bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiresistant organisms: bacteria and beyond
Authors: Sole Amparo 
Published: March 2022

Purpose of review
Infections with multiresistant organisms are an emerging problem, cause early mortality post lung transplantation and are sometimes associated with graft dysfunction. Frequently they raise questions about the selection of lung transplant candidates and therapeutic management post lung transplantation. There are no guidelines and management must be individualized. This review summarizes the available therapeutic options in cases of multidrug-resistant (MDR) organisms and outcomes after lung transplant.

Recent findings
Improvements in diagnosis, new and more effective drugs and the experience gained in the management of these infections in lung transplantation, lead to a more optimistic horizon than that found a decade ago.

Summary
Update on the management of Burkholderia cepacia complex, Mycobacterium abscessus complex, Aspergillus spp., Scedosporium spp. and Lomentospora prolificans infections. This review clarifies current posttransplant outcomes and adds a little hope in these scenarios.
Genetic Influence on Neurodevelopment in Nonsyndromic Craniosynostosis
Authors: Timberlake Andrew T. , Junn Alexandra , Flores Roberto , Staffenberg David A. , Lifton Richard P. , Persing John A. 
Published: March 2022

Background:
Nonsyndromic craniosynostosis is one of the most common anomalies treated by craniofacial surgeons. Despite optimal surgical management, nearly half of affected children have subtle neurocognitive deficits. Whereas timing and type of surgical intervention have been studied, the possibility of genetic influence on neurodevelopment in nonsyndromic craniosynostosis patients remains unexplored.

Methods:
The authors performed whole-exome sequencing for 404 case-parent trios with sporadic nonsyndromic craniosynostosis. Statistical analyses were performed to assess the burden of de novo mutations in cases compared to both expectation and 1789 healthy control trios. Individuals with and without each mutation class were analyzed, and the presence or absence of various types of neurodevelopmental delay were recorded alongside demographic information.

Results:
The authors identified a highly significant burden of damaging de novo mutations in mutation-intolerant [probability of loss of function intolerance (pLI) >0.9] genes in nonsyndromic craniosynostosis probands (p = 5.9 × 10−6). Children with these mutations had a two-fold higher incidence of neurodevelopmental delay (p = 0.001) and a more than 20-fold greater incidence of intellectual disability (p = 7.2 × 10−7), and were 3.6-fold more likely to have delays that persisted past 5 years of age (p = 4.4 × 10−4) in comparison with children with nonsyndromic craniosynostosis without these mutations. Transmitted loss of function mutations in high-pLI genes also conferred a 1.9-fold greater risk of neurodevelopmental delay (p = 4.5 ×10−4).

Conclusions:
These findings implicate genetic lesions concurrently impacting neurodevelopment and cranial morphogenesis in the pathoetiology of nonsyndromic craniosynostosis and identify a strong genetic influence on neurodevelopmental outcomes in affected children. These findings may eventually prove useful in determining which children with nonsyndromic craniosynostosis are most likely to benefit from surgical intervention.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Risk, III.
Hypertelorbitism Corrected by Facial Bipartition Improves Exotropia
Authors: Chen Kevin , Duvvuri Priya , Gibstein Alex , Nakfoor Bruce , Fisher Mark , Kawamoto Henry , Bradley James P. 
Published: March 2022

Background:
The purpose of this study was to detail perioperative ophthalmologic evaluations to characterize functional ocular outcomes after facial bipartition surgery.

Methods:
Patients with hypertelorbitism who underwent facial bipartition surgery were studied specifically for eye motility disorders by separating patients into rare craniofacial clefts (midline and paramedian) (n = 34) and craniofacial dysostosis (Apert, Crouzon, and Pfeiffer) (n = 74). Preoperative and postoperative (12 months) ophthalmologic examinations (with depth perception tests), computed tomography scans, and magnetic resonance imaging scans were analyzed.

