bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk Factors for Carriage of Antibiotic-resistant Bacteria in Healthy Children in the Community
Authors: Messina Nicole L. , Williamson Deborah A. , Robins-Browne Roy , Bryant Penelope A. , Curtis Nigel 
Published: April 2020

Background:
In addition to health care settings, antibiotic resistance has also been increasing in the community. Healthy children represent an important potential reservoir of antibiotic-resistant (AR) bacteria. However, strategies to reduce the spread of AR bacteria often fail to specifically address the factors that promote the carriage of AR bacteria in this population.
The objective of this review was to Identify risk factors for carriage of AR bacteria by healthy children.

Methods:
We did a systematic search of MEDLINE, Embase and PubMed for studies in developed (OECD) countries that assessed risk factors for carriage of AR bacteria in healthy children in the community. We excluded studies done before 1998 and studies of AR Streptococcus pneumoniae carriage in the absence of pneumococcal conjugate vaccination.

Results:
Of 1234 studies identified, 30 were eligible for inclusion. These studies assessed the impact of 49 risk factors on AR strains of S. pneumoniae, Haemophilus influenzae, Staphylococcus aureus, Streptococcus pyogenes and Escherichia coli. The majority of these risk factors were assessed in 2 or fewer studies per bacteria. Recent antibiotic consumption was associated with carriage of resistant respiratory bacteria (S. pneumoniae, H. influenzae); however, it was not consistently associated with carriage of AR bacteria in skin or stool (S. aureus and E. coli). For AR S. aureus, transmission within households appeared to have a greater impact than individual antibiotic use.

Conclusions:
The factors that promote carriage of AR bacteria by healthy children differed between bacterial species. To reduce reservoirs of AR bacteria in the community, it is essential for intervention strategies to target the specific risk factors for different bacteria.
The impact of bone cancer on the peripheral encoding of mechanical pressure stimuli
Authors: Kucharczyk Mateusz W. , Chisholm Kim I. , Denk Franziska , Dickenson Anthony H. , Bannister Kirsty , McMahon Stephen B. 
Published: April 2020

AbstractSkeletal metastases are frequently accompanied by chronic pain that is mechanoceptive in nature. Mechanistically, cancer-induced bone pain (CIBP) is mediated by peripheral sensory neurons innervating the cancerous site, the cell bodies of which are housed in the dorsal root ganglia (DRG). How these somatosensory neurons encode sensory information in CIBP remains only partly explained. Using a validated rat model, we first confirmed cortical bone destruction in CIBP but not sham-operated rats (day 14 after surgery, designated “late”-stage bone cancer). This occurred with behavioural mechanical hypersensitivity (Kruskal–Wallis H for independent samples; CIBP vs sham-operated, day 14;P< 0.0001). Next, hypothesising that the proportion and phenotype of primary afferents would be altered in the disease state, dorsal root ganglia in vivo imaging of genetically encoded calcium indicators and Markov Cluster Analysis were used to analyse 1748 late-stage CIBP (n = 10) and 757 sham-operated (n = 9), neurons. Distinct clusters of responses to peripheral stimuli were revealed. In CIBP rats, upon knee compression of the leg ipsilateral to the tumour, (1) 3 times as many sensory afferents responded (repeated-measures analysis of variance:P< 0.0001 [vs sham]); (2) there were significantly more small neurons responding (Kruskal–Wallis for independent samples (vs sham):P< 0.0001); and (3) approximately 13% of traced tibial cavity afferents responded (no difference observed between CIBP and sham-operated animals). We conclude that an increased sensory afferent response is present in CIBP rats, and this is likely to reflect afferent recruitment from outside of the bone rather than increased intraosseous afferent activity.
Heat shock protein 90 inhibitors block the antinociceptive effects of opioids in mouse chemotherapy-induced neuropathy and cancer bone pain models
Authors: Stine Carrie , Coleman Deziree L. , Flohrschutz Austin T. , Thompson Austen L. , Mishra Sanket , Blagg Brian S. , Largent-Milnes Tally M. , Lei Wei , Streicher John M. 
Published: April 2020

