bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptomic Profiling Reveals Claudin 18.2 as a Diagnostic Biomarker of Ménétrier’s Disease and the Role of Hedgehog Signaling in Pathogenesis
Authors: Shin Miyoung , Gabriel Tryston , Coffey Robert J. , Huh Won Jae 
Published: November 2023

ABSTRACTBoth Ménétrier’s disease (MD) and juvenile polyposis syndrome (JPS) are rare premalignant conditions that can lead to gastric cancer development. MD is an acquired disease without known causative mutations. MD patients are characterized by an increased expression of EGF receptor (EGFR) ligand and transforming growth factor alpha (TGF-α) in the stomach. JPS is inherited in an autosomal dominant pattern and is caused byBMPR1AorSMAD4mutations. It is characterized by multiple polyps throughout the gastrointestinal tract along with certainSMAD4mutations that can result in gastric polyposis. Although there are many distinct clinico- endoscopic and histopathologic features that differ between the two diseases, they also share similar features that often lead to misdiagnosis. This study aimed to identify markers that can help distinguish MD from JPS and to better understand the pathogenesis of MD by comparing differential gene expression patterns.Upon examination of MD and JPS microscopically, we found almost all cases have patchy areas mimicking each other, making it difficult to make a correct diagnosis with histopathologic examination alone. Comparative analysis between MD and JPS using ingenuity pathway analysis (IPA) revealed both common and differential gene signatures. Common gene signatures included estrogen receptor signaling, integrin signaling, mTOR signaling, and others, which may be responsible for histopathologic similarities. Among differential gene signatures, we found thatclaudin 18(CLDN18) is upregulated in MD and confirmed that CLDN18.2 (isoform of CLDN18) protein expression is higher in MD than JPS by immunohistochemistry. Comparative analysis between MD and normal control revealed the hedgehog (Hh) signaling pathway is upregulated in MD. Treatment with a hedgehog pathway inhibitor partially rescued the histopathologic phenotypes in a MD mouse model.The current study provides valuable insight into the potential underlying mechanism of why MD and JPS show similar clinico-pathologic features. We also identified a diagnostic marker CLDN18.2 that can help distinguish MD from JPS, genetically. Furthermore, it also shows that Hh signaling plays an important role in the pathogenesis of MD and can function as a potential therapeutic target.
Multi-omics characterization of lymphedema-induced adipose tissue from breast cancer patients
Authors: Karaman Sinem , Lehti Satu , Zhang Cheng , Taskinen Marja-Riitta , Käkelä Reijo , Mardinoglu Adil , Brorson Håkan , Alitalo Kari , Kivelä Riikka 
Published: November 2023

ABSTRACTObjectiveSecondary lymphedema (LE) following breast cancer surgery is a life-long complication, which currently has no cure. LE induces significant regional adipose tissue deposition, requiring liposuction as a treatment. Here, we aimed to elucidate the transcriptional, metabolomic, and lipidomic signature of the adipose tissue developed due to the surgery-induced LE in short- and long-term LE patients, and compared the transcriptomic landscape in LE to the obesity-induced adipose tissue.MethodsAdipose tissue biopsies were obtained from breast cancer-operated females with LE from the affected and non-affected arms (n=20 patients). To decipher molecular properties of the LE adipose tissue, we performed RNA sequencing, metabolomics, and lipidomics combined with bioinformatics analyses.ResultsIntegrative analysis of functional genomics revealed that inflammatory response, cell chemotaxis and angiogenesis were upregulated biological processes in the LE arm, indicating a sustained inflammation in the edematous adipose tissue, whereas, epidermal differentiation, cell-cell junction organization, water homeostasis and neurogenesis were, in turn, downregulated in the LE arm. Surprisingly, only few genes were found to be the same in the LE-induced and the obesity-induced adipose tissue expansion, indicating a different type of adipose tissue development in these two diseases. In metabolomics analysis, the concentration of a branched-chain amino acid valine was found to be reduced in the edematous arm together with downregulation of mRNA levels of its transporterSLC6A15. Lipidomics analyses did not show any significant differences between the diseased and healthy arm, suggesting that diet affects the lipid composition of the adipose tissue more than the LE.ConclusionsOur results provide a detailed molecular characterization of adipose tissue in secondary LE of breast cancer patients vs individuals with obesity. The results show distinct differences in transcriptomic signatures between LE patients vs individuals with obesity, but only minor differences in metabolome and lipidome between the diseased and the healthy arm.
Convolutional neural network model detected lasting behavioral changes in mouse with kanamycin-induced unilateral inner ear dysfunction
Authors: Noda Masao , Mari Shimada Dias , Sajjaviriya Chortip , Koshu Ryota , Saito Chizu , Ito Makoto , Koshimizu Taka-aki 
Published: November 2023

