bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cerebral cortical regions always connect with each other via the shortest paths
Authors: Lv Yifan , Kang Zili , Han Tianle , He Mengshen , Du Ruhai , Zhang Tuo , Liu Tianming , Ge Bao 
Published: June 2023

Abstract
In human society, the choice of transportation mode between two cities is largely influenced by the distance between the regions. Similarly, when neurons communicate with each other within the cerebral cortex, do they establish their connections based on their physical distance? In this study, we employed a data-driven approach to explore the relationships between fiber length and corresponding geodesic distance between the fiber’s two endpoints on brain surface. Diffusion-MRI-derived fiber streamlines were used to represent extra-cortical axonal connections between neurons or cortical regions, while geodesic paths between cortical points were employed to simulate intra-cortical connections. The results demonstrated that the geodesic distance between two cortical regions connected by a fiber streamline was greater than the fiber length most of the time, indicating that cortical regions tend to choose the shortest path for connection; whether it be an intra-cortical or extra-cortical route, especially when intra-cortical routes within cortical regions are longer than potential extrinsic fiber routes, there is an increased probability to establish fiber routes to connect the both regions. These findings were validated in a group of human brains and may provide insights into the underlying mechanisms of neuronal growth, connection, and wiring.
Thalamo-cortical and cerebello-cortical functional connectivity in development
Authors: Badke D’Andrea Carolina , Marek Scott , Van Andrew N , Miller Ryland L , Earl Eric A , Stewart Stephanie B , Dosenbach Nico U F , Schlaggar Bradley L , Laumann Timothy O , Fair Damien A , Gordon Evan M , Greene Deanna J 
Published: June 2023

Abstract
The thalamus is a critical relay center for neural pathways involving sensory, motor, and cognitive functions, including cortico-striato-thalamo-cortical and cortico-ponto-cerebello-thalamo-cortical loops. Despite the importance of these circuits, their development has been understudied. One way to investigate these pathways in human development in vivo is with functional connectivity MRI, yet few studies have examined thalamo-cortical and cerebello-cortical functional connectivity in development. Here, we used resting-state functional connectivity to measure functional connectivity in the thalamus and cerebellum with previously defined cortical functional networks in 2 separate data sets of children (7–12 years old) and adults (19–40 years old). In both data sets, we found stronger functional connectivity between the ventral thalamus and the somatomotor face cortical functional network in children compared with adults, extending previous cortico-striatal functional connectivity findings. In addition, there was more cortical network integration (i.e. strongest functional connectivity with multiple networks) in the thalamus in children than in adults. We found no developmental differences in cerebello-cortical functional connectivity. Together, these results suggest different maturation patterns in cortico-striato-thalamo-cortical and cortico-ponto-cerebellar-thalamo-cortical pathways.
A Retrospective, Observational Study of 12 Cases of Expanded-Access Customized Phage Therapy: Production, Characteristics, and Clinical Outcomes
Authors: Green Sabrina I , Clark Justin R , Santos Haroldo H , Weesner Kyle E , Salazar Keiko C , Aslam Saima , Campbell J William , Doernberg Sarah B , Blodget Emily , Morris Michele I , Suh Gina A , Obeid Karam , Silveira Fernanda P , Filippov Andrey A , Whiteson Katrine L , Trautner Barbara W , Terwilliger Austen L , Maresso Anthony 
Published: June 2023

Abstract

Background
Antimicrobial resistance (AMR) is undermining modern medicine, a problem compounded by bacterial adaptation to antibiotic pressures. Phages are viruses that infect bacteria. Their diversity and evolvability offer the prospect of their use as a therapeutic solution. Reported are outcomes of customized phage therapy for patients with difficult-to-treat antimicrobial resistant infections.

Methods
We retrospectively assessed 12 cases of customized phage therapy from a phage production center. Phages were screened, purified, sequenced, characterized, and Food and Drug Administration–approved via the IND (investigational new drug) compassionate-care route. Outcomes were assessed as favorable or unfavorable by microbiologic and clinical standards. Infections were device-related or systemic. Other experiences such as time to treatment, antibiotic synergy, and immune responses were recorded.

