitting oophorectomy specimens for pathologic evaluation.
Assessing the impact of a 2-day online workshop on spasticity
Authors: Antoniadou Eleftheria , Lakoumentas John , Dy Roselle , Tyllianakis Minos , Esquenazi Alberto
Published: July 2024

Background:

Οnline education has become widespread, but there has been little evaluation of its impact in terms of knowledge gain and acceptance. This article presents an assessment of a webinar on spasticity and botulinum toxin injection. The seminar aimed at health professionals working with patients with spasticity

Methods/Results:

It was conducted for 2 days; on the first day, a thorough analysis of spasticity was performed, whereas the second day focused on treatment, particularly botulinum toxin injections. The evaluation was performed using 2 questionnaires: the first rated the knowledge gain (questions prepared from the expert panel; evaluation was performed before the beginning and after the completion, plus a clinical case to justify the treatment), and the second rated acceptance (with a 5-point Likert scale. The results showed significant improvement (P < 0.001) in knowledge gain and positive acceptance by the participants (from max 100% to a min 69.81% agreement).

Conclusions:

An online workshop on spasticity management is not only acceptable but also has a positive impact on knowledge.
Effect of the Athletes’ Origin and Type of Impairment on Participation and the Likelihood of Winning a Medal in the Paralympic Games
Authors: Severin Anna Cecilia , Kinderen Annemarie , Baumgart Julia Kathrin
Published: July 2024

Objective

This study investigated whether the origin (acquired or congenital) and type of impairment affect the participation and likelihood of winning a medal in different sports at the Paralympic Games.

Design

We analyzed competition data and athlete biographies web scraped from the International Paralympic Committee’s website (www.Paralympic.org)

Results

In some sports, athletes with one origin or type of impairment were overrepresented. For example, 76% of Para-snowboarders had an acquired impairment. Furthermore, mixed effects logistic regression analyses showed that the origin of impairment had no effect on the likelihood of winning a medal in most sports. However, athletes with a congenital impairment had a significantly higher likelihood of winning a medal compared to those with an acquired impairment in Para-athletics, Para-alpine skiing, and Para-biathlon (odds ratio: 1.71, P < 0.01, odds ratio: 3.69, P = 0.002, and odds ratio: 3.70, P = 0.016, respectively). Athletes with a given origin-type of impairment combination also may have an advantage or disadvantage in some sports. For example, athletes with an acquired spinal cord injury win proportionally fewer medals in Para-powerlifting.

Conclusions

Understanding potential effects of the origin and type of impairment on participation and medaling chances in Paralympic sports can help shape the development of Para-sports and support talent identification.
Comparative Effectiveness of Exercise on Cardiorespiratory Function or Exercise Efficiency After Stroke
Authors: Zha Fubing , Wen Qiong , Zhou Mingchao , Shan Linlin , Wang Yulong
Published: July 2024

Objective

The network meta-analysis was to compare and rank the effectiveness of different exercises on cardiorespiratory function or exercise efficiency in poststroke patients.

Design

A network meta-analysis of randomized controlled trials was conducted. PubMed, Embase, Cochrane Library, and Web of Science were searched. The impact of exercises including individual and combination of aerobic exercise, resistance exercise, task-oriented training, gait training, breathing exercise, and regular rehabilitation training on 6-min walk test, peak oxygen consumption, maximum oxygen consumption, resting heart rate, resting systolic blood pressure, and resting diastolic blood pressure were assessed.

Results

In total, 36 studies were included in the meta-analysis. Aerobic exercise + GT (63.06%) had the highest likelihood of improving 6-min walk test performance in poststroke patients. Regular rehabilitation training + resistance exercise was the most favorable exercise in terms of 6-min walk test performance assessing by minimum clinically significant difference. Aerobic exercise + resistance exercise had the highest likelihood of improving peak oxygen consumption and reducing resting heart rate in poststroke patients.

