bluuebunny/crossref_metadata_2025_split huggingface dataset:
Renal impairment in a large-scale HIV preexposure prophylaxis implementation cohort
Authors: Drak Douglas , Mcmanus Hamish , Vickers Tobias , Heron Jack E. , Vaccher Stefanie , Zablotska Iryna , Guy Rebecca , Bavinton Benjamin , Jin Fengyi , Grulich Andrew E. , Bloch Mark , O’Connor Catherine C. , Gracey David M. 
Published: July 2021

Background:
HIV preexposure prophylaxis (PrEP) with fixed-dose tenofovir disoproxil fumarate (TDF) and emtricitabine has been associated with low rates of renal impairment in clinical trials. Large-scale PrEP implementation may result in higher rates, as the prevalence of associated risk factors may be higher than in trial populations.

Methods:
A posthoc analysis of EPIC-NSW, a large Australian multicentre PrEP implementation trial for patients at high risk of HIV infection. Participants were eligible for inclusion if they commenced PrEP between 1 March 2016 and 30 April 2018, and had renal function assessed at baseline and at least once more before the censor date. The primary outcome was new-onset renal impairment, defined as an estimated glomerular filtration rate (eGFR) <60 ml/min per 1.73 m2.

Results:
A total of 6808 participants were eligible for inclusion. Almost all were male (99%), with a median age of 35 years [interquartile range (IQR): 28–44]. Approximately one-quarter (26%) had a baseline eGFR <90 ml/min per 1.73 m2. Over a median follow-up period of 1.2 years (IQR: 0.6–1.7), the rate of renal impairment was 5.8 episodes per 1000 person-years [95% confidence interval (CI): 4.0–7.8]. In multivariable Cox regression, there was a higher risk of renal impairment in participants aged ≥50 years [hazard ratio (HR) 14.7, 95% CI: 5.0–43.3, P < 0.001] and those with an eGFR <90 ml/min per 1.73 m2 (HR 28.9, 95% CI: 6.9–121.9) at baseline.

Conclusion:
In a large-scale implementation study, TDF-containing PrEP was associated with a low risk of renal impairment overall, whereas older patients and those with preexisting renal dysfunction were at substantially increased risk.
Bacteriophages against enteropathogens: rediscovery and refinement of novel antimicrobial therapeutics
Authors: León Yrvin , Faherty Christina S. 
Published: July 2021

Purpose of review
Alarming rates of antibiotic resistance in bacteria and gastrointestinal dysbiosis associated with traditional antimicrobial therapy have led to renewed interests in developing bacteriophages as novel therapeutics. In this review, we highlight some of the recent advances in bacteriophage therapeutic development targeting important enteropathogens of the gastrointestinal tract.

Recent findings
Bacteriophages are viruses that infect bacteria, either to utilize the bacterial machinery to produce new progeny or stably integrate into the bacterial chromosome to ensure maintenance of the viral genome. With recent advances in synthetic biology and the discovery of CRISPR-Cas systems used by bacteria to protect against bacteriophages, novel molecular applications are taking us beyond the discovery of bacteriophages and toward innovative applications, including the targeting of bacterial virulence factors, the use of temperate bacteriophages, and the production of bacteriophage proteins as antimicrobial agents. These technologies offer promise to target enteropathogens without disrupting the healthy microbiota of the gastrointestinal tract. Moreover, the use of nanoparticle technology and other modifications are helping researchers circumvent the harsh gastrointestinal conditions that could limit the efficacy of bacteriophages against enteric pathogens.

Summary
This era of discovery and development offers significant potential to modify bacteriophages and overcome the global impact of enteropathogens.
Parental vaccine hesitancy: scope, causes, and potential responses
Authors: Cataldi Jessica R. , O’Leary Sean T. 
Published: July 2021

Purpose of review
We reviewed the literature about parental vaccine hesitancy, focusing on publications from October 2019 to April 2021 to describe patterns and causes of hesitancy and interventions to address hesitancy.

