bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hospital water as the source of healthcare-associated infection and antimicrobial-resistant organisms
Authors: Hayward Claire , Brown Melissa H. , Whiley Harriet 
Published: July 2022

Purpose of review
Drinking water is considered one of the most overlooked and underestimated sources of healthcare-associated infections (HAIs). Recently, the prevention and control of opportunistic premise plumbing pathogens (OPPPs) in healthcare water systems has been receiving increasing attention in infection control guidelines. However, these fail to address colonization of pathogens that do not originate from source water. Subsequently, this review explores the role of water and premise plumbing biofilm in HAIs. The potential mechanisms of contamination and transmission of antimicrobial-resistant (AMR) pathogens originating both from supply water and human microbiota are discussed.

Recent findings
OPPPs, such as Legionella pneumophila, Pseudomonas aeruginosa and Mycobacterium avium have been described as native to the plumbing environment. However, other pathogens, not found in the source water, have been found to proliferate in biofilms formed on outlets devices and cause HAI outbreaks.

Summary
Biofilms formed on outlet devices, such as tap faucets, showers and drains provide an ideal niche for the dissemination of antimicrobial resistance. Thus, comprehensive surveillance guidelines are required to understand the role that drinking water and water-related devices play in the transmission of AMR HAIs and to improve infection control guidelines.
Navigating the unknown: the coronavirus disease 2019 pandemic and solid organ transplantation
Authors: Safa Kassem , Kotton Camille N. 
Published: July 2022

Purpose of review
This review summarizes the impact of coronavirus disease 2019 (COVID-19) on solid organ transplantation and the most recent data pertinent to disease course and outcomes in this patient population.

Recent findings
The COVID-19 pandemic negatively impacted solid organ transplantation with decreased transplant rates in 2020 but improved in 2021, albeit not entirely to prepandemic levels. Mortality rates of COVID-19 in this patient population continued to be higher, although have improved with more available therapeutic options and vaccination. Immunosuppressed patients were found to require additional vaccine doses given blunted response and continue to be more vulnerable to the infection. Data on immunosuppression alteration when patients have COVID-19 are not available and is an area of ongoing research. Significant interaction with the metabolism of immunosuppression limits the use of some of the new antiviral therapies in patients with organ transplants. Finally, many logistical challenges continue to face the transplantation discipline, especially with pretransplant vaccine hesitancy, however acceptance of organs from donor who had COVID-19 recent infection or died from the infection is increasing.

Summary
Immunosuppressed solid organ transplant recipients continue to be vulnerable to COVID-19 infection with a blunted response to the available vaccines and will likely remain more susceptible to infection.
The American Association of Endocrine Surgeons Guidelines for the Definitive Surgical Management of Secondary and Tertiary Renal Hyperparathyroidism
Authors: Dream Sophie , Kuo Lindsay E. , Kuo Jennifer H. , Sprague Stuart M. , Nwariaku Fiemu E. , Wolf Myles , Olson John A. , Moe Sharon M. , Lindeman Brenessa , Chen Herbert 
Published: July 2022

