bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reusable tutorials for using cloud-based computing environments for the analysis of bacterial gene expression data from bulk RNA sequencing
Authors: Allers Steven , O’Connell Kyle A , Carlson Thad , Belardo David , King Benjamin L 
Published: July 2024

Abstract
This manuscript describes the development of a resource module that is part of a learning platform named “NIGMS Sandbox for Cloud-based Learning” https://github.com/NIGMS/NIGMS-Sandbox. The overall genesis of the Sandbox is described in the editorial NIGMS Sandbox at the beginning of this Supplement. This module delivers learning materials on RNA sequencing (RNAseq) data analysis in an interactive format that uses appropriate cloud resources for data access and analyses. Biomedical research is increasingly data-driven, and dependent upon data management and analysis methods that facilitate rigorous, robust, and reproducible research. Cloud-based computing resources provide opportunities to broaden the application of bioinformatics and data science in research. Two obstacles for researchers, particularly those at small institutions, are: (i) access to bioinformatics analysis environments tailored to their research; and (ii) training in how to use Cloud-based computing resources. We developed five reusable tutorials for bulk RNAseq data analysis to address these obstacles. Using Jupyter notebooks run on the Google Cloud Platform, the tutorials guide the user through a workflow featuring an RNAseq dataset from a study of prophage altered drug resistance in Mycobacterium chelonae. The first tutorial uses a subset of the data so users can learn analysis steps rapidly, and the second uses the entire dataset. Next, a tutorial demonstrates how to analyze the read count data to generate lists of differentially expressed genes using R/DESeq2. Additional tutorials generate read counts using the Snakemake workflow manager and Nextflow with Google Batch. All tutorials are open-source and can be used as templates for other analysis.
loco-pipe: an automated pipeline for population genomics with low-coverage whole-genome sequencing
Authors: Zhou Zehua T , Owens Gregory L , Larson Wesley A , Lou Runyang Nicolas , Sudmant Peter H 
Published: July 2024

Abstract

Summary
We developed loco-pipe, a Snakemake pipeline that seamlessly streamlines a set of essential population genomic analyses for low-coverage whole genome sequencing (lcWGS) data. loco-pipe is highly automated, easily customizable, massively parallelized, and thus is a valuable tool for both new and experienced users of lcWGS.

Availability and implementation
loco-pipe is published under the GPLv3. It is freely available on GitHub (github.com/sudmantlab/loco-pipe) and archived on Zenodo (doi.org/10.5281/zenodo.10425920).
isolateR: an R package for generating microbial libraries from Sanger sequencing data
Authors: Daisley Brendan , Vancuren Sarah J , Brettingham Dylan J L , Wilde Jacob , Renwick Simone , Macpherson Christine V , Good David A , Botschner Alexander J , Yen Sandi , Hill Janet E , Sorbara Matthew T , Allen-Vercoe Emma 
Published: July 2024

Abstract

Motivation
Sanger sequencing of taxonomic marker genes (e.g. 16S/18S/ITS/rpoB/cpn60) represents the leading method for identifying a wide range of microorganisms including bacteria, archaea, and fungi. However, the manual processing of sequence data and limitations associated with conventional BLAST searches impede the efficient generation of strain libraries essential for cataloging microbial diversity and discovering novel species.

Results
isolateR addresses these challenges by implementing a standardized and scalable three-step pipeline that includes: (1) automated batch processing of Sanger sequence files, (2) taxonomic classification via global alignment to type strain databases in accordance with the latest international nomenclature standards, and (3) straightforward creation of strain libraries and handling of clonal isolates, with the ability to set customizable sequence dereplication thresholds and combine data from multiple sequencing runs into a single library. The tool’s user-friendly design also features interactive HTML outputs that simplify data exploration and analysis. Additionally, in silico benchmarking done on two comprehensive human gut genome catalogues (IMGG and Hadza hunter-gather populations) showcase the proficiency of isolateR in uncovering and cataloging the nuanced spectrum of microbial diversity, advocating for a more targeted and granular exploration within individual hosts to achieve the highest strain-level resolution possible when generating culture collections.