Conclusion

Different types of exercise demonstrated the benefits of improving cardiorespiratory function in stroke patients. Further research is needed to determine the best exercise regimen to maximize the benefits of rehabilitation interventions for poststroke patients.
Prevalence of Self-reported COVID-19 Infection in Persons With Complicated Mild to Severe Traumatic Brain Injury
Authors: Pinto Shanti M. , Adams Leah M. , Chavez Audrie , Perrin Paul B. , Watanabe Thomas K. , Golden Katherine , Sterling Ally , Hoffman Jeanne M. , Daneshvar Daniel H. , Rabinowitz Amanda , Callender Librada , Hammond Flora M.
Published: July 2024

Objectives

The aims of the study are to describe the incidence of self-reported COVID-19 history in a longitudinal cohort of individuals with complicated mild to severe traumatic brain injury and describe demographic, injury, and functional differences based on history of COVID-19 infection.

Design

Individuals with complicated mild to severe traumatic brain injury aged 16 or older at time of injury who were enrolled in the Traumatic Brain Injury Model Systems longitudinal cohort study, completed a baseline or follow-up interview between October 1, 2021–March 31, 2023, and provided information about COVID-19 history and timing of COVID-19 infection was collected.

Results

Of the 3627 individuals included in the analysis, 29.5% reported a history of COVID-19 infection. Those with reported COVID-19 history tended to be younger, not of a racial/ethnic minority background, and greater functional status at follow-up based on the Glasgow Outcome Scale-Extended Scale compared with those with no reported COVID-19 history (P < 0.05). Among those with COVID-19 history, 61.8% did not receive medical care, 27.6% received medical care but no hospitalization, and 10.5% were hospitalized. Of those hospitalized, 21.4% required ventilator use.

Conclusions

Incidence of COVID-19 diagnosis and related hospitalization characteristics in persons with complicated mild to severe traumatic brain injury was similar to national incidence between March 2020–2023. Secondary effects of the COVID-19 pandemic on persons with traumatic brain injury require investigation.
Feasibility of a Neurorehabilitation Pipeline and an Automated Algorithm to Select Appropriate Treatments for Upper Extremity Motor Paralysis in Individuals With Chronic Stroke
Authors: Kuwahara Wataru , Kawakami Michiyuki , Okawada Megumi , Tanamachi Kenya , Sasaki Shun , Kamimoto Takayuki , Yamada Yuka , Tsuji Tetsuya , Kaneko Fuminari
Published: July 2024

Objective

This study aimed to investigate the feasibility of a neurorehabilitation pipeline and develop an algorithm to automatically select the appropriate treatment for individuals with upper extremity motor paralysis after stroke in the chronic phase.

Design

In experiment 1, eight post-stroke participants in the chronic phase who underwent treatment sustaining two to three phases were assessed before and after treatment. In experiment 2, a decision tree analysis was performed in which the dependent variable was set as the treatment option determined by a board-certified physiatrist for 95 poststroke participants; the independent variables were only motor function scores or both motor function scores and electromyogram variables.

Results

In experiment 1, the clinical assessment scores were improved significantly after treatment. Experiment 2 showed that the agreements of the model with only motor function scores as the independent variable and with motor function scores and electromyogram variables as the independent variables were 75.8% and 82.1%, respectively.

Conclusions

This novel treatment package is feasible for improvement of motor function in poststroke individuals with severe motor paralysis. The study also established an automated algorithm for selecting appropriate treatments for upper extremity motor paralysis after stroke, identifying standard values of key variables, including electromyography variables.
Trends in Operative Case Logs of Chief Residents in Surgery by Sex and Race
Authors: Zmijewski Polina , Park Yoon Soo , Hogan Sean , Holmboe Eric , Klingensmith Mary , Cortez Alexander , Lindeman Brenessa , Chen Herbert , Smith Brigitte , Fazendin Jessica
Published: July 2024

Objective:

To examine case logs reported by general surgery residents and identify potential disparities in operative experience.