Objective:To develop evidence-based recommendations for safe, effective, and appropriate treatment of secondary (SHPT) and tertiary (THPT) renal hyperparathyroidism.Background:Hyperparathyroidism is common among patients with chronic kidney disease, end-stage kidney disease, and kidney transplant. The surgical management of SHPT and THPT is nuanced and requires a multidisciplinary approach. There are currently no clinical practice guidelines that address the surgical treatment of SHPT and THPT.Methods:Medical literature was reviewed from January 1, 1985 to present January 1, 2021 by a panel of 10 experts in SHPT and THPT. Recommendations using the best available evidence was constructed. The American College of Physicians grading system was used to determine levels of evidence. Recommendations were discussed to consensus. The American Association of Endocrine Surgeons membership reviewed and commented on preliminary drafts of the content.Results:These clinical guidelines present the epidemiology and pathophysiology of SHPT and THPT and provide recommendations for work-up and management of SHPT and THPT for all involved clinicians. It outlines the preoperative, intraoperative, and postoperative management of SHPT and THPT, as well as related definitions, operative techniques, morbidity, and outcomes. Specific topics include Pathogenesis and Epidemiology, Initial Evaluation, Imaging, Preoperative and Perioperative Care, Surgical Planning and Parathyroidectomy, Adjuncts and Approaches, Outcomes, and Reoperation.Conclusions:Evidence-based guidelines were created to assist clinicians in the optimal management of secondary and tertiary renal hyperparathyroidism.
Implementation and Outcome of Robotic Liver Surgery in the Netherlands
Authors: Görgec Burak , Zwart Maurice , Nota Carolijn L. , Bijlstra Okker D. , Bosscha Koop , de Boer Marieke T. , de Wilde Roeland F. , Draaisma Werner A. , Gerhards Michael F. , Liem Mike S. , Lips Daan J. , Marsman Hendrik A. , Mieog J. Sven D. , Molenaar Quintus I. , Nijkamp Maarten , Te Riele Wouter W. , Terkivatan Türkan , Vahrmeijer Alexander L. , Besselink Marc G. , Swijnenburg Rutger-Jan , Hagendoorn Jeroen ,   for the Dutch Liver Collaborative Group
Published: July 2022

Objective:
To determine the nationwide implementation and surgical outcome of minor and major robotic liver surgery (RLS) and assess the first phase of implementation of RLS during the learning curve.

Background:
RLS may be a valuable alternative to laparoscopic liver surgery. Nationwide population-based studies with data on implementation and outcome of RLS are lacking.

Methods:
Multicenter retrospective cohort study including consecutive patients who underwent RLS for all indications in 9 Dutch centers (August 2014–March 2021). Data on all liver resections were obtained from the mandatory nationwide Dutch Hepato Biliary Audit (DHBA) including data from all 27 centers for liver surgery in the Netherlands. Outcomes were stratified for minor, technically major, and anatomically major RLS. Learning curve effect was assessed using cumulative sum analysis for blood loss.

Results:
Of 9437 liver resections, 400 were RLS (4.2%) procedures including 207 minor (52.2%), 141 technically major (35.3%), and 52 anatomically major (13%). The nationwide use of RLS increased from 0.2% in 2014 to 11.9% in 2020. The proportion of RLS among all minimally invasive liver resections increased from 2% to 28%. Median blood loss was 150 mL (interquartile range 50–350 mL] and the conversion rate 6.3% (n=25). The rate of Clavien-Dindo grade ≥III complications was 7.0% (n=27), median length of hospital stay 4 days (interquartile range 2–5) and 30-day/in-hospital mortality 0.8% (n=3). The R0 resection rate was 83.2% (n=263). Cumulative sum analysis for blood loss found a learning curve of at least 33 major RLS procedures.

Conclusions:
The nationwide use of RLS in the Netherlands has increased rapidly with currently one-tenth of all liver resections and one-fourth of all minimally invasive liver resections being performed robotically. Although surgical outcomes of RLS in selected patient seem favorable, future prospective studies should determine its added value.
Surface wave across crack-tip in a lattice model
Authors: Sharma Basant Lal 
Published: July 2022

For a triangular lattice of particles, with nearest neighbour interactions and a traction free boundary, there exists a surface wave band for out-of-plane motion. Interactions between such a surface wave and stationary crack tip in mode III are investigated. The discrete Helmholtz equation for scattered waves, that incorporates an anisotropy parameter for unequal spring constants in horizontal versus slant directions, is solved exactly. The coefficient of transmission from one crack face to another, as well as that owing to reflection on the same face, is obtained in a closed form; the same leads to an estimate of energy fraction of incident wave that is leaked at the crack tip via bulk waves. It is found, in terms of surface wave band, that the transmission coefficient attains its maximum magnitude above the mid-band while the energy leak is minimum at the upper-band limit. Besides surface wave propagation across crack tip, surface wave excitation due to incident bulk wave is also discussed.
This article is part of the theme issue ‘Wave generation and transmission in multi-scale complex media and structured metamaterials (part 1)’.
Localized waves in elastic plates with perturbed honeycomb arrays of constraints
Authors: Haslinger S. G. , Frecentese S. , Carta G. 
Published: July 2022