AbstractIn acute aminoglycoside ototoxicity to unilateral inner ear, physical abnormalities, such as nystagmus and postural alteration, are relieved within a few days by neural compensation. To examine exploratory behavior over an extended period, freely moving behavior of a mouse after unilateral kanamycin injection was recorded in a home-cage environment. A tail was excluded from deep learning-mediated object detection because of its delayed movement relative to the body. All detection results were confirmed by convolutional neural network classification model. In kanamycininjected mice, total distance moved in 15 minutes increased at 3 days after surgery. Moreover, the injured mouse turned frequently toward healthy side up to 17 days after surgery. Tail suspension and twist toward healthy side induced fast rotation of trunk around longitudinal axis with dorsal bending after 14 days. Our analysis strategy employing deep learning is useful to evaluate neuronal compensatory process and screen a drug candidate with therapeutic potency.
Movi: a fast and cache-efficient full-text pangenome index
Authors: Zakeri Mohsen , Brown Nathaniel K. , Ahmed Omar Y. , Gagie Travis , Langmead Ben 
Published: November 2023

AbstractEfficient pangenome indexes are promising tools for many applications, including rapid classification of nanopore sequencing reads. Recently, a compressed-index data structure called the “move structure” was proposed as an alternative to other BWT-based indexes like the FM index and r-index. The move structure uniquely achieves both O(r) space and O(1)-time queries, where r is the number of runs in the pangenome BWT. We implemented Movi, an efficient tool for building and querying move-structure pangenome indexes. While the size of the Movi’s index is larger than the r-index, it scales at a smaller rate for pangenome references, as its size is exactly proportional to r, the number of runs in the BWT of the reference. Movi can compute sophisticated matching queries needed for classification – such as pseudo-matching lengths and backward search – at least ten times faster than the fastest available methods, and in some cases more than 30-fold faster. Movi achieves this speed by leveraging the move structure’s strong locality of reference, incurring close to the minimum possible number of cache misses for queries against large pangenomes. We achieve still further speed improvements by using memory prefetching to attain a degree of latency hiding that would be difficult with other index structures like the r-index. Movi’s fast constant-time query loop makes it well suited to real-time applications like adaptive sampling for nanopore sequencing, where decisions must be made in a small and predictable time interval.
Exploring building blocks of cell organization by estimating network motifs using graph isomorphism network
Authors: Yu Yang , Wang Shuang , Xu Dong , Wang Juexin 
Published: November 2023

AbstractThe spatial arrangement of cells within tissues plays a pivotal role in shaping tissue functions. A critical spatial pattern is network motif as the building blocks of cell organization. Network motifs can be represented as recurring significant interconnections of cells with various types in a spatial cell-relation graph, i.e., enriched occurrences of isomorphic subgraphs in the graph, which is computationally infeasible to have an optimal solution with large-size (>3 nodes) subgraphs. We introduceTriangulation NetworkMotifNeuralNetwork (TrimNN), a neural network-based approach designed to estimate the prevalence of network motifs of any size in a triangulated cell graph. TrimNN simplifies the intricate task of occurrence regression by decomposing it into several binary present/absent predictions on small graphs. TrimNN is trained using representative pairs of predefined subgraphs and triangulated cell graphs to estimate overrepresented network motifs. On typical spatial omics samples within thousands of cells in dozens of cell types, TrimNN robustly infers the presence of a large-size network motif in seconds. In a case study using STARmap Plus technologies, TrimNN identified several biological meaningful large-size network motifs significantly enriched in a mouse model of Alzheimer’s disease at different months of age. TrimNN provides an accurate, efficient, and robust approach for quantifying network motifs, which helps pave the way to disclose the biological mechanisms underlying cell organization in multicellular differentiation, development, and disease progression.
Analyzing asymmetry in brain hierarchies with a linear state-space model of resting-state fMRI data
Authors: Benozzo Danilo , Baggio Giacomo , Baron Giorgia , Chiuso Alessandro , Zampieri Sandro , Bertoldo Alessandra 
Published: November 2023

