bluuebunny/crossref_metadata_2025 huggingface dataset:
Scientific Global Nursing Hackathon Experience
Authors: Mevawala Amynah S. , Strunk Faith A. , Haghiri-Vijeh Roya , Corless Inge B. , Ramaswamy Padmavathy , Kamp Kendra J. , Scott Sheryl , Gray Sarah
Published: July 2021

Background

Hackathons are organized to bring together both experienced and novice individuals from a variety of backgrounds to brainstorm creative solutions to complex issues. Hackathons may last from a few hours to a few days and may provide rewards for winning entries.

Purpose

In this article, we describe an experience with a scientific hackathon at an international nursing research congress in Calgary, Canada. We discuss the purpose, process, benefits, and challenges of this hackathon.

Approach

For this article, we have used a descriptive approach.

Outcomes

The scientific hackathon experience united international nursing scholars into a community with a common focus enabling the continuation of mutual, future endeavors.

Conclusion

Hackathons are a means of connecting novices and experts from different backgrounds to develop technology-based solutions for health care issues. The ideas generated at hackathons may be further developed to bring the project to fruition to positively impact health care.
Exploring and Comparing the Structure of Sexual Networks Affected by Neisseria gonorrhoeae Using Sexual Partner Services Investigation and Genomic Data
Authors: Town Katy , Learner Emily R. , Chivukula Vasanta L. , Mauk Kerry , Reimche Jennifer L. , Schmerer Matthew W. , Black Jamie , Pathela Preeti , Bhattacharyya Sanjib , Kerani Roxanne P. , Gieseker Karen E. , Fukuda Acasia , Sankaran Madeline , McNeil Candice J. , Spicknall Ian H. , Raphael Brian H. , St Cyr Sancta B. , Bernstein Kyle , Kersh Ellen N. , Kirkcaldy Robert D. , Schlanger Karen , Gernert Kim M. ,   for the SURRG Working Group
Published: July 2021

Background

Sexual networks are difficult to construct because of incomplete sexual partner data. The proximity of people within a network may be inferred from genetically similar infections. We explored genomic data combined with partner services investigation (PSI) data to extend our understanding of sexual networks affected by Neisseria gonorrhoeae (NG).

Methods

We used 2017–2019 PSI and whole-genome sequencing (WGS) data from 8 jurisdictions participating in Centers for Disease Control and Prevention’s Strengthening the US Response to Resistant Gonorrhea (SURRG) project. Clusters were identified from sexual contacts and through genetically similar NG isolates. Sexual mixing patterns were characterized by describing the clusters by the individual’s gender and gender of their sex partners.

Results

Our study included 4627 diagnoses of NG infection (81% sequenced), 2455 people received a PSI, 393 people were negative contacts of cases, and 495 were contacts with an unknown NG status. We identified 823 distinct clusters using PSI data combined with WGS data. Of cases that were not linked to any other case using PSI data, 37% were linked when using WGS data. Overall, 40% of PSI cases were allocated to a larger cluster when PSI and WGS data were combined compared with PSI data alone. Mixed clusters containing women, men who report sex with women, and men who report sex with men were common when using the WGS data either alone or in combination with the PSI data.

Conclusions

Combining PSI and WGS data improves our understanding of sexual network connectivity.
Comparison of Visual Search Behavior and Decision-making Accuracy in Expert and Novice Fencing Referees
Authors: Babadi Aghakhanpour Niloufar , Abdoli Behrouz , Farsi Alireza , Moeinirad Samira
Published: July 2021

SIGNIFICANCE

Perceptual-cognitive skills are the capacity of athletes to identify task-relevant information in the environment and integrate information with the knowledge available for decision making or controlling motor responses. Gaze behavior is one performance-related perceptual skill and a key factor affecting expertise affecting referee performance.

PURPOSE

The aim of this study was to compare visual search behavior and decision-making accuracy of expert and novice fencing referees.

METHOD

Twenty-eight referees were divided into expert (n = 14) and novice (n = 14) groups. Participants were fitted with mobile eye trackers and participated in tests that consisted of five blocks of 10 video clips. Videos are provided annually by the World Fencing Federation for referee testing.

RESULTS

The results showed a significant difference between the two groups in terms of the accuracy of decision making, number, duration, and location of fixations. Expert referees had higher decision-making accuracy compared with novice referees. Expert referees had fewer fixations than did novice referees. Fixations of expert referees were longer than those of novice referees, and the locations of fixations of expert and novice referees were different.