In this paper, we study wave propagation in elastic plates incorporating honeycomb arrays of rigid pins. In particular, we demonstrate that topologically non-trivial band-gaps are obtained by perturbing the honeycomb arrays of pins such that the ratio between the lattice spacing and the distance of pins is less than 3; conversely, a larger ratio would lead to the appearance of trivial stop-bands. For this purpose, we investigate band inversion of modes and calculate the valley Chern numbers associated with the dispersion surfaces near the band opening, since the present problem has analogies with the quantum valley Hall effect. In addition, we determine localized eigenmodes in strips, repeating periodically in one direction, that are subdivided into a topological and a trivial section. Finally, the outcomes of the dispersion analysis are corroborated by numerical simulations, where a time-harmonic point source is applied to a plate with finite arrays of rigid pins to create localized waves immune to backscattering.
This article is part of the theme issue ‘Wave generation and transmission in multi-scale complex media and structured metamaterials (part 1)’.
Illuminating the Druggable Genome through Patent Bioactivity Data
Authors: Magariños María Paula , Gaulton Anna , Félix Eloy , Kizilören Tevfik , Arcila Ricardo , Oprea Tudor , Leach Andrew R. 
Published: July 2022

AbstractThe patent literature is a potentially valuable source of bioactivity data. The SureChEMBL database (https://www.surechembl.org/) is a publicly available large-scale resource that contains compounds extracted on a daily basis from the full text, images and attachments of patent documents, through an automated text and image-mining pipeline. In this paper we describe a process to prioritise 3.7 million life science relevant patents obtained from SureChEMBL, according to how likely they were to contain bioactivity data for potent small molecules on less-studied targets, according to the classification developed by the Illuminating the Druggable Genome (IDG) project. The overall goal was to select a smaller number of patents that could be manually curated and incorporated into the ChEMBL database. We describe the approach taken, the results obtained, and provide some illustrative examples.
Linear Mixed-effects model to quantify the association between somatic cell count and milk production in Italian dairy herds
Authors: Luo Tiantian , Steeneveld Wilma , Nielen Mirjam , Zanini Lucio , Zecconi Alfonso 
Published: July 2022

AbstractMilk production loss due to mastitis in dairy herds is economically important. Before estimating the economic impacts of mastitis, it is crucial to quantify the association between mastitis and milk production. The objective of this study was to estimate the association between somatic cell count (SCC, as an indicator of intramammary infection due to mastitis) and milk production for dairy cows in Lombardy (Italy). The test-day (TD) records data of 3,816 dairy herds located in 3 different geographical areas of Lombardy from January 2016 to December 2018 were used. After data editing, the final dataset comprised 10,445,464 TD records from 2,970 farms and 826,831 cows. The analysis was carried out by using a mixed-effects model with seven fixed effects (geographical area, breed, days in milk, parity, season and year) and nested random effects for each cow and herd. The results indicated that the SCC had a negative association with milk production. When the SCC increased every two-fold, the milk production lost 0.830 (95% CI: −0.832, −0.828) kg/cow/day in the whole Lombardy. These results can be used for economic calculations on the costs of mastitis
Localized heterochrony integrates overgrowth potential of oncogenic clones
Authors: Blum Nicola , Harris Matthew P. 
Published: July 2022