Abstract
Heat shock protein 90 (Hsp90) is a ubiquitous signal transduction regulator, and Hsp90 inhibitors are in clinical development as cancer therapeutics. However, there have been very few studies on the impact of Hsp90 inhibitors on pain or analgesia, a serious concern for cancer patients. We previously found that Hsp90 inhibitors injected into the brain block opioid-induced antinociception in tail flick, paw incision, and HIV neuropathy pain. This study extended from that initial work to test the cancer-related clinical impact of Hsp90 inhibitors on opioid antinociception in cancer-induced bone pain in female BALB/c mice and chemotherapy-induced peripheral neuropathy in male and female CD-1 mice. Mice were treated with Hsp90 inhibitors (17-AAG, KU-32) by the intracerebroventricular, intrathecal, or intraperitoneal routes, and after 24 hours, pain behaviors were evaluated after analgesic drug treatment. Heat shock protein 90 inhibition in the brain or systemically completely blocked morphine and oxymorphone antinociception in chemotherapy-induced peripheral neuropathy; this effect was partly mediated by decreased ERK and JNK MAPK activation and by increased protein translation, was not altered by chronic treatment, and Hsp90 inhibition had no effect on gabapentin antinociception. We also found that the Hsp90 isoform Hsp90α and the cochaperone Cdc37 were responsible for the observed changes in opioid antinociception. By contrast, Hsp90 inhibition in the spinal cord or systemically partially reduced opioid antinociception in cancer-induced bone pain. These results demonstrate that Hsp90 inhibitors block opioid antinociception in cancer-related pain, suggesting that Hsp90 inhibitors for cancer therapy could decrease opioid treatment efficacy.
The Citrullinated and MMP-degraded Vimentin Biomarker (VICM) Predicts Early Response to Anti-TNFα Treatment in Crohn’s Disease
Authors: Mortensen Joachim H. , van Haaften Wouter T. , Karsdal Morten A. , Bay-Jensen Anne-Christine , Olinga Peter , Grønbæk Henning , Hvas Christian L. , Manon-Jensen Tina , Dijkstra Gerard , Dige Anders 
Published: April 2020

Background:
In Crohn’s disease (CD), 10% to 40% of patients do not respond to anti-tumor necrosis factor-α (TNFα) treatment. Currently, there are no biomarkers with adequate sensitivity to separate responders from nonresponders at an early stage.

Aim:
The aim of this study was to investigated whether early changes in the VICM (citrullinated and matrix metalloproteinase-degraded vimentin) biomarker were associated with response to anti-TNFα treatment in patients with CD.

Methods:
Serum VICM levels were measured by ELISA in 2 independent cohorts of CD patients (n=42) treated with anti-TNFα (infliximab or adalimumab). Response was determined by achieving clinical remission (Harvey Bradshaw Index<5).

Results:
Compared with baseline, VICM serum levels were reduced by anti-TNFα in the infliximab cohort (week 6 and 14) and in the adalimumab cohort (week 8). VICM was lower in the responders compared with the nonresponders [infliximab: week 6, P<0.05; area under the curve (AUC)=0.90; adalimumab: week 1, P<0.01 (AUC=0.91), and week 8, P<0.05 (AUC=0.86)], and were able to predict response to treatment after 1 week of treatment with an odds ratio of 42.5.

Conclusions:
The VICM biomarker was time dependently reduced in CD patients responding to anti-TNFα treatment. We suggest that VICM may be used as a marker for monitoring early response to anti-TNFα in patients with CD.
Reducing Hospitalization in Mild Acute Pancreatitis
Authors: Ahmed Awais , Kothari Darshan J. , Wardlaw Scott , Freedman Steven D. , Sheth Sunil G. 
Published: April 2020

Goals and Background:
Acute pancreatitis (AP) is a common emergency department (ED) diagnosis, amounting to enormous costs. Our previous pilot study demonstrated the feasibility of reducing hospitalization using an ED-based observation pathway. In this follow-up study, we hypothesize that the pathway is durable in clinical practice, outside of research supervision, and patients can safely be managed without hospitalization.

Study:
We reviewed patients prospectively enrolled in the observation pathway after the end of the pilot study. We compared outcomes to patients enrolled in our pilot study and with a historic cohort of patients admitted with mild AP. Our primary outcome was hospitalization rate during the enrollment period and secondary outcomes included length of stay, 30-day readmissions, mortality, and health care utilization.