Availability and implementation
isolateR is available at: https://github.com/bdaisley/isolateR.
Optimal refinement of strata to balance covariates
Authors: Brumberg Katherine , Small Dylan S , Rosenbaum Paul R 
Published: July 2024

Abstract
What is the best way to split one stratum into two to maximally reduce the within-stratum imbalance in many covariates? We formulate this as an integer program and approximate the solution by randomized rounding of a linear program. A linear program may assign a fraction of a person to each refined stratum. Randomized rounding views fractional people as probabilities, assigning intact people to strata using biased coins. Randomized rounding is a well-studied theoretical technique for approximating the optimal solution of certain insoluble integer programs. When the number of people in a stratum is large relative to the number of covariates, we prove the following new results: (i) randomized rounding to split a stratum does very little randomizing, so it closely resembles the linear programming relaxation without splitting intact people; (ii) the linear relaxation and the randomly rounded solution place lower and upper bounds on the unattainable integer programming solution; and because of (i), these bounds are often close, thereby ratifying the usable randomly rounded solution. We illustrate using an observational study that balanced many covariates by forming matched pairs composed of 2016 patients selected from 5735 using a propensity score. Instead, we form 5 propensity score strata and refine them into 10 strata, obtaining excellent covariate balance while retaining all patients. An R package optrefine at CRAN implements the method. Supplementary materials are available online.
A gain-of-function variant in SREBF1 causes generalized skin hyperpigmentation with congenital cataracts
Authors: Wang Huijun , Wu Yuan , Bassetti Jennifer A , Wang Zhaoyang , Oza Vikash S , Rangu Sneha A , McGivern Bobbi , Peng Sha , Liang Lina , Huang Shimiao , Gong Zhuoqing , Xu Zigang , Lin Zhimiao 
Published: July 2024

Abstract

Background
Lipid metabolism has essential roles in skin barrier formation and the regulation of skin inflammation. Lipid homeostasis regulates skin melanogenesis, although the underlying mechanism remains largely unknown. Sterol regulatory element binding protein 1 (SREBP-1) is a key transcription factor essential for cellular lipid metabolism. Loss-of-function variants in SREBF1 are responsible for autosomal-dominant ichthyosis follicularis, alopecia and photophobia syndrome, emphasizing the significance of lipid homeostasis in skin keratinization.

Objectives
To identify the genetic basis of a new entity featuring diffuse skin hyperpigmentation with congenital cataracts, and to unravel the underlying mechanism for the pathogenesis of the SREBF1 variant.

Methods
Whole-exome sequencing was performed to identify underlying genetic variants. Quantitative polymerase chain reaction, Western blot and immunofluorescence staining were used to assess the expression and the subcellular localization of the SREBF1 variant. The transcriptional activity of mutant SREBP-1 was determined by a luciferase reporter assay. A transgenic zebrafish model was constructed.

Results
Two unrelated patients presented with generalized skin hyperpigmentation with skin xerosis, congenital cataracts and extracutaneous symptoms. We identified a de novo nonsense variant c.1289C&gt;A (p.Ser430*) in SREBF1 in both patients. The variant encoded a truncated protein that showed preferential nucleus localization, in contrast to wild-type SREBP-1 which – in sterol-sufficient conditions – is mainly localized in the cytoplasm. The luciferase reporter assay revealed that the p.Ser430* mutant exhibited enhanced transcriptional activity. Cultured patient primary melanocytes showed increased melanin synthesis vs. those from healthy controls. At 35 days postfertilization, the p.Ser430* transgenic zebrafish model exhibited more black spots, along with upregulated expression of melanogenic genes.

Conclusions
We demonstrated that a gain-of-function variant of SREBF1 causes a previously undescribed disorder characterized by generalized skin hyperpigmentation and congenital cataracts. Our study reveals the involvement of SREBP-1 in melanogenesis and lens development, and paves the way for the development of novel therapeutic targets for skin dyspigmentation or cataracts.
Development and validation of machine learning models for predicting HER2-zero and HER2-low breast cancers
Authors: Huang Xu , Wu Lei , Liu Yu , Xu Zeyan , Liu Chunling , Liu Zaiyi , Liang Changhong 
Published: July 2024

Abstract

Objectives
To develop and validate machine learning models for human epidermal growth factor receptor 2 (HER2)-zero and HER2-low using MRI features pre–neoadjuvant therapy (NAT).

