bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sagittal Craniosynostosis: Comparing Surgical Techniques using 3D Photogrammetry
Authors: Abdel-Alim Tareq , Kurniawan Melissa , Mathijssen Irene , Dremmen Marjolein , Dirven Clemens , Niessen Wiro , Roshchupkin Gennady , van Veelen Marie-Lise 
Published: March 2023

OBJECTIVE:
The aim of this study is to compare three surgical interventions to correct sagittal synostosis: frontobiparietal remodeling (FBR), extended strip craniotomy (ESC), and spring assisted correction (SAC), based on 3D photogrammetry and operation characteristics.

METHODS:
All patients diagnosed with non-syndromic sagittal synostosis, born between 1991 and 2019, who underwent FBR, ESC or SAC, and had at least one postoperative 3D photogrammetry image taken during one of six follow-up moments until the age of six, were considered for this study. Operation characteristics, postoperative complications, re-interventions, and presence of intracranial hypertension were collected. To assess cranial growth, orthogonal cranial slices and 3D photocephalometric measurements were extracted automatically and evaluated from 3D photogrammetry images.

RESULTS:
A total of 322 postoperative 3D images from 218 patients were included. After correcting for age and gender, no significant differences were observed in 3D photocephalometric measurements. Mean cranial shapes suggest that postoperative growth and shape gradually normalize with higher OFC and ICV values compared to normal, regardless of type of surgery. Flattening of the vertex seems to persist after surgical correction. Our cranial 3D mesh processing tool has been made publicly available as a part of this study.

CONCLUSION:
Our findings suggest that until the age of six, there are no significant differences between the FBR, ESC, and SAC in their ability to correct sagittal synostosis with regard to 3D photocephalometric measurements. Therefore, efforts should be made to ensure early diagnosis so that minimally invasive surgery is still a viable treatment option.
Surgery-first orthognathic approach for correction of dentofacial deformity in unilateral cleft lip and palate
Authors: Liao Yu-Fang , Chen Yun-Fang , Chang Chun-Shin , Lu Ting-Chen , Chen Ying-An , Yao Chuan-Fong , Chen Philip Kuo-Ting , Chen Yu-Ray 
Published: March 2023

Background:
Although several studies have reported the advantages of the surgery-first approach for orthognathic correction of class III deformity, there is no report of the success of this approach for patients with cleft lip and palate. Therefore, the purpose of this study was to evaluate the stability and outcome of bimaxillary surgery for cleft-related dentofacial deformity using a surgery-first approach.

Methods:
Forty-one patients with unilateral cleft lip and palate who consecutively underwent Le Fort I and bilateral sagittal split osteotomies for skeletal class III deformity were included. Cone-beam computed tomography scans before surgery, 1-week post-surgery and after orthodontic treatment were used to measure the surgical and post-surgical changes in jaw position by landmarks, and outcomes of jaw protrusion and relation, incisor angle and occlusion, and menton deviation after treatment. Self-report questionnaires regarding satisfaction with overall appearance of the face and seven facial regions were administered after treatment.

Results:
A clinically insignificant relapse was found in the maxilla (< 1 mm) and mandible (< 2 mm). There was a significant improvement in the jaw protrusion and relation, incisor angle and occlusion, and menton deviation. Responses from the self-report questionnaires completed after treatment indicated patient satisfaction was high.

Conclusions:
These findings demonstrate surgical-orthodontic treatment with a surgery-first approach can successfully improve cleft-related dentofacial deformity in patients with unilateral cleft lip and palate.
SPECT/CT in Pleuroperitoneal Fistula Associated With Peritoneal Dialysis
Authors: Rojas-Rojas María M. , Camilo Perdomo , Gonzalo Ucrós , Bernal Patricia 
Published: March 2023

Abstract
Pleuroperitoneal fistula is a rare entity found in approximately 1.6% of patients with peritoneal dialysis. The pathophysiology is unknown, and it is usually associated with increased abdominal pressure. Upon pleural fluid analysis, a transudate with elevated glucose concentration is found, and the patients present with acute dyspnea, cough, and decrease in the ultrafiltration rate. We present the case of an 81-year-old woman with history of peritoneal dialysis presenting with recurrent pleural effusion. A peritoneal scintigraphy with 99mTc was performed confirming the diagnosis of pleuroperitoneal fistula.
Host-to-graft Propagation of α-synuclein in a Mouse Model of Parkinson’s Disease: Intranigral Versus Intrastriatal Transplantation
Authors: Patrigeon Maëlig , Brot Sébastien , Bonnet Marie-Laure , Belnoue Laure , Gaillard Afsaneh 
Published: March 2023

