bluuebunny/crossref_metadata_2025_split huggingface dataset:
Donor-specific antibodies in liver transplantation: challenges in diagnosis and determining clinical impact
Authors: Kim Steven C. , Foley David P. 
Published: October 2020

Purpose of review
Our understanding of the clinical impact of donor-specific antibodies in liver transplant recipients has evolved in recent years as outcomes for liver allografts have improved and advances in diagnostic testing have made recognition of antibody mediated rejection in transplant patients more sensitive.

Recent findings
Two main types of donor-specific antibodies – preformed and de novo – have been reported in the literature to have a negative impact on graft survival, and researchers have been able to further identify subclasses of class II donor-specific antibodies as being the most clinically impactful. Furthermore, there is evidence that donor-specific antibody formation can augment cellular rejection in liver grafts and lead to worsened clinical outcomes. Recent data have shown a higher prevalence of donor-specific antibody formation than previously reported.

Summary
This review explores the most recent literature regarding the clinical impact of both preformed and de-novo donor-specific antibodies and potential management guidelines for patients undergoing liver transplantation. The best practice guidelines for undergoing monitoring for donor-specific antibody formation and protocol biopsies in sensitized patients will depend on further multiinstitutional studies.
The use of organs from hepatitis C virus-viremic donors into uninfected recipients
Authors: Kahn Jeffrey A. 
Published: October 2020

Purpose of review
There has been an ongoing disparity between the number of organs available for solid organ transplantation (SOT) relative to the need. This has resulted in significant waitlist mortality, may affect transplant outcomes due to transplants being performed on sicker patients and may even increase healthcare costs due to extended hospital stays. Transplanting organs from hepatitis C virus (HCV)-infected donors into uninfected recipients (D+/R−) is now a reality, due to the advent of highly affective direct-acting antivirals (DAAs) which not only have very high efficacy, but also a favorable side effect and drug–drug interaction profile.

Recent findings
Data from multiple centers reporting outcomes of kidney, liver, heart, lung and liver-kidney transplant during the past few years reveal that SOT from HCV-infected donors into noninfected recipients is safe, efficacious and can result in excellent recipient outcomes, with an opportunity to decrease the time on the waitlist, waitlist mortality and to improve outcomes after transplant due to less morbidity at the time of surgery. When livers are the transplanted organ, 8–12 weeks of DAA treatment will be required. For other organs, 2–4 weeks is likely sufficient. The available DAAs have profiles such that patients with all genotypes, with or without renal insufficiency an on renal replacement therapy and those who fail treatment may be successfully treated, with a sustained virologic response rate of more than 95%. Based upon the available data, starting DAAs shortly after transplant will likely limit posttransplant complications. that This will require cooperation between the transplant team, transplant hospital and insurer providing medication coverage.

Summary
SOT from HCV infected recipients is safe, is associated with excellent outcomes and should be considered for recipients who would benefit from receiving an organ earlier than they would if they waited for an organ from an uninfected donor.
A Preliminary Investigation of Deficits in Executive Functions of Adults With Attention Deficit Hyperactivity Disorder
Authors: Alaghband-rad Javad , Dashti Behnoosh , Tehranidoost Mehdi , Zargarinejad Ghazaleh , FarhadBeigi Parvaneh 
Published: October 2020

Abstract
Several studies over the past two decades have investigated the neuropsychological deficits in children with attention deficit hyperactivity disorder (ADHD), but much less has been done on adults. This study aimed to assess the deficits in executive functions of adults with ADHD, especially in the areas of attention, inhibition, impulsivity, and planning. Twenty-four adults (18 years and older) diagnosed with ADHD according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition criteria, and also assessed with Conners' Adult ADHD Rating Scale, participated in the study. Executive functions in cases were compared with 20 matched controls through the three instruments of Tower of London (TOL), Continuous Performance Test (CPT), and Stroop test. Performance of cases was weaker than that of the control group in TOL. The difference was significant in subsequent thinking time in most of the trials and number of movements only at level 2. In CPT, the adults with ADHD made more commission errors. In addition, the ADHD cases made more errors in the word card of the Stroop test, and the time they spent reading all three cards was significantly longer than that of the control group. Our study suggests that several deficits in executive functions related to ADHD persist into adulthood, such as impairments in planning time and set shifting, response inhibition, impulsivity, and visuolingual processing. However, simple (visual-motor processing) and sustained attention might improve with age.
Retrospective Analysis of Factors Associated With a Revised Fall Prevention Bundle in Hospitalized Patients
Authors: Scheidenhelm Sandra , Astroth Kim Schafer , DeLong Karen , Starkey Cyndy , Wolfe David 
Published: October 2020

OBJECTIVE
The study aims to describe factors associated and injuries sustained with inpatients who fell while hospitalized and identify the impact of a revised fall-prevention bundle.

