bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Real-Time Speech Magnetic Resonance Imagings With Perceptual Speech Analysis in Evaluation Velopharyngeal Sphincter Function
Authors: Yildiz-Deger Tugba Feryal , Cinar Fatih , Baghaki Semih , Demiroz Anil , Polat Zahra , Kocer Naci , Aydin Yagmur
Published: July 2021

Identifying substantial data and their normative values related to velopharyngeal structures in cleft palate patients may have clinical significance, in order to selection of surgical intervention and prediction of postsurgical outcomes. Previous studies are lack of referring certain anatomic locations or distances that may have affect on speech intelligibility, especially in dynamic state. The aim of this study is to investigate effectiveness of magnetic resonance imagings on the velopharyngeal sphincter function and the correlation with speech intelligibility after functional cleft palate repair. Seventeen patients with repaired cleft palate by single surgeon were enrolled in this study.

Quantitative velopharyngeal measures from the oblique coronal plane and midsagittal plane in static and dynamic positions were collected. Patients’ speech intelligibility was evaluated by using Pittsburgh Weighted Speech Scale and nasalance score was also measured. Correlation analysis methods were used for evaluating relation between MRI gathered measurements and speech intelligibility scores for determining

consequential data.

Our study shows that the velar knee-posterior pharyngeal wall distance measurement while explosive sound production is the most related data with speech intelligibility. Although future works with more sample number is needed, according to current study the authors think magnetic resonance imagings is a very helpful method in providing reliable information.
Results of Lip Adhesion in Wide Unilateral Complete Cleft Lip Patients
Authors: Lee Hyun Seung , Bae Yong Chan , Seo Hyung Joon
Published: July 2021

Long-term follow-up results of many surgical techniques for lip adhesion are unavailable. Thus, we report the surgical results of patients who underwent lip adhesions performed by a single surgeon. We retrospectively analyzed two-dimensional photographs of 29 patients aged 1 year who underwent lip adhesion and definite lip repair. Among these patients, we analyzed the photographs of 20 patients aged 6 years who underwent secondary rhinoplasty. The ratio of the cleft side length to the noncleft side length was calculated. Only the upper lip length in the photographs of 1-year-olds was measured; both the upper lip and nose lengths were measured in the photographs of 6-year-olds. Lip width, vermilion height, and medial lip height on the cleft and non-cleft sides of 1-year-olds were not significantly different; the alar base width ratio was 1.17 ± 0.15, and the lateral lip height ratio was 0.91 ± 0.09 (P < 0.001). No significant differences were observed in lip width and vermilion height between the cleft and non-cleft sides of the upper lip of 6-year-olds; the alar base width ratio was 1.22 ± 0.16, medial lip height ratio was 1.11 ± 0.11, and lateral lip height ratio was 0.89 ± 0.09 (P < 0.05). There were no significant differences in the alar projection and nasal dome height on the cleft side of the nose; the nostril height and width ratios were 0.82 ± 0.11 and 1.31 ± 0.21 (P < 0.001), respectively. These consecutively performed lip adhesions for patients with wide unilateral complete cleft lip resulted in excellent long-term results. Therefore, lip adhesion for wide unilateral complete cleft lip is a reasonable alternative to presurgical molding.
Correction of Severe Facial Asymmetry in Patients With Unilateral Craniofacial Microsomia Using Computer-Aided Design/Computer-Aided Manufacturing Technology: An Evaluation of Postsurgical Results
Authors: Shetye Pradip R. , Grayson Barry H. , McCarthy Joseph G.
Published: July 2021

