bluuebunny/crossref_metadata_2025 huggingface dataset:
A 23-year-old male patient with Kimura’s disease without renal transplantation: a rare case report from Syria
Authors: Alsmoudi Hasan , Sleiay Mouhammed , Almohamed Ahmad , Hamsho Suaad , Alhadla Ahmad , Alqreea Mohammed , Alakhras Abdulkareem
Published: June 2024

Introduction and importance:

Kimura’s disease (KD) is a chronic, nonmalignant inflammatory disorder that primarily affects subcutaneous tissue. It is typically characterized by painless nodules in the head and neck regions, accompanied by elevated eosinophil and serum IgE levels. The purpose of this case study is to elucidate this rare disease, particularly in the Asian region and Syria, and to explore diagnostic and therapeutic methodologies with the objective of mitigating the number of undiagnosed patients suffering from this disease.

Case presentation:

A 23-year-old male patient presented to the Ear, Nose, and Throat (ENT) Department of the hospital with symptoms that had been initiated 7 months prior. The primary symptoms were pain and swelling in the left preauricular area, followed by subsequent swelling in the right preauricular area the next day. The patient experienced severe, intermittent pain, generalized pruritus, and systemic manifestations, including fever, chills, fatigue, malaise, anorexia, and a weight loss of 20 kg over the course of seven months. A fine-needle aspiration of the left parotid gland revealed the presence of lymphocytes at various maturation stages, with no evidence of abnormal cells. A diagnosis of KD was subsequently confirmed.

Clinical discussion:

To our knowledge, this case represents the second documented instance of KD in Syria. Furthermore, our case is among the extremely rare instances of KD in a patient without a history of renal transplantation.

Conclusion:

Further research is essential to ascertain the actual prevalence of this condition and to identify the most effective management strategies.
Utilizing Data and Alarm Champions to Enhance Alarm Management
Authors: Mullen Joellan , Sattari Sulimon , Rauch Melissa , Stein Fernando , Roy Kevin , Acorda Darlene E.
Published: June 2024

Background:

Nuisance and false alarms distract clinicians from urgent alerts, raising patient safety risks.

Local Problem:

High alarm rates in a pediatric progressive care unit resulted in experiencing 180-250 alarms per day or 1 alarm every 3 to 4 minutes per clinician.

Methods:

Through Plan-Do-Study-Act cycles, environmental, policy, and technology changes were implemented to decrease the average alarms/day/bed and percentage of time in alarm.

Interventions:

Alarm settings tailored to patient needs using features embedded within the patient monitoring system were implemented and monitored with the assistance of alarm champions.

Results:

The average number of alarms/day/bed decreased from 177.69 to 96.94 over the course of 10 years, a 45.45% reduction. The percentage of time in alarm decreased from 7.52% to 2.83%, a 62.37% reduction.

Conclusions:

Arming clinicians with technology to analyze real-time clinical data made alarms meaningful and actionable, decreasing false alarms without compromising patient safety.
Point-of-Care Ultrasound Evaluation of Pediatric Osteomyelitis in the Emergency Department
Authors: Tsung James W. , Rizvi Munaza B. , Rabiner Joni E.
Published: June 2024

Musculoskeletal and soft tissue complaints commonly present to the pediatric emergency department and literature supports the use point-of-care ultrasound (POCUS) in the diagnosis of these complaints. The diagnosis of osteomyelitis typically involves laboratory testing with inflammatory biomarkers, imaging with x-ray, and often magnetic resonance imaging with test results often not immediately available. We report a case series of children initially evaluated with POCUS for osteomyelitis. The POCUS may expedite diagnosis and treatment when used as the initial test in children with suspected osteomyelitis in the emergency department.
Sleep, Sleep Apnea, and Fatigue in People Living With HIV
Authors: Orr Jeremy E. , Velazquez Jazmin , Schmickl Christopher N. , Bosompra Naa-Oye , DeYoung Pamela N. , Gilbertson Dillon , Malhotra Atul , Grant Igor , Ancoli-Israel Sonia , Karris Maile Young , Owens Robert L.
Published: June 2024

Background:

People living with HIV (PLWH) often report fatigue even when viral load is suppressed. Obstructive sleep apnea (OSA), which is often associated with fatigue, is common in PLWH, but whether OSA explains fatigue in this population is unknown.

Setting:

Academic university-affiliated HIV and Sleep Medicine Clinics.

Methods:

PLWH, aged 18–65 years, with a body mass index of 20–35 kg/m2 and viral suppression (RNA <200 copies per mL), were recruited to undergo daytime questionnaires, including the Functional Assessment of Chronic Illness Therapy Fatigue Scale and Epworth Sleepiness Scale, 7 days of actigraphy (to determine daily sleep duration and activity amplitude and rhythms), and an in-laboratory polysomnography to assess for the presence and severity of OSA.

Results:

Of 120 subjects with evaluable data, 90 (75%) had OSA using the American Academy of Sleep Medicine 3% desaturation or arousal criteria, with an apnea–hypopnea index >5/h. There was no difference in Functional Assessment of Chronic Illness Therapy scores between those with and without OSA, although those with OSA did report more daytime sleepiness as measured using the Epworth Sleepiness Scale. In a multivariable model, predictors of fatigue included more variable daily sleep durations and decreased mean activity counts. Sleepiness was predicted by the presence of OSA.