AbstractThe study of functional brain connectivity in resting-state functional magnetic resonance imaging (rsfMRI) data has traditionally focused on zero-lag statistics. However, recent research has emphasized the need to account for dynamic aspects due to the complex patterns of time-varying co-activations among brain regions. In this regard, the importance of non-zero-lag statistics in studying complex brain interactions has been emphasized, both in terms of modeling and data analysis. Here, we show how a time-lag description is incorporated within the framework of dynamic causal modeling (DCM) resulting in an asymmetric state interaction matrix known as effective connectivity (EC). Asymmetry in EC is conventionally associated with the directionality of interactions between brain regions and is frequently employed to distinguish between incoming and outgoing node connections. We will revisit this interpretation by employing a decomposition of the EC matrix. This decomposition enables us to isolate the steady-state differential crosscovariance matrix, which is responsible for modeling the information flow and introducing time irreversibility. In other words, by modeling the off-diagonal part of the differential covariance, the system landscape may exhibit a curl steady-state flow component that breaks detailed balance and diverges the dynamics from equilibrium. Our empirical results reveal that only the outgoing strengths of the EC matrix relate with the flow described by the differential cross-covariance, while the so-called incoming strengths are primarily driven by the zero-lag covariance, specifically the precision matrix, thus reflecting conditional independence rather than directionality.
Ultra-Long-Term Delivery of Hydrophilic Drugs Using InjectableIn SituCross-Linked Depots
Authors: Lee Sohyung , Zhao Spencer , Jiang Weihua , Chen Xinyang , Zhu Lingyun , Joseph John , Agus Eli , Mary Helna Baby , Barooj Shumaim , Slaughter Kai , Cheung Krisco , Luo James N , Shukla Chetan , Gao Jingjing , Lee Dongtak , Balakrishnan Biji , Jiang Christopher , Gorantla Amogh , Woo Sukyung , Karp Jeffrey M , Joshi Nitin 
Published: November 2023

AbstractAchieving ultra-long-term release of hydrophilic drugs over several months remains a significant challenge for existing long-acting injectables (LAIs). Existing platforms, such asin situforming implants (ISFI), exhibit high burst release due to solvent efflux and microsphere-based approaches lead to rapid drug diffusion due to significant water exchange and large pores. Addressing these challenges, we have developed an injectable platform that, for the first time, achieves ultra-long-term release of hydrophilic drugs for over six months. This system employs a methacrylated ultra-low molecular weight pre-polymer (polycaprolactone) to createin situcross-linked depots (ISCD). The ISCD’s solvent-free design and dense mesh network, both attributed to the ultra-low molecular weight of the pre-polymer, effectively minimizes burst release and water influx/efflux.In vivostudies in rats demonstrate that ISCD outperforms ISFI by achieving lower burst release and prolonged drug release. We demonstrated the versatility of ISCD by showcasing ultra-long-term delivery of several hydrophilic drugs, including antiretrovirals (tenofovir alafenamide, emtricitabine, abacavir, and lamivudine), antibiotics (vancomycin and amoxicillin) and an opioid antagonist naltrexone. Additionally, ISCD achieved ultra-long-term release of the hydrophobic drug tacrolimus and enabled co-delivery of hydrophilic drug combinations encapsulated in a single depot. We also identified design parameters to tailor the polymer network, tuning drug release kinetics and ISCD degradation. Pharmacokinetic modeling predicted over six months of drug release in humans, significantly surpassing the one-month standard achievable for hydrophilic drugs with existing LAIs. The platform’s biodegradability, retrievability, and biocompatibility further underscore its potential for improving treatment adherence in chronic conditions.
A new cloud forest treeLychnodiscus bali(Sapindaceae), Critically Endangered from the Bali-Ngemba Forest reserve, N.W. Region, Cameroon
Authors: Cheek Martin , Onana Jean Michel , Lachenaud Olivier 
Published: November 2023