This is a retrospective study to evaluate the postsurgical position of the maxilla and mandible in 5 matured craniofacial patients with unilateral craniofacial microsomia who underwent 2 jaw surgical procedures using computerized surgical planning. The craniofacial surgeon and orthodontist completed the virtual surgical treatment plan with a biomedical engineer's assistance via a web meeting. The treatment plan of each patient included 2 jaw surgery with genioplasty. At the maxillary dental midline, the planned mean advancement was 4 mm; yaw, a rotational correction towards the unaffected side was 4.96 mm; and impaction was 2.74 mm. The mean advancement measured at point B was 10.5 mm, and the rotational correction towards the unaffected side was 6.58 mm. The mean advancement following genioplasty was 8.43 mm, and the mean transverse correction was 6.33 mm towards the midsagittal plane. The intermediate surgical splint, final surgical splint, bone graft templates, and cutting guides were constructed utilizing computer-aided design/computer-aided manufacturing technology. The surgeon executed the treatment plan in the operating room using appropriate computer-generated guides and splints. A postsurgical cone-beam computed tomography scan was obtained and superimposed on the surgical treatment plan using Simplant OMS 10.1 software. The cranial base was used as a reference for superimposition. Three-dimensional color-coded displacement maps were generated to visually and quantitatively assess the surgical outcome. There was a mean error of 0.88 mm (+0.30) for the position of the maxillary anatomical structures from the planned position, and the anterior mandibular anatomical structures were on average 0.96 mm (+0.26) from the planned position.
Evaluation of Nasal Function and Upper Airway Morphology After Bi-Maxillary Surgery Using Rhinomanometry and Computed Tomography
Authors: Tsutsui Takamitsu , Moroi Akinori , Yoshizawa Kunio , Takayama Akihiro , Saito Yuki , Ueki Koichiro
Published: July 2021

Purpose:

This study was performed to evaluate changes in nasal airflow, nasal airway resistance, nasal cross-sectional area, pharyngeal horizontal area, nasopharyngeal and oropharyngeal volume following Le Fort I osteotomy (L1) impaction with sagittal split ramus osteotomy (SSRO) in classes II and III.

Materials and Methods:

The subjects consisted of 35 patients (6 males and 29 females, 70 sides) 17 of which were diagnosed as class II and 18 as class III who underwent L1 and SSRO. Nasal airflow and resistance were measured using the rhinomanometry system (GM NR-6 EXECUTIVE) before and at 1 and 6 months after surgery. Nasal, cross-sectional area, and volume were measured using a 3-dimensional computed tomography respectively, before and 1-year after surgery.

Results:

Although a significant decrease was found in nasal volume after surgery (P = 0.0042), there was no difference between before and after surgery in the nasal airway resistance in class II.

A significant decrease in nasal volume was found after surgery (P = 0.0005) and there were no postoperative changes in both nasal airflow and resistance in class III.

Conclusion:

The study suggested that L1 impaction with SSRO did not worsen nasal function such as nasal airflow and nasal airway resistance, although nasal volume significantly decreased in both groups.
Relationship Between Masticatory Muscle Size and Bone Regeneration After Mandibular Angle Osteotomy
Authors: Huang Yuanliang , Yang Liya , Lin Yanxian , Mu Lin , Zhao Minghao , Ma Xiaoyang , Teng Li
Published: July 2021

Mandibular angle osteotomy with outer cortex grinding has become the preferred cosmetic procedure for correcting square faces. After surgery, bone hyperplasia at the mandibular angle affects the operation result. This study evaluated the effect of the masticatory muscles on bone repair. From January 2016 to January 2019, patients who underwent mandibular angle osteotomy with outer cortex grinding were retrospectively reviewed. Computed tomography data of these patients were collected, and the bone volume of the mandibular angle changes and its correlation with masticatory muscle morphology were analyzed. Computed tomography data measurement results showed that a large amount of bone in the mandibular angle area was removed by the operation; however, the long-term follow-up results showed that there was bone hyperplasia in the mandibular angle areas. Compared with the immediate postoperative bone volume, the difference was statistically significant (P < 0.01). The thickness and cross-sectional area of the masseter muscle were significantly related to bone regeneration (P < 0.01). This study suggests that mandibular angle osteotomy with outer cortex grinding could ablate the symptoms of a prominent mandibular angle; however, muscle-related bone hyperplasia in the mandibular angle area after surgery was a non-negligible event, which may significantly compromise surgical outcomes.
Assessing the Safety of a Novel Neonatal Anesthesia Protocol: A Review of 101 Patients With Early Cleft Lip Repair
Authors: Wlodarczyk Jordan R. , Higuchi Emma C. , Liu Alice , Urata Marcus M. , Gabreel Waleed , Wolfswinkel Erik M. , Lau Jennifer , Matar Marla , Magee William P. , Urata Mark M. , Hammoudeh Jeffrey A.
Published: July 2021