Conclusion:

OSA was very common in our cohort of PLWH, with those with OSA reporting more sleepiness but not more fatigue. Variability in sleep duration was associated with increased fatigue. Further study is needed to determine if treatment of OSA, or an emphasis on sleep consistency and timing, improves symptoms of fatigue in PLWH.
Artificial Intelligence Methods for the Argenta Classification of Deformational Plagiocephaly to Predict Severity and Treatment Recommendation
Authors: Nguyen Huan T. , Obinero Chioma G. , Wang Ellen , Boyd Alexandra K. , Cepeda Alfredo , Talanker Michael , Mumford Danielle , Littlefield Tim , Greives Matthew R. , Nguyen Phuong D.
Published: June 2024

Introduction

Deformational plagiocephaly (DP) can be classified into 5 severity types using the Argenta scale (AS). Patients with type III or higher require referral to craniofacial surgery for management. Primary care pediatricians (PCPs) are often the first to encounter patients with DP, but current screening methods are subjective, increasing the risk of bias, especially for clinicians with little exposure to this population. The authors propose the use of artificial intelligence (AI) to classify patients with DP using the AS and to make recommendations for referral to craniofacial surgery.

Methods

Vertex photographs were obtained for patients diagnosed with unilateral DP from 2019 to 2020. Using the photographs, an AI program was created to characterize the head contour of these infants into 3 groups based on the AS. The program was trained using photographs from patients whose DP severity was confirmed clinically by craniofacial surgeons. To assess the accuracy of the software, the AS predicted by the program was compared with the clinical diagnosis.

Results

Nineteen patients were assessed by the AI software. All 3 patients with type I DP were correctly classified by the program (100%). In addition, 4 patients with type II were correctly identified (67%), and 7 were correctly classified as type III or greater (70%).

Conclusions

Using vertex photographs and AI, the authors were able to objectively classify patients with DP based on the AS. If converted into a smartphone application, the program could be helpful to PCPs in remote or low-resource settings, allowing them to objectively determine which patients require referral to craniofacial surgery.
Improving communication among nursing staff at a children's hospital in the southern United States: a best practice implementation project
Authors: Keith Brandi B. , Upchurch Linda , Palokas Michelle , Christian Robin
Published: June 2024

Introduction:

Ineffective communication between health care professionals is one of the leading causes of medical errors and can result in adverse events and patient harm. Improving the effectiveness of communication in health care is a worldwide necessity.

Objective:

The aim of this project was to promote evidence-based practices regarding general communication principles among the nursing staff in one unit of a children's hospital in the southern United States.

Methods:

The project used JBI's Evidence Implementation Framework, together with two JBI audit tools (Practical Application of Clinical Evidence System and Getting Research into Practice). A baseline audit was conducted, followed by the implementation of targeted strategies. The project was completed with a follow-up audit to determine changes in practice.

Results:

Baseline data revealed 61% adherence with four audit criteria for effective communication in health care. Barriers included a lack of education of nursing staff regarding communication skills and less than optimal use of a structured communication tool. Targeted strategies to address the barriers included providing an educational module on communication to nursing staff and moving the structured communication tool to a more convenient location to increase its use. The post-implementation data revealed 81% adherence with the four audit criteria, a 20% increase from baseline results.

Conclusions:

Optimizing communication and monitoring the use of a structured communication tool has the potential to decrease the risk of medical errors among health care providers.

Spanish abstract:

http://links.lww.com/IJEBH/A217
Hollow-fibre infection model: adaptations for the culture and assessment of fastidious organisms
Authors: Mead Andrew , Azzariti Stefano , Pelligand Ludovic
Published: June 2024

The hollow-fibre infection model (HFIM) is a valuable in vitro platform for emulating antimicrobial drug pharmacokinetic profiles. Despite its potential, standardized protocols for HFIM operation, especially concerning fastidious organisms, are lacking. This study addresses this gap by examining challenges in culturing Pasteurella multocida and Actinobacillus pleuropneumoniae, two fastidious organisms, in the HFIM. Our findings reveal effective strategies to prevent system clogging, involving multiple freeze–thaw cycles of horse blood, centrifugation and cell straining to enhance the clarity of the Mueller-Hinton fastidious medium defined by the European Committee on Antimicrobial Susceptibility Testing and Clinical and Laboratory Standards Institute. Additionally, we propose that the provision of a CO2 atmosphere, along with the utilization of gas-permeable tubing and gas vent filters, significantly facilitates the growth of fastidious organisms. Remarkably, both P. multocida and A. pleuropneumoniae were sustained for a period of up to 10 days under these optimized conditions. This study provides crucial insights into the modifications necessary to successfully culture fastidious organisms in the HFIM, paving the way for more accurate and representative in vitro models for antimicrobial drug testing. These advancements hold promise for advancing research in the field of antimicrobial pharmacokinetics and efficacy against challenging pathogens.
Seroprevalence of Herpes simplex virus Type-1 IgG antibodies among pregnant women with recurrent abortions
Authors: Mohamed Dalal Abdelhamid , Ahmed Fatima , Hashim Hiba , Saeed Mohammed Ibrahim , Ibrahim Hiba Siddig
Published: June 2024