Background.
Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) and by the accumulation of misfolded α-synuclein (α-syn) in Lewy bodies. Ectopic transplantation of human fetal ventral mesencephalic DA neurons into the striatum of PD patients have provided proof-of-principle for the cell replacement strategy in this disorder. However, 10 to 22 y after transplantation, 1% to 27% of grafted neurons contained α-syn aggregates similar to those observed in the host brain. We hypothesized that intrastriatal grafts are more vulnerable to α-syn propagation because the striatum is not the ontogenic site of nigral DA neurons and represents an unfavorable environment for transplanted neurons. Here, we compared the long-term host-to-graft propagation of α-syn in 2 transplantation sites: the SNpc and the striatum.

Methods.
Two mouse models of PD were developed by injecting adeno-associated-virus2/9-human α-syn A53T into either the SNpc or the striatum of C57BL/6 mice. Mouse fetal ventral mesencephalic DA progenitors were grafted into the SNpc or into the striatum of SNpc or striatum of α-syn injected mice, respectively.

Results.
First, we have shown a degeneration of the nigrostriatal pathway associated with motor deficits after nigral but not striatal adeno-associated-virus-hαsyn A53T injection. Second, human α-syn preferentially accumulates in striatal grafts compared to nigral grafts. However, no differences were observed for phosphorylated α-syn, a marker of pathological α-syn aggregates.

Conclusions.
Taken together, our results suggest that the ectopic site of the transplantation impacts the host-to-graft transmission of α-syn.
Evaluation of the Diagnostic Performance of urine dipstick test for Detection of urinary tract infections in patients treated in Kenyan hospitals.
Authors: Maina John , Mwaniki John , Mwiti Franklin , Kiiru Susan , Katana Japhet , Wanja Fredrick , Mukaya Joel , Khasabuli Osborn , Asiimwe Benon , Gillespie Stephen , Stelling John , Mshana Stephen , Holden Matthew , Sabiiti Wilber , Kiiru John 
Published: March 2023

Abstract
Introduction
Culture is the gold-standard diagnosis for Urinary Tract Infections (UTIs). However, most hospitals in poor-resource countries lack adequately equipped laboratories and relevant expertise to perform culture and, therefore, rely heavily on dipstick tests for UTI diagnosis.
Research gap
In many Kenyan hospitals, routine evaluations are rarely done to assess the accuracy of popular screening tests such as the dipstick test. As such, there is a substantial risk of misdiagnosis emanating from inaccuracy in proxy screening tests. This may result in misuse, under-use, or over-use of antimicrobials.
Aim
The present study aimed to assess the accuracy of the urine dipstick test as a proxy for the diagnosis of urinary tract infections in selected Kenyan hospitals.
Methods
A hospital-based cross-sectional method was used in the present study. Utility of dipstick in the diagnosis of UTI was assessed using Mid stream urine against culture as gold standard
Results
The dipstick test predicted 1,416 positive UTIs, but only 1,027 were confirmed positive by culture, translating to a true prevalence of 54.1%. The sensitivity of the dipstick test was better when leukocytes and nitrite tests were combined (63.1%) than when the two tests were separate (62.6% and 50.7%, respectively). Similarly, the two tests combined had a better positive predictive value (87.0%) than either test alone. The nitrite test had the best specificity (89.8%) and negative predictive value (97.4%) than leukocytes esterase (L.E) or both tests combined. In addition, sensitivity in samples from the inpatients (69.2%) was higher than outpatients (62.7%). Furthermore, the dipstick test had a better sensitivity and positive predictive value among female (66.0% and 88.6%) patients than male patients (44.3% and 73.9%). Among the various patients' age groups, the dipstick test's sensitivity and positive predictive value were exceptionally high in patients ≥75 years (87.5% and 93.3%).
Conclusion
The prevalence discrepancies from the urine dipstick test and culture, the gold standard, indicate dipstick test inadequacy for accurate UTI diagnosis. The finding also demonstrates the need for urine culture for accurate UTI diagnosis. However considering it’s not always possible to perform a culture, especially in low resource settings, future studies can combine specific UTI symptoms and dipstick results to assess possible increase in the test’s sensitivity. There is also need to develop readily available and affordable algorithms that can detected UTI where culture is not available.
Engineered probiotics limit CNS autoimmunity by stabilizing HIF-1α in dendritic cells
Authors: Sanmarco Liliana M. , Rone Joseph M. , Polonio Carolina M. , Giovannoni Federico , Lahore Gonzalo Fernandez , Ferrara Kylynne , Gutierrez-Vazquez Cristina , Li Ning , Sokolovska Anna , Plasencia Agustin , Akl Camilo Faust , Nanda Payal , Heck Evelin S. , Li Zhaorong , Lee Hong-Gyun , Chao Chun-Cheih , Rejano-Gordillo Claudia M. , Fonseca-Castro Pedro H. , Illouz Tomer , Linnerbauer Mathias , Kenison Jessica E. , Barilla Rocky M. , Farrenkopf Daniel , Piester Gavin , Dailey Lucas , Kuchroo Vijay K. , Hava David , Wheeler Michael A. , Clish Clary , Nowarski Roni , Balsa Eduardo , Lora Jose M. , Quintana Francisco J. 
Published: March 2023