BACKGROUND
Approximately 1 million falls occur in hospitals annually, accounting for approximately 70% of inpatient accidents. Inpatient falls can result in physical injury, increased patient mortality and morbidity, decreased quality of life, and increased length of stay and cost.

METHODS
We used a retrospective review of patient fall data for adult inpatients who fell while hospitalized.

RESULTS
After reeducation and implementation of all elements of a revised fall-prevention bundle, there were fewer falls per patient day. We identified additional characteristics indicating when patients were more likely to be injured in a fall.

CONCLUSIONS
A fall-prevention bundle is effective in decreasing inpatient falls and falls with injury. Raising awareness of additional factors may decrease risk of injuries during an inpatient fall.
Enteral Feeding of Children on Noninvasive Respiratory Support: A Four-Center European Study*
Authors: Tume Lyvonne N. , Eveleens Renate D. , Mayordomo-Colunga Juan , López Jorge , Verbruggen Sascha C. A. T. , Fricaudet Marianne , Smith Clare , Garcia Cusco Mireia Garcia , Latten Lynne , Valla Frédéric V. 
Published: October 2020

Objectives:
To explore enteral feeding practices and the achievement of energy targets in children on noninvasive respiratory support, in four European PICUs.

Design:
A four-center retrospective cohort study.

Setting:
Four PICUs: Bristol, United Kingdom; Lyon, France; Madrid, Spain; and Rotterdam, The Netherlands.

Patients:
Children in PICU who required acute noninvasive respiratory support in the first 7 days. The primary outcome was achievement of standardized kcal/goal.

Interventions:
None.

Measurements and Main Results:
A total of 325 children were included (Bristol 104; Lyon 99; Madrid 72; and Rotterdam 50). The median (interquartile range) age and weight were 3 months (1–16 mo) and 5 kg (4–10 mo), respectively, with 66% admitted with respiratory failure. There were large between-center variations in practices. Overall, 190/325 (58.5%) received noninvasive respiratory support in order to prevent intubation and 41.5% after extubation. The main modes of noninvasive respiratory support used were high-flow nasal cannula 43.6%, bilevel positive airway pressure 33.2%, and continuous positive airway pressure 21.2%. Most children (77.8%) were fed gastrically (48.4% continuously) and the median time to the first feed after noninvasive respiratory support initiation was 4 hours (interquartile range, 1–9 hr). The median percentage of time a child was nil per oral while on noninvasive respiratory support was 4 hours (2–13 hr). Overall, children received a median of 56% (25–82%) of their energy goals compared with a standardized target of 0.85 of the recommended dietary allowance. Patients receiving step-up noninvasive respiratory support (p = < 0.001), those on bilevel positive airway pressure or continuous positive airway pressure (compared with high-flow nasal cannula) (p = < 0.001), and those on continuous feeds (p = < 0.001) achieved significantly more of their kcal goal. Gastrointestinal complications varied from 4.8—20%, with the most common reported being vomiting in 54/325 (16.6%), other complications occurred in 40/325 (12.3%) children, but pulmonary aspiration was rare 5/325 (1.5%).

Conclusions:
Children on noninvasive respiratory support tolerated feeding well, with relatively few complications, but prospective trials are now required to determine the optimal timing and feeding method for these children.
Brief Report: Seroadaptive Behaviors Varied Among Geographically Diverse iPrEx Participants
Authors: Truong Hong-Ha M. , Mehrotra Megha L. , Grant Robert M. ,   for the iPrEx Study Team
Published: October 2020

Background:
Seroadaptive behaviors refer to a wide range of harm reduction practices to decrease HIV transmission risk. Effective implementation of seroadaptive behaviors is dependent on knowledge of one's own serostatus and that of one's sexual partners. Partner-level and environmental-level attributes may affect seroadaptation practices. We assessed factors associated with seroadaptive behaviors.