Herpes Simplex Virus Type - 1 (HSV-1) is a large, enveloped DNA virus that has a relationship with socioeconomic background. The virus can transmitted through direct contact with infected skin lesions or body fluids.
Children may show asymptomatic or mucocutaneous vesicular eruptions, herpetic gingivostomatitis, acute herpetic pharyngotonsillitis, herpes labialis, herpes encephalitis, eczema herpeticum, and herpetic whitlow may occur.
In the last few years the prevalence of HSV-1 infection increases progressively, so, the main aim of this study is to study the seroprevalence of herpes simplex virus type-1 IgG antibodies among pregnant women with recurrent abortions.
The study confirmed a 29 (58%) were positive HSV-1-IgG and 21 (42%) were negative among cases (pregnant women) while 25 (100%) in control subject were negatives, and the possible risk factors i.e. age, Abortion, Blood transfusion, Contraceptive, Rash, have been examined in this study and showed no effect except previous history of TORCH test examination.,
The study settled that more than half of the pregnant women were found to be infected, and we recommended using both ELISA (IgM and IgG) and molecular techniques for detection, diagnosis and monitoring of viral infection.
Peripheral bloodGATA2expression impactsRNF213mutation penetrance and clinical severity in moyamoya disease
Authors: Mineharu Yohei , Kamata Takahiko , Tomoto Mei , Sato Noriaki , Tamada Yoshinori , Funaki Takeshi , Oichi Yuki , Harada Kouji H , Koizumi Akio , Kimura Tetsuaki , Inoue Ituro , Okuno Yasushi , Miyamoto Susumu , Arakawa Yoshiki
Published: June 2024

Background

The p.R4810K founder mutation in theRNF213gene confers susceptibility to moyamoya disease (MMD) and non-MMD intracranial artery disease. However, penetrance is incomplete, and the underlying molecular mechanism remains unknown.

Methods and Results

Transcriptome analysis of peripheral blood was conducted with 9 MMD patients and 5 unaffected mutation carriers from 4 familial MMD pedigrees. Bayesian network analysis identified upregulated gene modules associated with lipid metabolism and leukocyte development (includingGATA2andSLC45A3), and EGFR signaling (UBTD1). It also identified downregulated gene modules related to mitochondrial ribosomal proteins (RPS3AandRPL26), and cytotoxic T cell immunity (GZMAandTRGC1). TheGATA2network was replicated through WGCNA analysis and further examined in a case-control study, comprising 43 MMD patients, 16 non-MMD patients, 19 unaffected carriers, and 35 healthy controls.GATA2exhibited a significant linear correlation withSLC45A3and was significantly higher in MMD patients compared to age- and sex-matched unaffected carriers or wild-type controls. Among patients with the p.R4810K mutation, higherGATA2expression was associated with an earlier age of onset, bilateral involvement, and symptomatic disease onset.

Conclusions

Peripheral bloodGATA2expression was associated with increased penetrance of theRNF213mutation and more severe clinical manifestations in MMD.
The differential immunological impact of photon vs proton radiation therapy in high grade lymphopenia
Authors: Heather James M. , Kim Daniel W. , Sepulveda Sean M. , van Seventer Emily E. , Fish Madeleine G. , Corcoran Ryan , Hacohen Nir , Hong Theodore S. , Cobbold Mark
Published: June 2024

Radiation therapy has long been a cornerstone of cancer treatment. More recently, immune checkpoint blockade has also been applied across a variety of cancers, often leading to remarkable response rates. However, photon-based radiotherapy – which accounts for the vast majority – is also known to frequently induce profound lymphopenia, which might limit the efficacy of immune system based combinations. Proton beam therapy is known to produce a less drastic lymphopenia, which raises the possibility of greater synergy with immunotherapy.

In this study we aimed to explore the exact nature of the differential impact of the two radiation modalities upon the immune system. We used multiparametric flow cytometry and deep sequencing of rearranged TCRb loci to investigate a cohort of 20 patients with gastrointestinal tumors who received either therapy. Proton-treated patients remained relatively stable throughout treatment for most metrics considered, whereas those who received photons saw a profound depletion in naïve T cells, increase in effector/memory populations, and loss of TCR diversity. The repertoires of photon-treated patients underwent oligoclonal expansion after their lymphocyte count nadirs, particularly of CD8+ Temra cells, driving this reduction in diversity. Across the entire cohort, this reduction in post-nadir diversity inversely correlated with the overall survival time of those patients who died. This raises the possibility that increased adoption of proton-based or other lymphocyte sparing radiotherapy regimes may lead to better survival in cancer patients.
BacSC: A general workflow for bacterial single-cell RNA sequencing data analysis
Authors: Ostner Johannes , Kirk Tim , Olayo-Alarcon Roberto , Thöming Janne Gesine , Rosenthal Adam Z. , Häussler Susanne , Müller Christian L.
Published: June 2024

