bluuebunny/crossref_metadata_2025_split huggingface dataset:
Medication use evaluation of tocilizumab implementation in COVID-19 treatment guidelines: A causal inference approach
Authors: Goriacko Pavel , Moskowitz Ari , Ferguson Nadia , Khalique Saira , Hopkins Una , Quinn Nicholas , Sinnett Mark , Bellin Eran 
Published: June 2024

Abstract

Purpose
Introduction of new medications to health-system formularies is often not accompanied by assessments of their clinical impact on the local patient population. The growing availability of electronic health record (EHR) data and advancements in pharmacoepidemiology methods offer institutions the opportunity to monitor the medication implementation process and assess clinical effectiveness in the local clinical context. In this study, we applied novel causal inference methods to evaluate the effects of a formulary policy introducing tocilizumab therapy for critically ill patients with coronavirus disease 2019 (COVID-19).

Methods
We conducted a medication use evaluation utilizing EHR data from patients admitted to a large medical center during the 6 months before and after implementation of a formulary policy endorsing the use of tocilizumab for treatment of COVID-19. The impact of tocilizumab on 28-day all-cause mortality was assessed using a difference-in-differences analysis, with ineligible patients serving as a nonequivalent control group, and a matched analysis guided by a target trial emulation framework. Safety endpoints assessed included the incidence of secondary infections and liver enzyme elevations. Our findings were benchmarked against clinical trials, an observational study, and a meta-analysis.

Results
Following guideline modification, tocilizumab was administered to 69% of eligible patients. This implementation was associated with a 3.1% absolute risk reduction in 28-day mortality (odds ratio, 0.86; number needed to treat to prevent one death, 32) attributable to the inclusion of tocilizumab in the guidelines and an additional 8.6% absolute risk reduction (odds ratio, 0.65; number needed to treat to prevent one death, 12) linked to its administration. These findings were consistent with estimates from published literature, although the effect estimates from the difference-in-differences analysis exhibited imprecision.

Conclusion
Evaluating formulary management decisions through novel causal inference approaches offers valuable estimates of clinical effectiveness and the potential to optimize the impact of new medications on population outcomes.
Nasal Deviation and Facial Asymmetry in Patients Undergoing Rhinoplasty
Authors: Scott Brian L , Pearlman Steven 
Published: June 2024

Abstract

Background
The existing literature is conflicted on whether nasal deviation is primarily attributable to trauma or the result of asymmetric facial development.

Objectives
The aim of this study was to establish the prevalence of nasal trauma and facial asymmetry in patients undergoing rhinoplasty, and to determine if a correlation exists between the laterality of facial asymmetry and nasal deviation.

Methods
A retrospective review was undertaken of patients who had undergone primary rhinoplasty with the senior author over a 12-month period. Patient charts were reviewed and clinical photographs were analyzed.

Results
In total, 144 patients underwent rhinoplasty over the study period; 68 patients underwent revision rhinoplasty and were excluded. Of the 76 patients who underwent primary rhinoplasty, 9% reported prior nasal trauma, 68% had deviated nasal bones, 46% had deviated nasal tips, 70% had asymmetric midfaces, and 36% had deviated chins. In patients without prior trauma history, nasal bones were most commonly deviated towards the side of midface hypoplasia (53%, P = .008). The nasal tip was most commonly deviated contralateral to the side of septal deviation (59%, P = .001). There was no association between nasal bone and chin deviation. Nasal tip deviation was not associated with midface hypoplasia or chin deviation.

Conclusions
Nasal deviation is primarily driven by asymmetric facial growth rather than being the result of nasal trauma.

Level of Evidence: 3
GammaGateR: semi-automated marker gating for single-cell multiplexed imaging
Authors: Xiong Jiangmei , Kaur Harsimran , Heiser Cody N , McKinley Eliot T , Roland Joseph T , Coffey Robert J , Shrubsole Martha J , Wrobel Julia , Ma Siyuan , Lau Ken S , Vandekar Simon 
Published: June 2024

Abstract

Motivation
Multiplexed immunofluorescence (mIF) is an emerging assay for multichannel protein imaging that can decipher cell-level spatial features in tissues. However, existing automated cell phenotyping methods, such as clustering, face challenges in achieving consistency across experiments and often require subjective evaluation. As a result, mIF analyses often revert to marker gating based on manual thresholding of raw imaging data.

