bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sequential Assessment of External Nasal Deviation Angle Changes in Patients With a Deviated Nose Who Underwent Bilateral Osteotomy
Authors: Jo Ki Hun , Lee So Yeon , Kwon Jae Hwan , Kim Jooyeon 
Published: June 2024

Objective:
A deviated nose is traditionally classified as bony, cartilaginous, or combined deviation. Osteotomy is commonly used to correct bony deviation, and accurate surgical techniques and postoperative patient management are important for favorable outcomes. The authors investigated the change in the external nasal deviation angle over time using sequential clinical photographs to identify the optimal postoperative follow-up duration.

Methods:
Medical records and sequential standardized clinical photographs of 22 patients who underwent bilateral medial and lateral osteotomies without dorsal augmentation from January 1, 2014 to May 31, 2021, were retrospectively reviewed. Clinical photographs were classified into 4 periods: “a” preoperative, “b” postoperative day (POD) ≤3 weeks, “c” POD ≤9 weeks, and “d” POD >9 weeks. The angle of deviation (AoD) was measured in both frontal and chin-on-chest views for each period. Differences in AoD between temporally adjacent periods were analyzed.

Results:
Nineteen men and 3 women (mean age: 28.8 y) were included. Thirteen patients showed rightward deviation, whereas 9 showed leftward deviation. Eleven patients underwent surgery through an endonasal approach, whereas the other 11 underwent surgery through an external approach. In the frontal view, AoD differences (mean ± SD) between periods “a” and “b,” “b” and “c,” and “c” and “d” were 5.79 ± 3.36 degrees (P < 0.001), 1.44 ± 1.14 degrees (P < 0.001), and 1.07 ± 1.24 degrees (P < 0.05), respectively. In the chin-on-chest view, the values were 5.17 ± 2.69 degrees (P < 0.001), 2.06 ± 2.63 degrees (P < 0.001), and 1.46 ± 1.31 degrees (P < 0.001), respectively. No statistically significant difference in AoD differences was observed between the two approaches.

Conclusions:
Angle of deviation can change even 9 weeks after bilateral osteotomy. Thus, long-term follow-up using sequential clinical photographs is mandatory. If needed, close follow-up with early postoperative interventions may be required. The chin-on-chest view showed better sensitivity for assessing AoD than the frontal view.
Cleft Lip and Palate Surgery at a Rural African Hospital: A 13-Year Experience From Western Kenya
Authors: Rhodes Isaiah J. , Zhang Ashley , Arbuiso Sophia , Alston Chase C. , Medina Samuel J. , Liao Matthew , Nthumba Joseph , Chesang Patricia , Hayden Giles , Rhodes William R. , Otterburn David M. 
Published: June 2024

Introduction:
Most studies on the treatment of cleft lip and palate (CLP) in low-income and middle-income countries have reported on the experience of urban centers or surgical mission trips to rural locations. There is a paucity of literature on the experience of local teams providing orofacial cleft surgery in rural Sub-Saharan Africa. This study reports the efficacy and cost-effectiveness of cleft surgery performed by an all-local team in rural Kenya.

Methods:
A retrospective chart review was performed on all patients who received CLP repair at Kapsowar Hospital between 2011 and 2023. Information regarding patient age, sex, cleft etiology, surgical management, and home location was retrieved. For the most recent year of study (2023), the authors performed a financial audit of all costs related to the performance of unilateral cleft lip surgery. Descriptive statistics were performed.

Results:
The authors identified 381 CLP surgeries performed on 311 patients (197 male, 63.3%). The most common etiology of the cleft was left unilateral (28.3%). The average age of primary lip repair decreased from 46.3 months in 2008 to 2009 to 20.2 months in 2022 to 2023 (P<0.001). The average age of primary cleft palate repair decreased from 38.0 months in 2008 to 2009 to 25.3 months in 2022 to 2023 (P<0.001). Patients traveled from 23 districts to receive treatment. Age of treatment was not different when distinguished by sex, county poverty level, or travel time from the hospital. The total costs associated with cleft lip repair was $201.6.