Methods:
Men who have sex with men and transgender women were recruited from an HIV pre-exposure prophylaxis clinical trial (iPrEx) with study sites in the US, Peru, Ecuador, Brazil, Thailand, and South Africa. Partnership-level data were collected at the baseline visit for the 3 most recent partners. Participants were considered to have practiced seroadaptive behaviors if: (1) they believed their partner to be HIV-negative, that is, serosorting; or (2) no condomless receptive sex occurred with an HIV-positive or unknown status partner, that is, seropositioning.

Results:
Of 2331 participants, 41% always practiced seroadaptive behaviors, 36% sometimes did, and 23% never did. Participants enrolled at study sites in the US (P < 0.001) and Peru/Ecuador (P < 0.001) were more likely to practice seroadaptive behaviors, whereas transgender women were less likely to do so (P < 0.001). Seroadaptive behaviors were more likely to occur in relationships with steady partners (P = 0.005) and emotionally close relationships (P = 0.013).

Conclusions:
Seroadaptive behaviors were more frequently observed among iPrEx participants from the US, Peru, and Ecuador study sites and among participants in relationships with partners who they were more committed to and felt emotionally close to. Our findings suggest that seroadaptive behaviors may be influenced by social norms that vary geographically and culturally.
Outcome after surgical stabilization of rib fractures versus nonoperative treatment in patients with multiple rib fractures and moderate to severe traumatic brain injury (CWIS-TBI)
Authors: Prins Jonne T.H. , Van Lieshout Esther M.M. , Ali-Osman Francis , Bauman Zachary M. , Caragounis Eva-Corina , Choi Jeff , Christie D. Benjamin , Cole Peter A. , DeVoe William B. , Doben Andrew R. , Eriksson Evert A. , Forrester Joseph D. , Fraser Douglas R. , Gontarz Brendan , Hardman Claire , Hyatt Daniel G. , Kaye Adam J. , Ko Huan-Jang , Leasia Kiara N. , Leon Stuart , Marasco Silvana F. , McNickle Allison G. , Nowack Timothy , Ogunleye Temi D. , Priya Prakash , Richman Aaron P. , Schlanser Victoria , Semon Gregory R. , Su Ying-Hao , Verhofstad Michael H.J. , Whitis Julie , Pieracci Fredric M. , Wijffels Mathieu M.E. 
Published: October 2020

BACKGROUND
Outcomes after surgical stabilization of rib fractures (SSRF) have not been studied in patients with multiple rib fractures and traumatic brain injury (TBI). We hypothesized that SSRF, as compared with nonoperative management, is associated with favorable outcomes in patients with TBI.

METHODS
A multicenter, retrospective cohort study was performed in patients with rib fractures and TBI between January 2012 and July 2019. Patients who underwent SSRF were compared to those managed nonoperatively. The primary outcome was mechanical ventilation-free days. Secondary outcomes were intensive care unit length of stay and hospital length of stay, tracheostomy, occurrence of complications, neurologic outcome, and mortality. Patients were further stratified into moderate (GCS score, 9–12) and severe (GCS score, ≤8) TBI.

RESULTS
The study cohort consisted of 456 patients of which 111 (24.3%) underwent SSRF. The SSRF was performed at a median of 3 days, and SSRF-related complication rate was 3.6%. In multivariable analyses, there was no difference in mechanical ventilation-free days between the SSRF and nonoperative groups. The odds of developing pneumonia (odds ratio [OR], 0.59; 95% confidence interval [95% CI], 0.38–0.98; p = 0.043) and 30-day mortality (OR, 0.32; 95% CI, 0.11–0.91; p = 0.032) were significantly lower in the SSRF group. Patients with moderate TBI had similar outcome in both groups. In patients with severe TBI, the odds of 30-day mortality was significantly lower after SSRF (OR, 0.19; 95% CI, 0.04–0.88; p = 0.034).

CONCLUSION
In patients with multiple rib fractures and TBI, the mechanical ventilation-free days did not differ between the two treatment groups. In addition, SSRF was associated with a significantly lower risk of pneumonia and 30-day mortality. In patients with moderate TBI, outcome was similar. In patients with severe TBI a lower 30-day mortality was observed. There was a low SSRF-related complication risk. These data suggest a potential role for SSRF in select patients with TBI.