Recent findings
Recent studies expand understanding of the prevalence of vaccine hesitancy globally and highlight associated individual and contextual factors. Common concerns underlying hesitancy include uncertainty about the need for vaccination and questions about vaccine safety and efficacy. Sociodemographic factors associated with parental vaccine hesitancy vary across locations and contexts. Studies about psychology of hesitancy and how parents respond to interventions highlight the role of cognitive biases, personal values, and vaccination as a social contract or norm. Evidence-based strategies to address vaccine hesitancy include presumptive or announcement approaches to vaccine recommendations, motivational interviewing, and use of immunization delivery strategies like standing orders and reminder/recall programs. A smaller number of studies support use of social media and digital applications to improve vaccination intent. Strengthening school vaccine mandates can improve vaccination rates, but policy decisions must consider local context.

Summary
Vaccine hesitancy remains a challenge for child health. Future work must include more interventional studies to address hesitancy and regular global surveillance of parental vaccine hesitancy and vaccine content on social media.
Smile Train: A Sustainable Approach to Global Cleft Care
Authors: Smerica Abel M. , Hamilton Sarah C. , Dibbs Rami P. , Ferry Andrew M. , Hollier Larry H. 
Published: July 2021

Abstract
Smile Train, the largest global cleft nonprofit organization, employs a model of establishing partnerships with treatment centers and medical professionals in low- and middle-income countries (LMICs). Having a presence in over 90 countries throughout its history, the organization provides support for cleft lip and palate repair as well as comprehensive cleft care (CCC) for patients with clefts. With the goal of reducing disparities in access to quality surgical, anesthesia, and medical care, Smile Train strengthens partners with training, education, equipment, and patient support grants. Furthermore, safety and quality protocols have been put in place as guidelines for each partner center, and partnerships with other nongovernmental agencies were created to increase safety in the operating rooms. The founder of Smile Train desired to apply technology wherever possible to build sustainability within the treatment centers and surgeons supporting their own community. Smile Train's model, aimed at increased sustainability, is supplemented by technological advancements to assist in the safety and quality of cleft care services provided in LMIC treatment centers. Examples include centralized online data record keeping for every patient, virtual simulations and training, and mobile applications to enhance care. Recently, Smile Train's focus is expanding CCC with nutrition, oral health, speech, and nursing care programs to improve functional and psychosocial outcomes for patients following their procedure. Despite the challenges imposed by the COVID-19 pandemic, Smile Train continues to provide safe, efficacious, and CCC alongside their partners in LMICs further investing tremendous efforts towards the livelihood of children with clefts globally.
Orthognathic Surgery Rate in Cleft Care
Authors: Jacob Laya , Fahradyan Artur , Paulson Philip , Wlodarczyk Jordan R. , Wolfswinkel Erik M. , Jimenez Christian , Urata Mark M. , Hammoudeh Jeffrey A. 
Published: July 2021

Purpose:
To determine the true need for orthognathic surgery in patients with repaired cleft lip and/or palate (CL/P) at a high-volume craniofacial center.

Methods:
An institutional retrospective review of patients with CL/P born between 1975 and 2008 was performed. Patients with adequate documentation reflecting cleft care who were ≥ 18 years at the time of last craniofacial/dentistry follow-up were included. Patients with non-paramedian clefts or a comorbid craniofacial syndrome were excluded. Primary outcome variable was the total proportion of patients with CL/P who either underwent or were referred for orthognathic surgery Le Fort I (LF1) to correct midface hypoplasia. Secondary outcome variables were associations between cleft phenotype, midface hypoplasia severity, and number of cleft related surgeries with the eventual LF1 referral/recipiency.

Results:
One hundred seventy-seven patients with CL/P met inclusion criteria. A total of 90/177 (51%) patients underwent corrective LF1; however, 110/177 (62%) of patients were referred for surgery. Patients with secondary cleft palate involvement were referred for and underwent LF1 at significantly greater rates than those without secondary palate involvement (referred: 65% versus 13%, P = 0.001; underwent: 55% versus 0%, P < 0.001). Patients with bilateral cleft lip/palate were referred for and underwent LF1 at significantly higher rates than those with unilateral cleft lip/palate (referred: 71.0% versus 50.4%, P= 0.04; underwent: 84% versus 71%, P = 0.02). Number of secondary palate surgeries was positively correlated with increased LF1 referral (P = 0.02) but not LF1 recipiency (P = 0.15).