CONCLUSIONS

According to the results of this study, it can be concluded that the difference in visual search behavior of expert and novice referees was one of the factors contributing to better decision making of expert referees.
A Rare Case of Fatal Self-Poisoning With Sodium Nitrite
Authors: Barranco Rosario , Frigiolini Francesca Maria Elena , Orcioni Giulio Fraternali , Malandrino Mery , Salomone Alberto , Ventura Francesco
Published: July 2021

Fatal sodium nitrite poisonings are unusual in the forensic setting. Suicide by poisoning includes drug overdose, the inhalation of toxic gasses, and poisoning from pesticides and chemical substances. Sodium nitrite is an inorganic compound usually seen as a crystalline powder that is very water soluble. Sodium nitrite is used mostly in the food industry (as a preservative) and in medical field (as an antidote to cyanide poisoning), and if ingested in large enough amounts, it can be fatal.

The ingestion of sodium nitrite can cause severe methemoglobinemia, which is a metabolic disorder characterized by an inability of hemoglobin (which gets oxidized into methemoglobin) to bind (and therefore carry) oxygen. Severe cases of this condition, if not treated, can be fatal.

We describe a case of fatal self-poisoning with sodium nitrite; in particular, the article focuses on the autoptic and toxicological investigations that enabled the correct diagnosis to be established.
Reactive Intralymphovascular Immunoblastic Proliferations Mimicking Aggressive Lymphomas
Authors: Fang Hong , Wang Wei , Zhang Linsheng , Shen Qi , Yuan Ji , Reichard Kaaren K. , Hu Zhihong , Medeiros L. Jeffrey
Published: July 2021

Reactive intralymphovascular immunoblastic proliferations (ILVIPs) may mimic aggressive lymphomas and are rarely reported. Herein, we characterize the clinicopathologic features of 8 patients with ILVIPs. No patients had lymphadenopathy, hepatosplenomegaly, or other findings suggestive of lymphoma. The ILVIPs involved the small or large intestine (n=5) and appendix (n=3). Patients were evaluated for abdominal pain, suspected appendicitis, intestinal obstruction, diverticulitis, volvulus, or tumor resection. Histologic sections showed expanded lymphovascular spaces filled by intermediate to large immunoblasts, positive for CD38, CD43, CD45, CD79a, and MUM1/IRF4 in all cases tested. Five of 6 (83%) cases were positive for CD30. CD20 was weakly positive in a subset of cells in 2 (25%) cases, and PAX5 was weakly positive in 4 (50%) cases. The immunoblasts expressed polytypic light chains in all cases tested. In 1 case, a subset of immunoblasts expressed T-cell markers indicating the presence of a T-cell component. The immunoblasts were negative for ALK, BCL-2, BCL-6, CD10, CD56, CD138, and Epstein-Barr virus–encoded small RNA in all cases assessed. The proliferation index shown by Ki-67 was high with a median of 80%. In all 6 cases tested, the immunoblasts were shown within lymphatic channels highlighted by D2-40. In conclusion, ILVIPs can be rarely observed in patients with inflammatory or infectious conditions, especially in gastrointestinal tract surgical specimens. The immunoblasts are predominantly of B-lineage with a postgerminal center immunophenotype and are located within lymphatic channels. It is essential to distinguish reactive ILVIPs from aggressive lymphomas to avoid unnecessary therapy.
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.

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.

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

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

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.
Prediction of prokaryotic transposases from protein features with machine learning approaches
Authors: Wang Qian , Ye Jun , Xu Teng , Zhou Ning , Lu Zhongqiu , Ying Jianchao
Published: July 2021

Identification of prokaryotic transposases (Tnps) not only gives insight into the spread of antibiotic resistance and virulence but the process of DNA movement. This study aimed to develop a classifier for predicting Tnps in bacteria and archaea using machine learning (ML) approaches. We extracted a total of 2751 protein features from the training dataset including 14852 Tnps and 14852 controls, and selected 75 features as predictive signatures using the combined mutual information and least absolute shrinkage and selection operator algorithms. By aggregating these signatures, an ensemble classifier that integrated a collection of individual ML-based classifiers, was developed to identify Tnps. Further validation revealed that this classifier achieved good performance with an average AUC of 0.955, and met or exceeded other common methods. Based on this ensemble classifier, a stand-alone command-line tool designated TnpDiscovery was established to maximize the convenience for bioinformaticians and experimental researchers toward Tnp prediction. This study demonstrates the effectiveness of ML approaches in identifying Tnps, facilitating the discovery of novel Tnps in the future.
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

Background

MGMT 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.