LEVEL OF EVIDENCE
Therapeutic, level IV.
Acute Kidney Injury in a Predominantly African American Cohort of Kidney Transplant Recipients With COVID-19 Infection
Authors: Shrivastava Pritika , Prashar Rohini , Khoury Nadeen , Patel Anita , Yeddula Sirisha , Kitajima Toshihiro , Nagai Shunji , Samaniego Milagros 
Published: October 2020

Background.
Renal involvement in severe or critical acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is frequent. Acute kidney injury (AKI) in African American (AA) kidney transplant recipients (KTRs) with COVID-19 is not well described. We report our experience with a predominantly AA cohort (79%) of KTRs with COVID-19 infections in the Detroit Metropolitan area.

Methods.
In this retrospective, single-center study, we identified 39 KTRs who tested positive for SARS-CoV-2 between March 16 and April 25, 2020. Data from electronic medical records were retrieved and compared between KTRs without AKI and KTRs with AKI.

Results.
One patient was excluded due to delayed graft function. Final analysis of AKI in KTRs with proven COVID-19 was done on 38 patients of which 30 were AA (79%). AKI occurred in 71.1% of COVID-19 KTRs (n = 27), of whom 6 (22.2%) patients required HD. The incidence of AKI in our cohort was 71% (27/38). AKI rate among AA was 76.7% versus 50% in non-AA cohort (P = 0.195). In a univariate logistic regression analysis, AA race was not significantly associated with AKI odds ratio (3.4; CI, 0.68-17.4; P = 0.14). After risk adjustment by race, patients with diabetes showed a significantly higher risk of AKI (adjusted odds ratio, 19.85; CI, 1.65-58.66; P = 0.012). KTRs with AKI had more preexisting renin angiotensin aldosterone system inhibitor use than KTRs without AKI (P = 0.03).

Conclusions.
KTRs infected with SARS-CoV-2 have a high incidence of AKI, with associated increased morbidity and mortality. Although no racial differences in mortality were noted in our KTRs with AKI, we await data from registries to help elucidate this difference.
Early Changes in Kidney Transplant Immunosuppression Regimens During the COVID-19 Pandemic
Authors: Bae Sunjae , McAdams-DeMarco Mara A. , Massie Allan B. , Ahn JiYoon B. , Werbel William A. , Brennan Daniel C. , Lentine Krista L. , Durand Christine M. , Segev Dorry L. 
Published: October 2020

Background.
Kidney transplant recipients have higher risk of infectious diseases due to their reliance on immunosuppression. During the current COVID-19 pandemic, some clinicians might have opted for less potent immunosuppressive agents to counterbalance the novel infectious risk. We conducted a nationwide study to characterize immunosuppression use and subsequent clinical outcomes during the first 5 months of COVID-19 pandemic in the United States.

Methods.
Using data from the Scientific Registry of Transplant Recipients, we studied all kidney-only recipients in the United States from January 1, 2017, to March 12, 2020 (“prepandemic” era; n = 64 849) and from March 13, 2020, to July 31, 2020 (“pandemic” era; n = 5035). We compared the use of lymphocyte-depleting agents (versus basiliximab or no induction) and maintenance steroids (versus steroid avoidance/withdrawal) in the pandemic era compared with the prepandemic era. Then, we compared early posttransplant outcomes by immunosuppression regimen during the pandemic era.

Results.
Recipients in the pandemic era were substantially less likely to receive lymphocyte-depleting induction agents compared with their prepandemic counterparts (aOR = 0.400.530.69); similar trends were found across subgroups of state-level COVID-19 incidence, donor type, and recipient age. However, lymphocyte-depleting induction agents were associated with decreased rejection during admission (aOR = 0.110.230.47) but not with increased mortality in the pandemic era (aHR = 0.130.471.66). On the other hand, the use of maintenance steroids versus early steroid withdrawal remained similar (aOR = 0.711.071.62).