Bacterial single-cell RNA sequencing has the potential to elucidate within-population heterogeneity of prokaryotes, as well as their interaction with host systems. Despite conceptual similarities, the statistical properties of bacterial single-cell datasets are highly dependent on the protocol, making proper processing essential to tap their full potential. We present BacSC, a fully data-driven computational pipeline that processes bacterial single-cell data without requiring manual intervention. BacSC performs data-adaptive quality control and variance stabilization, selects suitable parameters for dimension reduction, neighborhood embedding, and clustering, and provides false discovery rate control in differential gene expression testing. We validated BacSC on a broad selection of bacterial single-cell datasets spanning multiple protocols and species. Here, BacSC detected subpopulations inKlebsiella pneumoniae, found matching structures ofPseudomonas aeruginosaunder regular and low-iron conditions, and better represented subpopulation dynamics ofBacillus subtilis. BacSC thus simplifies statistical processing of bacterial single-cell data and reduces the danger of incorrect processing.
Deviations from normative functioning underlying emotional episodic memory revealed cross-scale neurodiverse alterations linked to affective symptoms in distinct psychiatric disorders
Authors: Xiao Yang , Li Mingzhu , Zhang Xiao , Zhang Yuyanan , Ge Yuqi , Lu Zhe , Ma Mengying , Song Yuqing , Tan Hao-Yang , Zhang Dai , Yue Weihua , Yan Hao
Published: June 2024

Background

Affective symptoms are a prevalent psychopathological feature in various psychiatric disorders. However, the underlying neurobiological mechanisms are complex and not yet fully understood.

Methods

We used normative modelling to establish a reference for neurofunctional activation of functional magnetic resonance imaging based on an emotional episodic memory task, which is frequently used to study affective symptoms in psychiatric disorders. This normative reference was derived from a large dataset of healthy individuals (n = 409), and used to evaluate individualized functional alterations by calculating deviations from this reference in a clinical dataset of 328 participants, which included 168 healthy controls and patients with major depressive disorder (MDD, n = 56), bipolar disorder (BD, n = 31), and schizophrenia (SZ, n = 73). The neurofunctional deviations were mapped to emotional networks with specific emotional functions and used to predict affective symptoms in different mental disorders. The microscale cellular signatures underlying macroscale variations were identified using imaging transcriptomic analysis, and associated with affective symptoms.

Results

We observed distinct patterns of cross-scale neural alterations linked to affective symptoms in three psychiatric disorders. Macroscale neural dysfunctions in distinct disorders were embedded into non-overlapping emotional networks and significantly associated with affective symptoms. The oligodendrocytes may mediate the network-specific impairments, and microglia for MDD, astrocytes for BD, and excitatory neurons for SZ as replicable cell-type correlates of affective symptoms.

Conclusions

These findings have potential implications for the understanding of unique neuropathological patterns of affective symptoms in distinct psychiatric disorders and improving individualized treatment response.
AllergenAI: a deep learning model predicting allergenicity based on protein sequence
Authors: Yang Chengyuan , Negi Surendra S , Schein Catherine H , Braun Werner , Kim Pora
Published: June 2024

Innovations in protein engineering can help redesign allergenic proteins to reduce adverse reactions in sensitive individuals. To accomplish this aim, a better knowledge of the molecular properties of allergenic proteins and the molecular features that make a protein allergenic is needed. We present a novel AI-based tool, AllergenAI, to quantify the allergenic potential of a given protein. Our approach is solely based on protein sequences, differentiating it from previous tools that use some knowledge of the allergens’ physicochemical and other properties in addition to sequence homology. We used the collected data on protein sequences of allergenic proteins as archived in the three well-established databases, SDAP 2.0, COMPARE, and AlgPred 2, to train a convolutional neural network and assessed its prediction performance by cross-validation. We then used Allergen AI to find novel potential proteins of the cupin family in date palm, spinach, maize, and red clover plants with a high allergenicity score that might have an adverse allergenic effect on sensitive individuals. By analyzing the feature importance scores (FIS) of vicilins, we identified a proline-alanine-rich (P-A) motif in the top 50% of FIS regions that overlapped with known IgE epitope regions of vicilin allergens. Furthermore, using∼ 1600 allergen structures in our SDAP database, we showed the potential to incorporate 3D information in a CNN model. Future, incorporating 3D information in training data should enhance the accuracy. AllergenAI is a novel foundation for identifying the critical features that distinguish allergenic proteins.
Population History and Admixture of the Fulani People from the Sahel
Authors: Fortes-Lima Cesar A. , Diallo Mame Yoro , Janoušek Václav , Černý Viktor , Schlebusch Carina M.
Published: June 2024

The Fulani people, one of the most important pastoralist groups in sub-Saharan Africa, are still largely underrepresented in population genomic research. They speak a Niger-Congo language called Fulfulde or Pulaar and live in scattered locations across the Sahel/Savannah Belt, from the Atlantic Ocean to Lake Chad. According to historical records, their ancestors spread from Futa Toro in the Middle Senegal Valley to Futa-Jallon in Guinea, and then eastward into the Sahel belt over the past 1500 years. However, the earlier history of this traditionally pastoral population has not been well studied. To uncover the genetic structure and ancestry of this widespread population, we gathered genome-wide genotype data from 460 individuals across 18 local Fulani populations, along with comparative data from both modern and ancient worldwide populations. This represents the most geographically wide-scaled genome-wide study of the Fulani to date. We revealed a genetic component closely associated with all local Fulani populations, suggesting a shared ancestral component possibly linked to the beginning of African pastoralism in the Green Sahara. Comparison to ancient DNA results also identified the presence of an ancient Iberomaurusian associated component across all Fulani groups, providing novel insights into their deep genetic history. Additionally, our genetic data indicate a later Fulani expansion from the western to the eastern Sahel, characterized by a clinal pattern and admixture with several other African populations north of the equator.
Increasing the representation of minoritized youth for inclusive and reproducible brain-behavior associations
Authors: Ramduny Jivesh , Uddin Lucina Q. , Vanderwal Tamara , Feczko Eric , Fair Damien A. , Kelly Clare , Baskin-Sommers Arielle
Published: June 2024