Results:
Among craniofacial cleft patients, mean interdacryon distance was reduced from 39 ± 4 mm to 17 ± 2 mm, with strabismus improved from 88 percent (exotropia 82 percent) preoperatively to only 29 percent postoperatively. Depth perception improved to a lesser degree, with abnormal tests at a rate of 79 percent preoperatively to 56 percent postoperatively. Wider hypertelorbitism had a higher degree of strabismus. Among craniofacial dysostotic patients, mean interdacryon distance was reduced from 37 ± 3 mm to 17 ± 2 mm, and strabismus improved from 55 percent to only 14 percent. Depth perception improved to a lesser degree, with 68 percent abnormal tests preoperatively and 46 percent postoperatively. Apert patients had more V-pattern strabismus and exotropia (79 percent) than did other craniofacial dysostosis patients (42 percent).

Conclusions:
The authors’ data indicate that facial bipartition for hypertelorbitism—known to improve periorbital aesthetics—also improves eye motility disturbances. Thus, vision problems related to exotropia should be considered a functional indication for facial bipartition surgery in patients with hypertelorbitism.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, IV.
Reasons for PrEP Discontinuation After Navigation at Sexual Health Clinics: Interactions Among Systemic Barriers, Behavioral Relevance, and Medication Concerns
Authors: Unger Zoe D. , Golub Sarit A. , Borges Christine , Edelstein Zoe R. , Hedberg Trevor , Myers Julie 
Published: March 2022

Background:
Pre-exposure prophylaxis (PrEP) for HIV prevention requires engagement throughout the PrEP care continuum. Using data from a PrEP navigation program, we examine reasons for PrEP discontinuation.

Setting:
Participants were recruited from New York City Health Department Sexual Health Clinics with PrEP navigation programs.

Methods:
Participants completed a survey and up to 3 interviews about PrEP navigation and use. This analysis includes 94 PrEP initiators that were PrEP-naive before their clinic visit, started PrEP during the study, and completed at least 2 interviews. Interview transcripts were reviewed to assess reasons for PrEP discontinuation.

Results:
Approximately half of PrEP initiators discontinued PrEP during the study period (n = 44; 47%). Most participants (71%) noted systemic issues (insurance or financial problems, clinic or pharmacy logistics, and scheduling barriers) as reasons for discontinuation. One-third cited medication concerns (side effects, potential long-term side effects, and medication beliefs; 32%) and behavioral factors (low relevance of PrEP because of sexual behavior change; 34%) as contributing reasons. Over half (53.5%) highlighted systemic issues alone, while an additional 19% attributed discontinuation to systemic issues in combination with other factors. Of those who discontinued, approximately one-third (30%) restarted PrEP during the follow-up period, citing resolution of systemic issues or behavior change that increased PrEP relevance.

Conclusions:
PrEP continuation is dependent on interacting factors and often presents complex hurdles for patients to navigate. To promote sustained engagement in PrEP care, financial, clinic, and pharmacy barriers must be addressed and counseling and navigation should acknowledge factors beyond sexual risk that influence PrEP use.
A Novel High-throughput Droplet Digital PCR-based Indel Quantification Method for the Detection of Circulating Donor-derived Cell-free DNA After Kidney Transplantation
Authors: Verhoeven Jeroen G.H.P. , Boer Karin , Peeters Annemiek M.A. , Clahsen-van Groningen Marian C. , Roodnat Joke I. , van de Wetering Jacqueline , Nieboer Daan , Bost Douglas A. , Baan Carla C. , Hesselink Dennis A. 
Published: March 2022

Background.
Donor-derived cell-free DNA (ddcfDNA) is a promising minimally invasive biomarker for acute rejection (AR) in kidney transplant recipients. To assess the diagnostic value of ddcfDNA as a marker for AR, ddcfDNA was quantified at multiple time points after kidney transplantation with a novel high-throughput droplet digital PCR indel method that allowed for the absolute quantification of ddcfDNA.

Methods.
In this study, ddcfDNA in plasma samples from 223 consecutive kidney transplant recipients was analyzed pretransplantation; at 3, 7, and 180 d after transplantation; and at time of for-cause biopsies obtained within the first 180 d after transplantation.

Results.
Median (interquartile range) ddcfDNA concentration was significantly higher on day 3 (58.3 [17.7-258.3] copies/mL) and day 7 (25.0 [10.4-70.8] copies/mL) than on day 180 after transplantation (4.2 [0.0-8.3] copies/mL; P < 0.001 and P < 0.001, respectively). At time of biopsy-proven AR (BPAR), between day 11 and day 180 after transplantation, ddcfDNA concentration was significantly higher (50.0 [25.0-108.3] copies/mL) than those when biopsies showed non-AR (0.0 [0.0-15.6] copies/mL; P < 0.05). ddcfDNA concentration within the first 10 d after transplantation showed no significant difference between recipients with BPAR and those with non-AR in their biopsy or between recipients with BPAR and ddcfDNA measured at day 3 and day 7.