Results
Fifty requests for phage therapy were received. Customized phages were generated for 12 patients. After treatment, 42% (5/12) of cases showed bacterial eradication and 58% (7/12) showed clinical improvement, with two-thirds of all cases (66%) showing favorable responses. No major adverse reactions were observed. Antibiotic-phage synergy in vitro was observed in most cases. Immunological neutralization of phages was reported in 5 cases. Several cases were complicated by secondary infections. Complete characterization of the phages (morphology, genomics, and activity) and their production (methods, sterility, and endotoxin tests) are reported.

Conclusions
Customized phage production and therapy was safe and yielded favorable clinical or microbiological outcomes in two-thirds of cases. A center or pipeline dedicated to tailoring the phages against a patient's specific AMR bacterial infection may be a viable option where standard treatment has failed.
Neonatal Paenibacilliosis: Paenibacillus Infection as a Novel Cause of Sepsis in Term Neonates With High Risk of Sequelae in Uganda
Authors: Ericson Jessica E , Burgoine Kathy , Kumbakumba Elias , Ochora Moses , Hehnly Christine , Bajunirwe Francis , Bazira Joel , Fronterre Claudio , Hagmann Cornelia , Kulkarni Abhaya V , Kumar M Senthil , Magombe Joshua , Mbabazi-Kabachelor Edith , Morton Sarah U , Movassagh Mercedeh , Mugamba John , Mulondo Ronald , Natukwatsa Davis , Kaaya Brian Nsubuga , Olupot-Olupot Peter , Onen Justin , Sheldon Kathryn , Smith Jasmine , Ssentongo Paddy , Ssenyonga Peter , Warf Benjamin , Wegoye Emmanuel , Zhang Lijun , Kiwanuka Julius , Paulson Joseph N , Broach James R , Schiff Steven J 
Published: June 2023

Abstract

Background
Paenibacillus thiaminolyticus may be an underdiagnosed cause of neonatal sepsis.

Methods
We prospectively enrolled a cohort of 800 full-term neonates presenting with a clinical diagnosis of sepsis at 2 Ugandan hospitals. Quantitative polymerase chain reaction specific to P. thiaminolyticus and to the Paenibacillus genus were performed on the blood and cerebrospinal fluid (CSF) of 631 neonates who had both specimen types available. Neonates with Paenibacillus genus or species detected in either specimen type were considered to potentially have paenibacilliosis, (37/631, 6%). We described antenatal, perinatal, and neonatal characteristics, presenting signs, and 12-month developmental outcomes for neonates with paenibacilliosis versus clinical sepsis due to other causes.

Results
Median age at presentation was 3 days (interquartile range 1, 7). Fever (92%), irritability (84%), and clinical signs of seizures (51%) were common. Eleven (30%) had an adverse outcome: 5 (14%) neonates died during the first year of life; 5 of 32 (16%) survivors developed postinfectious hydrocephalus (PIH) and 1 (3%) additional survivor had neurodevelopmental impairment without hydrocephalus.

Conclusions
Paenibacillus species was identified in 6% of neonates with signs of sepsis who presented to 2 Ugandan referral hospitals; 70% were P. thiaminolyticus. Improved diagnostics for neonatal sepsis are urgently needed. Optimal antibiotic treatment for this infection is unknown but ampicillin and vancomycin will be ineffective in many cases. These results highlight the need to consider local pathogen prevalence and the possibility of unusual pathogens when determining antibiotic choice for neonatal sepsis.
Long-term Real-world Protection Afforded by Third mRNA Doses Against Symptomatic Severe Acute Respiratory Syndrome Coronavirus 2 Infections, Coronavirus Disease 19-related Emergency Attendances and Hospitalizations Amongst Older Singaporeans During an Omicron XBB Wave
Authors: Wee Liang En , Pang Deanette , Chiew Calvin , Tan Janice , Lee Vernon , Ong Benjamin , Lye David Chien , Tan Kelvin Bryan 
Published: June 2023

Abstract

Background
Literature on long-term real-world vaccine effectiveness of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) booster vaccines (up to and beyond 360 days) is scarce. We report estimates of protection against symptomatic infection, emergency department (ED) attendances and hospitalizations up to and beyond 360 days post-receipt of booster messenger RNA (mRNA) vaccines among Singaporeans aged ≥60 years during an Omicron XBB wave.