Results
To address the need for an evaluable semi-automated algorithm, we developed GammaGateR, an R package for interactive marker gating designed specifically for segmented cell-level data from mIF images. Based on a novel closed-form gamma mixture model, GammaGateR provides estimates of marker-positive cell proportions and soft clustering of marker-positive cells. The model incorporates user-specified constraints that provide a consistent but slide-specific model fit. We compared GammaGateR against the newest unsupervised approach for annotating mIF data, employing two colon datasets and one ovarian cancer dataset for the evaluation. We showed that GammaGateR produces highly similar results to a silver standard established through manual annotation. Furthermore, we demonstrated its effectiveness in identifying biological signals, achieved by mapping known spatial interactions between CD68 and MUC5AC cells in the colon and by accurately predicting survival in ovarian cancer patients using the phenotype probabilities as input for machine learning methods. GammaGateR is a highly efficient tool that can improve the replicability of marker gating results, while reducing the time of manual segmentation.

Availability and implementation
The R package is available at https://github.com/JiangmeiRubyXiong/GammaGateR.
How Immunocompromised Hosts Were Left Behind in the Quest to Control the COVID-19 Pandemic
Authors: Boeckh Michael , Pergam Steven A , Limaye Ajit P , Englund Janet , Corey Lawrence , Hill Joshua A 
Published: June 2024

Abstract
The immunocompromised population was disproportionately affected by the severe acute respiratory syndrome coronavirus 2 pandemic. However, these individuals were largely excluded from clinical trials of vaccines, monoclonal antibodies, and small molecule antivirals. Although the community of scientists, clinical researchers, and funding agencies have proven that these therapeutics can be made and tested in record time, extending this progress to vulnerable and medically complex individuals from the start has been a missed opportunity. Here, we advocate that it is paramount to plan for future pandemics by investing in specific clinical trial infrastructure for the immunocompromised population to be prepared when the need arises.
From microcosm to macrocosm: adaptive radiation of Darwin’s finches
Authors: Grant Peter R , Grant B Rosemary 
Published: June 2024

Abstract
In this Perspective we show the value of studying living organisms in the field to understand their history. Darwin’s finches are an iconic example of the early stages of speciation in a young adaptive radiation that produced 18 species in little more than a million years. The question they pose is how and why so many species originated and diversified rapidly. A long-term study of four species of finches on the small island of Daphne Major, combined with genomic investigations, provide some answers in terms of extrinsic and intrinsic factors. Beak size and shape, as well as body size, are key heritable features involved in both ecological and reproductive isolation, and their evolution by natural selection was caused by competitor species during prolonged droughts. Introgressive hybridization of related species is rare but recurring, apparently widespread, increases genetic variation, and does not incur a fitness cost. Hybridization can produce a new species. We use a phylogeny based on whole genome sequences of the four finches to infer morphological transitions in their radiation. Several lines of evidence indicate that some species are missing from the early phase of the radiation due to extinction. Combining these results, we re-cast the classical allopatry-then-sympatry theory of adaptive radiation as a competition-selection-hybridization process that generates a diversity of species.
Acquisitions of behavioral health treatment facilities from 2010 to 2021
Authors: Thornburg Ben , McGinty Emma B , Eddelbuettel Julia , Kennedy-Hendricks Alene , Braun Robert T , Eisenberg Matthew D 
Published: June 2024

