bluuebunny/crossref_metadata_2025 huggingface dataset:
Utility of PD-1, PD-L1, and IDO-1 Stains in Ocular Extranodal Marginal Zone Lymphoma (MZL) and Diffuse Large B-cell Lymphoma (DLBCL)
Authors: Craig Alexander , Güney Ekin , Pekmezci Melike , Bloomer Michele , Laszik Zoltan , Ohgami Robert S. , Toland Angus , Vogel Hannes , Forns Taylor , Wang Endi , Rubenstein James , Wen Kwun Wah
Published: June 2024

Extranodal marginal zone lymphoma (EMZL) is the most common subtype of ocular lymphomas. Diffuse large B-cell lymphoma (DLBCL) and EMZL with large-cell transformation present diagnostic challenges. Radiotherapy is the standard treatment for ocular lymphomas, but complications and relapse are common. Diagnostic utility in challenging cases, as well as treatment options using immune checkpoint inhibitors, are unclear in ocular lymphomas. We herein investigated the PD-1, PD-L1, and IDO1 staining patterns in 20 cases of ocular lymphomas, including EMZL (n=14), EMZL with increased large cells (n=2), and DLBCL (n=4). PD-1, PD-L1, and IDO1 staining was not detected in lymphoma cells in any cases but was observed within the tumor microenvironment in all cases. Positivity for PD-1, PD-L1, and IDO1 in inflammatory cells was seen either intratumorally or peritumorally. In all 6 cases with significantly more large B cells, the density of PD-1, PD-L1, and IDO1 expression in the tumor microenvironment was higher than that of the remaining 14 cases without large B cells (P-value<0.0001), whereas other clinicopathologic features showed no statistical correlation. Increased expression of PD-1, PD-L1, and IDO1 in the inflammatory milieu in cases with large cells may provide diagnostic utility in small biopsies as well as therapeutic potential.
IDENTIFICATION OF A NOVEL SEPSIS PROGNOSIS MODEL: BASED ON TRANSCRIPTOME AND PROTEOME ANALYSIS
Authors: Chen Haoran , Xue Haoyue , Tang Xinyi , Wang Chen , Li Xiaomin , Xie Yongpeng
Published: June 2024

Sepsis is a highly prevalent and deadly disease. Currently, there is a lack of ideal biomarker prognostis models for sepsis. We attempt to construct a model capable of predicting the prognosis of sepsis patients by integrating transcriptomic and proteomic data. Through analysis of proteomic and transcriptomic data, we identified 25 differentially expressed genes (DEGs). Single-factor Cox-Lasso regression analysis identified 16 DEGs (overall survival-DEGs) associated with patient prognosis. Through multifactor Cox-Lasso regression analysis, a prognostic model based on these 16 genes was constructed. Kaplan-Meier survival analysis and receiver operating characteristic curve analysis were used to further validate the high stability and good predictive ability of this prognostic model with internal and external data. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of overall survival-DEGs and differentially expressed genes between high and low-risk groups based on the prognostic model revealed significant enrichment in immune-related pathways, particularly those associated with viral regulation.
Cutaneous tuberculosis an unusual localization: A case report

Authors: ZIAD Fatima , Benaissa Elmostafa , Ait sahel Omar , MAAROUFI Abdelkhaleq , Ben lahlou Yassine , Maleb Adil , Chadli Mariama , Elouennass Mostafa
Published: June 2024

Tuberculosis is a major public health problem worldwide. In Morocco, tuberculosis is still endemic, with almost 30,000 cases notified annually.
The distribution of tuberculosis cases according to localization shows a significant percentage of extra- pulmonary tuberculosis (43%) compared with 57% for Pulmonary tuberculosis.
Cutaneous tuberculosis is an exceptional extra-pulmonary form of the disease, with an incidence of 0.5% to 2% of cases. Given that the clinical symptoms of cutaneous tuberculosis are variable and nonspecific, diagnosis is not always easy.
We report a rare case of cutaneous tuberculosis in a patient with a history of pulmonary and cutaneous sarcoidosis.
Ribosome Phenotypes Enable Rapid Antibiotic Susceptibility Testing inEscherichia coli
Authors: Farrar Alison , Turner Piers , El Sayyed Hafez , Feehily Conor , Chatzimichail Stelios , Crook Derrick , Andersson Monique , Oakley Sarah , Barrett Lucinda , Nellåker Christoffer , Stoesser Nicole , Kapanidis Achillefs
Published: June 2024

Rapid antibiotic susceptibility tests (ASTs) are an increasingly important part of clinical care as antimicrobial resistance (AMR) becomes more common in bacterial infections. Here, we use the spatial distribution of fluorescently labelled ribosomes to detect intracellular changes associated with antibiotic susceptibility in singleE. colicells using a convolutional neural network (CNN). By using ribosome-targeting probes, a single fluorescence cell image provides data for cell segmentation and susceptibility phenotyping. Using 50,722 images of cells from an antibiotic-susceptible laboratory strain ofE. coli, we showed that antibiotics with different mechanisms of action result in distinct ribosome phenotypes, which can be identified by a CNN with high accuracy (99%, 96%, and 91% for ciprofloxacin, gentamicin, and chloramphenicol). With 6E. colistrains isolated from bloodstream infections, we used 34,205 images of ribosome phenotypes to train a CNN that could classify susceptible cells with 92% accuracy and resistant cells with 99% accuracy. Such accuracies correspond to the ability to differentiate susceptible and resistant samples with 99% confidence with just 2 cells, meaning that this method could eliminate lengthy sample culturing steps and could determine in vitro susceptibility with 30 minutes of antibiotic treatment. Our ribosome phenotype method should also be able to identify phenotypes in other strains and species.
Imaging single particle profiler to study nanoscale bioparticles using conventional confocal microscopy
Authors: Sych Taras , Görgens André , Steiner Loïc , Gucluer Gozde , Huge Ylva , Alamdari Farhood , Johansson Markus , Aljabery Firas , Sherif Amir , Gabrielsson Susanne , EL Andaloussi Samir , Sezgin Erdinc
Published: June 2024