Background:

A recent study of 21 institutions noted significant differences between the number of cases reported during general surgery residency by trainees who are underrepresented in medicine (URiM) versus trainees who are not URiM (non-URiM). This study also identified differences between female residents and male residents. We partnered with the Accreditation Council for Graduate Medical Education to examine case logs reported from all accredited general surgery programs in the United States. This is the first time these data have been examined nationally.

Methods:

We examined total case logs submitted by graduating residents between 2017 and 2022. Group differences in mean reported case logs were examined using paired t tests for female versus male and URiM versus non-URiM overall case numbers.

Results:

A total of 6458 residents submitted case logs from 319 accredited programs. Eight-hundred fifty-four (13%) were URiM and 5604 (87%) were non-URiM. Over the 5-year study period, URM residents submitted 1096.95 (SD ± 160.57) major cases versus 1115.96 (±160.53) for non-URiM residents (difference = 19 cases, P = 0.001). Case logs were submitted by 3833 (60.1%) male residents and 2625 (39.9%) female residents over the 5-year study period. Male residents reported 1128.56 (SD ± 168.32) cases versus 1091.38 (±145.98) cases reported by females (difference = 37.18, P < 0.001). When looking at surgeon chief and teaching assistant cases, there was no significant difference noted between cases submitted by URiM versus non- URiM residents. However, male residents reported significantly more in both categories than their female peers (P < 0.001).

Conclusions:

Overall, URiM residents submitted fewer cases in the 5-year study period than their non-URiM peers. The gap in submitted cases between male and female residents was more pronounced, with male residents submitting significantly more cases than their female counterparts. This finding was consistent and statistically significant throughout the entire study period, in most case categories, and without narrowing of difference over time. A difference of 30 to 40 cases can amount to 1 to 3 months of surgical training and is a concerning national trend deserving the attention of every training program and our governing institutions.
Wild yeast isolation by middle school students reveals features of North American oak populations ofSaccharomyces cerevisiaeandKluyveromyces lactis
Authors: Yeager Randi , Heasley Lydia , Baker Nolan , Shrivastava Vatsal , Woodman Julie , McMurray Michael
Published: July 2024

Features of the natural life cycle of the budding yeastSaccharomyces cerevisiaewere crucial to its domestication as a laboratory experimental model, especially the ability to maintain stable haploid clones and cross them at will to combine alleles via meiosis. Stable haploidy results from mutations inHO, which encodes an endonuclease required for haploid-specific mating-type switching. Previous studies found an unexpected diversity ofHOalleles among natural isolates within a small geographic area. We developed a hands-on field and laboratory activity for middle school students in Denver, Colorado, USA to isolate wild yeast from oak bark, identify species via DNA sequencing, and sequenceHOfromS. cerevisiaeisolates. We find limitedHOdiversity in North American oak isolates, pointing to efficient, continuous dispersal across the continent. By contrast, we isolated the “dairy yeast”,Kluyveromyces lactis, from a tree <10 m away and found that it represents a new population distinct from an oak population in an adjacent state, pointing to high genetic diversity. The outreach activity partnered middle school, high school, and university students in making scientific discoveries and can be adapted to other locations and natural yeast habitats. Indeed, a pilot sampling activity in southeast Texas yieldedS. cerevisiaeoak isolates with a new allele ofHOand, from a nearby prickly pear cactus, a heat-tolerant isolate ofSaccharomyces paradoxus.
Integrin-deficient T cell leukemia accumulates in the central nervous system
Authors: Lux Samantha Y. , Chen Cynthia , Subhan Bibi S. , Okuniewska Martyna , Chung Hyunsoo , Vernejoul Jonah B. , Martin Kathleen A. , Caslin Asha Y. , Schiavo Jennifer K. , Froemke Robert C. , Cammer Michael , Schwab Susan R.
Published: July 2024