Conclusions.
Unfortunately, ddcfDNA concentration is not a good biomarker to detect AR within the first 10 d after transplantation; however, BPAR occurring after 10 d after transplantation can be detected in kidney transplant recipients by ddcfDNA using a novel and unique high-throughput droplet digital PCR indel method.
An Assessment of Ineligible Donor Use in Solid Organ Transplant
Authors: DeRoos Luke J. , Tapper Elliot B. , Lavieri Mariel S. , Hutton David W. , Parikh Neehar D. 
Published: March 2022

Background.
In the United States, the demand for organ transplants far outpaces available organs. The use of Organ Procurement and Transplantation Network–defined ineligible donors is an immediate method for increasing donations. However, the use of ineligible donors varies across organ procurement organizations (OPOs), and its association with recipient survival remains unclear.

Methods.
We evaluated ineligible donor use from 2008 to 2020 by OPO and its association with graft and recipient survival across demographics.

Results.
In this study of 297 223 organ donations, 42 184 (14%) did not meet eligibility criteria as defined by the Organ Procurement and Transplantation Network. Log-rank tests on Kaplan-Meier curves suggested differences in graft and patient survival between eligible and ineligible recipients for kidney and liver transplants (P ≤ 0.01 for all). Recipients of ineligible kidney and liver donations saw a 2.20% and 9.38% decrease in 10-y graft survival probability, respectively. There were no statistically significant graft and patient survival differences for recipients of ineligible heart, lung, and pancreas donations. Multivariate proportional hazard models showed eligibility was associated with kidney, liver, and lung graft survival (P ≤ 0.02 for all). However, if OPOs increased ineligible donor use to meet the current 75th percentile use rate, there could be as many as 1000 transplants and 6291 life-years gained annually.

Conclusions.
Ineligible donor use can provide significant survival benefit for patients who would otherwise never receive a transplant. Methods to reduce regional heterogeneity in ineligible donor use could increase the number of transplants and improve outcomes for waiting patients.
Neurocognitive and psychiatric post-coronavirus disease 2019 conditions: pathogenic insights of brain dysfunction following severe acute respiratory syndrome coronavirus 2 infection
Authors: García-Grimshaw Miguel , Sankowski Roman , Valdés-Ferrer Sergio Iván 
Published: March 2022

Purpose of review
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of coronavirus disease 2019 (COVID-19), can trigger a myriad of neuropsychiatric manifestations. As a 2-year-old disease (at the writing of this manuscript), its long-term cognitive and neuropsychiatric implications, known as post-COVID-19 conditions, are incompletely recognized and mechanistically obscure.

Recent findings
Fatigue, anxiety, depression, posttraumatic stress disorder, and cognitive dysfunction are reported more frequently in COVID-19 survivors than in matching, non-COVID-19 population. Risk factors are unclear, including comorbidities, age at COVID-19 onset, or disease severity; women, however, have been reported to be at increased risk than men. Although the frequency of these symptoms decreases over time, at least one in five will have persistent cognitive and neuropsychiatric manifestations one year after recovering from COVID-19.

Summary
Neurocognitive and psychiatric post-COVID-19 long-term conditions are frequent and complex multifactorial sequelae. Several acute and chronic factors such as hypoxemia, cerebral thrombotic and inflammatory endothelial damage, and disruption of the blood-brain barrier (leading to parenchymal translocation of pro-inflammatory molecules, cytokines, and cytotoxic T lymphocytes) are involved, leading to microglial activation and astrogliosis. As an evolving topic, evidence derived from prospective studies will expand our understanding of post-COVID-19 these long-term outcomes.
A critical appraisal of the singularity theorems
Authors: Senovilla José M. M. 
Published: March 2022