Population neuroscience datasets allow researchers to estimate reliable effect sizes for brain-behavior associations because of their large sample sizes. However, these datasets undergo strict quality control to mitigate sources of noise, such as head motion. This practice often excludes a disproportionate number of minoritized individuals. We employ motion-ordering and motion-ordering+resampling (bagging) to test if these methods preserve functional MRI (fMRI) data in the Adolescent Brain Cognitive Development Study (N=5,733). Black and Hispanic youth exhibited excess head motion relative to data collected from White youth, and were discarded disproportionately when using conventional approaches. Both methods retained more than 99% of Black and Hispanic youth. They produced reproducible brain-behavior associations across low-/high-motion racial/ethnic groups based on motion-limited fMRI data. The motion-ordering and bagging methods are two feasible approaches that can enhance sample representation for testing brain-behavior associations and fulfill the promise of consortia datasets to produce generalizable effect sizes across diverse populations.
Canine Mammary Tumours (CMTs) exploit Mitochondrial Cholesterol for aggressive reprogramming
Authors: Hardy Liana , Kannan Brindha , Rigon Manuel , Benton-Hawthorn Genevieve , L. Previdelli Renato , M. Reichler Iris , Guscetti Franco , P. Kowalewski Mariusz , Campanella Michelangelo
Published: June 2024

In human breast cancer the mitochondrial translocator protein (TSPO) aids pro-survival cellular response by facilitating the formation of mitochondrial contact sites with the nucleus termed Nucleus Associated Mitochondria (NAM). Here, we show that TSPO positively associates with the aggressiveness of tissues and cells isolated from Canine Mammary Tumours (CMTs). TSPO is also readily upregulated in reprogrammed mammary tumour cells following long-term deprivation of oestrogen or exposure to the endocrine chemotherapeutic (ET) agent Tamoxifen. The latter triggers mitochondrial handling of cholesterol which is facilitated by TSPO whose upregulation reduces susceptibility to Tamoxifen. TSPO binding ligands boost, on the other hand, the efficacy of Tamoxifen and Chemotherapy agents. In aggressive canine mammary tumour cells, TSPO repression impairs the NF-kB pattern thus confirming the pro-survival role of the NAM uncovered in the human counterpart.

Mitochondrial cholesterol handling via TSPO emerges therefore as a signature in the aggressive reprogramming of CMTs thus advancing our understanding of the molecular mechanisms underpinning this pathology. A novel target mechanism to improve bio-marking and therapeutic protocols is here proposed.
Chromosome-level genome assembly of autotetraploidSelenicereus megalanthusand gaining genomic insights into the evolution of trait patterning in diploid and polyploid pitaya species
Authors: Zaman Qamar U , Hui Liu , Nazir Mian Faisal , Wang Guoqing , Garg Vanika , Ikram Muhammad , Raza Ali , Lv Wei , Khan Darya , Khokhar Aamir Ali , You Zhang , Chitikineni Annapurna , Usman Babar , Jianpeng Cui , Yang Xulong , Zuo Shiyou , Liu Peifeng , Kumar Sunjeet , Guo Mengqi , Zhu Zhi-Xin , Dwivedi Girish , Qin Yong-Hua , Varshney Rajeev K. , Wang Hua-Feng
Published: June 2024

Yellow pitaya (Selenicereus megalanthus, 2n=4x=44) breeding remains severely hindered due to lacking a reference genome. Here we report yellow pitaya’s high-quality chromosome-level genome assembly and link the phenotypic trait with genomic data, based on Hi-C, ATAC, and RNA-seq data of specific tissues. We declared yellow pitaya as an autotetraploid with a 7.16 Gb genome size (harboring 27,246 high confidence genes) and majorly evolved from diploid ancestors, which remains unknown. Beyond generating the genome assembly, we explored the 3D chromatin organization which revealed insights into the genome, compartments A (648 and 519), compartments B (728 and 1064), topologically associated domains-TADs (3376 and 2031), and varying numbers of structural variations (SVs) in diploid and polyploid pitaya species, respectively. Overall, TAD boundaries were enriched with the motifs ofAP2,WRKY18/60/75,MYB63/116,PHL2, andGATA8in both pitaya species. By linking the open chromatin genomic structure to function, we identified the major changes in betalains biosynthesis pathway in diploid and polyploid pitaya. Moreover, the higher genetic expression ofSmeADH1[Chr11, Compartment A (135400000 - 135500000), genes inside the TAD region (135480000 - 135520000)], and lower expression ofHuDOPA[Chr11, Compartment A (87100000 - 87200000), genes inside the TAD region (87160000-87200000)] acts as a key regulator of yellow and red color on the pericarp of polyploid and diploid pitaya, respectively. In addition, higher expression ofHuCYP76AD1genes in diploid pitaya and lower expression ofSmeCYP76AD1in polyploid pitaya potentially created the difference in the oxidase process that led to the production of betacyanin and betaxanthin, respectively. Furthermore, our results revealed not only the type of motifs that play a potential role in trait patterning but we also further uncovered that motif count in TAD-boundaries may impact the gene expression within the TAD regions of diploid and polyploid pitaya. Our valuable genomic resource and comparison of 3D euchromatin architecture of diploid and polyploid pitaya species will not only aid in the advancement of molecular breeding efforts but also offer insights into the organization of genomes, SVs, compartmentalization (A and B), and TADs, which have the potential to strengthen the idea of TADs-based trait improvement to achieve global food security.
Multiple Targets, One Goal: Compounding life‐extending effects through Polypharmacology
Authors: Avchaciov K. , Clay K. J. , Denisov K. , Burmistrova O. , Petrascheck M. , Fedichev P.
Published: June 2024