Abstract
Private equity (PE) and other for-profit ownership of behavioral health (mental health and substance use) treatment facilities have become increasingly prevalent, but data on these acquisitions are not readily available. In this study, we describe a novel database that contains information on the universe of behavioral health acquisitions that occurred between 2010 and 2021. We found that the frequency of behavioral health facilities involved in acquisitions increased substantially, from 32 facilities in 2010 to 1330 in 2021. The total number of facilities involved in acquisitions was 2806. Most of these facilities provided outpatient services only (N = 2073) and offered only mental health services (N = 1428). Private equity-backed acquisitions accounted for around 60% of all acquisition activity (N = 1678 facilities PE, N = 1128 facilities other for-profit). 25% of acquired facilities were located within 20 miles of one another (N = 561), 50% occurred within 80 miles (N = 1403), and 75% occurred within 319 miles (N = 2104). Future research should evaluate the effects of this consolidation on behavioral healthcare access, quality, spending, and patient outcomes.
Metabolome profiling and transcriptome analysis unveiling the crucial role of magnesium transport system for magnesium homeostasis in tea plants
Authors: Li Jing , Wen Ting , Zhang Ruiming , Hu Xinlong , Guo Fei , Zhao Hua , Wang Pu , Wang Yu , Ni Dejiang , Wang Mingle 
Published: June 2024

Abstract
Magnesium (Mg2+) is a crucial nutrient for the growth and development of Camellia sinensis and is closely related to the quality of tea. However, the underlying mechanisms responding to low-Mg 2+ stress in tea plants remain largely unknown. In this study, photosynthetic parameters, metabolomics, and transcriptomics were utilized to explore the potential effects of low Mg2+ on the growth and metabolism of C. sinensis. Low-Mg2+ treatment increased the ratio of shoot dry weight to root dry weight but decreased the photosynthesis of C. sinensis. Forty and thirty metabolites were impacted by Mg2+ shortage in C. sinensis shoots and roots, respectively. Integrated transcriptome and metabolome analyses revealed the possible reasons for the decreased contents of chlorophyll and catechins and the increased theanine content in C. sinensis roots. Weighted gene co-expression network analysis indicated that the Mg2+ transport system was essential in the regulation of Mg2+ homeostasis in C. sinensis, in which CsMGT5 was identified to be the key regulator according to CsMGT5-overexpressing and complementary assays in Arabidopsis thaliana. Moreover, silencing of CsMGT5 in vivo reduced the content of chlorophyll in C. sinensis shoots. In addition, CsMGT5 might collaborate with ammonium transporters to keep the amino acid content steady, suggesting its potential application for tea quality improvement. All these findings demonstrate the key roles of CsMGTs for Mg2+ homeostasis in C. sinensis, providing a theoretical basis for Mg2+ efficient utilization in plants.
Soil microbial community response to corrinoids is shaped by a natural reservoir of vitamin B12
Authors: Hallberg Zachary F , Nicolas Alexa M , Alvarez-Aponte Zoila I , Mok Kenny C , Sieradzki Ella T , Pett-Ridge Jennifer , Banfield Jillian F , Carlson Hans K , Firestone Mary K , Taga Michiko E 
Published: June 2024

Abstract
Soil microbial communities perform critical ecosystem services through the collective metabolic activities of numerous individual organisms. Most microbes use corrinoids, a structurally diverse family of cofactors related to vitamin B12. Corrinoid structure influences the growth of individual microbes, yet how these growth responses scale to the community level remains unknown. Analysis of metagenome-assembled genomes suggests that corrinoids are supplied to the community by members of the archaeal and bacterial phyla Thermoproteota, Actinobacteria, and Proteobacteria. Corrinoids were found largely adhered to the soil matrix in a grassland soil, at levels exceeding those required by cultured bacteria. Enrichment cultures and soil microcosms seeded with different corrinoids showed distinct shifts in bacterial community composition, supporting the hypothesis that corrinoid structure can shape communities. Environmental context influenced both community- and taxon-specific responses to specific corrinoids. These results implicate corrinoids as key determinants of soil microbiome structure and suggest that environmental micronutrient reservoirs promote community stability.
Whole-genome resequencing reveals the uniqueness of Subei yak
Authors: Guo Shaoke , Yu Tianjun , Wang Xingdong , Zhao Shuangquan , Zhao Erjun , Ainierlitu  , Ba Teer , Gan Manyu , Dong Cunmei , Naerlima  , Yin Lian , Ke Xikou , Dana Dawuti , Guo Xian 
Published: June 2024