T cell acute lymphoblastic leukemia (T-ALL), a devastating childhood cancer, rapidly invades the central nervous system (CNS) and localizes to the meninges. T-ALL is aggressively treated with high-dose, CNS-directed chemotherapy; this regime results in lasting neurotoxicity and in some cases ultimately fails to protect from meningeal relapse. The paucity of knowledge about T-ALL entry and persistence in the CNS has limited the development of targeted therapies for decades. Here, we addressed whether VLA-4 and LFA-1, two integrins that mediate normal T cell entry to the CNS and that have been successfully targeted in patients for treatment of autoimmune disease, were similarly required in T-ALL. In the process, we uncovered an entirely unexpected role for these integrins in CNS disease. Not only were these integrins dispensable for T-ALL to reach the CNS, integrin-deficient T-ALL accumulated in the CNS compared to control T-ALL. Mechanistically, loss of integrins accelerated T-ALL proliferation in the CNS, suggesting that integrin-mediated interactions may promote quiescence in this space and highlighting the importance of niche-specific regulation of disease. Integrin blockade strongly synergized with anti-proliferative chemotherapy to treat CNS disease, indicating that combination therapy might be a powerful therapeutic strategy.
Modeling Mountain Pine Beetle Abundance and Distribution in a Changing Climate
Authors: Xie Xiaoqi , Brush Micah , Lewis Mark A.
Published: July 2024

The range of mountain pine beetle (Dendroctonus ponderosaeHopkins) is primarily constrained by climate, with winter temperatures playing a crucial role. Climate change is likely to increase the number of warm days and decrease cold days compared to historical norms, making higher latitudes more suitable habitats. In this work, we explore the potential impacts of environmental covariates on outbreaks of mountain pine beetle under climate change in a selected lodgepole pine area in Alberta. We employ a hierarchical model to examine mountain pine beetle dynamics approaching the end of the century. Our analysis assesses the impact of various climatic covariates and estimates the probability and expected number of infestations across different climate change scenarios. Our results from the hierarchical model underscore the critical role of degree days and overwinter survival probability, displaying an overall trend towards a higher probability and a greater number of outbreaks with increasing temperature. Our results indicate that Alberta is likely to experience widespread infestations in the future.
Dynamic Localization of Leukemia Stem Cells via CXCL12 Regulates Leukemia Progression
Authors: Wang Chen , Pan Yi , Dong Ruochen , Zhou WenXuan , Meng XiaDuo , Shi Yao , Nistala Ravi , Hammer Richard D. , Li Linheng , Kang XunLei
Published: July 2024

The processes that govern leukemia progression and remission are poorly understood. Our research reveals that the CXCL12 gradient, traditionally associated with LSC quiescence and survival, critically determines LSC localization and associated behavior. Specifically, CXCL12 guides LSCs to either the quiescent niche in the metaphysis, characterized by N-cadherin-expressing mesenchymal stromal cells (N-cad+MSCs), or the proliferative niche in the central marrow (CM), marked by sinusoidal endothelial cells and associated stromal cells. We identified that the CXCL12 gradient is finely regulated by the interplay between dipeptidyl peptidase 4 (DPP4) on LSCs and glypican-3 (GPC3) on N-cad+MSCs. DPP4 deactivates CXCL12, while GPC3 inhibits DPP4, resulting in a higher CXCL12 concentration in the metaphysis and a lower concentration in the CM. This differential gradient facilitates leukemia progression by promoting LSC quiescence and survival in the metaphysis versus relative proliferation and apoptosis in the CM. Depletion ofDpp4from LSCs orCxcl12from N-cad+MSCs disrupts this gradient, mobilizing LSCs from the metaphysis to the CM and significantly hindering leukemia development. Our findings redefine the role of CXCL12 in LSC behavior and provide a clearer understanding of leukemia progression. This novel insight highlights the potential for targeted therapeutic strategies that disrupt the CXCL12 gradient to treat minimal residual LSCs, offering a promising path toward a lasting cure for acute myeloid leukemia (AML).
Evolution into chaos – implications of the trade-off between transmissibility and immune evasion
Authors: Sayyar Golsa , Garab Ábel , Röst Gergely
Published: July 2024