ABSTRACTSomatic oncogenic mutations are frequent and can occur early during development. The result is the formation of a patchwork of mutant clones. Such mosaicism has been implicated in a broad range of developmental anomalies however their etiology is poorly understood. Patients carrying a common somatic oncogenic mutation in either PIK3CA or AKT1, can present with disproportionally large digits or limbs. How mutant clones, carrying an oncogenic mutation that often drives unchecked proliferation leads to controlled and coordinated overgrowth is unknown. We use the zebrafish to explore growth dynamics of oncogenic clones during development. In subset of clones, we observe a local increase in proportion of the fin skeleton closely resembling patient overgrowth phenotypes. We unravel the cellular and developmental mechanisms of these overgrowths and pinpoint the cell type and timing of clonal expansion. Coordinated overgrowth is associated with rapid clone expansion during early pre-chondrogenic phase of bone development inducing a heterochronic shift that drives the change in bone size. Our study details how development integrates and translates growth potential of oncogenic clones, thereby shaping the phenotypic consequences of somatic mutations.
Testing the Limits of SMILES-based De Novo Molecular Generation with Curriculum and Deep Reinforcement Learning
Authors: Mokaya Maranga , Imrie Fergus , van Hoorn Willem P. , Kalisz Aleksandra , Bradley Anthony R. , Deane Charlotte M. 
Published: July 2022

1AbstractDeep reinforcement learning methods have been shown to be potentially powerful tools for de novo design. Recurrent neural network (RNN)-based techniques are the most widely used methods in this space. In this work, we examine the behaviour of RNN-based methods when there are few (or no) examples of molecules with the desired properties in the training data. We find that targeted molecular generation is often possible, but the diversity of generated molecules is often reduced, and it is not possible to control the composition of generated molecular sets. To help overcome these issues, we propose a new curriculum learning-inspired, recurrent Iterative Optimisation Procedure that enables the optimisation of generated molecules for seen and unseen molecular profiles and allows the user to control whether a molecular profile is explored or exploited. Using our method, we generate specific and diverse sets of molecules with up to 18 times more scaffolds than standard methods for the same sample size. However, our results also point to significant limitations of one-dimensional molecular representations as used in this space. We find that the success or failure of a given molecular optimisation problem depends on the choice of SMILES.
Distinguishing imported cases from locally acquired cases within a geographically limited genomic sample of an infectious disease
Authors: Didelot Xavier , Helekal David , Kendall Michelle , Ribeca Paolo 
Published: July 2022

ABSTRACTThe ability to distinguish imported cases from locally acquired cases has important consequences for the selection of public health control strategies. Genomic data can be useful for this, for example using a phylogeographic analysis in which genomic data from multiple locations is compared to determine likely migration events between locations. However, these methods typically require good samples of genomes from all locations, which is rarely available. Here we propose an alternative approach that only uses genomic data from a location of interest. By comparing each new case with previous cases from the same location we are able to detect imported cases, as they have a different genealogical distribution than that of locally acquired cases. We show that, when variations in the size of the local population are accounted for, our method has good sensitivity and excellent specificity for the detection of imports. We applied our method to data simulated under the structured coalescent model and demonstrate relatively good performance even when the local population has the same size as the external population. Finally, we applied our method to several recent genomic datasets from both bacterial and viral pathogens, and show that it can, in a matter of seconds or minutes, deliver important insights on the number of imports to a geographically limited sample of a pathogen population.
Cell Type Specific DNA Signatures of Transcription Factor Binding
Authors: Awdeh Aseel , Turcotte Marcel , Perkins Theodore J. 
Published: July 2022

AbstractTranscription factors (TFs) bind to different parts of the genome in different types of cells. These differences may be due to alterations in the DNA-binding preferences of a TF itself, or mechanisms such as chromatin accessibility, steric hindrance, or competitive binding, that result in a DNA “signature” of differential binding. We propose a method called SigTFB (Signatures of TF Binding), based on deep learning, to detect and quantify cell type specificity in a TF’s DNA-binding signature. We conduct a wide scale investigation of 194 distinct TFs across various cell types. We demonstrate the existence of cell type specificity in approximately 30% of the TFs. We stratify our analysis by different antibodies for the same TF, to rule out the possibility of certain technical artifacts, yet we find that cell type specificity estimates are largely consistent when the same TF is assayed with different antibodies. To further explain the biology behind a TF’s cell type specificity, or lack thereof, we conduct a wide scale motif enrichment analysis of all TFs in question. We show that the presence of alternate motifs correlates with a higher degree of cell type specificity in TFs, such as ATF7, while finding consistent motifs throughout is usually associated with the absence of cell type specificity in a TF, such as CTCF. In particular, we observe that several important TFs show distinct DNA binding signatures in different cancer cell types, which may point to important differences in modes of action. Moreover, we find that motif enrichment sometimes correlates with gene expression in TFs with higher cell type specificity. Our comprehensive investigation provides a basis for further study of the mechanisms behind differences in TF-DNA binding in different cell types.
Atypical hypnotic compound ML297 restores sleep architecture following emotionally-valenced learning, to promote memory consolidation and hippocampal network activation during recall
Authors: Martinez Jessy D. , Brancaleone William P. , Peterson Kathryn G. , Wilson Lydia G. , Aton Sara J. 
Published: July 2022