Abstract
Subei yak is an essential local yak in the Gansu Province, which genetic resource has recently been discovered. It is a meat-milk dual-purpose variety with high fecundity and relatively stable population genetic structure. However, its population genetic structure and genetic diversity are yet to be reported. Therefore, this study aimed to identify molecular markers of Subei yak genome by whole-genome resequencing, and to analyze the population structure and genetic diversity of Subei yak. This study screened 12,079,496 single nucleotide polymorphism (SNP) molecular markers in the 20 Subei yaks genome using whole-genome resequencing technology. Of these SNPs, 32.09% were located in the intronic region of the genome. Principal component analysis, phylogenetic analysis, and population structure analysis revealed that the Subei yak belonged to an independent group in the domestic yak population. A selective clearance analysis was carried out on Subei yak and other domestic yaks, and the genes under positive selection were annotated. The functional enrichment analysis showed that Subei yak possessed prominent selection characteristics in terms of external environment perception, hypoxia adaptation, and muscle development. Furthermore, Subei yak showed excellent muscle fat deposition and meat quality traits. Thus, this study will serve as a reference for discovering population structure, genetic evolution, and other unique traits of Subei yak and for expanding the genetic variation catalog of yaks.
Structural analysis of code-based algorithms of the NIST post-quantum call
Authors: González de la Torre M A , Encinas L Hernández , García J I Sánchez 
Published: June 2024

Abstract
Code-based cryptography is currently the second most promising post-quantum mathematical tool for quantum-resistant algorithms. Since in 2022 the first post-quantum standard Key Encapsulation Mechanism, Kyber (a latticed-based algorithm), was selected to be established as standard, and after that the National Institute of Standards and Technology post-quantum standardization call focused in code-based cryptosystems. Three of the four candidates that remain in the fourth round are code-based algorithms. In fact, the only non-code-based algorithm (SIKE) is now considered vulnerable. Due to this landscape, it is crucial to update previous results about these algorithms and their functioning. The Fujisaki-Okamoto transformation is a key part of the study of post-quantum algorithms and in this work we focus our analysis on Classic McEliece, BIKE and HQC proposals, and how they apply this transformation to obtain IND-CCA semantic security. Since after security the most important parameter in the evaluation of the algorithms is performance, we have compared the performance of the code-based algorithms of the NIST call considering the same architecture for all of them.
Primary pericardial synovial sarcoma requiring emergency salvage right atrial debulking: a case report
Authors: Ravishankar Ramanish , Makam Rishab , Loubani Mahmoud , Chaudhry Mubarak , Hussain Azar 
Published: June 2024

Abstract
A 52-year-old gentleman presented with symptoms of breathlessness and type 1 respiratory failure. His CT pulmonary angiogram showed a heterogenous, oval-shaped lesion between the heart and diaphragm with a right atrial (RA) filling defect, pericardial thickening and pulmonary metastasis. An RA debulking salvage operation confirmed this to be a pericardial tumour and further cytology and immunohistochemistry testing confirmed a primary synovial sarcoma. After 12 days in intensive care for ventilation, the patient was successfully discharged on warfarin and underwent oncology follow-up for chemotherapy. Following a 15-month follow-up, no mortality was observed despite the aggressive nature of the tumour.
DMC1 and RAD51 bind FxxA and FxPP motifs of BRCA2 via two separate interfaces
Authors: Miron Simona , Legrand Pierre , Dupaigne Pauline , van Rossum-Fikkert Sari E , Ristic Dejan , Majeed Atifa , Kanaar Roland , Zinn-Justin Sophie , Zelensky Alex N 
Published: June 2024