Predicting viral evolution presents a significant challenge and is a critical public health priority. In response to this challenge, we develop a novel model for viral evolution that considers a trade-off between immunity evasion and transmissibility. The model selects for a new strain with the highest invasion fitness, taking into account this trade-off. When the dominant strain of the pathogen is highly transmissible, evolution tends to favor immune evasion, whereas for less contagious strains the direction of evolution leads toward increasing transmissibility. Assuming a linear functional form of this trade-off, we can express the long-term evolutionary patterns following the emergence of subsequent strains by a non-linear difference equation. We provide sufficient criteria for when evolution converges, and successive strains exhibit similar transmissibility. We also identify scenarios characterized by a two-periodic pattern in upcoming strains, indicating a situation where a highly transmissible but not immune-evasive strain is replaced by a less transmissible but highly immune-evasive strain, and vice versa, creating a cyclic pattern. Finally, we show that under certain conditions, viral evolution becomes chaotic and thus future transmissibilites become unpredictable in the long run. Visualization via bifurcation diagrams elucidates our analytical findings, revealing complex dynamic behaviors that include the presence of multiple periodic solutions and extend to chaotic regimes. Our analysis provides valuable insights into the complexities of viral evolution in the light of the trade-off between immune evasion and transmissibility.
SPACEc: A Streamlined, Interactive Python Workflow for Multiplexed Image Processing and Analysis
Authors: Tan Yuqi , Kempchen Tim N. , Becker Martin , Haist Maximilian , Feyaerts Dorien , Xiao Yang , Su Graham , Rech Andrew J. , Fan Rong , Hickey John W. , Nolan Garry P.
Published: July 2024

Multiplexed imaging technologies provide insights into complex tissue architectures. However, challenges arise due to software fragmentation with cumbersome data handoffs, inefficiencies in processing large images (8 to 40 gigabytes per image), and limited spatial analysis capabilities. To efficiently analyze multiplexed imaging data, we developed SPACEc, a scalable end-to-end Python solution, that handles image extraction, cell segmentation, and data preprocessing and incorporates machine-learning-enabled, multi-scaled, spatial analysis, operated through a user-friendly and interactive interface.
Attention-based frontal-posterior coupling for visual consciousness in the human brain
Authors: Zhang Xilei , Zhang Chao , Wu Xiqian , Zhou Wenjing , He Sheng , Jiang Yi , Zhang Kai , Wang Liang
Published: July 2024

We usually perceive what we are attending to. How goal-directed attention contributes to conscious perception remains yet elusive. Here we combined a novel psychophysical paradigm with intracranial electroencephalography data to investigate this issue in the human brain. Relative to unattended conditions, goal-directed attention modulated early activity and inter-regional connectivity, even though this part of attention failed to predict image detectability. Later, the coupling between the frontal and posterior brain got established and maintained but the signals exchanged did not inform fine-grained image contents but instead reflect success or failure of attentional capture. This part of captured attention proportionally predicted image detectability. These results attribute consciousness to attention-based coupling between the frontal and posterior brain as a whole, rather than activity of either part alone.
Bird population trend analyses for a monitoring scheme with a highly structured sampling design
Authors: Rieger Mirjam R. , Grüneberg Christoph , Oberhaus Michael , Trautmann Sven , Parepa Madalin , Anthes Nils
Published: July 2024