Single particle profiler is a unique methodology to study nanoscale bioparticles such as liposomes, lipid nanoparticles, extracellular vesicles and lipoproteins in single particle and high throughput manner. The original version requires the single photon counting modules for data acquisition. Here, we present imaging-based SPP (iSPP) which can be performed by imaging a spot over time in common imaging mode with photomultiplier tubes. We also provide a user-friendly software with graphical user interface to facilitate the application of this technique. We demonstrate that iSPP can be used to decipher lipid-protein interactions, membrane modifications by drugs and the heterogeneity of extracellular vesicles isolated from cells lines and urine of human donors.
Loss of chromosome cytoband 13q14.2 orchestrates breast cancer pathogenesis and drug response
Authors: Shahrouzi Parastoo , Azimzade Youness , Brankiewicz Wioletta , Bhatia Sugandha , Kunke David , Richard Derek , Tekpli Xavier , Kristensen Vessela N. , Duijf Pascal H.G.
Published: June 2024

Breast cancer (BCa) is a major global health challenge, characterized by chromosomal instability (CIN) and subsequent acquisition of extensive somatic copy number alterations (CNAs). CNAs including amplifications and deletions, significantly influence intra-tumor heterogeneity and the tumor microenvironment (TME). Among these, the loss of chromosome 13q14.2 emerges as a considerable factor in BCa pathogenesis and treatment responses. We provide evidence that this genomic alteration is under positive selective pressure, correlating with poorer patient survival. Furthermore, through multi-omic andin vitroanalyses, we uncover a dual role of 13q14.2 loss: it confers a survival advantage to tumor cells and modulate the cell cycle and pro-apoptotic pathways in cancer cells, affecting macrophages population in the TME, while paradoxically increasing tumor susceptibility toBCL2inhibitors. These findings suggest that targeting 13q14.2 as a biomarker in BCa could enhance the efficacy of existing treatments and offer a new avenue for improving clinical outcomes in BCa.

Abstract Figure

Figure 1.

Graphical abstract
Single-cell dynamics of genome-nucleolus interactions captured by nucleolar laser microdissection (NoLMseq)
Authors: Walavalkar Kaivalya , Gupta Shivani , Kresoja-Rakic Jelena , Raingeval Mathieu , Mungo Chiara , Santoro Raffaella
Published: June 2024

Gene position in the nuclear space plays an important role in gene regulation. This is exemplified by repressive chromatin domains frequently contacting nuclear lamina or nucleoli. The nucleolus undergoes structural changes in response to various cellular states, potentially impacting genome organization. However, how the 3D-genome organization responds to nucleolar states has remained underinvestigated due to the lack of methods able to identify nucleolar associated domains (NADs) in single cells and under nucleolar stress. To address this, we developed NoLMseq, a method combining laser-capture microdissection and DNA sequencing to map NADs in single cells. NoLMseq identified many unexplored features of chromosome organization around single nucleoli such as NAD heterogeneity among ESCs, culminating in two major populations with distinct chromatin states. NADs prevalently contact nucleoli in a monoallelic manner and allelic nucleolar contact frequency mirrors gene expression and chromatin states. NoLMseq also revealed how chromosomes reorganise around nucleoli under nucleolar stress conditions, highlighting the importance of nucleolus integrity in genome organization and 3D-genome response to nucleolar stress. The results demonstrated that NoLMseq accurately measures chromosome contacts around single healthy and stressed nucleoli and it will be a critical tool to study NADs within biological populations and determine how the 3D-genome responds to nucleolar stress in healthy and disease states.
Cryo-electron tomography reveals the microtubule-bound form of inactive LRRK2
Authors: Chen Siyu , Basiashvili Tamar , Hutchings Joshua , Sanz Murillo Marta , Villagran Suarez Amalia , Alegrio Louro Jaime , Leschziner Andres E. , Villa Elizabeth
Published: June 2024