Methods
Five hundred and sixteen breast cancer patients post-NAT surgery were randomly divided into training (n = 362) and internal validation sets (n = 154) for model building and evaluation. MRI features (tumour diameter, enhancement type, background parenchymal enhancement, enhancement pattern, percentage of enhancement, signal enhancement ratio, breast oedema, and apparent diffusion coefficient) were reviewed. Logistic regression (LR), support vector machine (SVM), k-nearest neighbour (KNN), and extreme gradient boosting (XGBoost) models utilized MRI characteristics for HER2 status assessment in training and validation datasets. The best-performing model generated a HER2 score, which was subsequently correlated with pathological complete response (pCR) and disease-free survival (DFS).

Results
The XGBoost model outperformed LR, SVM, and KNN, achieving an area under the receiver operating characteristic curve (AUC) of 0.783 (95% CI, 0.733-0.833) and 0.787 (95% CI, 0.709-0.865) in the validation dataset. Its HER2 score for predicting pCR had an AUC of 0.708 in the training datasets and 0.695 in the validation dataset. Additionally, the low HER2 score was significantly associated with shorter DFS in the validation dataset (hazard ratio: 2.748, 95% CI, 1.016-7.432, P = .037).

Conclusions
The XGBoost model could help distinguish HER2-zero and HER2-low breast cancers and has the potential to predict pCR and prognosis in breast cancer patients undergoing NAT.

Advances in knowledge
HER2-low–expressing breast cancer can benefit from the HER2-targeted therapy. Prediction of HER2-low expression is crucial for appropriate management. MRI features offer a solution to this clinical issue.
Desmoid fibromatosis: interventional radiology (sometimes) to the rescue for an atypical disease
Authors: Garnon Julien , Cazzato Roberto Luigi , Autrusseau Pierre-Alexis , Koch Guillaume , Weiss Julia , Gantzer Justine , Kurtz Jean-Emmanuel , Gangi Afshin 
Published: July 2024

Abstract
Desmoid fibromatosis (DF) is a rare locally aggressive soft tissue tumour that is characterized as benign as it cannot metastasize. It was managed until recently like sarcomas, that is, with radical surgical resection combined or not with radiotherapy. However, this approach was associated with a high rate of recurrence and significant morbidity. The management of this disease has progressively changed to a more conservative approach given the fact that DF may spontaneously stop to grow or even shrink in more than half of the cases. Should treatment be required, recent guidelines recommend choosing between systemic therapies, which include principally chemotherapy and tyrosine kinase inhibitors, and local treatments. And this is where the interventional radiologist may have an important role in treating the disease. Various ablation modalities have been reported in the literature to treat DF, notably high-intensity focused ultrasound and cryoablation. Results are promising and cryoablation is now mentioned in recent guidelines. The interventional radiologist should nevertheless apprehend the disease in its globality to understand the place of percutaneous treatments among the other therapeutic options. The goal of this review is therefore to present and discuss the role of interventional radiology in the management of DF.
Assembly/disassembly control of gold nanorods with uniform orientation on anionic polymer brush substrates
Authors: Yang Jingyan , Sekizawa Yu , Shi Xu , Ijiro Kuniharu , Mitomo Hideyuki 
Published: July 2024

Abstract
Sophisticated control of the spatial arrangement of gold nanorods provides significant advantages in the design of plasmonic systems. However, dynamic modulation of the gold nanorod spatial arrangements remains challenging. Here, we present a novel strategy for dynamic control of thermo-responsive gold nanorods with uniform alignment on a solid substrate using polymer brushes. In this system, cationic and thermo-responsive gold nanorods were immobilized into anionic polymer brushes via moderate electrostatic interactions, providing vertically aligned gold nanorod arrays. Upon heating, the gold nanorods were assembled while maintaining their vertical orientation within the polymer brushes. They returned to the original state upon cooling, indicating reversible assembly/disassembly. It is noticeable that this system exhibits rapid changes in nanostructure arrangement even when immobilized in the polymer brush substrate on a solid substrate rather than those dispersed in solution. Importantly, the gold nanorods showed good adhesion stability in polymer brushes without any significant detachment during washing and thermal cycling processes but performed assembly formation even at largely separated conditions, indicating the traveling of considerable distances similar to the lateral diffusion of membrane proteins in cell membranes. In addition to providing unprecedented control over gold nanorod spatial configurations, our approach introduces a versatile platform for developing advanced plasmonic devices.
Functional states of prelimbic and related circuits during the acquisition of a GO/noGO task in rats
Authors: Muñoz-Redondo Carmen , Parras Gloria G , Andreu-Sánchez Celia , Martín-Pascual Miguel Ángel , Delgado-García José M , Gruart Agnès 
Published: July 2024