AbstractSleep plays a critical role in consolidating many forms of hippocampus-dependent memory. While various classes of hypnotic drugs have been developed in recent years, it remains unknown whether, or how, some of them affect sleep-dependent memory consolidation mechanisms. We find that ML297, a recently-developed candidate hypnotic agent targeting a new mechanism (activating GIRK1-subunit containing G-protein coupled inwardly rectifying potassium [GIRK] channels), alters sleep architecture in mice over the first 6 h following a single-trial learning event. Following contextual fear conditioning (CFC), ML297 reversed post-CFC reductions in NREM sleep spindle power and REM sleep amounts and architecture, renormalizing sleep features to what was observed at baseline, prior to CFC. Renormalization of post-CFC REM sleep latency, REM sleep amounts, and NREM spindle power were all associated with improved contextual fear memory (CFM) consolidation. We find that improvements in CFM consolidation due to ML297 are sleep-dependent, and are associated with increased numbers of highly-activated dentate gyrus (DG), CA1, and CA3 neurons during CFM recall. Together our findings suggest that GIRK1 channel activation restores normal sleep architecture - including REM sleep, which is normally suppressed following CFC - and increases the number of hippocampal neurons incorporated into the CFM engram during memory consolidation.Significance StatementBoth REM and NREM sleep are thought to be important for consolidating hippocampus-dependent memories. We find that GIRK1 activator ML297, administered after single-trial fear learning, restores REM sleep that is normally suppressed after learning fearful associations. This restoration is associated with improvements in fear memory storage, resulting in more robust hippocampus activation in the context of subsequent memory recall. Thus this drug, which also has antiepileptic and anxiolytic properties, may be useful for promoting normal, restorative sleep that benefits memory storage.
The roles of isolation and interspecific interaction in generating the functional diversity of an insular mammal radiation
Authors: Nations Jonathan A. , Kohli Brooks A. , Handika Heru , Achmadi Anang S. , Polito Michael J. , Rowe Kevin C. , Esselstyn Jacob A. 
Published: July 2022

AbstractCommunities that occupy similar environments but vary in the richness of closely related species can illuminate how functional variation and species richness interact to fill ecological space in the absence of abiotic filtering, though this has yet to be explored on an oceanic island where the processes of community assembly may differ from continental settings. In discrete montane communities on the island of Sulawesi, local murine rodent (rats and mice) richness ranges from 7 to 23 species. We measured 17 morphological, ecological, and isotopic traits, both individually and grouped into 5 multivariate traits in 40 species, to test for the expansion or packing of functional space among nine murine communities. We employed a novel probabilistic approach for integrating intraspecific and community-level trait variance into functional richness. Trait-specific and phylogenetic diversity patterns indicate dynamic community assembly due to variable niche expansion and packing on multiple niche axes. Locomotion and covarying traits such as tail length emerged as a fundamental axis of ecological variation, expanding functional space and enabling the niche packing of other traits such as diet and body size. Though trait divergence often explains functional diversity in island communities, we found that phylogenetic diversity facilitates functional space expansion in some conserved traits such as cranial shape, while more labile traits are overdispersed both within and between island clades, suggesting a role of niche complementarity. Our results evoke interspecific interactions, differences in trait lability, and the independent evolutionary trajectories of each of Sulawesi’s 6 murine clades as central to generating the exceptional functional diversity and species richness in this exceptional, insular radiation.