Parkinson’s Disease (PD) is the second most common neurodegenerative disorder. Mutations in leucine-rich repeat kinase 2 (LRRK2), a multi-domain protein containing both a kinase and a GTPase, are a leading cause of the familial form of PD. Pathogenic LRRK2 mutations increase LRRK2 kinase activity. While the bulk of LRRK2 is found in the cytosol, the protein associates with membranes where its Rab GTPase substrates are found, and under certain conditions, with microtubules. Integrative structural studies using single-particle cryo-electron microscopy (cryo-EM) andin situcryo-electron tomography (cryo-ET) have revealed the architecture of microtubule-associated LRRK2 filaments, and that formation of these filaments requires LRRK2’s kinase to be in the active-like conformation. However, whether LRRK2 can interact with and form filaments on microtubules in its autoinhibited state, where the kinase domain is in the inactive conformation and the N-terminal LRR domain covers the kinase active site, was not known. Using cryo-ET, we show that full-length LRRK2 can oligomerize on microtubules in its autoinhibited state. Both WT-LRRK2 and PD-linked LRRK2 mutants formed filaments on microtubules. While these filaments are stabilized by the same interfaces seen in the active-LRRK2 filaments, we observed a new interface involving the N-terminal repeats that were disordered in the active-LRRK2 filaments. The helical parameters of the autoinhibited-LRRK2 filaments are different from those reported for the active-LRRK2 filaments. Finally, the autoinhibited-LRRK2 filaments are shorter and less regular, suggesting they are less stable.
Multiomic insights into sucrose accumulation in sugarcane
Authors: Aono Alexandre Hild , Pimenta Ricardo José Gonzaga , Diniz Jéssica Faversani , Carrasco Marishani Marin , Hosaka Guilherme Kenichi , Correr Fernando Henrique , Garcia Ana Letycia Basso , Costa Estela Araujo , Coutinho Alisson Esdras , Pinto Luciana Rossini , Landell Marcos Guimarães de Andrade , Xavier Mauro Alexandre , Perecin Dilermando , Carneiro Monalisa Sampaio , Balsalobre Thiago Willian , Kuroshu Reginaldo Massanobu , Margarido Gabriel Rodrigues , de Souza Anete Pereira
Published: June 2024

Sugarcane (Saccharumspp.) holds significant economic importance in sugar and biofuel production. Despite extensive research, understanding highly quantitative traits, such as sucrose content, remains challenging due to the complex genomic landscape of the crop. In this study, we conducted a multiomic investigation to elucidate the genetic architecture and molecular mechanisms governing sucrose accumulation in sugarcane. Using a biparental cross (IACSP95-3018 × IACSP93-3046) and a genetically diverse collection of sugarcane genotypes, we evaluated the soluble solids (Brix) and sucrose content (POL) across various years and environments. Both populations were genotyped using a genotyping-by-sequencing (GBS) approach, with single nucleotide polymorphisms (SNPs) identified via bioinformatics pipelines. Genotype‒phenotype associations were established using a combination of traditional linear mixed-effect models and machine learning algorithms. Furthermore, we conducted an RNA sequencing (RNA-Seq) experiment on genotypes exhibiting distinct Brix and POL profiles across different developmental stages. Differentially expressed genes (DEGs) potentially associated with variations in sucrose accumulation were identified. All findings were integrated through a comprehensive gene coexpression network analysis. Strong correlations among the evaluated characteristics were observed, with estimates of modest to high heritabilities. By leveraging a broad set of SNPs identified for both populations, we identified several SNPs potentially linked to phenotypic variance. Our examination of genes close to these markers facilitated the association of such SNPs with DEGs in genotypes with contrasting sucrose levels. Through the integration of these results with a gene coexpression network, we delineated a set of genes potentially involved in the regulatory mechanisms of sucrose accumulation in sugarcane, collectively contributing to the definition of this critical phenotype. Our findings constitute a significant resource for biotechnology and plant breeding initiatives. Furthermore, our genotype‒phenotype association models hold promise for application in genomic selection, offering valuable insights into the molecular underpinnings governing sucrose accumulation in sugarcane.
Dachsous and Fat coordinately repress the Dachs-Dlish-Approximated complex to control growth
Authors: Matakatsu Hitoshi , Fehon Richard G.
Published: June 2024

Two protocadherins, Dachsous (Ds) and Fat (Ft), regulate organ growthin Drosophilavia the Hippo pathway. Ds and Ft bind heterotypically to regulate the abundance and subcellular localization of a ‘core complex’ consisting of Dachs, Dlish and Approximated. This complex localizes to the junctional cortex where it promotes growth by repressing the pathway kinase Warts. Ds is believed to promote growth by recruiting and stabilizing the core complex at the junctional cortex, while Ft represses growth by promoting degradation of core complex components.

Here, we examine the functions of intracellular domains of Ds and Ft and their relationship to the core complex. While Ds promotes accumulation of the core complex proteins in cortical puncta, it is not required for core complex assembly. Indeed, the core complex assembles maximally in the absence of both Ds and Ft. Furthermore, while Ds promotes growth in the presence of Ft, it represses growth in the absence of Ft by removing the core complex from the junctional cortex. Ft similarly recruits core complex components, however it normally promotes their degradation. Our findings reveal that Ds and Ft constrain tissue growth by repressing the default ’on’ state of the core complex.
Phage-plasmid hybrids are found throughout diverse environments and encode niche-specific functional traits
Authors: Mullet J. , Zhang L. , Pruden A. , Brown C.L.
Published: June 2024

Phage-plasmids are unique mobile genetic elements that function as plasmids and temperate phages. While it has been observed that such elements often encode antibiotic resistance genes and defense system genes, little else is known about other functional traits they encode. Further, no study to date has documented their environmental distribution and prevalence. Here, we performed genome sequence mining of public databases of phages and plasmids utilizing a random forest classifier to identify phage-plasmids. We recovered 5,742 unique phage-plasmid genomes from a remarkable array of disparate environments, including human, animal, plant, fungi, soil, sediment, freshwater, wastewater, and saltwater environments. The resulting genomes were used in a comparative sequence analysis, revealing functional traits/accessory genes associated with specific environments. Host-associated elements contained the most defense systems (including CRISPR and anti-CRISPR systems) as well as antibiotic resistance genes, while other environments, such as freshwater and saltwater systems, tended to encode components of various biosynthetic pathways. Interestingly, we identified genes encoding for certain functional traits, including anti-CRISPR systems and specific antibiotic resistance genes, that were enriched in phage-plasmids relative to both plasmids and phages. Our results highlight that phage-plasmids are found across a wide-array of environments and likely play a role in shaping microbial ecology in a multitude of niches.