Analysis of lifespan‐extending compounds suggested the most effective geroprotectors target multiple biogenic amine receptors. To test this hypothesis, we used graph neural networks to predict such polypharmacological compounds and evaluated them inC. elegans. Over 70% of the selected compounds extended lifespan, with effect sizes in the top 5% compared to the DrugAge database. This reveals that rationally designing polypharmacological compounds enables the design of geroprotectors with exceptional efficacy.

Key takeaways

The most effective known geroprotectors act by polypharmacological mechanisms.

Graph neural networks predicted polypharmacological geroprotectors with a hit rate of 70%.

The predicted polypharmacological geroprotectors are exceptionally effective.

The predicted polypharmacological mechanism was experimentally confirmed.

Rationally designing polypharmacological compounds results in geroprotectors with exceptional efficacy.
INCREASED CHLOROPLAST OCCUPANCY IN BUNDLE SHEATH CELLS OF RICEhap3HMUTANTS REVEALED BY CHLORO-COUNT, A NEW DEEP LEARNING-BASED TOOL
Authors: Lambret-Frotte Julia , Buarque de Gusmão Pedro P. , Smith Georgia , Lo Shuen-Fang , Yu Su-May , Hendron Ross W. , Kelly Steven , Langdale Jane A.
Published: June 2024

There is an increasing demand to boost photosynthesis in rice to increase yield potential. Chloroplasts are the site of photosynthesis, and increasing the number and size of these organelles in the in leaf is a potential route to elevate leaf-level photosynthetic activity. Notably, bundle sheath cells do not make a significant contribution to overall carbon fixation in rice and thus various attempts are being made to increase chloroplast content in this cell type. In this study we developed and applied a deep learning tool named Chloro-Count to demonstrate that loss ofOsHAP3Hfunction in rice increases chloroplast occupancy in bundle sheath cells by 50%. Although limited to a single season, when grown in the fieldOshap3Hmutants exhibited increased numbers of tillers and panicles as compared to controls or gain of function mutants. The implementation of Chloro-Count enabled precise quantification of chloroplasts in loss- and gain-of-functionOsHAP3Hmutants and facilitated a comparison between 2D and 3D quantification methods. In wild-type rice, as the dimensions of bundle sheath cells increase, the volume of individual chloroplasts also increases. However, the larger the chloroplasts the fewer there are per bundle sheath cell. This observation revealed that a mechanism operates in bundle sheath cells to restrict chloroplast occupancy as cell dimensions increase. That mechanism is unperturbed inOshap3Hmutants. The use of Chloro-Count also revealed that 2D quantification, upon which most previous studies have relied, is compromised by the positioning of chloroplasts within the cell. Chloro-Count is therefore a valuable tool for accurate and high-throughput quantification of chloroplasts that has enabled the robust characterization ofOsHAP3Heffects on chloroplast biogenesis in rice. Whereas previous studies have increased chloroplast occupancy in bundle sheath cells by increasing the size of individual chloroplasts, loss ofOsHAP3Hfunction leads to an increase in chloroplast numbers.
Eco-evolutionary Guided Pathomics Analysis to Predict DCIS Upstaging
Authors: Xiao Yujie , Elmasry Manal , Bai Ji Dong K. , Chen Andrew , Chen Yuzhu , Jackson Brooke , Johnson Joseph O. , Gillies Robert J. , Prasanna Prateek , Chen Chao , Damaghi Mehdi
Published: June 2024

Cancers evolve in a dynamic ecosystem. Thus, characterizing cancer’s ecological dynamics is crucial to understanding cancer evolution and can lead to discovering novel biomarkers to predict disease progression. Ductal carcinoma in situ (DCIS) is an early-stage breast cancer characterized by abnormal epithelial cell growth confined within the milk ducts. In this study, we show that ecological analysis of hypoxia and acidosis biomarkers can significantly improve prediction of DCIS upstaging. First, we developed a novel eco-evolutionary designed approach to define habitats in the tumor intraductal microenvironment based on oxygen diffusion distance. Then, we identified cancer cells with metabolic phenotypes attributed to their habitats, including CA9 for hypoxia responding phenotype, and LAMP2b for acid adapted phenotype. Traditionally these markers have shown limited predictive capabilities for DCIS progression, if any. However, when analyzed from an ecological perspective, their power to differentiate between non-upstaged and upstaged DCIS increased significantly. Second, we discovered distinct niches with spatial patterns of these biomarkers and used the distribution of such niches to predict patient upstaging. The niches were characterized by pattern analysis of both cellular and spatial features. With a 5-fold validation on the biopsy cohort, we trained a random forest classifier to achieve the area under curve (AUC) of 0.74. Our results affirm the importance of tumor ecological features in eco-evolutionary-designed approaches for novel biomarkers discovery.