Results:
Over a 2-year period 165 patients met criteria for AP with 118 (71.5%) having mild AP. Fifty-four of 118 patients (45.8%) were enrolled in the observation pathway and of these, 45 patients were discharged from the ED, reducing hospitalization by 31.2%, compared with pilot study (22.2%) and historic cohort (0%) (P<0.05). Median length of stay was shorter [19.9 (observation) vs. 72.0 h (historic cohort), P<0.01]. There were fewer radiographic examinations in the observation cohorts (pilot and current study) than in the historic cohort (P<0.05), with similar 30-day readmissions, and no reported deaths.

Conclusions:
This follow-up study demonstrates the durability of an observation-based pathway to manage mild AP outside of a research protocol and maintain its ability to reduce hospitalizations without affecting readmission rates or mortality.
Thermal Ablation Versus Cryotherapy or Loop Excision to Treat Women Positive for Cervical Precancer on Visual Inspection With Acetic Acid Test: Pilot Phase of a Randomized Controlled Trial
Authors: Pinder Leeya F. , Parham Groesbeck P. , Basu Partha , Muwonge Richard , Lucas Eric , Nyambe Namakau , Sauvaget Catherine , Mwanahamuntu Mulindi H. , Sankaranarayanan Rengaswamy , Prendiville Walter 
Published: April 2020

(Abstracted from Lancet Oncol 2020;21:175–184)
Cervical cancer has a long and treatable precancerous phase, is easily screened for, and is common enough to justify population-based screening even in low- and middle-income countries (LMICs). The standard treatment in high-income countries is large loop excision of the transformation zone (LLETZ).
Anticipatory oculomotor responses in parents of children with attention deficit hyperactivity disorder
Authors: Chamorro Yaira , Ramírez-Dueñas María de Lourdes , Matute Esmeralda 
Published: April 2020

ObjectiveDiminished inhibitory control has been proposed as a core characteristic and potential endophenotype of attention deficit hyperactivity disorder (ADHD). If this is the case, one would expect to find this trait among first-degree relatives of individuals with ADHD. The aim of this study, therefore, was to determine whether the oculomotor measures typically related to inhibitory control failures in individuals with ADHD are also observed among those relatives.MethodsUsing prosaccadic and antisaccadic tasks in gap and overlap conditions, we assessed a group of unaffected parents of children with ADHD symptoms and compared them to a group of unaffected parents of children with typical development. Direction errors, anticipatory errors and saccadic reaction times were analyzed. We also determined the presence of ADHD behaviors (in adulthood and childhood) in all participants.ResultsNo between-group differences were observed for the antisaccadic measures, but the group of parents of children with ADHD made more anticipatory responses on the prosaccadic-gap task than the parents of controls. A moderate association between these anticipatory errors and dimensional inattention scores was also found.ConclusionsSaccadic performance differed between the two groups of parents, as those with children with ADHD showed a failure to withhold the initiation of responses in the absence of external control references (gap condition) on tasks with low cognitive load (prosaccadic). These anticipatory responses were related to inattention traits. Our results support the familial compound of ADHD as a multifactorial disorder.
Identifying common pharmacotherapies associated with reduced COVID-19 morbidity using electronic health records
Authors: Castro Victor M , Ross Rachel A , McBride Sean M , Perlis Roy H 
Published: April 2020

AbstractObjectiveAbsent a vaccine or any established treatments for the novel and highly infectious coronavirus-19 (COVID-19), rapid efforts to identify potential therapeutics are required. We sought to identify commonly prescribed medications that may be associated with lesser risk of morbidity with COVID-19 across 6 Eastern Massachusetts hospitals.DesignIn silico cohort using electronic health records from individuals evaluated in the emergency department between March 4, 2020 and July 12, 2020.SettingEmergency department and inpatient settings from 2 academic medical centers and 4 community hospitals.ParticipantsAll individuals presenting to an emergency department and undergoing COVID-19 testing.Main Outcome or MeasureInpatient hospitalization; documented requirement for mechanical ventilation.ResultsAmong 7,360 individuals with COVID-19 positive test results by PCR, 3,693 (50.2%) were hospitalized in one of 6 hospitals. In models adjusted for sociodemographic features and overall burden of medical illness, medications significantly associated with diminished risk for hospitalization included ibuprofen and sumatriptan. Among individuals who were hospitalized, 962(26.0%) were admitted to the intensive care unit and 608 (16.5%) died; ibuprofen and naproxen were also more commonly prescribed among individuals not requiring intensive care.ConclusionsThese preliminary findings suggest that electronic health records may be applied to identify medications associated with lower risk of morbidity with COVID-19, but larger cohorts will be required to address the substantial problem of confounding by indication, such that extreme caution is warranted in interpreting nonrandomized results.Trial RegistrationNoneSummary BoxesSection 1: What is already known on this topicAbsent a vaccine or any established treatments for the novel and highly infectious coronavirus-19 (COVID-19), rapid efforts to identify potential therapeutics are required.Section 2: What this study addsThis cohort study across 6 hospitals identified medications enriched among individuals positive for COVID-19 who are less likely to experience adverse outcomes including hospitalization, intensive care, or death.
Estimated regional white matter hyperintensity burden, resting state functional connectivity, and cognitive functions in older adults
Authors: Jaywant Abhishek , Dunlop Katharine , Victoria Lindsay W. , Oberlin Lauren , Lynch Charles J. , Respino Matteo , Kuceyeski Amy , Scult Matthew , Hoptman Matthew , Liston Conor , O’Dell Michael W. , Alexopoulos George S. , Perlis Roy H. , Gunning Faith M. 
Published: April 2020