Conclusions:
Adequately staffed hospitals in rural locations can meaningfully address a regional CLP backlog more cost-effectively than surgical mission trips.
Optic Neuritis After COVID-19 Vaccination: A Case Series and a Review of Literature
Authors: Yang Sheng-Chi , Lee Yu-Kuei , Chuang Ming-Tsung , Hsu Huai-Wen , Chang Hsu-Yang , Chang Yi-Sheng 
Published: June 2024

Background:
The coronavirus disease (COVID-19) pandemic broke out in March 2020, causing tremendous damage to public health and more than 6 million deaths. After authorization for the emergency use of COVID-19 vaccines, various adverse events have been reported, including optic neuritis. COVID-19 vaccination was implemented in Taiwan in March 2021.

Methods:
We report patients who developed optic neuritis after COVID-19 vaccination at one university-affiliated tertiary hospital, between March 2021 and December 2022. We also provided a literature review of optic neuritis cases after COVID-19 vaccination.

Results:
Five patients who developed optic neuritis after COVID-19 vaccination have been identified. Four brands of vaccine used were as follows: Moderna, Pfizer-BioNTech, Medigen, and Oxford AstraZeneca. Optic neuritis developed after the first dose of vaccination in 4 patients, whereas in 1 patient, it developed after the second shot. In the 3 patients with poor initial visual acuity, intravenous methylprednisolone pulse therapy achieved substantial improvement.

Conclusions:
Optic neuritis is a rare but potentially vision-threatening adverse effect of COVID-19 vaccination. We suggest early diagnosis and treatment to maximize visual outcomes.
Successful Treatment of Both Refractory Neuroleptic Malignant Syndrome and Subsequent Catatonia With Electroconvulsive Therapy in a Patient With Suspected Kufs Disease
Authors: Celik Sacha , de Gennaro Veronica , C.-P.-Silva João , Swierkosz-Lenart Kevin , von Gunten Armin 
Published: June 2024

Abstract
We describe a patient suffering from probable Kufs disease who developed a neuroleptic malignant syndrome (NMS) after use of an antipsychotic agent over some weeks during hospitalization due to neuropsychiatric symptoms. Transferred to the neurology department, the patient quickly developed catatonic features. She did not respond to usual medical treatment but did respond to electroconvulsive therapy (ECT). The patient worsened following a nosocomial SARS-CoV-2 infection but improved again during a second course of ECT. We discuss Kufs disease as a potential risk factor for NMS and address the link between NMS and catatonia as well as the indication for ECT in both disorders. We also discuss the impact of SARS-CoV-2 infection on the clinical outcome. We describe the long recovery process and the secondary worsening of the patient on a cognitive level.
An open-source alignment method for multichannel infinite-conjugate microscopes using a ray transfer matrix analysis model
Authors: Cairns Gemma S. , Patton Brian R. 
Published: June 2024

Multichannel, infinite-conjugate optical systems easily allow implementation of multiple image paths and imaging modes into a single microscope. Traditional optical alignment methods which rely on additional hardware are not always simple to implement, particularly in compact open-source microscope designs. We present here an alignment algorithm and process to position the lenses and cameras in a microscope using only image magnification measurements. We show that the resulting positioning accuracy is comparable to the axial resolution of the microscope. Ray transfer matrix analysis is used to model the imaging paths when the optics are both correctly and incorrectly aligned. This is used to derive the corresponding image magnifications. We can then extract information about the lens positions using simple image-based measurements to determine whether there is misalignment of the objective lens to sample distance (working distance) and with what magnitude and direction the objective lens needs to be adjusted. Using the M4All open-source 3D printable microscope system in combination with the OpenFlexure microscope, we validate the alignment method and highlight its usability. We provide the model and an example implementation of the algorithm as an open-source Jupyter Notebook.This article is part of the Theo Murphy meeting issue ‘Open, reproducible hardware for microscopy’.
FOXP3+ Regulatory T Cells Require TBET to Regulate Activated CD8+ T Cells During Recovery from Influenza Infection
Authors: Mambetsariev Nurbek , Torres Acosta Manuel A. , Liu Qianli , Flores Carla P. Reyes , Joudi Anthony M. , Helmin Kathryn A. , Gurkan Jonathan K. , Steinert Elizabeth M. , Morales-Nebreda Luisa , Singer Benjamin D. 
Published: June 2024