Methods

We 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.

Findings

There 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).

Interpretation

Quantitative MGMT methylation may provide additional prognostic value. This is important when assessing clinical and research therapies.
Evaluating 87Sr/86Sr isotope ratios and Sr mass fractions in otoliths of different European freshwater fish species as fishery management tool in an Alpine foreland with limited geological variability
Authors: Zitek Andreas , Oehm Johannes , Schober Michael , Tchaikovsky Anastassiya , Irrgeher Johanna , Retzmann Anika , Thalinger Bettina , Traugott Michael , Prohaska Thomas
Published: July 2021

The focus of this study was to assess the potential of otolith microchemistry as a fishery management tool for different European freshwater fish species in an Alpine foreland with a diverse range of different water bodies but low geological variation. 87Sr/86Sr isotope and Sr/Ca ratios in water samples from 26 habitat sites in a pre-alpine catchment region around lake Chiemsee, Germany, an important region for recreational and economic fisheries, were analysed. 87Sr/86Sr isotope ratios and the Sr mass fractions in otoliths of 246 fish out of 16 species were determined using (laser ablation) inductively coupled plasma mass spectrometry ((LA)-ICP-MS). Habitats could be discriminated into three distinct strontium isotope regions (SIGs) and seven clusters with characteristic 87Sr/86Sr isotope and Sr/Ca ratios. The direct comparison of 87Sr/86Sr isotope ratios in water and otolith samples allowed to identify fish that might have been a) migrating b) transferred from other water bodies or c) stocked from fish farms. Sr/Ca ratios in water and the Sr mass fraction in otoliths were highly correlated, although significant differences between species from the same environment could be documented. Sr mass fractions in sagittae of Perca fluviatilis were about 60 % of those in sagittae of Coregonus spp and of lapilli of roach Rutilus rutilus from the same habitats. Different partition factors for water to otolith Sr/Ca mass fractions were determined for different species. Discrimination of fish otoliths by 87Sr/86Sr isotope ratios and Sr mass fractions according to habitat clusters was possible with success rates ranging from 92 % to 100 % for cyprinids, European perch Perca fluviatilis, whitefish Coregonus spp. and European grayling Thymallus thymallus, and was 74 % for salmonids. Otolith microchemistry proved to have great potential to serve as a fishery management tool at smaller spatial scales such as in the studied Alpine foreland when considering the limited variation of 87Sr/86Sr isotope and Sr/Ca ratios, the type and spatial distribution of habitats, and the species and question under investigation.

Highlights

Otolith microchemistry applied in in area with limited geological variability

Fish transferred, stocked or migrated were identified

Regressions between Sr/Ca ratios in water predict Sr mass fractions in otoliths

Species specific Sr discrimination from water into otoliths

European freshwater fish species assigned to habitat clusters of origin
PatchPerPixMatch for Automated 3d Search of Neuronal Morphologies in Light Microscopy
Authors: Mais Lisa , Hirsch Peter , Managan Claire , Wang Kaiyu , Rokicki Konrad , Svirskas Robert R. , Dickson Barry J. , Korff Wyatt , Rubin Gerald M. , Ihrke Gudrun , Meissner Geoffrey W. , Kainmueller Dagmar
Published: July 2021

Studies of individual neurons in the Drosophila nervous system are facilitated by transgenic lines that sparsely and repeatably label respective neurons of interest. Sparsity can be enhanced by means of intersectional approaches like the split-GAL4 system, which labels the positive intersection of the expression patterns of two (denser) GAL4 lines. To this end, two GAL4 lines have to be identified as labelling a neuron of interest. Current approaches to tackling this task include visual inspection, as well as automated search in 2d projection images, of single cell multi-color flip-out (MCFO) acquisitions of GAL4 expression patterns. There is to date no automated method available that performs full 3d search in MCFO imagery of GAL4 lines, nor one that leverages automated reconstructions of the labelled neuron morphologies. To close this gap, we propose PatchPerPixMatch, a fully automated approach for finding a given neuron morphology in MCFO acquisitions of Gen1 GAL4 lines. PatchPerPixMatch performs automated instance segmentation of MCFO acquisitions, and subsequently searches for a target neuron morphology by minimizing an objective that aims at covering the target with a set of well-fitting segmentation fragments. Patch-PerPixMatch is computationally efficient albeit being full 3d, while also highly robust to inaccuracies in the automated neuron instance segmentation. We are releasing PatchPerPixMatch search results for ~30,000 neuron morphologies from the Drosophila hemibrain in ~20,000 MCFO acquisitions of ~3,500 Gen1 GAL4 lines.