SummaryDendritic cells (DCs) control the generation of self-reactive pathogenic T cells. Thus, DCs are considered attractive therapeutic targets for autoimmune diseases. Using single-cell and bulk transcriptional and metabolic analyses in combination with cell-specific gene perturbation studies we identified a negative feedback regulatory pathway that operates in DCs to limit immunopathology. Specifically, we found that lactate, produced by activated DCs and other immune cells, boosts NDUFA4L2 expression through a mechanism mediated by HIF-1α. NDUFA4L2 limits the production of mitochondrial reactive oxygen species that activate XBP1-driven transcriptional modules in DCs involved in the control of pathogenic autoimmune T cells. Moreover, we engineered a probiotic that produces lactate and suppresses T-cell autoimmunity in the central nervous system via the activation of HIF-1α/NDUFA4L2 signaling in DCs. In summary, we identified an immunometabolic pathway that regulates DC function, and developed a synthetic probiotic for its therapeutic activation.
S3-CIMA: Supervised spatial single-cell image analysis for the identification of disease-associated cell type compositions in tissue
Authors: Babaei Sepideh , Christ Jonathan , Makky Ahmad , Zidane Mohammed , Wistuba-Hamprecht Kilian , Schürch Christian M. , Claassen Manfred 
Published: March 2023

AbstractThe spatial organization of various cell types within the tissue microenvironment is a key element for the formation of physiological and pathological processes, including cancer and autoimmune diseases. Here, we present S3-CIMA, a weakly supervised convolutional neural network model that enables the detection of disease-specific microenvironment compositions from high-dimensional proteomic imaging data. We demonstrate the utility of this approach by determining cancer outcome- and cellular signaling-specific spatial cell state compositions in highly multiplexed fluorescence microscopy data of the tumor microenvironment in colorectal cancer. Moreover, we use S3-CIMA to identify disease onset-specific changes of the pancreatic tissue microenvironment in type 1 diabetes using imaging mass cytometry data. We evaluated S3-CIMA as a powerful tool to discover novel disease-associated spatial cellular interactions from currently available and future spatial biology datasets.
A machine-readable specification for genomics assays
Authors: Booeshaghi A. Sina , Chen Xi , Pachter Lior 
Published: March 2023

AbstractUnderstanding the structure of sequenced fragments from genomics libraries is essential for accurate read preprocessing. Currently, different assays and sequencing technologies require custom scripts and programs that do not leverage the common structure of sequence elements present in genomics libraries. We presentseqspec, a machine-readable specification for libraries produced by genomics assays that facilitates standardization of preprocessing and enables tracking and comparison of genomics assays. The specification and associatedseqspeccommand line tool is available athttps://github.com/IGVF/seqspec.
A Spatiotemporal Map of Co-Receptor Signaling Networks Underlying B Cell Activation
Authors: Susa Katherine J. , Bradshaw Gary A. , Eisert Robyn J. , Schilling Charlotte M. , Kalocsay Marian , Blacklow Stephen C. , Kruse Andrew C. 
Published: March 2023