IMPORTANCE

Phage-plasmids are a novel, hybrid class of mobile genetic element which retain aspects of both phages and plasmids. However, whether phage-plasmids represent merely a rarity or are instead important players in horizontal gene transfer and other important ecological processes has remained a mystery. Here, we document that these hybrids are encountered across a broad range of distinct environments and encode niche-specific functional traits, including the carriage of antibiotic biosynthesis genes and both CRISPR and anti-CRISPR defense systems. These findings highlight phage-plasmids as an important class of mobile genetic element with diverse roles in multiple distinct ecological niches.
PSMF1variants cause a phenotypic spectrum from early-onset Parkinson’s disease to perinatal lethality by disrupting mitochondrial pathways
Authors: Magrinelli Francesca , Tesson Christelle , Angelova Plamena R. , Salazar-Villacorta Ainara , Rodriguez Jose A. , Scardamaglia Annarita , Chung Brian Hon-Yin , Jaconelli Matthew , Vona Barbara , Esteras Noemi , Kwong Anna Ka-Yee , Courtin Thomas , Maroofian Reza , Alavi Shahryar , Nirujogi Raja , Severino Mariasavina , Lewis Patrick A. , Efthymiou Stephanie , O’Callaghan Benjamin , Buchert Rebecca , Sofan Linda , Lis Pawel , Pinon Chloé , Breedveld Guido J. , Chui Martin Man-Chun , Murphy David , Pitz Vanessa , Makarious Mary B. , Cassar Marlene , Hassan Bassem A. , Iftikhar Sana , Rocca Clarissa , Bauer Peter , Tinazzi Michele , Svetel Marina , Samanci Bedia , Hanağası Haşmet A. , Bilgiç Basar , Obeso José A. , Kurtis Monica M. , Cogan Guillaume , Başak Ayşe Nazlı , Kiziltan Güneş , Gül Tuğçe , Yalçın Gül , Elibol Bülent , Barišić Nina , Ng Earny Wei-Sen , Fan Sze-Shing , Hershkovitz Tova , Weiss Karin , Raza Alvi Javeria , Sultan Tipu , Azmi Alkhawaja Issam , Froukh Tawfiq , E Alrukban Hadeel Abdollah , Fauth Christine , Schatz Ulrich A. , Zöggeler Thomas , Zech Michael , Stals Karen , Varghese Vinod , Gandhi Sonia , Blauwendraat Cornelis , Hardy John A. , Lesage Suzanne , Bonifati Vincenzo , Haack Tobias B. , Bertoli-Avella Aida M. , Steinfeld Robert , Alessi Dario R. , Steller Hermann , Brice Alexis , Abramov Andrey Y. , Bhatia Kailash P. , Houlden Henry
Published: June 2024

Dissecting biological pathways highlighted by Mendelian gene discovery has provided critical insights into the pathogenesis of Parkinson’s disease (PD) and neurodegeneration. This approach ultimately catalyzes the identification of potential biomarkers and therapeutic targets. Here, we identifyPSMF1as a new gene implicated in PD and childhood neurodegeneration. We find that biallelicPSMF1missense and loss-of-function variants co-segregate with phenotypes from early-onset PD and parkinsonism to perinatal lethality with neurological manifestations across 15 unrelated pedigrees with 22 affected subjects, showing clear genotype-phenotype correlation.PSMF1encodes the proteasome regulator PSMF1/PI31, a highly conserved, ubiquitously expressed partner of the 20S proteasome and neurodegeneration-associated F-box-O 7 and valosin-containing proteins. We demonstrate thatPSMF1variants impair mitochondrial membrane potential, dynamics and mitophagy in patient-derived fibroblasts. Additionally, we develop models ofpsmf1knockdownDrosophilaandPsmf1conditional knockout mouse exhibiting age-dependent motor impairment, with diffuse gliosis in mice. These findings unequivocally link defective PSMF1 to early-onset PD and neurodegeneration and suggest mitochondrial dysfunction as a mechanistic contributor.
Comparison between 70% ethyl alcohol and 10% formalin as fixative mediums in surgical cooperation campaigns: a pilot study
Authors: Montero Javier Arredondo , Vega Elena Carracedo , Fortes Paula Ortolá , Anaut Mónica Bronte , de Azúa-Ciria Yerani Ruiz , Fernández-Ariza Adriana , Ibérico Alejandra Moreno , Rodríguez Jessica Paulina , Pascual Carlos Bardají , Troyas Rosa Guarch
Published: June 2024

Background

The lack of adequate resources in international cooperation limits the study of anatomopathological specimens. The literature on potentially inexpensive and available fixation media is scarce.

Material and methods

Our surgical team prospectively collected specimens during cooperation campaigns developed in Senegal. Lesions were fixed in parallel in 10% formalin (FF) and 70% ethyl alcohol (AF). Hematoxylin and eosin sections (HE) and immunohistochemistry (IHC) techniques were performed. Images were anonymized and assessed by two senior and two junior pathologists, who evaluated the quality of staining and diagnostic feasibility using an anonymized questionnaire.