AbstractFOXP3+ regulatory T (Treg) cells are necessary to coordinate resolution of lung inflammation and a return to homeostasis after respiratory viral infections, but the specific molecular requirements for these functions and the cell types governed by Treg cells remain unclear. This question holds significance as clinical trials of Treg cell transfer therapy for respiratory viral infection are being planned and executed. Here, we report causal experiments in mice determining that Treg cells are necessary to control the numbers of activated CD8+ T cells during recovery from influenza infection. Using a genetic strategy paired with adoptive transfer techniques, we determined that Treg cells require the transcription factor TBET to regulate these potentially pro-inflammatory CD8+ T cells. Surprisingly, we found that Treg cells are dispensable for the generation of CD8+ lung tissue resident-memory T (Trm) cells yet similarly influence the transcriptional programming of CD8+ Trm and activated T cells. Our study highlights the role of Treg cells in regulating the CD8+ T cell response during recovery from influenza infection.
Cannabinoid CB2 receptors enhance high-fat diet evoked peripheral neuroinflammation
Authors: Hosoki Haruka , Asahi Toru , Nozaki Chihiro 
Published: June 2024

AbstractIt is known that cannabinoid type 2 (CB2) receptor has anti-inflammatory role, therefore animals without CB2 receptors show enhanced inflammation and pain in the model of chronic pain e.g. neuropathic pain. We previously proposed the upregulated leptin signaling at the peripheral nerve as one of the underlying molecular mechanisms of pain exacerbation in nerve-injured CB2 knockouts, as they displayed robust upregulation of leptin receptors and leptin signaling in peripheral nerve. Due to these past results we hypothesized that CB2 receptor deficiency might also modify the peripheral neuroinflammation lead by chronic exposure to high fat diet (HFD). Interestingly, CB2 knockout animals showed the significant resistance to the HFD-induced neuroinflammation. Namely, 5-week feeding of HFD induced substantial hypersensitivity in WT animals, while tactile sensitivity of HFD-fed CB2 knockouts remained intact. HFD-fed WT animals also displayed the robust upregulation of chemokine CXCR4 expression with increased macrophage infiltration, which was never observed in HFD-fed CB2 knockout mice. Moreover, 5-week HFD-exposure lead significant increase of CD11b+Ly6G-Ly6Chighcells and decrease of CD11b+Ly6G+Ly6Clowcells in the spleen of WT animals, which was also not found in either HFD-fed CB2 knockouts or standard diet-fed WT and CB2 animals. Together with past report, these results suggest that CB2 receptors might have the double-sided regulatory role in context of the inflammation development, or more widely, immune system regulation. We propose that CB2 signaling is not always anti-inflammatory and could take pro-inflammatory role depending on the cause of the inflammation.
Conserved mycobacterial sRNA B11 regulates lipooligosaccharide synthesis at post-transcriptional level
Authors: Wang Chuan , Bei Cheng , Fan Yufeng , Liu Qingyun , Ding Yue , Takiff Howard E , Gao Qian 
Published: June 2024

AbstractExtractable glycolipids of mycobacteria, such as lipooligosaccharides (LOS), play key roles in responding to environmental stress and altering the host immune response. However, although the biosynthesis of LOS is likely controlled at multiple levels to ensure proper composition of the cell wall, the key regulators are currently unknown. Here, we studied B11, a conserved mycobacterial sRNA, and found that it post-transcriptionally regulates LOS synthesis inMycobacteria marinum. Deletion of B11 alters the colony morphology and RNA sequencing combined with mass spectrometry identified several genes in the LOS synthesis locus that are regulated by B11. We found that B11 uses the cytosine-rich loops of its rho-independent transcriptional terminator to interact with guanine-tracks adjacent to the ribosome binding sites of its target genes, thereby impeding translation and promoting mRNA degradation by RNase E. These comprehensive functional studies of mycobacterial sRNA B11 demonstrate sRNA-based regulation of cell wall synthesis in mycobacteria.ImportanceDespite being identified for more than a decade, the functional characterization and regulatory mechanisms of mycobacterial sRNAs remain largely unexplored. We present here the most comprehensive functional study of mycobacterial sRNAs to date, employing convincible target screening using multifaceted experimental approaches and phenotype analysis. Our work reveals how synthesis of mycobacterial lipooligosaccharides (LOS), one of the crucial extractable glycolipids involved in environmental stress response and host immune modulation, is regulated at the post-transcriptional level by the conserved sRNA B11. Furthermore, our discovery of a highly conserved sRNA exhibiting distinct functions across mycobacterial species exemplifies divergent functional evolution among sRNAs.
Scalable Condition-relevant Cell Niche Analysis of Spatial Omics Data with Taichi
Authors: Cui Yan , Yuan Zhiyuan 
Published: June 2024