Code

https://github.com/Kainmueller-Lab/PatchPerPixMatch

Results

https://pppm.janelia.org
Generalizing Bayesian phylogenetics to infer shared evolutionary events
Authors: Oaks Jamie R. , Wood Perry L. , Siler Cameron D. , Brown Rafe M.
Published: July 2021

Many processes of biological diversification can simultaneously affect multiple evolutionary lineages. Examples include multiple members of a gene family diverging when a region of a chromosome is duplicated, multiple viral strains diverging at a “super-spreading” event, and a geological event fragmenting whole communities of species. It is difficult to test for patterns of shared divergences predicted by such processes, because all phylogenetic methods assume that lineages diverge independently. We introduce a Bayesian phylogenetic approach to relax the assumption of independent, bifurcating divergences by expanding the space of topologies to include trees with shared and multifurcating divergences. This allows us to jointly infer phylogenetic relationships, divergence times, and patterns of divergences predicted by processes of diversification that affect multiple evolutionary lineages simultaneously or lead to more than two descendant lineages. Using simulations, we find the new method accurately infers shared and multifurcating divergence events when they occur, and performs as well as current phylogenetic methods when divergences are independent and bifurcating. We apply our new approach to genomic data from two genera of geckos from across the Philippines to test if past changes to the islands’ landscape caused bursts of speciation. Unlike our previous analyses restricted to only pairs of gecko populations, we find evidence for patterns of shared divergences. By generalizing the space of phylogenetic trees in a way that is independent from the likelihood model, our approach opens many avenues for future research into processes of diversification across the life sciences.

Significance statement

Phylogenetic models have long assumed that lineages diverge independently. Processes of diversification that are of interest in biogeography, epidemiology, and genome evolution, violate this assumption by affecting multiple evolutionary lineages. To relax the assumption of independent divergences and infer patterns of divergences predicted by such processes, we introduce a new way of conceptualizing, modeling, and inferring phylogenetic trees. We apply the new approach to genomic data from geckos distributed across the Philippines, and find support for patterns of shared divergences predicted by repeated fragmentation of the archipelago by interglacial rises in sea level.
The U.S. COVID-19 Trends and Impact Survey, 2020-2021: Continuous real-time measurement of COVID-19 symptoms, risks, protective behaviors, testing and vaccination
Authors: Salomon Joshua A. , Reinhart Alex , Bilinski Alyssa , Chua Eu Jing , La Motte-Kerr Wichada , Rönn Minttu M. , Reitsma Marissa , Morris Katherine Ann , LaRocca Sarah , Farag Tamar , Kreuter Frauke , Rosenfeld Roni , Tibshirani Ryan J.
Published: July 2021

The U.S. COVID-19 Trends and Impact Survey (CTIS) is a large, cross-sectional, Internet-based survey that has operated continuously since April 6, 2020. By inviting a random sample of Facebook active users each day, CTIS collects information about COVID-19 symptoms, risks, mitigating behaviors, mental health, testing, vaccination, and other key priorities. The large scale of the survey – over 20 million responses in its first year of operation – allows tracking of trends over short timescales and allows comparisons at fine demographic and geographic detail. The survey has been repeatedly revised to respond to emerging public health priorities. In this paper, we describe the survey methods and content and give examples of CTIS results that illuminate key patterns and trends and help answer high-priority policy questions relevant to the COVID-19 epidemic and response. These results demonstrate how large online surveys can provide continuous, real-time indicators of important outcomes that are not subject to public health reporting delays and backlogs. The CTIS offers high value as a supplement to official reporting data by supplying essential information about behaviors, attitudes toward policy and preventive measures, economic impacts, and other topics not reported in public health surveillance systems.