Results

Three surgical specimens were included: 1 lymph node (3 HE, 4 IHC), one seborrheic keratosis (2 HE, 5 IHC), and one branchial remnant (2 HE, 2 IHC). Fixation times were similar in all the specimens (10-13 days). All FF HE were diagnostic. AF H&E was 100% diagnostic in the 5/7 sections and 75% in the remaining sections. In most cases, pathologists preferred FF. CK7, P40, EMA, CKAE1/AE3, and TTF1 were 100% diagnostic in both groups. CD20, CD45, and EMA were 100% diagnostic (FF) and 75% diagnostic (AF). CD10 was 75% diagnostic (FF) and 25% diagnostic (AF). BCL6 was 75% diagnostic (FF) and 100% diagnostic (AF). IHC preferences were inconsistent.

Conclusions

70% ethyl alcohol has a worse fixation profile than 10% formalin but allows diagnosis in most cases. The immunoreactivity observed is variable depending on the tissue and the stain used. Based on these findings, it can be considered an inexpensive, readily available, and potentially helpful fixation medium for diagnosis in developing countries where surgical cooperation campaigns are conducted. Nevertheless, future studies of larger sample sizes and characterizing other histologic subtypes are needed to confirm these findings.
Prevalence of pregnancy termination and associated factors among married women in Papua New Guinea: a nationally representative cross-sectional survey
Authors: Maviso McKenzie , Aines Paula Z. , Potjepat Gracelyn P. , Geregl Nancy , Mola Glen D.L. , Bolnga John W.
Published: June 2024

Background

Pregnancy termination or induced abortion is not decriminalized, and access to safe abortion services is largely unavailable in Papua New Guinea (PNG). However, the practice is common throughout the country. This study aimed to estimate the prevalence and determine factors associated with pregnancy termination among married women aged 15–49 in PNG.

Methods

Secondary data from the 2016–2018 PNG Demographic and Health Survey (PNGDHS) was used. A total weighted samples of 6,288 married women were included. Complex Sample Analysis method was used to account for the cluster design and sample weight of the study. Chi-square tests and multivariable logistic regression were used to assess factors associated with pregnancy termination. Adjusted odds ratios (aORs) with 95% Confidence Intervals (CIs) were reported.

Results

The prevalence of pregnancy termination was 5.3%. Nearly half (45.2%) of all pregnancy terminations occurred in the Highlands region. Women aged 35–44 years (aOR = 8.54; 95% CI: 1.61–45.26), not working (aOR = 6.17; 95% CI: 2.26–16.85), owned a mobile phone (aOR = 3.77; 95% CI: 1.60–8.84), and lived in urban areas (aOR = 5.66; 95% CI: 1.91–16.81) were more likely to terminate a pregnancy. Women who experienced intimate partner violence (IPV) were 2.27 times (aOR = 2.27; 95% CI: 1.17–4.41) more likely to terminate a pregnancy compared to those who did not experience IPV. Women with unplanned pregnancies were 6.23 times (aOR = 6.23; 95% CI: 2.61–14.87) more likely to terminate a pregnancy. Women who knew about modern contraceptive methods and made independent decisions for contraceptive use were 3.38 and 2.54 times (aOR = 3.38; 95% CI: 1.39–8.18 and aOR = 2.54; 95% CI: 1.18–5.45, respectively) more likely to terminate a pregnancy.

Conclusion

The findings highlight the role of sociodemographic and maternal factors in pregnancy termination among married women in PNG. Maternal age, occupation, mobile phone ownership, place of residence, IPV, unplanned pregnancy, knowledge of modern contraceptive methods, and decision-maker for contraceptive use were significantly associated with pregnancy termination. Efforts aimed at reducing unplanned pregnancies and terminations should focus on improving easy access to contraceptives and comprehensive sexual and reproductive health education for married couples. Post-abortion care should also be integrated into the country’s legal framework and added as an important component of existing sexual and reproductive health services.
Bionnica: A Deep Neural Network Architecture for Colorectal Polyps’ Premalignancy Risk Evaluation
Authors: Babuc Diogen , Ivaşcu Todor , Ardelean Melania , Onchiş Darian
Published: June 2024

The third most prevalent cancer nowadays is colorectal cancer. Colonoscopy is an important procedure in the stage of detection of polyps’ malignancy because it helps in early identification and establishes effective therapy. This paper explores specific deep-learning architectures for the binary classification of colorectal polyps and considers the evaluation of their premalignancy risk. The main scope is to create a custom-based deep learning architecture that classifies adenomatous, hyperplastic, and serrated polyps’ samples into benign and premalignant based on images from the colonoscopic dataset. Each image’s output is modified through masked autoencoders which enhance the classification performance of the proposed model, calledBionnica. From the four evaluated state-of-the-art deep learning models (ZF NET, VGG-16, AlexNet, and ResNet-50), our experiments showed that ResNet-50 and ZF NET are most accurate (above 84%), with ResNet-50 excelling at indicating patients with premalignant colorectal polyps (above 92%). ZF NET is the fastest at handling 700 images. Our proposed deep learning model,Bionnica, is more performant than ZF NET and provides an efficient classification of colorectal polyps given its simple structure. The advantage of our model comes from the custom enhancement interpretability with a rule-based layer that guides the learning process and supports medical personnel in their decisions.
Health Security Across the Spectrum: Exploring the Impact of Socioeconomic Factors on Health Insurance Uptake in India
Authors: Chatterjee Madhubrota , Aditya Alok , Choudhary Prashant Kumar
Published: June 2024