AbstractTissues are composed of heterogeneous cell niches, which can be investigated using spatial omics technologies. Large consortia have accumulated vast amounts of spatially resolved data, which typically assign slice-level condition labels without considering intra-slice heterogeneity, particularly differential cell niches that respond to certain perturbations. Here, we present Taichi, an efficient and scalable method for condition-relevant cell niche analysis that does not rely on pre-defined discrete spatial clustering. Taichi utilizes a scalable spatial co-embedding approach that effectively accounts for batch effects, incorporating advanced label refinement and graph heat diffusion techniques to explore condition-relevant cell niches across extensive multi-slice and multi-condition spatial omics datasets. Comprehensive benchmarks demonstrate Taichi’s ability to precisely identify condition-relevant niches under various levels of perturbations. We showcase Taichi’s effectiveness in accurately delineating major shifts in cell niches in a mouse model of diabetic kidney disease compared to a normal group, revealing disease-specific cell-cell interactions and spatial gene expression patterns. Furthermore, Taichi can identify key subtype-relevant niches between colorectal cancer patient groups with significantly different survival outcomes. Moreover, we demonstrate that Taichi can help discover more fine-grained clinical properties within the originally coarse-defined patient groups in large-scale tumor spatial atlases, reflecting intra-group heterogeneity obscured previously. Additionally, we combine Taichi and tensor decomposition to discover higher-order biomarkers relevant to the immunotherapy response of triple-negative breast cancer. Finally, we highlight Taichi’s speed and scalability by confirming its unique applicability in large-scale scenarios containing up to 16 million cells in ∼ 12 minutes. Taichi provides a powerful tool for mining disease-relevant spatially resolved insights in the era of big data in spatial biology.
ProTrek: Navigating the Protein Universe through Tri-Modal Contrastive Learning
Authors: Su Jin , Zhou Xibin , Zhang Xuting , Yuan Fajie 
Published: June 2024

AbstractProTrek redefines protein exploration by seamlessly fusing sequence, structure, and natural language function (SSF) into an advanced tri-modal language model. Through contrastive learning, ProTrek bridges the gap between protein data and human understanding, enabling lightning-fast searches across nine SSF pairwise modality combinations. Trained on vastly larger datasets, ProTrek demonstrates quantum leaps in performance: (1) Elevating protein sequence-function interconversion by 30-60 fold; (2) Surpassing current alignment tools (i.e., Foldseek and MMseqs2) in both speed (100-fold acceleration) and accuracy, identifying functionally similar proteins with diverse structures; and (3) Outperforming ESM-2 in 9 of 11 downstream prediction tasks, setting new benchmarks in protein intelligence. These results suggest that ProTrek will become a core tool for protein searching, understanding, and analysis.
Wounding triggers invasive progression in human basal cell carcinoma
Authors: Yerly Laura , Andreatta Massimo , Garnica Josep , Nardin Charlée , Domizio Jeremy Di , Aubin François , Gilliet Michel , Carmona Santiago J. , Kuonen François 
Published: June 2024

AbstractThe interconnection between wound healing and cancer has long been recognized, as epitomized by the expression “cancer is a wound that does not heal”. However, the impact of inducing a wound, such as through biopsy collection, on the progression of established tumors remains largely unknown. In this study, we apply single-cell spatial transcriptomics to characterize the heterogeneity of human basal cell carcinoma (BCC) and identify a wound response gene program as the most prominent feature of highly invasive BCC. To explore the causal relationship between wounding and cancer invasive progression, we perform a longitudinal experiment to compare human tumors at baseline and one week post-biopsy. Our results demonstrate that biopsy collection triggers, in proximity of the wound, the same transcriptional cancer cell state observed in highly invasive BCC. This cancer cell transcriptional switch is coupled with morphological changes and the transcriptional reprogramming of cancer-associated fibroblasts (CAFs). This study provides evidence that wounding triggers invasive progression of established human tumors and warrants further research on the potentially harmful effects of biopsies and wound-inducing treatments.
Motor cortex perineuronal net modulation improves motor function in a Parkinson’s disease mouse model
Authors: Benacom David , Chataing Camille , Prochiantz Alain , Di Nardo Ariel A. 
Published: June 2024