Population trends derived from systematic monitoring programmes are essential to identify species of conservation concern and to evaluate conservation measures. However, monitoring data pose several challenges for statistical analysis, including spatial bias due to an unbalanced sampling of landscapes or habitats, variation in observer expertise, frequent observer changes, and overdispersion or zero-inflation in the raw data. An additional challenge arises from so-called ‘rolling’ survey designs, where each site is only visited once within each multi-year rotation cycle. We developed a GAMM-based workflow that addresses these challenges and exemplify its application with the highly structured data from the Ecological Area Sampling (EAS) in the German federal state North-Rhine Westphalia (NRW). First, we derive a routine that allows informed decisions about the most appropriate combination of distribution family (Poisson or negative binomial), model covariates (e.g., habitat characteristics), and zero-inflation formulations to reflect species-specific data distributions. Second, we develop a correction factor that buffers population trend estimates for variation in observer expertise as reflected in variation in total bird abundance. Third, we integrate landscape-specific trends that adjust for between-year variation in the representation of habitat or landscape types within the yearly subset of sampled sites. In a consistency check, we found good match between our GAMM-based EAS trends and TRIM-based trends from the standard German common Bird monitoring scheme. The study provides a template script forRstatistical software so the workflow can be adapted to other monitoring programmes with comparable survey designs and data structures.
PIEZO1-Mediated Mechanotransduction Regulates Collagen Synthesis on Nanostructured 2D and 3D Models of Fibrosis
Authors: Rashidi Neda , Harasymowicz Natalia S. , Savadipour Alireza , Steward Nancy , Tang Ruhang , Oswald Sara , Guilak Farshid
Published: July 2024

Progressive fibrosis causes tissue malfunction and organ failure due to the pathologic accumulation of a collagen-rich extracellular matrix. In vitro models provide useful tools for deconstructing the roles of specific biomechanical or biological mechanisms involved in these processes and identifying potential therapeutic targets. In particular, recent studies have implicated cellular mechanosensing of substrate micro- and nanoscale architecture as a regulator of fibrosis. In this study, we investigated how the mechanosensitive ion channel PIEZO1 and intracellular mechanotransduction pathways influence fibrotic gene and protein expression in adipose-derived stem cells (hASCs). Specifically, we examined the role of PIEZO1 and the mechano-sensitive transcription factors YAP/TAZ in sensing aligned or non-aligned substrate architecture to regulate collagen formation. We utilized both 2D microphotopatterned substrates and 3D electrospun polycaprolactone (PCL) substrates to study the role of culture dimensionality. We found that PIEZO1 regulates collagen production in hASCs in a manner that is sensitive to substrate architecture. Activation of PIEZO1 induced significant morphological changes in hASCs, particularly when they were cultured on aligned substrates. While YAP translocated to the cytoplasm following PIEZO1 activation, depleting YAP and TAZ did not change collagen expression significantly downstream of PIEZO1 activation, implying that YAP/TAZ translocation out of the nucleus and increased collagen production may be independent outputs of PIEZO1 activation. Our studies demonstrate a role for PIEZO1 in cellular mechanosensing of substrate architecture and provide targetable pathways for treating fibrosis as well as for enhancing tissue-engineered and regenerative approaches for fibrous tissue repair.
Predicting the physiological effects of multiple drugs using electronic health record
Authors: Jeon Junhyeok , Hong Eujin , Kim Jong-Yeup , Lee Suehyun , Kim Hyun Uk
Published: July 2024

Various computational models have been developed to understand the physiological effects of drug-drug interactions, which can contribute to more effective drug treatments. However, they mostly focus on interactions of only two drugs, and do not consider the patient information. To address this challenge, we use publicly available electronic health record (EHR), MIMIC-IV, to develop machine learning models that predict the physiological effects of two or more drugs. This study involves extensive preprocessing of laboratory measurement data, prescription data and patient data. The resulting machine learning models predict potential abnormalities across 20 selected measurement items (e.g., concentrations of metabolites and blood cells) in the form of a sentence. The models showed an average AUROC of 0.75, and age, specific active pharmaceutical ingredients, and gender appeared to be the most influential features. The model development process showcased in this study can be extended to other measurement items for a target EHR.
Cerebral Microvascular Density, Permeability of the Blood-Brain Barrier, and Neuroinflammatory Responses Indicate Early Aging Characteristics in a Marfan Syndrome Mouse Model
Authors: Curry-Koski T , Curtin L , Esfandiarei M. , Currier Thomas T.
Published: July 2024