Conclusions:
The incidence of orthognathic surgery redundant in patients with repaired CL/P was 51% at our institution, marginally above the higher end of previously reported rates. However, this number is an underrepresentation of the true requirement for LF1 as 62% of patients were referred for surgical intervention of midface hypoplasia. This distinction should be considered when counseling families.
Pathophysiologic Review of Blow-Out Fracture and Blow-Out Fracture Extended to Subarachnoid Space Due to Air Gun Injury
Authors: Lee Da Woon , Ryu Heongrae , Kim Jun Hyuk , Choi Hwan Jun 
Published: July 2021

Abstract
Blow-out fracture is usually caused by direct traumatic events in the periorbital area. But in this case, the authors introduce a case in which the medial orbital wall was fractured directly through the medial rectus muscle by high pressure air gun.
A 38-year-old man was injured in his right periorbital area after being hit by high pressure air gun. He had mild ecchymosis and subconjunctival hemorrhage. He had a normal light reflex and intraocular pressure of 14 mm Hg. A facial computed tomography scan confirmed a blow-out fracture of the medial orbital floor with multiple extensive subcutaneous emphysema in the right hemifacial area. Free air was also seen near the basal cistern and Sylvian fissure, indicating a pneumocephalus. The operation was performed after swelling and emphysema were subsided. Intraoperative, medial rectus muscle was damaged. After the operation, no abnormal findings were observed in the ophthalmic examination. Also, the free air findings, which were observed in preoperative x-ray, have disappeared.
This case is a rare case in which an orbital wall has been fractured directly through the medial rectus muscle due to an air gun injury. Therefore, we should always kept in mind that blow-out fractures can occur even with unusual mechanisms.
Geriatric Assessment Is Associated With Reduced Mortality at 1 Year for Older Adults Admitted to a Major Trauma Center
Authors: Ibitoye Sarah E. , Braude Philip , Carter Ben , Rickard Frances , Deakin Helen , Martin Rebecca , Thompson Julian , Walton Benjamin , Shipway David 
Published: July 2021

Objective:
To evaluate the effect of geriatrician review on 1-year mortality in older adults admitted with trauma.

Background:
Comprehensive geriatric assessment (CGA) has been associated with improved outcomes in older adults with hip fracture, but has not been evaluated in a broader trauma population.

Methods:
Trauma patients aged ≥ 65years admitted to an English Major Trauma Centre between November 2018 and September 2019 were included. Patients were divided into 3 cohorts: no geriatric assessment, reactive geriatric assessment, and proactive CGA. The primary outcome was time to mortality, secondary outcomes were time to discharge and frequency of complications. Analyses were adjusted for factors known to be associated with outcomes including age, frailty, injury severity, and complications.

Results:
Five hundred eighty-five patients were included (no geriatric assessment = 125; reactive geriatric assessment = 134; proactive CGA = 326): median age was 81 years (IQR 74-88); 326 (55.7%) were women; 297 (50.8%) were living with frailty (Clinical Frailty Scale ≥5). Median Injury Severity Score was 13 (IQR9-25). At 1-year follow-up, 147 (25.1%) patients had died. In multivariate analysis, both types of geriatric assessment were associated with reduced mortality [reactive aHR = 0.31, 95% CI 0.18–0.53; proactive adjusted hazard ratio (aHR) = 0.41, 95% CI 0.26–0.64]. There was no association between either type of geriatric assessment and length of stay (reactive aHR = 0.84, 95% CI 0.62–1.15; proactive aHR = 0.80, 95% CI 0.63–1.02).

Conclusions:
Geriatrician assessment is associated with reduced mortality in older adults admitted following trauma. Further research should focus on defining optimal models of geriatrician intervention.
Challenges in Anesthesia Management for Peroral Endoscopic Myotomy: A Retrospective Analysis
Authors: Yurtlu Derya A. , Aslan Fatih 
Published: July 2021

Background:
Peroral endoscopic myotomy (POEM) is used to treat achalasia with efficacy and reliability. However, during the procedure potential complications require attention in terms of anesthesia. This study aimed to investigate complications of the POEM procedure and its effects on arterial blood gas (ABG) parameters, peak airway pressures (PIP), hemodynamics, and postoperative analgesia requirements.