Purpose:

Our study introduces a novel anesthetic protocol for neonates without using volatile agents with the goal to minimize potentially neurotoxic and pro-apoptotic agents. The authors evaluated the short-term safety and efficacy of our anesthetic protocol in patients undergoing early cleft lip repair (ECLR).

Methods:

A retrospective review of ECLR patients who underwent repair before 2.5 months of age within the last 4.3 years was performed. This sample was comprised of 2 groups, those who received either a standard volatile gas-based regimen or a dexmedetomidine-based neonatal anesthetic protocol (DBNAP). Patient demographics, medication dosing, anesthetic time (induction to extubation), major and minor complications, and medication side effects were compared between the 2 cohorts.

Results:

A total of 101 patients underwent ECLR. All patients were American Society of Anesthesiologists class 1 or 2. Mean age at surgery was 31 ± 13 days and mean anesthetic time was 179 ± 36 minutes. DBNAP was used in 65 patients while the standard anesthetic protocol was used in 36 patients. Patient weight was significantly lower in the DBNAP group (4.01 ± 0.61 versus 4.38 ± 0.72 kg, P 
= 0.007). There were no significant differences between the 2 cohorts when comparing anesthetic time, emergence time, complication rate, or medication side effects.

Conclusion:

For patients undergoing ECLR, DBNAP is perioperatively equivalent to the anesthetic standard of care, demonstrating no major complications and acceptable rates of minor complications and medication side effects.
Effect of One-Stage Bilateral Cleft Lip, Nose, and Alveolus Repair Following Nasoalveolar Molding on the Premaxilla Position at Preadolescence: An 8-Year Retrospective Study
Authors: Traube Isaac M. , Cutting Court B. , Grayson Barry H. , Shetye Pradip R.
Published: July 2021

Background/Purpose:

This paper describes the changes in maxillary arch morphology in infants with bilateral cleft lip and palate (BCLP) following nasoalveolar molding (NAM) and with follow up to assess the need for secondary alveolar bone grafting (ABG) and premaxillary repositioning surgery at preadolescence.

Methods/Description:

Treatment records of infants with BCLP treated with NAM between 2003 and 2013 were reviewed. Patients with complete BCLP who underwent NAM and had complete sets of maxillary casts at T 0 pre-NAM (mean = 27 days), T 1 post-NAM (mean = 6 months and 5 days), and T 2 before palate surgery (mean = 11 months and 15 days) were included. The sample comprised 23 infants (18 male, 5 female). Casts were digitized and analyzed using three dimensional software. The need for secondary ABG and premaxillary repositioning surgery was assessed at preadolescent follow-up (mean = 8.3 years).

Results:

Cleft width was reduced on average by 4.73 mm (SD±3.15 mm) and 6.56 mm (SD±4.65) on the right and left sides, respectively. At T 1, 13 (56.52%) patients underwent bilateral gingivoperiosteoplasty (GPP), 8 (34.78%) patients unilateral GPP, and 2 patients (8.7%) did not undergo GPP. 34/46 clefts sites (73.91%) underwent GPP while 12 (26.08%) did not. At preadolescent follow-up of 19 patients, 7 patients (36.84%) did not need ABG on either side, 8 (42.10%) needed ABG on 1 side, and 4 (21.05%) needed ABG on both sides. None of the patients needed premaxillary repositioning surgery.