Abstract
In vertebrates, the BRCA2 protein is essential for meiotic and somatic homologous recombination due to its interaction with the RAD51 and DMC1 recombinases through FxxA and FxPP motifs (here named A- and P-motifs, respectively). The A-motifs present in the eight BRC repeats of BRCA2 compete with the A-motif of RAD51, which is responsible for its self-oligomerization. BRCs thus disrupt RAD51 nucleoprotein filaments in vitro. The role of the P-motifs is less studied. We recently found that deletion of Brca2 exons 12–14 encoding one of them (the prototypical ‘PhePP’ motif), disrupts DMC1 but not RAD51 function in mouse meiosis. Here we provide a mechanistic explanation for this phenotype by solving the crystal structure of the complex between a BRCA2 fragment containing the PhePP motif and DMC1. Our structure reveals that, despite sharing a conserved phenylalanine, the A- and P-motifs bind to distinct sites on the ATPase domain of the recombinases. The P-motif interacts with a site that is accessible in DMC1 octamers and nucleoprotein filaments. Moreover, we show that this interaction also involves the adjacent protomer and thus increases the stability of the DMC1 nucleoprotein filaments. We extend our analysis to other P-motifs from RAD51AP1 and FIGNL1.
Site-specific regulation of RNA editing with ribose-modified nucleoside analogs in ADAR guide strands
Authors: Jauregui-Matos Victorio , Jacobs Olivia , Ouye Randall , Mozumder Sukanya , Salvador Prince J , Fink Kyle D , Beal Peter A 
Published: June 2024

Abstract
Adenosine Deaminases Acting on RNA (ADARs) are enzymes that catalyze the conversion of adenosine to inosine in RNA duplexes. These enzymes can be harnessed to correct disease-causing G-to-A mutations in the transcriptome because inosine is translated as guanosine. Guide RNAs (gRNAs) can be used to direct the ADAR reaction to specific sites. Chemical modification of ADAR guide strands is required to facilitate delivery, increase metabolic stability, and increase the efficiency and selectivity of the editing reaction. Here, we show the ADAR reaction is highly sensitive to ribose modifications (e.g. 4′-C-methylation and Locked Nucleic Acid (LNA) substitution) at specific positions within the guide strand. Our studies were enabled by the synthesis of RNA containing a new, ribose-modified nucleoside analog (4′-C-methyladenosine). Importantly, the ADAR reaction is potently inhibited by LNA or 4′-C-methylation at different positions in the ADAR guide. While LNA at guide strand positions −1 and −2 block the ADAR reaction, 4′-C-methylation only inhibits at the −2 position. These effects are rationalized using high-resolution structures of ADAR-RNA complexes. This work sheds additional light on the mechanism of ADAR deamination and aids in the design of highly selective ADAR guide strands for therapeutic editing using chemically modified RNA.
Single-neuron projectome-guided analysis reveals the neural circuit mechanism underlying endogenous opioid antinociception
Authors: Dou Yan-Nong , Liu Yuan , Ding Wen-Qun , Li Qing , Zhou Hua , Li Ling , Zhao Meng-Ting , Li Zheng-Yi-Qi , Yuan Jing , Wang Xiao-Fei , Zou Wang-Yuan , Li Anan , Sun Yan-Gang 
Published: June 2024

ABSTRACT
Endogenous opioid antinociception is a self-regulatory mechanism that reduces chronic pain, but its underlying circuit mechanism remains largely unknown. Here, we showed that endogenous opioid antinociception required the activation of mu-opioid receptors (MORs) in GABAergic neurons of the central amygdala nucleus (CEA) in a persistent-hyperalgesia mouse model. Pharmacogenetic suppression of these CEAMOR neurons, which mimics the effect of MOR activation, alleviated the persistent hyperalgesia. Furthermore, single-neuron projection analysis revealed multiple projectome-based subtypes of CEAMOR neurons, each innervating distinct target brain regions. We found that the suppression of axon branches projecting to the parabrachial nucleus (PB) of one subtype of CEAMOR neurons alleviated persistent hyperalgesia, indicating a subtype- and axonal-branch-specific mechanism of action. Further electrophysiological analysis revealed that suppression of a distinct CEA-PB disinhibitory circuit controlled endogenous opioid antinociception. Thus, this study identified the central neural circuit that underlies endogenous opioid antinociception, providing new insight into the endogenous pain modulatory mechanisms.