SummaryWe describeLychnodiscus bali(Sapindaceae) a new species to science, from the Bali Ngemba Forest Reserve of NW Region Cameroon, the last major remnant of cloud forest in the Bamenda Highlands of Cameroon, recently evidenced as a Tropical Important Plant Area (TIPA or IPA). Confined on current evidence to upper submontane forest, the species is threatened by expanding habitat clearance for farms and is assessed as Critically Endangered. A small tree, attaining 3–4 m height, it is the first new species to be added to this Guineo-Congolian tree genus in 50 years, the third recorded from Cameroon, and takes the number of species in the genus to eight. It has the highest known altitudinal range (1700 – 1950 m alt.), of any species of the genus.Previously identified asLychnodiscus grandifolius, the new species differs in the shorter length of the distal leaflets (12 – 18 cm vs 22 – 39 cm long), in the abaxial surface lacking glands (vs glands flat and conspicuous), tertiary nerves hairy (vs glabrous), flowers at anthesis 8 – 11 mm long (vs 5 – 7 mm long).Lychnodiscus baliis described, illustrated and its extinction risk assessment as Critically Endangered is presented. We discuss its discovery in the context of other recently discovered and highly threatened or even extinct plant species in the Cameroon Highlands, and the importance of their conservation.We present an updated key to the identification of the species of the genus,and discuss its classification in the context of recent molecular phylogenomic studies. Previously placed in Cupanieae by Radlkofer, the authors contend thatLychnodiscusshould now be placed in the reconstituted Nepheliaeae in the revised 2021 intrafamilial classification of Buerki et al., probably close to the generaAporrhizaandLaccodiscus. However, until the genus is included in molecular studies this cannot be confirmed and its sister relationship remains speculative.
Renal mechanotransduction is an essential regulator of renin
Authors: Hill Rose Z. , Shirvan Sepenta , Burquez Sebastian , Dubin Adrienne E. , Servin-Vences M. Rocio , Miner Jeffrey H. , Patapoutian Ardem 
Published: November 2023

AbstractThe kidneys tightly control the composition of our internal environment to maintain homeostasis in the face of external variability. The regulation of blood volume begins in the kidneys and is essential for vertebrate life in terrestrial environments where salt and water availability are unpredictable1,2. Renin synthesis and release by juxtaglomerular granular cells of the kidney is the rate-limiting step in a hormonal cascade that modulates blood volume, filtration, and salt balance2. Renin is stimulated during hypovolemia and salt deprivation in response to chemical cues released from sympathetic efferent neurons and the macula densa onto the juxtaglomerular granular cells. Renin levels are also proposed to be modulated by mechanical forces elicited by changes in blood volume and/or pressure exerted upon juxtaglomerular cells2–4. However, the identity and significance of the juxtaglomerular mechanotransducer(s) was unknown. We found that the force-gated ion channel PIEZO2 is expressed in juxtaglomerular granular cells and in neighboring mesangial cells. Selective genetic ablation of PIEZO2 dysregulated the renin-angiotensin-aldosterone system by elevating renin, raising systemic blood pressure, inducing glomerular hyperfiltration, and exaggerating the hormonal response to volume depletion. These findings demonstrate that PIEZO2 contributes to renal blood volume sensing and kidney functionin vivo.
Validation and Responsiveness of the English version of the Chemotherapy-Induced Alopecia Distress Scale (CADS) in Breast Cancer Patients
Authors: Kraehenbuehl L. , Kang D. , Bang A. S. , Ketosugbo K. F. , Hay J. , Patil Sujata , Goldfarb S. , Cho J. , Lacouture M. E. 
Published: November 2023