The 2020 Nobel prize in Physics has revived the interest in the singularity theorems and, in particular, in the Penrose theorem published in 1965. In this short paper, I briefly review the main ideas behind the theorems and then proceed to an evaluation of their hypotheses and implications. I will try to dispel some common misconceptions about the theorems and their conclusions, as well as to convey some of their rarely mentioned consequences. In particular, a discussion of space–time extensions in relation to the theorems is provided. The nature of the singularity inside black holes is also analysed.This article is part of the theme issue ‘The future of mathematical cosmology, Volume 1’.
Reformulating scalar–tensor field theories as scalar–scalar field theories using a novel geometry
Authors: Horndeski Gregory W. 
Published: March 2022

In this paper, I shall show how the notions of Finsler geometry can be used to construct a similar geometry using a scalar field,
f
, on the cotangent bundle of a differentiable manifold
M
. This will enable me to use the second vertical derivatives of
f
, along with the differential of a scalar field
φ
on
M
, to construct a Lorentzian metric on
M
that depends upon
φ
. I refer to a field theory based upon a manifold with such a Lorentzian structure as a scalar–scalar field theory. We shall study such a theory when
f
is chosen so that the resultant metric on
M
has the form of a Friedmann–Lemaître–Robertson–Walker metric, and the Lagrangian has a particularly simple form. It will be shown that the scalar–scalar theory determined by the Lagrangian can generate self-inflating universes, which can be pieced together to form multiverses with non-Hausdorff topologies, in which the global time function multifurcates at
t
= 0. Some of the universes in these multiverses begin explosively, and then settle down to a period of much quieter accelerated expansion, which can be followed by a collapse to its original, pre-expansion state.

This article is part of the theme issue ‘The future of mathematical cosmology, Volume 1’.
Geometrical origins of the universe dark sector: string-inspired torsion and anomalies as seeds for inflation and dark matter
Authors: Mavromatos Nick E. 
Published: March 2022

In a modest attempt to present potentially new paradigms in cosmology, including its inflationary epoch, and initiate discussions, I review in this article some novel, string-inspired cosmological models, which entail a purely geometrical origin of the dark sector of the Universe but also of its observed matter-antimatter asymmetry. The models contain gravitational (string-model independent, Kalb–Ramond (KR)) axion fields coupled to primordial gravitational anomalies via CP-violating interactions. The anomaly terms are four-space–time-dimensional remnants of the Green–Schwarz counterterms appearing in the definition of the field strength of the spin-one antisymmetric tensor field of the (bosonic) massless gravitational string multiplet, which also plays the role of a totally antisymmetric component of torsion. I show how in such cosmologies the presence of primordial gravitational waves can lead to anomaly condensates and dynamical inflation of a ‘running-vacuum-model’ type, without external inflatons, but also to leptogenesis in the radiation era due to anomaly induced Lorentz and CPT violating KR axion backgrounds. I also discuss how the torsion-related KR-axion could acquire a mass during the QCD epoch, thus playing the role of (a component of) dark matter. Phenomenological considerations of the inflationary and post-inflationary (in particular, modern) eras of the model are briefly discussed, including its potential for alleviating the observed tensions in the cosmological data of the current epoch.
This article is part of the theme issue ‘The future of mathematical cosmology, Volume 1’.
Immunogenicity and safety of a recombinant adenovirus type-5 COVID-19 vaccine in adults: data from a randomised, double-blind, placebo-controlled, single-dose, phase 3 trial in Russia
Authors: Lioznov Dmitry , Amosova Irina , Sheetikov Savely A. , Zornikova Ksenia V. , Serdyuk Yana , Efimov Grigory A. , Tsyferov Mikhail , Khmelevskii Mikhail , Afanasiev Andrei , Khomyakova Nadezhda , Zubkov Dmitry , Tikhonov Anton , Zhu Tao , Barreto Luis , Dzutseva Vitalina 
Published: March 2022