AbstractThe B cell receptor (BCR) signals together with a multi-component co-receptor complex to initiate B cell activation in response to antigen binding. This process underlies nearly every aspect of proper B cell function. Here, we take advantage of peroxidase-catalyzed proximity labeling combined with quantitative mass spectrometry to track B cell co-receptor signaling dynamics from 10 seconds to 2 hours after BCR stimulation. This approach enables tracking of 2,814 proximity-labeled proteins and 1,394 quantified phosphosites and provides an unbiased and quantitative molecular map of proteins recruited to the vicinity of CD19, the key signaling subunit of the co-receptor complex. We detail the recruitment kinetics of essential signaling effectors to CD19 following activation, and then identify new mediators of B cell activation. In particular, we show that the glutamate transporter SLC1A1 is responsible for mediating rapid metabolic reprogramming immediately downstream of BCR stimulation and for maintaining redox homeostasis during B cell activation. This study provides a comprehensive map of the BCR signaling pathway and a rich resource for uncovering the complex signaling networks that regulate B cell activation.
Genetic dysregulation of an endothelial Ras signaling network in vein of Galen malformations
Authors: Zhao Shujuan , Mekbib Kedous Y. , van der Ent Martijn A. , Allington Garrett , Prendergast Andrew , Chau Jocelyn E. , Smith Hannah , Shohfi John , Ocken Jack , Duran Daniel , Furey Charuta G. , Le Hao Thi , Duy Phan Q. , Reeves Benjamin C. , Zhang Junhui , Nelson-Williams Carol , Chen Di , Li Boyang , Nottoli Timothy , Bai Suxia , Rolle Myron , Zeng Xue , Dong Weilai , Fu Po-Ying , Wang Yung-Chun , Mane Shrikant , Piwowarczyk Paulina , Fehnel Katie Pricola , See Alfred Pokmeng , Iskandar Bermans J. , Aagaard-Kienitz Beverly , Kundishora Adam J. , DeSpenza Tyrone , Greenberg Ana B.W. , Kidanemariam Seblewengel M. , Hale Andrew T. , Johnston James M. , Jackson Eric M. , Storm Phillip B. , Lang Shih-Shan , Butler William E. , Carter Bob S. , Chapman Paul , Stapleton Christopher J. , Patel Aman B. , Rodesch Georges , Smajda Stanislas , Berenstein Alejandro , Barak Tanyeri , Erson-Omay E. Zeynep , Zhao Hongyu , Moreno-De-Luca Andres , Proctor Mark R. , Smith Edward R. , Orbach Darren B. , Alper Seth L. , Nicoli Stefania , Boggon Titus J. , Lifton Richard P. , Gunel Murat , King Philip D. , Jin Sheng Chih , Kahle Kristopher T. 
Published: March 2023

ABSTRACTTo elucidate the pathogenesis of vein of Galen malformations (VOGMs), the most common and severe congenital brain arteriovenous malformation, we performed an integrated analysis of 310 VOGM proband-family exomes and 336,326 human cerebrovasculature single-cell transcriptomes. We found the Ras suppressor p120 RasGAP (RASA1) harbored a genome-wide significant burden of loss-of-functionde novovariants (p=4.79×10-7). Rare, damaging transmitted variants were enriched in Ephrin receptor-B4 (EPHB4) (p=1.22×10-5), which cooperates with p120 RasGAP to limit Ras activation. Other probands had pathogenic variants inACVRL1,NOTCH1,ITGB1, andPTPN11.ACVRL1variants were also identified in a multi-generational VOGM pedigree. Integrative genomics defined developing endothelial cells as a key spatio-temporal locus of VOGM pathophysiology. Mice expressing a VOGM-specificEPHB4kinase-domain missense variant exhibited constitutive endothelial Ras/ERK/MAPK activation and impaired hierarchical development of angiogenesis-regulated arterial-capillary-venous networks, but only when carrying a “second-hit” allele. These results illuminate human arterio-venous development and VOGM pathobiology and have clinical implications.
Breast Cancers That Disseminate to Bone Marrow Acquire Aggressive Phenotypes through CX43-related Tumor-Stroma Tunnels
Authors: Sinha Saptarshi , Callow Brennan W. , Farfel Alex P. , Roy Suchismita , Chen Siyi , Rajendran Shrila , Buschhaus Johanna M. , Espinoza Celia R. , Luker Kathryn E. , Ghosh Pradipta , Luker Gary D. 
Published: March 2023