Methods:
Data from 220 patients who underwent POEM between 2014 and 2017 were retrospectively assessed. During the procedure, ABG samples, PIP, mean arterial pressure, and heart rate were recorded. The effects of the procedure and paracentesis on ABG, PIP, mean arterial pressure, heart rate, perioperative complications, and postoperative analgesia requirements were assessed.

Results:
Data from 220 POEM patients were analyzed. During the procedure, the mean PaCO2 was 48.27±6.34 mm Hg, which was significantly higher than the PaCO2 values before and after the procedure. The mean increase in maximum PIP was 5.90±3.49 cmH2O during the procedure. However, there was a significant decrease in PaCO2 and PIP values in cases with paracentesis compared with those without paracentesis. With regards to complications, subcutaneous emphysema (48, 21.8%), pneumoperitoneum requiring decompression (66, 30%), pneumothorax (1, 0.5%), aspiration pneumonia (1, 0.5%), and bronchospasm (5, 2.2%) were observed during the procedure. In the postoperative period, 58 patients (26%) had additional analgesia requirements because of visual analog scale values >3.

Conclusion:
Periprocedural abdominal decompression with veress needle led to a reduction in arterial PaCO2 and PIP, and improved postoperative analgesia. Serious complications because of perioperative aspiration and CO2 insufflation were observed during the POEM procedure.
Prediction of Liver Transplant Rejection With a Biologically Relevant Gene Expression Signature
Authors: Levitsky Josh , Kandpal Manoj , Guo Kexin , Zhao Lihui , Kurian Sunil , Whisenant Thomas , Abecassis Michael 
Published: July 2021

Background.
Noninvasive biomarkers distinguishing early immune activation before acute rejection (AR) could more objectively inform immunosuppression management in liver transplant recipients (LTRs). We previously reported a genomic profile distinguishing LTR with AR versus stable graft function. This current study includes key phenotypes with other causes of graft dysfunction and uses a novel random forest approach to augment the specificity of predicting and diagnosing AR.

Methods.
Gene expression results in LTRs with AR versus non-AR (combination of other causes of graft dysfunction and normal function) were analyzed from single and multicenter cohorts. A 70:30 approach (61 ARs; 162 non-ARs) was used for training and testing sets. Microarray data were normalized using a LT-specific vector.

Results.
Random forest modeling on the training set generated a 59-probe classifier distinguishing AR versus non-AR (area under the curve 0.83; accuracy 0.78, sensitivity 0.70, specificity 0.81, positive predictive value 0.54, negative predictive value [NPV] 0.89; F-score 0.61). Using a locked threshold, the classifier performed well on the testing set (accuracy 0.72, sensitivity 0.67, specificity 0.73, positive predictive value 0.48, NPV 0.86; F-score 0.56). Probability scores increased in samples preceding AR versus non-AR, when liver function tests were normal, and decreased following AR treatment (P < 0.001). Ingenuity pathway analysis of the genes revealed a high percentage related to immune responses and liver injury.

Conclusions.
We have developed a blood-based biologically relevant biomarker that can be detected before AR-associated graft injury distinct from LTR never developing AR. Given its high NPV (“rule out AR”), the biomarker has the potential to inform precision-guided immunosuppression minimization in LTRs.
HLA Alleles Cw12 and DQ4 in Kidney Transplant Recipients Are Independent Risk Factors for the Development of Posttransplantation Diabetes
Authors: Phagura Nuvreen , Hussain Azm , Culliford Alice , Hodson James , Evison Felicity , Gallier Suzy , Borrows Richard , Lane Hanna A. , Briggs David , Sharif Adnan 
Published: July 2021

Background.
The association between specific HLA alleles and risk for posttransplantation diabetes (PTDM) in a contemporary and multiethnic kidney transplant recipient cohort is not clear.

Methods.
In this single-center analysis, data were retrospectively analyzed for 1560 nondiabetic kidney transplant recipients at a single center between 2007 and 2018, with median follow-up of 33 mo (interquartile range 8–73). HLA typing methodology was by DNA analysis and reported at the resolution required for the national allocation scheme. Diagnosis of PTDM was aligned with International Consensus recommendations.