Conclusions.
The use of lymphocyte-depleting induction agents has decreased in favor of basiliximab and no induction during the COVID-19 pandemic. However, this shift might have resulted in increases in rejection with no clear reductions in posttransplant mortality.
Lost in translation: No effect of repeated optogenetic cortico-striatal stimulation on compulsivity in rats
Authors: de Oliveira Amanda R. , Reimer Adriano E. , Simandl Gregory J. , Nagrale Sumedh S. , Widge Alik S. 
Published: October 2020

AbstractBACKGROUNDThe orbitofrontal cortex-ventromedial striatum (OFC-VMS) circuitry is widely believed to drive compulsive behavior. Hyperactivating this pathway in inbred mice produces excessive and persistent self-grooming, which has been considered a model for human compulsivity. We aimed to replicate these findings in outbred rats, where there are few reliable compulsivity models.METHODS27 male Long-Evans rats implanted with optical-fibers into VMS and with opsins delivered into OFC received optical stimulation at parameters that produce OFC-VMS plasticity and compulsive grooming in mice. We then evaluated rats for compulsive self-grooming at six timepoints: before, during, immediately after and one hour after each stimulation, one and two weeks after the ending of a 6-day stimulation protocol. To further test for effects of OFC-VMS hyperstimulation, we ran animals in three standard compulsivity assays: marble burying, nestlet shredding, and operant attentional setshifting.RESULTSOFC-VMS stimulation did not increase self-grooming or induce significant changes in nestlet shredding, marble burying, or set-shifting in rats. Follow-on evoked potential studies verified that the mouse protocol did alter OFC-VMS synaptic weighting.CONCLUSIONSIn sum, although physiological changes were observed in the OFC-VMS circuitry, we could not reproduce in a strongly powered study in rats a model of compulsive behavior previously reported in mice. If optogenetic effects on behavior do not reliably transfer between rodent species, this may have important implications for designing rodent-to-human translational pipelines.
Tracking changes in behavioural dynamics using prediction error
Authors: Lorimer Tom , Goodridge Rachel , Bock Antonia K. , Agarwal Vitul , Saberski Erik , Sugihara George , Rifkin Scott A. 
Published: October 2020

AbstractAutomated analysis of video can now generate extensive time series of pose and motion in freely-moving organisms. This requires new quantitative tools to characterize behavioural dynamics. For the model roundwormCaenorhabditis elegans, body pose can be accurately quantified from video as coordinates in a single low-dimensional space. We focus on this well-established case as an illustrative example and propose a method to reveal subtle variations in behaviour at high time resolution. Our data-driven method, based on empirical dynamic modeling, quantifies behavioural change as prediction error with respect to a time-delay-embedded ‘attractor’ of behavioural dynamics. Because this attractor is constructed from a user-specified reference data set, the approach can be tailored to specific behaviours of interest at the individual or group level. We validate the approach by detecting small changes in the movement dynamics ofC. elegansat the initiation and completion of delta turns. We then examine an escape response initiated by an aversive stimulus and find that the method can track return to baseline behaviour in individual worms and reveal variations in the escape response between worms. We suggest that this general approach – defining dynamic behaviours using reference attractors and quantifying dynamic changes using prediction error – may be of broad interest and relevance to behavioural researchers working with video-derived time series.
A cross-species drug discovery pipeline to identify and validate new treatments for osteosarcoma
Authors: Somarelli Jason A. , Rupprecht Gabrielle , Altunel Erdem , Flamant Etienne M. , Rao Sneha , Sivaraj Dharshan , Lazarides Alexander L. , Hoskinson Sarah M. , Sheth Maya U. , Cheng Serene , Kim So Young , Ware Kathryn E. , Agarwal Anika , Cullen Mark M. , Selmic Laura E. , Everitt Jeffrey I. , McCall Shannon J. , Eward Cindy , Eward William C. , Hsu S. David 
Published: October 2020

AbstractPurposeOsteosarcoma is a rare but aggressive bone cancer that occurs primarily in children. Like other rare cancers, treatment advances for osteosarcoma have stagnated, with little improvement in survival for the past several decades. Developing new treatments has been hampered by extensive genomic heterogeneity and limited access to patient samples to study the biology of this complex disease.Experimental designTo overcome these barriers, we combined the power of comparative oncology with patient-derived models of cancer and high-throughput chemical screens in a cross-species drug discovery pipeline.ResultsCouplingin vitrohigh-throughput drug screens on low-passage and established cell lines within vivovalidation in patient-derived xenografts we identify the proteasome and CRM1 nuclear export pathways as therapeutic sensitivities in osteosarcoma, with dual inhibition of these pathways inducing synergistic cytotoxicity.ConclusionsThese collective efforts provide an experimental framework and set of new tools for osteosarcoma and other rare cancers to identify and study new therapeutic vulnerabilities.