AbstractEstrogen receptor-positive (ER+) breast cancer commonly disseminates to bone marrow, where interactions with mesenchymal stromal cells (MSCs) shape disease trajectory. We modeled these interactions with tumor-MSC co-cultures and used an integrated transcriptome-proteome-network-analyses workflow to identify a comprehensive catalog of contact-induced changes. Conditioned media from MSCs failed to recapitulate genes and proteins, some borrowed and others tumor-intrinsic, induced in cancer cells by direct contact. Protein-protein interaction networks revealed the rich connectome between ‘borrowed’ and ‘intrinsic’ components. Bioinformatics prioritized one of the ‘borrowed’ components,CCDC88A/GIV, a multi-modular metastasis-related protein that has recently been implicated in driving a hallmark of cancer, growth signaling autonomy. MSCs transferred GIV protein to ER+ breast cancer cells (that lack GIV) through tunnelling nanotubes via connexin (Cx)43-facilitated intercellular transport. Reinstating GIV alone in GIV-negative breast cancer cells reproduced ∼20% of both the ‘borrowed’ and the ‘intrinsic’ gene induction patterns from contact co-cultures; conferred resistance to anti-estrogen drugs; and enhanced tumor dissemination. Findings provide a multiomic insight into MSC→tumor cell intercellular transport and validate how transport of one such candidate, GIV, from the haves (MSCs) to have-nots (ER+ breast cancer) orchestrates aggressive disease states.
Pharmacologically targeting KRASG12Din PDAC models: tumor cell intrinsic and extrinsic impact
Authors: Kumarasamy Vishnu , Frangou Costakis , Wang Jianxin , Wan Yin , Dynka Andrew , Rosenheck Hanna , Dey Prasenjit , Abel Ethan V. , Knudsen Erik S. , Witkiewicz Agnieszka K. 
Published: March 2023

AbstractPancreatic ductal adenocarcinoma (PDAC) is an aggressive disease for which new therapeutic interventions are needed. Here we assessed the cellular response to pharmacological KRAS inhibition, which target the central oncogenic factor in PDAC. In a panel of PDAC cell lines, pharmaceutical inhibition of KRASG12Dallele, with MRTX1133 yields variable efficacy in the suppression of cell growth and downstream gene expression programs in 2D culture. CRISPR screens identify new drivers for enhanced therapeutic response that regulate focal adhesion and signaling cascades, which were confirmed by gene specific knockdowns and combinatorial drug synergy. Interestingly, MRTX1133 is considerably more efficacious in the context of 3D cell cultures andin vivoPDAC patient-derived xenografts. In syngeneic models, KRASG12Dinhibition elicits potent tumor regression that did not occur in immune-deficient hosts. Digital spatial profiling on tumor tissues indicates that MRTX1133 activates interferon-γ signaling and induces antigen presentation that modulate the tumor microenvironment. Further investigation on the immunological response using single cell sequencing and multispectral imaging reveals that tumor regression is associated with suppression of neutrophils and influx of effector CD8+T-cells. Thus, both tumor cell intrinsic and extrinsic events contribute to response and credential KRASG12Dinhibition as promising strategy for a large percentage of PDAC tumors.
Uncovering the Environmental Conditions Required forPhyllachora maydisInfection and Tar Spot Development on Corn in the United States for Use as Predictive Models for Future Epidemics
Authors: Webster Richard W. , Nicolli Camila , Allen Tom W. , Bish Mandy D. , Bissonette Kaitlyn , Check Jill C. , Chilvers Martin I. , Duffeck Maíra R. , Kleczewski Nathan , Luis Jane Marian , Mueller Brian D. , Paul Pierce A. , Price Paul P. , Robertson Alison E. , Ross Tiffanna J. , Schmidt Clarice , Schmidt Roger , Schmidt Teryl , Shim Sujoung , Telenko Darcy E. P. , Wise Kiersten , Smith Damon L. 
Published: March 2023

AbstractPhyllachora maydisis a fungal pathogen causing tar spot of corn (Zea maysL.), a new and emerging, yield-limiting disease in the United States. Since being first reported in Illinois and Indiana in 2015,P. maydiscan now be found across much of the corn growing of the United States. Knowledge of the epidemiology ofP. maydisis limited but could be useful in developing tar spot prediction tools. The research presented here aims to elucidate the environmental conditions necessary for the development of tar spot in the field and the creation of predictive models to anticipate future tar spot epidemics. Extended periods (30-day windowpanes) of moderate ambient temperature were most significant for explaining the development of tar spot. Shorter periods (14- to 21-day windowpanes) of moisture (relative humidity, dew point, number of hours with predicted leaf wetness) were negatively correlated with tar spot development. These weather variables were used to develop multiple logistic regression models, an ensembled model, and two machine learning models for the prediction of tar spot development. This work has improved the understanding ofP. maydisepidemiology and provided the foundation for the development of a predictive tool for anticipating future tar spot epidemics.