Methods
We conducted a population-based cohort study including all Singaporeans aged ≥60 years with no documented prior SARS-CoV-2 infection who had previously received ≥3 doses of mRNA vaccines (BNT162b2/mRNA-1273), over a 4-month period during transmission of Omicron XBB. We reported the adjusted incidence-rate-ratio (IRR) for symptomatic infections, ED attendances and hospitalizations at different time-intervals from both first and second boosters, using Poisson regression; with the reference group being those who received their first booster 90 to 179 days prior.

Results
In total, 506 856 boosted adults were included, contributing 55 846 165 person-days of observation. Protection against symptomatic infections among those who received a third vaccine dose (first booster) waned after 180 days with increasing adjusted IRRs; however, protection against ED attendances and hospitalizations held up, with comparable adjusted IRRs with increasing time from third vaccine doses (≥360 days from third dose: adjusted IRR [ED attendances] = 0.73, 95% confidence interval [CI] = .62–.85; adjusted IRR [hospitalization] = 0.58, 95% CI = .49–.70).

Conclusions
Our results highlight the benefit of a booster dose in reducing ED attendances and hospitalizations amongst older adults aged ≥60 years with no documented prior SARS-CoV-2 infection, during an Omicron XBB wave; up to and beyond 360 days post-booster. A second booster provided further reduction.
Urinary single-cell sequence analysis of the urinary macrophage in different outcomes of membranous nephropathy
Authors: Liu Xi , Zhao Yu , Niu Yangyang , Xie Qionghong , Nie Hao , Jin Yun , Zhang Yingying , Lu Yuqiu , Zhu Saiya , Zuo Wei , Yu Chen 
Published: June 2023

ABSTRACT

Background
Great progress has been made in the diagnosis and treatment of membranous nephropathy (MN). However, a significant number of patients do not respond to immunosuppressive therapy and eventually progress to end-stage kidney disease. To investigate the mechanism of different outcome of MN, we performed single-cell sequencing to analyze the urine cells of patients with and without complete remission of MN.

Methods
Urine single-cell RNA sequencing was performed on 12 healthy controls (HC) and 15 patients with MN. The patients were divided into a complete remission group (CR, n = 9) and a no remission group (NR, n = 6).

Results
(i) Macrophages were the largest group in urine cells, comprising 48.02%, 68.96% and 20.95% in the HC, CR and NR groups, respectively. (ii) Urinary macrophages expressing FIColin-1 and S100 calcium-binding protein A8 were mainly found in the HC and CR groups, indicating that they were derived from bone marrow and peripheral blood, while the urinary macrophages expressing the regulator of G-protein signaling 1 (RGS1) and HLA-DPA1, mainly found in the NR group, were derived from renal resident macrophages. (iii) In healthy adults, urine macrophages expressed the metallothionein family, indicating that they can regulate anti-inflammatory and proinflammatory functions bidirectionally. In the CR group, the urine macrophages showed strong proinflammatory properties. In the NR group, the urinary macrophages mainly associated with the level of proteinuria and the impaired renal function.

Conclusions
Our study firstly delineated the differences in urinary cell maps between healthy individuals and MN patients with CR or NR outcomes. Not only the origin but also the function of urine macrophages were different in the HC, CR and NR groups.
A Novel Enzymatic Hydrolysis Method for Urine Aldosterone Quantification: A Case for Reassessing Clinical Cut-Offs of Primary Aldosteronism
Authors: Yazdanpanah Mehrdad , Delaney Sarah R , Beriault Daniel R 
Published: June 2023

Abstract

Background
Primary aldosteronism (PA) is a common endocrine cause of secondary hypertension. The aldosterone/renin ratio is an important tool for PA screening, and dynamic testing in serum or urine is used to confirm the diagnosis. While LC-MS/MS is considered the gold standard for testing, there is significant interlaboratory variability between the extraction procedures, which can impact diagnostic interpretation. To help overcome this, we present a simple and accurate LC-MS/MS method for the quantification of both serum and urine aldosterone using a novel enzymatic hydrolysis procedure.

Methods
Serum and urine aldosterone was extracted and measured by LC-MS/MS. Urine-conjugated aldosterone glucuronide was hydrolyzed using a genetically modified glucuronidase enzyme. The assay precision, accuracy, limit of quantification, recovery, and carryover were evaluated and the new assay cut-offs were proposed.