Abstract
GO/noGO tasks enable assessing decision-making processes and the ability to suppress a specific action according to the context. Here, rats had to discriminate between 2 visual stimuli (GO or noGO) shown on an iPad screen. The execution (for GO) or nonexecution (for noGO) of the selected action (to touch or not the visual display) were reinforced with food. The main goal was to record and to analyze local field potentials collected from cortical and subcortical structures when the visual stimuli were shown on the touch screen and during the subsequent activities. Rats were implanted with recording electrodes in the prelimbic cortex, primary motor cortex, nucleus accumbens septi, basolateral amygdala, dorsolateral and dorsomedial striatum, hippocampal CA1, and mediodorsal thalamic nucleus. Spectral analyses of the collected data demonstrate that the prelimbic cortex was selectively involved in the cognitive and motivational processing of the learning task but not in the execution of reward-directed behaviors. In addition, the other recorded structures presented specific tendencies to be involved in these 2 types of brain activity in response to the presentation of GO or noGO stimuli. Spectral analyses, spectrograms, and coherence between the recorded brain areas indicate their specific involvement in GO vs. noGO tasks.
Comprehensive Review on the Use of Oral Cholera Vaccine (OCV) in Ethiopia: 2019 to 2023
Authors: Edosa Moti , Jeon Yeonji , Gedefaw Abel , Hailu Dejene , Mesfin Getachew Edlawit , Mogeni Ondari D , Jang Geun Hyeog , Mukasa David , Yeshitela Biruk , Getahun Tomas , Lynch Julia , Bouhenia Malika , Worku Demlie Yeshambel , Hussen Mukemil , Wossen Mesfin , Teferi Mekonnen , Park Se Eun 
Published: July 2024

Abstract

Background
Cholera outbreaks in Ethiopia necessitate frequent mass oral cholera vaccine (OCV) campaigns. Despite this, there is a notable absence of a comprehensive summary of these campaigns. Understanding national OCV vaccination history is essential to design appropriate and effective cholera control strategies. Here, we aimed to retrospectively review all OCV vaccination campaigns conducted across Ethiopia between 2019 and 2023.

Methods
The OCV request records from 2019 to October 2023 and vaccination campaign reports for the period from 2019 to December 2023 were retrospectively accessed from the Ethiopia Public Health Institute (EPHI) database. Descriptive analysis was conducted using the retrospective data collected.

Results
From 2019 to October 2023, Ethiopian government requested 32 044 576 OCV doses (31 899 576 doses to global stockpile; 145 000 doses to outside of stockpile). Around 66.3% of requested doses were approved; of which 90.4% were received. Fifteen OCV campaigns (12 reactive and 3 pre-emptive) were conducted, including five two-dose campaigns with varying dose intervals and single-dose campaigns partially in 2019 and entirely in 2021, 2022 and 2023. Overall vaccine administrative coverage was high; except for Tigray region (41.8% in the 1st round; 2nd round didn't occur). The vaccine administrative coverage records were documented, but no OCV coverage survey data was available.

Conclusions
This study represents the first comprehensive review of OCV campaigns in Ethiopia spanning the last five years. Its findings offer valuable insights into informing future cholera control strategies, underscoring the importance of monitoring and evaluation despite resource constraints. Addressing the limitations in coverage survey data availability is crucial for enhancing the efficacy of future campaigns.
Ethiopia National Cholera Elimination Plan 2022–2028: Experiences, Challenges, and the Way Forward
Authors: Hussen Mukemil , Worku Demlie Yeshambel , Edosa Moti , Kebede Mandefro , Wossen Mesfin , Mulugeta Chane Azeb , Abate Girma , Hailu Asfaw Wondosen , Hailu Dejene , Teferi Mekonnen , Jeon Yeonji , Gedefaw Abel , Park Se Eun 
Published: July 2024