Results.
PTDM developed in 231 kidney transplant recipients. Exploring 99 HLA alleles, the presence of Cw12, B52, B38, B58, DQ4, A80, and DR13 and the absence of DQ3 and DR04 were associated with significant increases in PTDM risk. In a multivariable Cox regression model, adjusting for other clinical risk factors for PTDM, the presence of Cw12 (hazard ratio [HR], 1.57; 95% CI, 1.08-2.27; P = 0.017) and DQ4 (HR, 1.78; 95% CI, 1.07-2.96; P = 0.026) were found to be independent risk factors for PTDM. There was also evidence that the presence of B58 increases PTDM risk within the subgroup of recipients of White ethnicity (HR, 5.01; 95% CI, 2.20-11.42; P < 0.001).

Conclusion.
Our data suggest that specific HLA alleles can be associated with PTDM risk, which can be used pretransplantation for PTDM risk stratification. However, association is not causality, and this work requires replication and further investigation to understand underlying biological mechanisms.
Familiarity in Mild Cognitive Impairment as a Function of Patients’ Clinical Outcome 4 Years Later
Authors: Bastin Christine , Bahri Mohamed A. , Giacomelli Fabrice , Miévis Frédéric , Lemaire Christian , Degueldre Christian , Balteau Evelyne , Guillaume Bénédicte , Salmon Eric 
Published: July 2021

Objectives:
The current study addresses the nature of memory difficulties in amnestic mild cognitive impairment (aMCI). Whereas recollection is consistently found to be impaired in aMCI, the results on familiarity are divergent. One potential factor that could explain this divergence in findings relates to the heterogeneity of aMCI patients, so that only those aMCI patients who develop Alzheimer disease (AD) may present with impaired familiarity. The present study aimed at testing this hypothesis.

Methods:
A group of 45 aMCI patients and a group of 26 healthy older adults performed a verbal recognition memory test with the Remember/Know paradigm to assess recollection and familiarity processes. All participants were followed for 4 years with clinical and neuropsychological testing. At the end of follow-up, 22 aMCI patients progressed to AD and 23 aMCI patients remained stable. Initial memory performance was compared between the 3 groups.

Results:
Whereas recollection was severely diminished in all aMCI patients, familiarity accuracy (and consequently global recognition accuracy) was found to be impaired only in aMCI patients who subsequently developed AD.

Conclusion:
These findings suggest that the enrichment of the aMCI population with predementia stage patients may modulate the likelihood to observe familiarity deficits, and impaired global recognition accuracy may accompany incipient AD.
Extent of MGMT promoter methylation modifies the effect of temozolomide on overall survival in patients with glioblastoma: a regional cohort study in Southeast Scotland
Authors: Poon Michael TC , Keni Shivank , Vimalan Vineeth , Ip Chak , Smith Colin , Erridge Sara , Weir Christopher J , Brennan Paul M 
Published: July 2021

AbstractBackgroundMGMT methylation in glioblastoma predicts response to temozolomide but dichotomising methylation status may mask the true prognostic value of quantitative MGMT methylation. This study evaluated whether extent of MGMT methylation interacts with the effect of temozolomide on overall survival.MethodsWe included consecutive glioblastoma patients diagnosed (April 2012-May 2020) at a neuro-oncology centre. All patients had quantitative MGMT methylation measured using pyrosequencing. Those with MGMT methylated tumours were stratified into high and low methylation groups based on a cut-off using Youden index on 2-year survival. Our accelerated failure time survival models included extent of MGMT methylation, age, post-operative Karnofsky performance score, extent of resection, temozolomide regimen and radiotherapy.FindingsThere were 414 patients. Optimal cut-off point using Youden index was 25.9% MGMT methylation. The number of patients in the unmethylated, low and high methylation groups was 223 (53.9%), 81 (19.6%) and 110 (26.6%), respectively. In the adjusted model, high (hazard ratio [HR] 0.60, 95% confidence intervals [CI] 0.46-0.79, p=0.005) and low (HR 0.67, 95%CI 0.50-0.89, p<0.001) methylation groups had better survival compared to unmethylated group. There was no evidence for interaction between MGMT methylation and completed temozolomide regimen (interaction term for low methylation p=0.097; high methylation p=0.071). This suggests no strong effect of MGMT status on survival in patients completing temozolomide regimen. In patients not completing the temozolomide regimen, higher MGMT methylation predicted better survival (interaction terms p<0.001).InterpretationQuantitative MGMT methylation may provide additional prognostic value. This is important when assessing clinical and research therapies.