Significance statement

The U.S. COVID-19 Trends and Impact Survey (CTIS) has operated continuously since April 6, 2020, collecting over 20 million responses. The largest public health survey ever conducted in the United States, CTIS was designed to facilitate detailed demographic and geographic analyses, track trends over time, and accommodate rapid response to emerging priorities. Using examples of CTIS results illuminating trends in symptoms, risks, mitigating behaviors, testing and vaccination in relation to evolving high-priority policy questions over 12 months of the pandemic, we illustrate the value of online surveys for tracking patterns and trends in COVID outcomes as an adjunct to official reporting, and showcase unique insights that would not be visible through traditional public health reporting.
A network-based approach reveals the dysregulated transcriptional regulation in non-alcohol fatty liver disease
Authors: Yang Hong , Arif Muhammad , Yuan Meng , Li Xiangyu , Shong Ko Eun , Turkez Hasan , Nielsen Jens , Uhlén Mathias , Borén Jan , Cheng Zhang , Mardinoglu Adil
Published: July 2021

Non-alcohol-related fatty liver disease (NAFLD) is a leading cause of chronic liver disease worldwide. We performed network analysis to investigate the dysregulated biological processes in the disease progression and revealed the molecular mechanism underlying NAFLD. Based on network analysis, we identified a highly conserved disease-associated gene module across three different NAFLD cohorts and highlighted the predominant role of key transcriptional regulators associated with lipid and cholesterol metabolism. In addition, we revealed the detailed metabolic differences between heterogenous NAFLD patients through integrative systems analysis of transcriptomic data and liver-specific genome-scale metabolic model. Furthermore, we identified transcription factors (TFs), including SREBF2, HNF4A, SREBF1, YY1 and KLF13, showing regulation of hepatic expression of genes in the NAFLD-associated modules and validated the TFs using data generated from a mouse NAFLD model. In conclusion, our integrative analysis facilitated our understanding of the regulatory mechanism of these perturbed TFs and associated biological processes.
Role of non-specific interactions in the phase-separation and maturation of macromolecules
Authors: Krishnan Rakesh , Ranganathan Srivastav , Maji Samir K , Padinhateeri Ranjith
Published: July 2021

Phase separation of biomolecules could be mediated by both specific and non-specific interactions. How the interplay between non-specific and specific interactions along with polymer entropy influences phase separation is an open question. We address this question by simulating self-associating molecules as polymer chains with a short core stretch that forms the specifically interacting functional interface, and longer non-core regions that participate in non-specific/promiscuous interactions. Our results show that the interplay of specific (strength, ϵsp) and non-specific interactions (strength, ϵns) could result in phase separation of polymers and its transition to solid-like aggregates (mature state). In the absence of ϵns, the polymer chains do not dwell long enough in the vicinity of each other to undergo phase separation and transition into a mature state. On the other hand, in the limit of strong ϵns, the assemblies cannot transition into the mature state and form a non-specific assembly, suggesting an optimal range of interactions favoring mature multimers. In the scenario where only a fraction (Nfrac) of the non-core regions participate in attractive interactions, we find that a slight modifications to either ϵns or Nfrac can result in a dramatically altered self-assembled states. Using a combination of heterogeneous and homogeneous mix of polymers, we establish how this interplay between interaction energies dictates the propensity of biomolecules to find the correct binding partner at dilute concentrations in crowded environments.

Author Summary

Biological function relies on the ability of biomolecules to bind to specific interaction partners. In the crowded cellular milieu, the process of biomolecules binding to specific interaction partners to carry out a function is non-trivial. A mere diffusion-limited meeting of interaction partners in space does not ensure biomolecular function. Rather, even when in contact these molecules have to find the correct orientations to carry out function. Further, for dynamic biomolecules such as polymers, the functional configuration is often one of several possible configurations. In this scenario, assuming the functional configuration after binding involves overcoming of a significant entropic barrier. Therefore, the interacting biomolecules have to dwell in contact long enough before they reorganize to find the functional orientation! While functional contacts offer an enthalpic gain, they are often only a small fraction of all protein-protein interactions. Therefore, in this paper, we study the role played by non-functional, promiscuous interactions in shaping the thermodynamics and kinetics of formation of specific interactions. Our results suggest that there exists an optimal range of non-specific interaction strengths which promotes the process of biomolecular complexes finding the functional configurations.