Marfan Syndrome (MFS) is a connective tissue disorder due to mutations in fibrillin-1 (Fbn1), where aFbn1missense mutation (Fbn1C1039G/+) can result in systemic increases in the bioavailability and signaling of transforming growth factor-β (TGF-β). In a well-established mouse model of MFS (Fbn1C1041G/+), pre-mature aging of the aortic wall and the progression of aortic root aneurysm are observed by 6-months-of-age. TGF-β signaling has been implicated in cerebrovascular dysfunction, loss of blood-brain barrier (BBB) integrity, and age-related neuroinflammation. We have reported that pre-mature vascular aging in MFS mice could extend to cerebrovasculature, where peak blood flow velocity in the posterior cerebral artery (PCA) of 6-month-old (6M) MFS mice was reduced, similarly to 12-month-old (12M) control mice. Case studies of MFS patients have documented neurovascular manifestations, including intracranial aneurysms, stroke, arterial tortuosity, as well as headaches and migraines, with reported incidence of pain and chronic fatigue. Despite these significant clinical observations, investigation into cerebrovascular dysfunction and neuropathology in MFS remains limited. Using 6M-control (C57BL/6) and 6M-MFS (Fbn1C1041G/+) and healthy 12M-control male and female mice, we test the hypothesis that abnormal Fbn1 protein expression is associated with altered cerebral microvascular density, BBB permeability, and neuroinflammation in the PCA-perfused hippocampus, all indicative of a pre-mature aging brain phenotype.

Using Glut1 staining, 6M-MFS mice and 12M-CTRL similarly present decreased microvascular density in the dentate gyrus (DG), cornu ammonis 1 (CA1), and cornu ammonis 3 (CA3) regions of the hippocampus. 6M-MFS mice exhibit increased BBB permeability in the DG, CA1, and CA3 as evident by Immunoglobulin G (IgG) staining, which was more comparable to 12M-CTRL mice. 6M-MFS mice show a higher number of microglia in the hippocampus compared to age-matched control mice, a pattern resembling that of 12M-CTRL mice.

This study represents the first known investigation into neuropathology in a mouse model of MFS and indicates that the pathophysiology underlying MFS leads to a systemic pre-mature aging phenotype. This study is crucial for identifying and understanding MFS-associated neurovascular and neurological abnormalities, underscoring the need for research aimed at improving the quality of life and managing pre-mature aging symptoms in MFS and related connective tissue disorders.
MetaGXplore: Integrating Multi-Omics Data with Graph Convolutional Networks for Pan-cancer Patient Metastasis Identification
Authors: Jiang Tao , Jiang Haiyang , Ma Xinyi , Xu Minghao , Zhang Wentao
Published: July 2024

The spread of cancer cells from the primary tumor to distant anatomical sites, known as tumor metastasis, poses a significant challenge in clinical prognosis, impairing treatment efficacy and reducing patient survival time. Current methods for predicting and diagnosing tumor metastasis rely heavily on extensive examinations and subjective clinical judgments. Accurate and rapid prediction of tumor metastasis likelihood remains an unresolved challenge, crucial for guiding effective clinical interventions and extending patient survival. Additionally, identifying key genes highly associated with metastasis probability is a pressing issue, essential for providing valuable insights into the potential identification of tumor metastasis-specific biomarkers. We developed MetaGXplore, a pioneering Graph Convolutional Neural Network (GCN)-based framework designed to predict metastasis probability by integrating pan-cancer multi-omic datasets with a protein-protein interaction network, while also identifying key genes involved in the metastatic process. Multiomics datasets offer a comprehensive view of cancer biology, enhancing accuracy in metastasis forecasting through superior deep learning algorithms. Our classification model results were interpreted with GNNExplainer. The efficacy of MetaGXplore was validated via model evaluations, graph structure analysis, and multi-omics data assessment. Enrichment analysis of key genes further explored their biological roles.
CoPR: Collective Pattern Recognition—a Framework for Microbial Community Activity Analysis
Authors: Vidanaarachchi Rajith , Tang Sen Lin , Halgamuge Saman
Published: July 2024