AbstractThe 6-OHDA mouse model recapitulates midbrain dopaminergic cell loss and associated motor deficits akin to those observed in Parkinson’s disease. Emerging evidence suggests that modulating interneurons in the primary motor cortex could offer a means to mitigate symptoms. In the cortex, perineuronal nets (PNNs), a specialized extracellular matrix structure generally present around fast-spiking parvalbumin interneurons, can modulate neural activity and circuit plasticity. We found that removing PNNs through unilateral or bilateral ChABC injection in the motor cortex temporarily altered motor behavior. Surprisingly, bilateral reduced motor cortex PNNs are observed two weeks after unilateral 6-OHDA midbrain lesions, whereas five weeks after lesion, PNNs return to control levels. Subsequent bilateral ChABC injections significantly improved motor function in 6-OHDA animals only when associated with motor stimulation involving enriched housing and daily motor training. Thus, PNN modulation in the motor cortex of a Parkinson’s disease model enables local circuits to adapt to the loss of dopaminergic inputs, resulting in improved motor behavior.
Aberrant TNF signaling in pancreatic lymph nodes of patients with Type 1 Diabetes
Authors: Abedi Maryam , Rai Priyadarshini , Zhou Yeqiao , Liu Chengyang , Johnson Isabelle , Chandra Aditi , Fasolino Maria , Rostami Susan , Kaestner Klaus H. , Naji Ali , Faryabi Robert B. , Vahedi Golnaz 
Published: June 2024

AbstractThe therapeutic landscape for Type 1 Diabetes (T1D) is rapidly changing as ongoing clinical trials aim to delay beta-cell loss by inhibiting proinflammatory cytokines. However, the precise timing and cellular contexts of cytokine dysregulation remains unknown. We generated the largest existing measurement of gene expression and chromatin accessibility in ∼1 million immune cells from the pancreatic lymph nodes and spleens of 34 T1D and non-diabetic organ donors. Our study revealed heightened gene activity of the tumor necrosis factor (TNF) pathway and subsequent chromatin remodeling in central memory CD4+T cells residing in the pancreatic lymph nodes of T1D and non-diabetic islet-autoantibody positive donors. These findings, validated in mice, offer a mechanism underlying the efficacy of TNF inhibitors, currently undergoing clinical trials to delay T1D onset.
cfDNA UniFlow: A unified preprocessing pipeline for cell-free DNA data from liquid biopsies
Authors: Röner Sebastian , Burkard Lea , Speicher Michael R. , Kircher Martin 
Published: June 2024

AbstractBackgroundCell-free DNA (cfDNA), a broadly applicable biomarker commonly sourced from urine or blood, is extensively used for research and diagnostic applications. In various settings, genetic and epigenetic information is derived from cfDNA. However, a unified framework for its processing is lacking, limiting the universal application of innovative analysis strategies and the joining of data sets.FindingsHere, we describe cfDNA UniFlow, a unified, standardized, and ready-to-use workflow for processing cfDNA samples. The workflow is written in Snakemake and can be scaled from stand -alone computers to cluster environments. It includes methods for processing raw genome sequencing data as well as specialized approaches for correcting sequencing errors, filtering, and quality control. Sophisticated methods for detecting copy number alterations and estimating and correcting GC-related biases are readily incorporated. Furthermore, it includes methods for extracting, normalizing and visualizing coverage signals around user defined regions in case-control settings. Ultimately, all results and metrics are aggregated in a unified report, enabling easy access to a wide variety of information for further research and downstream analysis.ConclusionsWe provide an automated pipeline for processing cell-free DNA sampled from liquid biopsies, including a wide variety of additional functionalities like bias correction and signal extraction. With our focus on scalability and extensibility, we provide a foundation for future cfDNA research and faster clinical applications.Issue SectionTechnical NoteAvailability and implementationSource code and extensive documentation is available on our GitHub repository (https://github.com/kircherlab/cfDNA-UniFlow).