Conclusions:

Nasoalveolar molding treatment significantly improves the position of the premaxilla before primary repair, and there is a significant reduction in the need for secondary ABG and premaxillary repositioning surgery at preadolescence.
Robotic Kidney Transplant: The Modern Era Technical Revolution
Authors: Tzvetanov Ivo G. , Tulla Kiara A. , Di Cocco Pierpaolo , Spaggiari Mario , Benedetti Enrico
Published: July 2021

Since the mid 20th century, transplantation has been a fast-developing field of contemporary medicine. The technical aspects of transplant operations were developed in the 1950s, with little significant change for >50 y. Those techniques allowed completion of various organ transplants and successful patient outcomes, but they also carried the inherent disadvantages of open surgery, such as postoperative pain, wound complications and infections, and prolonged length of hospital stay. The introduction and adoption of minimally invasive surgical techniques in the early 1990s to various surgical specialties including general, gynecologic, and urologic surgery led to significant improvements in postoperative patient care and outcomes. Organ transplantation, with its precision demanding vascular anastomoses, initially had been considered infeasible to accomplish with conventional laparoscopic devices. The institution of robotic surgical technology in the late 1990s and its subsequent wide utilization in fields of surgery changed its accessibility and acceptance. With the steady camera, 3D views, and multidirectional wrist motions, surgical robotics opened new horizons for technically demanding surgeries such as transplantation to be completed in a minimally invasive fashion. Furthermore, the hope was this technique could find a niche to treat patients who otherwise are not deemed surgical candidates in many fields including transplantation. Here in, robotics in kidney transplantation and its ability to help provide equity through access to transplantation will be discussed.
A 2-fold Approach to Polyoma Virus (BK) Nephropathy in Kidney Transplants: Distinguishing Direct Virus Effects From Cognate T Cell–mediated Inflammation
Authors: Halloran Philip F. , Madill-Thomsen Katelynn S. , Böhmig Georg A. , Myslak Marek , Gupta Gaurav , Kumar Dhiren , Viklicky Ondrej , Perkowska-Ptasinska Agnieszka , Famulski Konrad S.
Published: July 2021

Background.

BK nephropathy (BKN) in kidney transplants diagnosed by histology is challenging because it involves damage from both virus activity and cognate T cell–mediated inflammation, directed against alloantigens (rejection) or viral antigens. The present study of indication biopsies from the Integrated Diagnostic System in the International Collaborative Microarray Study Extension study measured major capsid viral protein 2 (VP2) mRNA to assess virus activity and a T cell–mediated rejection (TCMR) classifier to assess cognate T cell–mediated inflammation.

Methods.

Biopsies were assessed by local standard-of-care histology and by genome-wide microarrays and Molecular Microscope Diagnostic System (MMDx) algorithms to detect rejection and injury. In a subset of 102 biopsies (50 BKN and 52 BKN-negative biopsies with various abnormalities), we measured VP2 transcripts by real-time polymerase chain reaction.

Results.

BKN was diagnosed in 55 of 1679 biopsies; 30 had cognate T cell–mediated activity assessed by by MMDx and TCMR lesions, but only 3 of 30 were histologically diagnosed as TCMR. We developed a BKN probability classifier that predicted histologic BKN (area under the curve = 0.82). Virus activity (VP2 expression) was highly selective for BKN (area under the curve = 0.94) and correlated with acute injury, atrophy–fibrosis, macrophage activation, and the BKN classifier, but not with the TCMR classifier. BKN with molecular TCMR had more tubulitis and inflammation than BKN without molecular TCMR. In 5 BKN cases with second biopsies, VP2 mRNA decreased in second biopsies, whereas in 4 of 5 TCMR classifiers, scores increased. Genes and pathways associated with BKN and VP2 mRNA were similar, reflecting injury, inflammation, and macrophage activation but none was selective for BKN.

Conclusions.