Background

Microbial community activities provide essential information on understanding bacterial communities. Unfortunately, they are generally not directly observable. We rely on longitudinal abundance profiles to get insight into microbial community activities. Often datasets do not have sufficient longitudinal sampling points to successfully apply our algorithms. Hence, in this paper, we are interested in analysing multiple datasets from similar environments to alleviate the aforementioned problem. Furthermore, we wish to see whether collective pattern recognition would enhance our understanding of microbial community activities.

Results

In this paper, we present CoPR, a framework for collective microbial longitudinal abundance data. Our visualisation shows that a single pattern for temporal abundance variation does not exist. However, it also indicates that even complete individuality does not exist. Consequently, our visualisation highlights the individuality and conformity in the temporal variation of abundance profiles of similar host environments. We also identify different characteristics in the TVAP (Temporal Variation of Abundance Profile) patterns with regards to cohesion and separation.

Conclusions

CoPR helps gain essential insights into the microbial communities and their heterogeneity through visualisation tools. This paper also highlights the choice between individuality and conformity in microbial community data analysis.
Somatic instability of theFGF14-SCA27B GAA•TTC repeat reveals a marked expansion bias in the cerebellum
Authors: Pellerin David , Méreaux Jean-Loup , Boluda Susana , Danzi Matt C. , Dicaire Marie-Josée , Davoine Claire-Sophie , Genis David , Spurdens Guinevere , Ashton Catherine , Hammond Jillian M. , Gerhart Brandon J. , Chelban Viorica , Le Phuong U. , Safisamghabadi Maryam , Yanick Christopher , Lee Hamin , Nageshwaran Sathiji K. , Matos-Rodrigues Gabriel , Jaunmuktane Zane , Petrecca Kevin , Akbarian Schahram , Nussenzweig André , Usdin Karen , Renaud Mathilde , Bonnet Céline , Ravenscroft Gianina , Saporta Mario A. , Napierala Jill S. , Houlden Henry , Deveson Ira W. , Napierala Marek , Brice Alexis , Molina Porcel Laura , Seilhean Danielle , Zuchner Stephan , Durr Alexandra , Brais Bernard
Published: July 2024

Spinocerebellar ataxia 27B (SCA27B) is a common autosomal dominant ataxia caused by an intronic GAA•TTC repeat expansion inFGF14. Neuropathological studies have shown that neuronal loss is largely restricted to the cerebellum. Although the repeat locus is highly unstable during intergenerational transmission, it remains unknown whether it exhibits cerebral mosaicism and progressive instability throughout life. We conducted an analysis of theFGF14GAA•TTC repeat somatic instability across 156 serial blood samples from 69 individuals, fibroblasts, induced pluripotent stem cells, and post-mortem brain tissues from six controls and six patients with SCA27B, alongside methylation profiling using targeted long-read sequencing. Peripheral tissues exhibited minimal somatic instability, which did not significantly change over periods of more than 20 years. In post-mortem brains, the GAA•TTC repeat was remarkably stable across all regions, except in the cerebellar hemispheres and vermis. The levels of somatic expansion in the cerebellar hemispheres and vermis were, on average, 3.15 and 2.72 times greater relative to other examined brain regions, respectively. Additionally, levels of somatic expansion in the brain increased with repeat length and tissue expression ofFGF14. We found no significant difference in methylation of wild-type and expandedFGF14alleles in post-mortem cerebellar hemispheres between patients and controls. In conclusion, our study revealed that theFGF14GAA•TTC repeat exhibits a cerebellar-specific expansion bias, which may explain the pure and late-onset cerebellar involvement in SCA27B.