To ensure that healthcare services are accessible, health insurance is receiving increased amounts of attention in debates among health experts. The current disease pattern has forced people to rely on intensive care, which has increased both the cost of treatment and the frequency of accessing healthcare facilities. This paper has focused on various socioeconomic and demographic determinants of choice that are important for ensuring the use of various types of health insurance schemes or programs among the older population in India. Using the Longitudinal Survey of Aging in India (LASI) Wave-1 2020 data, the total sample used for this study included 66,658 elderly individuals aged 45 years and older. Both binary association and multinomial logistic regression were employed to examine the associations of all the socioeconomic and demographic determinants with people having and not having access to different health insurance. The findings showed that there is a greater incidence of government health insurance than of community, employer, or private health insurance among people in all categories based on demographic, geographical, economic distribution, and health status, with chronic diseases showing some impact on people choosing to be insured. This study recommends that policy actions be taken to make the health insurance market transparent and reduce the chances of failure.

Contributions to the literature

The current epidemiological transition, along with the prospective demographic transition of more people in later stages of life that India is currently facing and will experience in the coming decades, has raised severe concerns about the accessibility of healthcare services.

Knowing the factors and reasons for choosing certain health insurance schemes is highly important for tracing the actual lags in the Indian health insurance market and will help policymakers formulate health insurance policies.

The need to make the Indian health insurance market transparent.

reducing the chances of failure of health insurance schemes
Investigating Genetic and Familial Risks in Childhood ALL: A Longitudinal Virtual Study Using aiHumanoid Simulations of TEL-AML1 Gene Fusion
Authors: Danter WR
Published: June 2024

Acute Lymphoblastic Leukemia (ALL) is the most common childhood cancer, presenting significant challenges in early diagnosis and effective treatment. Recent advances in gene profiling have identified a pivotal role for the TEL-AML1 (ETV6-RUNX1) gene fusion, present in about one quarter of pediatric ALL cases. This gene fusion is often associated with a more benign course and requires additional genetic abnormalities known asSecond Hits, to cause overt leukemia. Our current study utilizes Fuzzy Cognitive Maps (FCMs) to model the intricate genetic interplays and potential progression paths of ALL in children, focusing on those with the TEL-AML1 gene fusion within a familial leukemia context.

In this virtual longitudinal study, we leverage cohorts of aiHumanoid simulations to explore the foundational role of the TEL-AML1 fusion gene in the genesis of ALL, examining its impact when combined with a family history of leukemia. The simulations predict how genetic and environmental factors might influence disease onset and progression, providing a platform for early diagnosis and progression monitoring.

Our findings suggest that family history significantly increases the risk and modifies the disease course in carriers of the TEL-AML1 fusion gene, indicating a need for targeted surveillance and potential early interventions in these high-risk groups.
Internalizing Psychiatric Symptoms in People with Mosaicism for Trisomy 21
Authors: Brown Ruth C. , D’Aguilar Allison , Hurshman Quinn , NailorZee Rebekah , York Timothy P. , Capone George , Amstadter Ananda B. , Jackson-Cook Colleen
Published: June 2024

People with mosaicism for trisomy 21 have been shown to exhibit the many of same phenotypic traits present in people with non-mosaic Down syndrome, but with varying symptom severity. However, the behavioral phenotype of people with mosaic Down syndrome (mDS) has not been well characterized. This study aimed to examine the prevalence of self-report and caregiver-report symptoms of depression and anxiety among a sample of 62 participants with mDS aged 12 - 46, and assess their association with the percentage of trisomy 21 in blood and/or buccal mucosa cells. The results showed that 53% of the participants reported clinically significant depression symptoms and 76% reported clinically significant anxiety symptoms. No clear associations were observed between the percentage of trisomic cells and total anxiety or depression, but a significant positive association between the proband-reported specific fears subscale and the percentage of trisomic cells in buccal specimens was detected (r= .43,p= .007). This study highlights the high occurrence of depression and anxiety symptoms in individuals with mDS and the need for routine assessment to optimize their care. It also demonstrates the ability of people with mDS to complete these evaluations, thereby supporting their inclusion in research studies/clinical trials.
Clinical phenotype and management of sound-induced pain: Insights from adults with pain hyperacusis
Authors: Jahn Kelly N. , Kashiwagura Sean Takamoto , Yousuf Muhammad Saad
Published: June 2024

Pain hyperacusis, also known as noxacusis, causes physical pain in response to everyday sounds that do not bother most people. How sound causes excruciating pain that can last for weeks or months in otherwise healthy individuals is not well understood, resulting in a lack of effective treatments. To address this gap, we identified the most salient physical and psychosocial consequences of debilitating sound-induced pain and reviewed the interventions that sufferers have sought for pain relief to gain insights into the underlying mechanisms of the condition. Adults (n= 32) with pain hyperacusis attended a virtual focus group to describe their sound-induced pain. They completed three surveys to identify common symptoms and themes that defined their condition and to describe their use of pharmaceutical and non-pharmaceutical therapies for pain relief. All participants endorsed negative effects of pain hyperacusis on psychosocial and physical function. Most reported sound-induced burning (80.77%), stabbing (76.92%), throbbing (73.08%), and pinching (53.85%) that occurs either in the ear or elsewhere in the body (i.e., referred pain). Participants reported using numerous pharmaceutical and non-pharmaceutical interventions to alleviate their pain with varying degrees of pain relief. Benzodiazepines and nerve blockers emerged as the most effective analgesic options while non-pharmaceutical therapies were largely ineffective. Symptoms of pain hyperacusis and therapeutic approaches are largely consistent with peripheral mechanistic theories of pain hyperacusis (e.g., trigeminal nerve involvement). An interdisciplinary approach to clinical studies and the development of animal models is needed to identify, validate, and treat the pathological mechanisms of pain hyperacusis.
Co-isolation ofPenicillium citrinumand its cell-switching partnerMeyerozyma guilliermondiifrom a geothermal power plant
Authors: Bregnard Danaé , Cailleau Guillaume , van Zonneveld Wart , Regenspurg Simona , Bindschedler Saskia , Junier Pilar
Published: June 2024