AbstractObjectiveWhite matter hyperintensities (WMH) are linked to deficits in cognitive functioning, including cognitive control and memory; however, the structural and functional mechanisms are largely unknown. We investigated the relationship between estimated regional disruptions to white matter fiber tracts from WMH, resting state functional connectivity (RSFC), and cognitive functions in older adults.DesignCross-sectional study.SettingCommunity.ParticipantsFifty-eight cognitively-healthy older adults.MeasurementsTasks of cognitive control and memory, structural MRI, and resting state fMRI. We estimated the disruption to white matter fiber tracts from WMH and its impact on gray matter regions in the cortical and subcortical frontoparietal network, default mode network, and ventral attention network by overlaying each subject’s WMH mask on a normative tractogram dataset. We calculated RSFC between nodes in those same networks.ResultsThe interaction of estimated regional WMH burden and RSFC in cortico-striatal regions of the default mode network and frontoparietal network was associated with memory retrieval. Models predicting working memory, cognitive inhibition, and set-shifting were not significant.ConclusionsFindings highlight the role of circuit-level alterations at the structural and functional levels in resting state networks that are related to WMH and impact memory retrieval in older adults.
Residual-matching: An efficient alternative to random sampling in human subjects research recruitment
Authors: Hooyman Andrew , Huentelman Matthew J. , Schaefer Sydney Y. 
Published: April 2020

ABSTRACTGiven the time- and resource-intense nature of human subjects research, we have developed a more intelligent approach to participant recruitment above and beyond random sampling that leverages pilot or preliminary results to reduce the overall number of participants needed for recruitment from an existing electronic cohort or database. Using open-access data from the General Social Survey (GSS) of the National Opinion Research Center, we generated pilot and validation datasets through a simulation to establish moderate and weak relationships based on linear regression. We then compared the performance of our residual-matching method against random sampling in their probabilities of achieving a given level of statistical power as well as their prediction accuracies. Results showed that the residual-matching method was superior to random sampling, yielding smaller sample sizes with equivalent mean square error. We therefore advocate the use of residual matching when scaling up pilot studies to conserve time and resources in larger follow-up studies.
Mapping the human praxis network: an investigation of white matter disconnection in apraxia
Authors: Rosenzopf Hannah , Wiesen Daniel , Basilakos Alexandra , Yourganov Grigori , Bonilha Leonardo , Rorden Christopher , Fridriksson Julius , Karnath Hans-Otto , Sperber Christoph 
Published: April 2020