Results
The liquid chromatography method allowed for adequate separation of the aldosterone peak from closely eluting peaks. Significant in vitro aldosterone loss was observed during acid-catalyzed hydrolysis of urine, which was corrected with the addition of the internal standard to the urine before the hydrolysis step. Glucuronidase catalyzed hydrolysis of urine aldosterone glucuronide displays good correlation with the corrected acid-catalyzed hydrolysis. Serum aldosterone showed good agreement with reference values and the consensus range reported for external quality assessment specimens.

Conclusion
A simple, fast, and highly accurate method for the detection of serum and urine aldosterone has been developed. The proposed novel enzymatic procedure allows for short hydrolysis time and compensates for urine aldosterone loss during the hydrolysis step.
Assessing stress physiology within a conservation breeding program for an endangered species
Authors: Falconer S , McAdie M , Mastromonaco G , Schulte-Hostedde A I 
Published: June 2023

Abstract
Conservation breeding programs typically involve the management of individuals both in and ex situ, so it is vital to understand how the physiology of managed species changes in these environments to maximize program outcomes. The Vancouver Island marmot (VIM; Marmota vancouverensis) is one species that has been managed in a conservation breeding program to recover the critically low wild population. Previous research has shown there are differences in hair glucocorticoid concentrations for VIMs in different managed groups in the program. Therefore, we used &gt;1000 blood samples collected since the program’s inception to assess the neutrophil to lymphocyte (N:L) ratio among captive, pre-release, post-release and wild populations as another metric of stress. In situ VIM populations were found to have a significantly higher N:L ratio than ex situ populations, suggesting that the wild is a more physiologically challenging environment than managed care. Moreover, the effect of age, sex and the month of sampling on the N:L ratio were found to be different for each population. Age had the greatest magnitude of effect in the wild population, and sex was only significant in ex situ populations. This study provided previously unknown insights into the physiology of VIMs and increased post-release monitoring will be useful in the future to fully understand how physiology may be contributing to differences in survival of VIMs in the program.
Shakespeare and Plautus: exploring metrical influence
Authors: Christensen Alexander 
Published: June 2023

Abstract
Scholars have recognized for some time that Shakespeare’s early comedies drew much from Plautine comedy. Although these points of influence have long been established, discussion of Plautus’ influence on Shakespeare has not often moved beyond them to broader questions of whether he had any influence over Shakespeare’s tragedies, over his later career in general, or over more specific techniques of playwriting, like characterization or metrical composition. This article takes up these latter two issues. I argue that Shakespeare’s use of metrical variation in his most sympathetic characters’ soliloquies correlates closely with Plautus’ practice of using polymetric songs to introduce his most sympathetic characters. As examples, I analyse Shakespeare’s Hamlet and Plautus’ Trinummus. Though no conclusive evidence can be found to prove that Shakespeare digested Plautus’ metrics in addition to his comic plots, the article suggests that Plautus’ influence on Shakespeare could run deeper than previously thought.
Endothelial CCRL2 induced by disturbed flow promotes atherosclerosis via chemerin-dependent β2 integrin activation in monocytes
Authors: Tang Chaojun , Chen Guona , Wu Fan , Cao Yiren , Yang Fei , You Tao , Liu Chu , Li Menglu , Hu Shuhong , Ren Lijie , Lu Qiongyu , Deng Wei , Xu Ying , Wang Guixue , Jo Hanjoong , Zhang Yonghong , Wu Yi , Zabel Brian A , Zhu Li 
Published: June 2023

Abstract

Aims
Chemoattractants and their cognate receptors are essential for leucocyte recruitment during atherogenesis, and atherosclerotic plaques preferentially occur at predilection sites of the arterial wall with disturbed flow (d-flow). In profiling the endothelial expression of atypical chemoattractant receptors (ACKRs), we found that Ackr5 (CCRL2) was up-regulated in an endothelial subpopulation by atherosclerotic stimulation. We therefore investigated the role of CCRL2 and its ligand chemerin in atherosclerosis and the underlying mechanism.