Progresses in geothermal energy and deep drilling technologies have opened a new window into the terrestrial subsurface. This provides direct access to deep geothermal fluids used to produce heat and electricity, creating an opportunity to isolate and characterize novel microbial strains from these extreme habitats. In this study, we report the co-isolation of two fungal strains.Penicillium citrinum(strain HEK1) was isolated first and thought to be axenic. However, upon exposure to stress (frost and ethanol), a second strain, corresponding to the dimorphic yeastMeyerozyma guilliermondii(strain HEK2), appeared in HEK1 cultures. Strain HEK2 appeared first in the cultures and was followed by the subsequent re-growth of strain HEK1, underscoring their close relationship. Moreover, strain HEK2, able to switch from yeast cells to pseudohyphae when growing alone, did not produce pseudohyphae when in direct contact with strain HEK1. Altogether, our results indicate an intricate interaction between these strains that may allow them to thrive in the deep subsurface. These two fungi represent the first fungal strains isolated from deep geothermal fluids. Their presence within the fluids was confirmed through molecular analysis. The isolation of these strains emphasizes the importance of considering fungi when investigating microbial diversity in subsurface geothermal environments.

Graphical abstract

Highlights

First fungal strains isolated from a geothermal power plant

The two fungal strains were co-isolated from a geothermal fluid used for heat production

Surprising isolation of the cell-switching yeast upon stress exposure of an apparently axenic culture of the filamentous fungus

Fungal strains with high resistance to stressors and no apparent competition for carbon sources
Phagolysosomes break down the membrane of a non-apoptotic corpse independent of macroautophagy
Authors: Kolli Shruti , Kline Cassidy J. , Rad Kimya M. , Wehman Ann M.
Published: June 2024

Cell corpses must be cleared in an efficient manner to maintain tissue homeostasis and regulate immune responses. Ubiquitin-like Atg8/LC3 family proteins promote the degradation of membranes and internal cargo during both macroautophagy and corpse clearance, raising the question how macroautophagy contributes to corpse clearance. Studying the clearance of non-apoptotic dying polar bodies inCaenorhabditis elegansembryos, we show that the LC3 ortholog LGG-2 is enriched in the polar body phagolysosome independent of membrane association or autophagosome formation. We demonstrate that ATG-16.1 and ATG-16.2, which promote membrane association of lipidated Atg8/LC3 proteins, redundantly promote polar body membrane breakdown in phagolysosomes independent of their role in macroautophagy. We also show that the lipid scramblase ATG-9 is needed for autophagosome formation in early embryos but is dispensable for timely polar body membrane breakdown or protein cargo degradation. These findings demonstrate that macroautophagy is not required to promote polar body degradation, in contrast to recent findings with apoptotic corpse clearance inC. elegansembryos. Determining how membrane association of Atg8/LC3 promotes the breakdown of different types of cell corpses in distinct cell types or metabolic states is likely to give insights into the mechanisms of immunoregulation during normal development, physiology, and disease.
A failure to discriminate social from non-social touch at the circuit level may underlie social avoidance in autism
Authors: Chari Trishala , Hernandez Ariana , Couto João , Portera-Cailliau Carlos
Published: June 2024

Social touch is critical for communication and to impart emotions and intentions. However, certain autistic individuals experience aversion to social touch, especially when it is unwanted. We used a novel social touch assay and Neuropixels probes to compare neural responses to social vs. non-social interactions in three relevant brain regions: vibrissal somatosensory cortex, tail of striatum, and basolateral amygdala. We find that wild type (WT) mice showed aversion to repeated presentations of an inanimate object but not of another mouse. Cortical neurons cared most about touch context (social vs. object) and showed a preference for social interactions, while striatal neurons changed their preference depending on whether mice could choose or not to interact. Amygdalar and striatal neurons were preferentially modulated by forced object touch, which was the most aversive. In contrast, theFmr1knockout (KO) model of autism found social and non-social interactions equally aversive and displayed more aversive facial expressions to social touch when it invaded their personal space. Importantly, whenFmr1KO mice could choose to interact, neurons in all three regions did not discriminate social valence. Thus, a failure to differentially encode social from non-social stimuli at the circuit level may underlie social avoidance in autism.
Partially dissociable roles of the Orbitofrontal cortex and dorsal Hippocampus in context-dependent (hierarchical) reward prediction and contextual inference in learning
Authors: Peterson Sophie , Chavira Jose , Arango Alex Garcia , Seamans David , Cimino Emma , Keiflin Ronald
Published: June 2024