Significance

Our results affirm the importance of spatial and ecological features in eco-evolutionary-designed biomarkers discovery studies in the era of digital pathology.
ReducedSH3RF3may protect against Alzheimer’s disease by lowering microglial pro-inflammatory responses via modulation of JNK and NFkB signaling
Authors: Patel Ronak , Cheng Rong , Cardona Christopher L. , Angeles Ellen , Singh Gunjandeep , Miller Sabrina , Ashok Archana , Teich Andrew F. , Piriz Angel , Maldonado Aleyda , Jiménez-Velázquez Ivonne , Mayeux Richard , Lee Joseph H. , Sproul Andrew A.
Published: June 2024

Understanding how high-risk individuals are protected from Alzheimer’s disease (AD) may illuminate potential therapeutic targets. We identified protective genetic variants inSH3RF3/POSH2that delayed the onset of AD among individuals carrying thePSEN1G206Amutation.SH3RF3acts as a JNK pathway scaffold and activates NFκB signaling. While effects ofSH3RF3knockdown in human neurons were subtle, including decreased ptau S422, knockdown in human microglia significantly reduced inflammatory cytokines in response to either a viral mimic or oAβ42. This was associated with reduced activation of JNK and NFκB pathways in response to these stimuli. Pharmacological inhibition of JNK or NFκB signaling phenocopiedSH3RF3knockdown. We also foundPSEN1G206Amicroglia had reduced inflammatory response to oAβ42. Thus, further reduction of microglial inflammatory responses inPSEN1G206Amutant carriers by protective variants inSH3RF3might reduce the link between amyloid and neuroinflammation to subsequently delay the onset of AD.

Graphical Abstract
Recurrent disruption of tumour suppressor genes in cancer by somatic mutations in cleavage and polyadenylation signals
Authors: Kainov Yaroslav , Hamid Fursham , Makeyev Eugene V.
Published: June 2024

The expression of eukaryotic genes relies on the precise 3’-terminal cleavage and polyadenylation of newly synthesized pre-mRNA transcripts. Defects in these processes have been associated with various diseases, including cancer. While cancer-focused sequencing studies have identified numerous driver mutations in protein-coding sequences, noncoding drivers – particularly those affecting the cis-elements required for pre-mRNA cleavage and polyadenylation – have received less attention. Here, we systematically analysed cancer somatic mutations affecting 3’UTR polyadenylation signals using the Pan-Cancer Analysis of Whole Genomes (PCAWG) dataset. We found a striking enrichment of cancer-specific somatic mutations that disrupt strong and evolutionarily conserved cleavage and polyadenylation signals within tumour suppressor genes. Further bioinformatics and experimental analyses conducted as a part of our study suggest that these mutations have a profound capacity to downregulate the expression of tumour suppressor genes. Thus, this work uncovers a novel class of noncoding somatic mutations with significant potential to drive cancer progression.
A Host Enzyme Reduces Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) by Inactivating Intestinal Lipopolysaccharide
Authors: Wang Zhiyan , Ojogun Nore , Liu Yiling , Gan Lu , Xiao Zeling , Feng Jintao , Jiang Wei , Chen Yeying , Zou Benkun , Yu Cheng-Yun , Li Changshun , Ashuo Asha , Li Xiaobo , Fu Mingsheng , Wu Jian , Chu Yiwei , Munford Robert , Lu Mingfang
Published: June 2024

The incidence of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) has been increasing world-wide. Since gut-derived bacterial lipopolysaccharides (LPS) can travel via the portal vein to the liver and play an important role in producing hepatic pathology, it seemed possible that (1) LPS stimulates hepatic cells to accumulate lipid, and (2) inactivating LPS can be preventive. Acyloxyacyl hydrolase (AOAH), the eukaryotic lipase that inactivates LPS and oxidized phospholipids, is produced in the intestine, liver, and other organs. We fed mice either normal chow or a high-fat diet for 28 weeks and found thatAoah−/−mice accumulated more hepatic lipid than didAoah+/+mice. In young mice, before increased hepatic fat accumulation was observed,Aoah−/−mouse livers increased their abundance of Sterol Regulatory Element-Binding Protein 1 (SREBP1) and the expression of its target genes that promote fatty acid synthesis.Aoah−/−mice also increased hepatic expression of CD36 and Fabp3, which mediate fatty acid uptake, and decreased expression of fatty acid oxidation-related genes Acot2 and Ppar-α. Our results provide evidence that increasing AOAH abundance in the gut, bloodstream and/or liver may be an effective strategy for preventing or treating MASLD.
Chemical mate choice copying inDrosophila melanogaster
Authors: Mitchell Bloo , Abbott Alexandria , Brown Ashanti , Skinner Lacy , Umarova Elmira , Kohlmeier Philip
Published: June 2024