Methods and results
By analysing scRNA-seq data of the left carotid artery under d-flow and scRNA-seq datasets GSE131776 of ApoE−/− mice from the Gene Expression Omnibus database, we found that CCRL2 was up-regulated in one subpopulation of endothelial cells in response to d-flow stimulation and atherosclerosis. Using CCRL2−/−ApoE−/− mice, we showed that CCRL2 deficiency protected against plaque formation primarily in the d-flow areas of the aortic arch in ApoE−/− mice fed high-fat diet. Disturbed flow induced the expression of vascular endothelial CCRL2, recruiting chemerin, which caused leucocyte adhesion to the endothelium. Surprisingly, instead of binding to monocytic CMKLR1, chemerin was found to activate β2 integrin, enhancing ERK1/2 phosphorylation and monocyte adhesion. Moreover, chemerin was found to have protein disulfide isomerase-like enzymatic activity, which was responsible for the interaction of chemerin with β2 integrin, as identified by a Di-E-GSSG assay and a proximity ligation assay. For clinical relevance, relatively high serum levels of chemerin were found in patients with acute atherothrombotic stroke compared to healthy individuals.

Conclusions
Our findings indicate that d-flow-induced CCRL2 promotes atherosclerotic plaque formation via a novel CCRL2-chemerin-β2 integrin axis, providing potential targets for the prevention or therapeutic intervention of atherosclerosis.
IHM-DB: a curated collection of metagenomics data from the Indian Himalayan Region, and automated pipeline for 16S rRNA amplicon-based analysis (AutoQii2)
Authors: Khatri Abhishek , Thakur Aman , Lepcha Ayush , Acharya Vishal , Kumar Rakshak 
Published: June 2023

Abstract
Indian Himalayan metagenome database (IHM-DB) is a web-based database consisting of information on metagenomic datasets from various databases and publications that are specifically reported from the Indian Himalayan Region (IHR). The online interface allows users to view or download the dataset-specific information for the respective states, category-wise, or according to the hypervariable region. The IHM-DB also provides an opportunity for the users to access the metagenomic publications from the IHR as well as upload their microbiome information to the website. Additionally, an open-source 16S rRNA amplicon-based automated bioinformatics pipeline, AutoQii2, allows users to analyze the single-end and paired-end raw reads. AutoQii2 provides an automated approach for performing analysis such as quality check, adapter and chimera removal and exploits the latest ribosomal database project classifier for taxonomic assignments. The source code of the AutoQii2 pipeline is available at https://gitlab.com/khatriabhi2319/autoqii2.
Database URL https://ham.ihbt.res.in/ihmdb and https://fgcsl.ihbt.res.in/ihmdb
Impact of frailty on hiatal hernia repair: a nationwide analysis of in-hospital clinical and healthcare utilization outcomes
Authors: Lee Y , Huo B , McKechnie T , Agzarian J , Hong D 
Published: June 2023

Summary
Previous studies recommend a watch-and-wait approach to paraesophageal hernia (PEH) repair due to an increased risk for mortality. While contemporary studies suggest that elective surgery is safe and effective, many patients presenting with PEH are elderly. Therefore, we assessed the impact of frailty on in-hospital outcomes and healthcare utilization among patients receiving PEH repair. This retrospective population-based cohort study assessed patients from the National Inpatient Sample database who received PEH repair between October 2015 to December 2019. Demographic and perioperative data were gathered, and frailty was measured using the 11-item modified frailty index. The outcomes measured were in-hospital mortality, complications, discharge disposition, and healthcare utilization. Overall, 10,716 patients receiving PEH repair were identified, including 1442 frail patients. Frail patients were less often female and were more often in the lowest income quartile compared to robust patients. Frail patients were at greater odds for in-hospital mortality [odds ratio (OR) 2.83 (95% CI 1.65–4.83); P &lt; 0.001], postoperative ICU admissions [OR 2.07 (95% CI 1.55–2.78); P &lt; 0.001], any complications [OR 2.18 (95% CI 1.55–2.78); P &lt; 0.001], hospital length of stay [mean difference (MD) 1.75 days (95% CI 1.30–2.210; P &lt; 0.001], and total admission costs [MD $5631.65 (95% CI $3300.06–$7.963.24); P &lt; 0.001] relative to their robust patients. While PEH repair in elderly patients is safe and effective, frail patients have an increased rate of in-hospital mortality, postoperative ICU admissions, complications, and total admission costs. Clinicians should consider patient frailty when identifying the most appropriate surgical candidates for PEH repair.