Abstract
Cholera remains a significant public health concern in Ethiopia. More than 15.9 million Ethiopians, constituting 15% of the total population, live in areas with a history of recurrent cholera outbreaks. The last 9 years of national cholera surveillance data show the country has been experiencing cholera outbreaks every year. The current cholera outbreak, starting in August 2022, has affected the entire country, with 841 reported cases and a 3.13% case fatality rate (CFR) in 2022, and &gt;30 000 cases with nearly a 1.4% CFR in 2023. In line with “Ending Cholera—A Global Roadmap to 2030,” the government of Ethiopia is committed to eliminate cholera in the country and has prepared its “National Cholera Elimination Plan (NCP): 2022–2028” with aims to achieve zero local transmission in cholera hotspot areas by 2028 and 90% fatality reduction from the recent (2020–2022) average of 1.8% CFR. The plan is multisectoral, has a clear coordination platform, contains all interventions with in-depth situational analysis, is concordant with existing plans and strategies, and is cascaded at the regional level and implemented with existing government and public structures. Nationwide, total 118 cholera hotspot woredas (districts) were identified, and a comprehensive situation analysis of the existing cholera outbreak response capacity was assessed. This multisectoral and multiyear NCP has forecasted around US$404 million budget estimates with &gt;90% allocated to improving the country's water, sanitation, and hygiene (US$222 million; 55% of total NCP budget) and case management (US$149 million; 37%). The cholera vaccination strategy included in the NCP exhibited a 5-year oral cholera vaccine (OCV) introduction plan with 2 doses (30 604 889 doses) and single dose (3 031 266 doses) in selected cholera hotspot areas. However, its implementation is challenged due to a lack of financial support, inability to get the requested vaccine for targeted hotspot woredas (due to the current shortage of doses in the OCV global stockpile), recurrent cholera outbreaks, and high humanitarian needs in the country. It is recommended to have a sustainable financial mechanism to support implementation, follow the requested vaccine doses, and reorganize the planned coordination platform to foster the implementation.
Dissecting Water, Sanitation, and Hygiene (WaSH) to Assess Risk Factors for Cholera in Shashemene, Oromia Region, Ethiopia
Authors: Hailu Dejene , Jeon Yeonji , Gedefaw Abel , Kim Jong-Hoon , Mraidi Ramzi , Getahun Tomas , Mogeni Ondari D , Mesfin Getachew Edlawit , Jang Geun Hyeog , Mukasa David , Pak Gi Deok , Kim Deok Ryun , Ayele Abebe Samuyel , Yeshitela Biruk , Edosa Moti , Worku Demlie Yeshambel , Park Se Eun , Teferi Mekonnen 
Published: July 2024

Abstract

Background
Cholera outbreaks have afflicted Ethiopia, with nearly 100 000 cases and 1030 deaths reported from 2015 to 2023, emphasizing the critical need to understand water, sanitation, and hygiene (WaSH) risk factors.

Methods
We conducted a cross-sectional household (HH) survey among 870 HHs in Shashemene Town and Shashemene Woreda, alongside extracting retrospective cholera case data from the Ethiopian Public Health Institute database. Relationships between WaSH and sociodemographic/economic-levels of HHs were examined. WaSH status and cholera attack rates (ARs) were described at kebele-level using geospatial mapping, and their association was statistically analyzed.

Results
Access to basic drinking water, sanitation, and hygiene facilities was limited, with 67.5% (95% confidence interval, 64.4–70.6), 73.4% (70.3–76.3), and 30.3% (27.3–33.3) of HHs having access, respectively. Better WaSH practices were associated with urban residence (adjusted odds ratio, 1.7, [95% confidence interval, 1.1–2.7]), higher educational levels (2.7 [1.2–5.8]), and wealth (2.5 [1.6–4.0]). The association between cholera ARs and at least basic WaSH status was not statistically significant (multiple R2 = 0.13; P = .36), although localized effects were suggested for sanitation (Moran I = 0.22; P = .024).

Conclusions
Addressing gaps in WaSH access and hygiene practices is crucial for reducing cholera risk. Further analyses with meaningful covariates and increased sample sizes are necessary to understand the association between cholera AR and specific WaSH components.