Mate choice is a critical decision especially for females that requires time and energy to assess potential partners’ genetic quality. Consequently, in many species, females have evolved the ability to utilize social information by copying the mate choices of others, usually based on visual cues. However, many species, especially invertebrates, primarily rely on chemical not visual cues. Using chemical rather than visual cues provides several advantages such as not requiring active observation of copulations. Despite of that, empirical evidence for the existence of chemical mate choice copying is scarce. UsingDrosophila melanogaster, we provide the first demonstration of chemical mate choice copying. Females exposed to a recently mated select the same male genotype as the teacher female mated with at a higher frequency than expected by chance. Chemical mate choice copying requires sensing both male and female cues, which might indicate that other females have chosen that male genotype. Our work suggests that females, in the presence of mated females, increase choosiness at the virgin stage, elevating sexual selection on male traits. This study provides novel evidence that exploiting social information is more prevalent in flies than previously assumed.
Different resource partitioning explains plant species richness patterns in tropical alpine ecosystems
Authors: Kandziora Martha , Vásquez Diana L. A. , Brochmann Christian , Gizaw Abel , Gustafsson Lovisa , Chala Desalegn , Galbany-Casals Mercè , Kolář Filip , Sklenář Petr , Nürk Nicolai M. , Schmickl Roswitha
Published: June 2024

Species co-existence based on resource partitioning modulates biodiversity patterns across latitudes and altitudes. Resource partitioning can occur via specialisation or separation in the geographic range or niche. Here, we compare two tropical alpine ecosystems with similar climates to test for geographic range and climatic niche partitioning strategies in explaining species richness difference. We compare the species-rich tropical alpine ecosystem in the South American Andes with the more species-poor one in the eastern African mountains. We combine phylogenomic data for three locally diversified plant lineages in each region with occurrence records and estimate climatic niche and geographic range metrics (size and overlap). We found that the Andean species have overall larger niches than the African species, thus smaller niches indicating specialisation is not the explanation for the higher species richness in the Andes. Instead, for species with overlapping geographic ranges, we found that the Andean species tend to show less niche overlap than the African species, indicating more effective niche separation. Taken together, we propose that different degrees of niche separation in geographically overlapping species, and hence, a different pattern of resource partitioning, explain the differences in species richness between the two tropical alpine ecosystems.
Allopolyploidy enhances survival advantages for urban environments in the native plant genusCommelina
Authors: Shimomai Hina , Taichi Nakata , Katsuhara Koki R. , Kato Seiji , Ushimaru Atushi , Ohmido Nobuko
Published: June 2024

Background and Aims

Urbanization-induced environmental changes have profound effects on the geographical distribution limits in natural plant species. Polyploidization, an influential dynamic genome change, may determine survival potentials of plant species in urban environments. This study focused on the native plants,Commelina communisL. (Cc) and closely related subspecies,C. communisf.ciliata(Masam.) Murata (Ccfc) which have different chromosome numbers (e.g. Cc: 2n = 88, Ccfc: 2n = 46). The aim is to investigate polyploidization effects on natural plant distribution in urban environments.

Methods

The geographical distribution across urban-rural gradients was investigated at a total of 218 sites in Japan. Stomata size and density were measured and compared between Cc and Ccfc. Flow cytometry was used to determine genome size and polyploidy. Chromosome karyotyping was performed by using the GISH method.

Key results

Urban areas were exclusively dominated by Cc, while Cc and Ccfc coexisted in rural areas. Cc had larger and fewer stomata and more than twice genome size than Ccfc. GISH results indicated that Cc possesses Ccfc and another unknown genome, suggesting allopolyploidy.

Conclusions

These results show that the ploidy difference affects the geographical distribution, the stomata traits, and genome size between Cc and Ccfc. In addition, GISH results indicate that Cc has Ccfc and another unknown genome, suggesting Cc is an allopolyploid and these two species of the genusCommelinaare distinct. Therefore, not only polyploid but also allopolyploid contributes to Cc to enhance survival potentials in urban environments compared to Ccfc. This is the first investigation to clarify the distribution difference related to urban environments, the difference in stomata traits and genome size, and to conduct chromosome composition inCommelinaspecies.
RNA-Protein Interaction Prediction without High-Throughput Data: An Overview and Benchmark ofin silicoTools
Authors: Krautwurst Sarah , Lamkiewicz Kevin
Published: June 2024

RNA-protein interactions (RPIs) are crucial for accurately operating various processes in and between organisms across kingdoms of life. Mutual detection of RPI partner molecules depends on distinct sequential, structural, or thermodynamic features, which can be determined via experimental and bioinformatic methods. Still, the underlying molecular mechanisms of many RPIs are poorly understood. It is further hypothesized that many RPIs are not even described yet. Computational RPI prediction is continuously challenged by the lack of data and detailed research of very specific examples. With the discovery of novel RPI complexes in all kingdoms of life, adaptations of existing RPI prediction methods are necessary. Continuously improving computational RPI prediction is key in advancing the understanding of RPIs in detail and supplementing experimental RPI determination. The growing amount of data covering more species and detailed mechanisms support the accuracy of prediction tools, which in turn support specific experimental research on RPIs. Here, we give an overview of RPI prediction tools that do not use high-throughput data as the user’s input. We review the tools according to their input, usability, and output. We then apply the tools to known RPI examples across different kingdoms of life. Our comparison shows that the investigated prediction tools do not favor a certain species and equip the user with results varying in degree of information, from an overall RPI score to detailed interacting residues. Furthermore, we provide a guide tree to assist users which RPI prediction tool is appropriate for their available input data and desired output.

Contact

sarah.krautwurst@uni-jena.de