AbstractPurposeThis study aimed to validate the chemotherapy-induced alopecia distress scale (CADS) in a diverse English-speaking population and patients with endocrine treatment- induced alopecia (EIA).ObjectiveChemotherapy and endocrine therapy commonly cause alopecia in breast cancer patients, leading to significant psychological and social challenges. The CADS was developed to assess the psychosocial impact of alopecia, but its generalizability beyond Korean patients requires further investigation.MethodsData from the CHANCE study (NCT02530177), which focused on non-metastatic breast cancer, was used. The cohort included 256 patients, and CADS data were collected at baseline, six months after chemotherapy completion, or 12 months after initiating endocrine therapy. The CADS questionnaire comprised 17 items covering physical and emotional health, daily activities, and relationships. Reliability was assessed using Cronbach’s alpha, and responsiveness was measured by effect size.ResultsThe CADS exhibited good reliability, with a Cronbach’s alpha of 0.91 for the overall score, indicating acceptable internal consistency in both chemotherapy (0.89) and endocrine therapy (0.86) groups. Longitudinal responsiveness was supported by an effect size of 0.49 between decreasing satisfaction with hair growth and increasing emotional distress. Cross-sectional validity was confirmed, with effect sizes of 0.91 and 0.92 for satisfaction with hair growth and emotional and activity domains, respectively.ConclusionThe CADS is a valid and responsive tool for assessing the psychosocial impact of chemotherapy-induced alopecia and endocrine treatment-induced alopecia in a diverse Western patient population.
National diagnostic reference levels for digital diagnostic and screening mammography in Uganda
Authors: Odongo Denish , Musisi Alen , Okello Richard Omara , Bongomin Felix , Erem Geoffrey 
Published: November 2023

AbstractIntroductionScreening and diagnostic mammography are associated with some risk of radiation-induced breast cancer. This study was conducted to establish the National Diagnostic Reference Levels (NDRLs) for digital diagnostic and screening mammography in Uganda to achieve breast radiation dose optimization.MethodsA cross-sectional study was conducted among female participants recruited by a consecutive sampling from three selected Hospitals with digital mammography in Uganda. The study variables extracted from the mammography machines were exposure factors, compressed breast thickness (CBT), and Average Glandular Dose (AGD) of two standard mammogram views. The stratified National DRL was derived by calculating 75thpercentile of the AGD across all the samples at various CBT ranges for both screening and diagnostic mammography in craniocaudal (CC) and mediolateral oblique (MLO) views.ResultsWe included 300 participants with mean ages of 50.28±9.32 and 47.45±13.45 years for the screening and diagnostic mammography, respectively. There were statistically significant positive correlations between AGD and exposures factors (mAs, kVp) (all p-values<0.0001). For screening mammography, mAs demonstrated a strong positive correlation (r = 0.8369 in CC, 0.8133 in MLO), whereas kVp showed positive correlation with relatively lower coefficients (r = 0.3700 in CC, 0.3080 in MLO). In diagnostic mammography, mAs exhibited an even stronger positive correlation (r = 0.8987 in CC, 0.8762 in MLO), and kVp maintained a positive correlation with somewhat lower coefficients (r = 0.4954 in CC, 0.3597 in MLO). In screening mammography, for CBT within the range of (7-39)mm, the NDRLs were (1.5mGy, 1.66mGy) in CC) and MLO views. For CBT in the range of (40-59)mm, the NDRLs were (1.78mGy, 1.87mGy), and for CBT in the range of (60-99)mm, the NDRLs were (2.18mGy, 2.22mGy). For diagnostic mammography, the NDRLs were established as (1.7mGy, 1.91mGy), (2.00mGy, 2.09mGy), and (2.63mGy, 2.81mGy) for CBT ranges of (7-39)mm, (40-59)mm, and (60-99)mm, respectively.ConclusionThe NDRLs for digital screening and diagnostic mammography in Uganda have been proposed for the first time. The NDRL values in mammography should be specific to CBT ranges and mammographic views for both diagnostic and screening mammography.