Reward cues are often ambiguous; what is good in one context is not necessarily good in another context. To solve this ambiguity, animals form hierarchical associations in which the context acts as a gatekeeper in the retrieval of the appropriate cue-evoked memory, ensuring context-appropriate behavior. These hierarchical associative structures also influence future learning by promoting the formation of new context-dependent associations (leading to the inference of context-dependency for new associations). The orbitofrontal cortex (OFC) and the dorsal hippocampus (DH) are both proposed to encode a “cognitive map” that includes the representation of hierarchical, context-dependent, associations. However the causal role of the OFC and DH in the different functional properties of hierarchical associations remains controversial. Here we used chemogenetic inactivations, in rats, to examine the role of OFC and DH in 1) the contextual regulation of performance, and 2) the contextual learning bias conferred by hierarchical associations. We show that OFC is required for both manifestations of hierarchical associations. In contrast, DH contribution appears limited to the contextual learning bias. This study provides novel insight into the different functional properties of context-dependent hierarchical associations, and establishes the OFC as a critical orchestrator of these different contextual effects.
Attosecond two-color x-ray free-electron lasers with dual chirp-taper configuration and bunching inheritance
Authors: Sun Hao , Wang Xiaofan , Zhang Weiqing
Published: June 2024

Attosecond x-ray pulses play a crucial role in the study of ultrafast phenomena occurring within inner and valence electrons. To achieve attosecond time-resolution studies and gain control over electronic wave functions, it is crucial to develop techniques capable of generating and synchronizing two-color x-ray pulses at the attosecond scale. In this paper, we present a novel approach for generating attosecond pulse pairs using a dual chirp-taper free-electron laser with bunching inheritance. An electron beam with a sinusoidal energy chirp, introduced by the external laser, passes through the main undulator and afterburner, both with tapers. Two-color x-ray pulses are generated from the main undulator and the afterburner, respectively, with temporal separations of several femtoseconds and energy separations of tens of electron volts. Notably, the afterburner is much shorter than the main undulator due to the bunching inheritance, which reduces the distance between two source points and alleviates the beamline focusing requirements of the two-color pulses. A comprehensive stability analysis is conducted in this paper, considering the individual effects of shot noise from self-amplified spontaneous emission and carrier-envelope phase jitter of the few-cycle laser. The results show that the radiation from the afterburner exhibits excellent stability in the proposed scheme, which is beneficial for x-ray pump-probe experiments. The proposed scheme opens up new possibilities for attosecond science enabled by x-ray attosecond pump-probe techniques and coherent control of ultrafast electronic wave packets in quantum systems.

Published by the American Physical Society
2024
Low-depth Clifford circuits approximately solve MaxCut
Authors: Muñoz-Arias Manuel H. , Kourtis Stefanos , Blais Alexandre
Published: June 2024

We introduce a quantum-inspired approximation algorithm for MaxCut based on low-depth Clifford circuits. We start by showing that the solution unitaries found by the adaptive quantum approximation optimization algorithm (ADAPT-QAOA) for the MaxCut problem on weighted fully connected graphs are (almost) Clifford circuits. Motivated by this observation, we devise an approximation algorithm for MaxCut, ADAPT-Clifford, that searches through the Clifford manifold by combining a minimal set of generating elements of the Clifford group. Our algorithm finds an approximate solution of MaxCut on an N-vertex graph by building a depth O(N) Clifford circuit. The algorithm has runtime complexity O(N2) and O(N3) for sparse and dense graphs, respectively, and space complexity O(N2), with improved solution quality achieved at the expense of more demanding runtimes. We implement ADAPT-Clifford and characterize its performance on graphs with positive and signed weights. The case of signed weights is illustrated with the paradigmatic Sherrington-Kirkpatrick model, for which our algorithm finds solutions with ground-state mean energy density corresponding to ∼94% of the Parisi value in the thermodynamic limit. The case of positive weights is investigated by comparing the cut found by ADAPT-Clifford with the cut found with the Goemans-Williamson (GW) algorithm. For both sparse and dense instances we provide copious evidence that, up to hundreds of nodes, ADAPT-Clifford finds cuts of lower energy than GW.

Published by the American Physical Society
2024
Competitive superconductivity and charge density wave in Mo-doped kagome superconductor
CsV3Sb5
Authors: Zhu K. J. , Nie L. P. , Lei B. , Wang M. J. , Sun K. L. , Deng Y. Z. , Tian M. L. , Wu T. , Chen X. H.
Published: June 2024

In the kagome superconductors AV3Sb5 (A = K, Rb, Cs), understanding the charge-density-wave (CDW) state and its entanglement with the superconducting ground state is still a challenging issue. Here, by measuring the electrical transport, magnetic susceptibility, Hall effect, and V51 nuclear magnetic resonance (NMR), the evolution of superconductivity (SC) and the CDW is comprehensively studied in Cs(V1−xMox)3Sb5. In contrast with previously reported results for other doped cases, the CDW transition temperature slightly increases to ∼100 K with increasing Mo doping. Meanwhile, the SC is quickly suppressed and vanishes above x=0.02. The anomalous Hall effect (AHE), which is tied to the exotic nature of the CDW state in pristine CsV3Sb5, is also strongly suppressed and completely disappears above x=0.07. Further V51 NMR investigation on the CDW state in Cs(V0.95Mo0.05)3Sb5 indicates that a short-range stripelike CDW evolves from the original triple-Q CDW state with increasing Mo doping, which largely reduces the density of states at the Fermi level. This result provides a self-consistent explanation for the disappearance of both SC and the AHE by increasing Mo doping, which offers insights into the competitive behavior between SC and the CDW state in the kagome superconductors AV3Sb5.

Published by the American Physical Society
2024