AbstractLeft hemispheric cerebral stroke can cause apraxia, a motor-cognitive disorder characterised by deficits of higher-order motor skills such as the failure to accurately produce meaningful gestures. This disorder provides unique insights into the anatomical and cognitive architecture of the human praxis system. The present study aimed to map the structural brain network that is damaged in apraxia. We assessed the ability to perform meaningful gestures with the hand in 101 patients with chronic left hemisphere stroke. Structural white matter fibre damage was directly assessed by diffusion tensor imaging and fractional anisotropy mapping. We used multivariate topographical inference on tract-based fractional anisotropy topographies to identify white matter disconnection associated with apraxia. We found relevant pathological white matter alterations in a densely connected fronto-temporo-parietal network of short and long association fibres. Hence, the findings suggest that heterogeneous topographical results in previous lesion mapping studies might not only result from differences in study design, but also from the general methodological limitations of univariate topographical mapping in uncovering the structural praxis network. A striking role of middle and superior temporal lobe disconnection, including temporo-temporal short association fibres, was found, suggesting strong involvement of the temporal lobe in the praxis network. Further, the results stressed the importance of subcortical disconnections for the emergence of apractic symptoms. Our study provides a fine-grain view into the structural connectivity of the human praxis network and suggests a potential value of disconnection measures in the clinical prediction of behavioural post-stroke outcome.
Glycosaminoglycan binding motif at S1/S2 proteolytic cleavage site on spike glycoprotein may facilitate novel coronavirus (SARS-CoV-2) host cell entry
Authors: Kim So Young , Jin Weihua , Sood Amika , Montgomery David W. , Grant Oliver C. , Fuster Mark M. , Fu Li , Dordick Jonathan S. , Woods Robert J. , Zhang Fuming , Linhardt Robert J. 
Published: April 2020

AbstractSevere acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) has resulted in a pandemic and continues to spread around the globe at an unprecedented rate. To date, no effective therapeutic is available to fight its associated disease, COVID-19. Our discovery of a novel insertion of glycosaminoglycan (GAG)-binding motif at S1/S2 proteolytic cleavage site (681-686 (PRRARS)) and two other GAG-binding-like motifs within SARS-CoV-2 spike glycoprotein (SGP) led us to hypothesize that host cell surface GAGs might be involved in host cell entry of SARS-CoV-2. Using a surface plasmon resonance direct binding assay, we found that both monomeric and trimeric SARS-CoV-2 spike more tightly bind to immobilized heparin (KD= 40 pM and 73 pM, respectively) than the SARS-CoV and MERS-CoV SGPs (500 nM and 1 nM, respectively). In competitive binding studies, the IC50of heparin, tri-sulfated non-anticoagulant heparan sulfate, and non-anticoagulant low molecular weight heparin against SARS-CoV-2 SGP binding to immobilized heparin were 0.056 μM, 0.12 μM, and 26.4 μM, respectively. Finally, unbiased computational ligand docking indicates that heparan sulfate interacts with the GAG-binding motif at the S1/S2 site on each monomer interface in the trimeric SARS-CoV-2 SGP, and at another site (453-459 (YRLFRKS)) when the receptor-binding domain is in an open conformation. Our study augments our knowledge in SARS-CoV-2 pathogenesis and advances carbohydrate-based COVID-19 therapeutic development.
Hype versus hope: Deep learning encodes more predictive and robust brain imaging representations than standard machine learning
Authors: Abrol Anees , Fu Zening , Salman Mustafa , Silva Rogers , Du Yuhui , Plis Sergey , Calhoun Vince 
Published: April 2020

AbstractPrevious successes of deep learning (DL) approaches on several complex tasks have hugely inflated expectations of their power to learn subtle properties of complex brain imaging data, and scale to large datasets. Perhaps as a reaction to this inflation, recent critical commentaries unfavorably compare DL with standard machine learning (SML) approaches for the analysis of brain imaging data. Yet, their conclusions are based on pre-engineered features which deprives DL of its main advantage: representation learning. Here we evaluate this and show the importance of representation learning for DL performance on brain imaging data. We report our findings from a large-scale systematic comparison of SML approaches versus DL profiled in a ten-way age and gender-based classification task on 12,314 structural MRI images. Results show that DL methods, if implemented and trained following the prevalent DL practices, have the potential to substantially improve compared to SML approaches. We also show that DL approaches scale particularly well presenting a lower asymptotic complexity in relative computational time, despite being more complex. Our analysis reveals that the performance improvement saturates as the training sample size grows, but shows significantly higher performance throughout. We also show evidence that the superior performance of DL is primarily due to the excellent representation learning capabilities and that SML methods can perform equally well when operating on representations produced by the trained DL models. Finally, we demonstrate that DL embeddings span a comprehensible projection spectrum and that DL consistently localizes discriminative brain biomarkers, providing an example of the robustness of prediction relevance estimates. Our findings highlight the presence of non-linearities in brain imaging data that DL frameworks can exploit to generate superior predictive representations for characterizing the human brain, even with currently available data sizes.