ABSTRACTBackgroundTo determine the immunogenicity, efficacy, reactogenicity, and safety of a single dose of recombinant adenovirus type-5 vectored COVID-19 vaccine (Ad5-nCoV, 5 × 1010 viral particles per 0.5 mL dose), we conducted a single-dose, randomised, double-blind, placebo-controlled, parallel group (3:1 Ad5-nCoV:placebo), phase 3 trial (Prometheus).MethodsFrom 11-September-2020 to 05-May-2021, across six sites in the Russian Federation, 496 participants were injected with either placebo or Ad5-nCoV expressing the full-length spike (S) protein from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).ResultsSeroconversion (the primary endpoint) rates of 78.5% (95% CI: 73.9; 82.6) against receptor binding domain (RBD), 90.6% (95% CI: 87.2; 93.4) against S protein and 59% (95% CI: 53.3; 64.6) against neutralising SARS-CoV2 antibodies 28 days post-vaccination. Geometric mean titres (GMTs) were also elevated for antibodies against the RBD (405.32 [95% CI: 361.58; 454.46]) and S protein (678.86 [95% CI: 607.44; 754.40]) compared to the GMT of neutralising antibodies against SARS-CoV-2 (16.73 [95% CI: 15.36; 18.22]). Using an IFN-γ ELISpot assay after stimulating the cells with full-length S protein we showed that the Ad5-nCoV vaccine induced the most robust cellular immune response on Days 14 and 28. Up to Day 28, the primary and all secondary endpoints of the Ad5-nCoV vaccine were statistically superior to the placebo (р <0.001). Systemic reactions were reported in 113 of 496 (22.8%) participants (Ad5-nCoV, 26.9%; Placebo, 10.5%), and local reactions were reported in 108 (21.8%) participants (Ad5-nCoV, 28.5%; Placebo, 1.6%). These were generally mild and resolved within 7 days after vaccination. Of the six serious adverse events reported, none of the events were vaccine related. There were no deaths or premature withdrawals.ConclusionA single-dose of Ad5-nCoV vaccine induced a marked specific humoral and cellular immune response with a favourable safety profile.Trial RegistrationClinicalTrials.gov: NCT04540419
Stack Mapping Anchor Points (SMAP): a versatile suite of tools for read-backed haplotyping
Authors: Schaumont Dries , Veeckman Elisabeth , Van der Jeugt Felix , Haegeman Annelies , van Glabeke Sabine , Bawin Yves , Lukasiewicz Joanna , Blugeon Sebastien , Barre Philippe , Leyva-Pérez Maria de la O , Byrne Stephen , Dawyndt Peter , Ruttink Tom 
Published: March 2022

ABSTRACTHere we present SMAP, a software package that implements a suite of computational tools to extract multi-allelic haplotypes using read-backed haplotyping. SMAP tools first perform accurate read processing and analyze read mapping distributions across sample sets. Then, two complementary modules can be invoked for haplotype calling: SMAP haplotype-sites combines known Single Nucleotide Polymorphisms (SNPs) and/or read mapping position polymorphisms (SMAPs) to reconstruct compressed, read-reference-encoded haplotype strings. In contrast, SMAP haplotype-window works independent of prior knowledge of polymorphisms, groups reads by locus, defines a window enclosed between two custom border sequences, and retains the entire corresponding DNA sequence as haplotype. Haplotype-window is, among many applications, especially useful for high-throughput CRISPR/Cas mutation screens. Either way, SMAP creates a single integrated haplotype call table across all loci and samples. SMAP haplotyping is extremely versatile and can be applied to highly multiplex amplicon sequencing (HiPlex), Shotgun (e.g. whole genome shotgun (WGS) sequencing, probe capture and RNA-Seq), or Genotyping-by-Sequencing (GBS) data; and to Illumina short reads, PacBio and MinION long reads. SMAP creates discrete genotype calls for individuals of any ploidy or quantitative haplotype frequency spectra for Pool-Seq data, and can scale from tens to thousands of loci and/or samples. SMAP, including the source code written in Python is available at https://gitlab.com/truttink/smap, and a detailed user manual and guidelines for accurate read processing is available at https://ngs-smap.readthedocs.io/, under the GNU Affero General Public License v3.0.
Fast analyzing, exploring and sharing quantitative omics data using omicsViewer
Authors: Meng Chen 
Published: March 2022

AbstractSummaryTo facilitate the biological interpretation of omics data, we developed a general omics data visualization platform termed omicsViewer, enabling interactive visualization of statistical results and performing downstream analyses directly in response to features and samples selected. Multiple hypotheses and parameters can be evaluated in a few clicks. In addition, users can share the platform and statistical results with collaborators and the public in different ways.Availability and ImplementationThe project page ishttps://github.com/mengchen18/omicsViewerContactchen.meng@tum.de