Risk–benefit decisions in BKN may be assisted by quantitative assessment of the 2 major pathologic processes, virus activity and cognate T cell–mediated inflammation.
Recruitment hotspots and bottlenecks mediate the distribution of corals on a Caribbean reef
Authors: Edmunds Peter J.
Published: July 2021

Recruitment hotspots are locations where organisms are added to populations at high rates. On tropical reefs where coral abundance has declined, recruitment hotspots are important because they have the potential to promote population recovery. Around St. John, US Virgin Islands, coral recruitment at five sites revealed a hotspot that has persistent for 14 years. Recruitment created a hotspot in density of juvenile corals that was 600 m southeast of the recruitment hotspot. Neither hotspot led to increased coral cover, thus revealing the stringency of the demographic bottleneck impeding progression of recruits to adult sizes and preventing population growth. Recruitment hotspots in low-density coral populations are valuable targets for conservation and sources of corals for restoration.
RUFY4 exists as two translationally regulated isoforms, that localize to the mitochondrion in activated macrophages
Authors: Valečka Jan , Camosseto Voahirana , McEwan David G. , Terawaki Seigo , Liu Zhuangzhuang , Strock Eva , Almeida Catarina R. , Su Bing , Dikic Ivan , Liang Yinming , Gatti Evelina , Pierre Philippe
Published: July 2021

We report here that RUFY4, a newly characterized member of the ‘RUN and FYVE domain-containing’ family of proteins previously associated with autophagy enhancement, is highly expressed in alveolar macrophages (AM). We show that RUFY4 interacts with mitochondria upon stimulation by microbial-associated molecular patterns of AM and dendritic cells. RUFY4 interaction with mitochondria and other organelles is dependent on a previously uncharacterized OmpH domain located immediately upstream of its C-terminal FYVE domain. Further, we demonstrate that
rufy4
messenger RNA can be translated from an alternative translation initiation codon, giving rise to a N-terminally truncated form of the molecule lacking most of its RUN domain and with enhanced potential for its interaction with mitochondria. Our observations point towards a role of RUFY4 in selective mitochondria clearance in activated phagocytes.
Having a stake in the future and perceived population density influence intergenerational cooperation
Authors: Chang Chia-chen , Kristensen Nadiah P. , Le Nghiem Thi Phuong , Tan Claudia L. Y. , Carrasco L. Roman
Published: July 2021

Intergenerational common-pool resource games represent a new experimental paradigm in which the current generation's decision to cooperate or defect influences future generations who cannot reciprocate, providing key insights for sustainability science. We combine experimental and theoretical approaches to assess the roles of having a stake in the future (50% chance to pass the resource on to themselves in the next generation) and reminders of the presence of others (exposure to people-chatting sounds) on intergenerational cooperation. We find that, as expected, having a stake in the future increases cooperation with future generations, except when participants are also exposed to people-chatting sounds. We hypothesize that this interaction effect occurs because people-chatting sounds trigger a perception of large group size, which reduces the chance of individuals and their descendants benefiting from the pool in the future, thus reducing cooperation. Our results highlight the context-dependent effect of having a future stake on intergenerational cooperation for resource sustainability, and suggest an area of future work for environmental messaging.
Weekly population testing could stop this pandemic and prevent the next
Authors: Peto Julian
Published: July 2021

The rapid spread of the SARS-COV-2 delta variant in the UK despite high vaccination coverage will inevitably accelerate when social restrictions end unless testing and contact tracing become much more effective. To minimize further social and economic damage, the effect on R of introducing weekly population testing as social restrictions are relaxed should be evaluated. The large increase in testing capacity required can be achieved with self-taken saliva samples analysed by RT-LAMP in local testing facilities. The costs and effectiveness can be evaluated in whole-city demonstration studies. A local population register in each city or district is essential to issue weekly invitations, manage sample collection, monitor results and achieve rapid notification of households and other contacts when a test is positive. In the UK, weekly test invitations should be managed, like vaccination invitations, by the NHS, with social and financial support for quarantined households to make self-isolation acceptable. A framework for effective population testing that had been established and evaluated during this pandemic could be rapidly reinstated to suppress the next pandemic while vaccines for a new and perhaps more deadly virus are developed and rolled out.
Spatiotemporal droplet dispersion measurements demonstrate face masks reduce risks from singing: results from the COvid aNd FacEmaSkS Study (CONFESS)
Authors: Ho Kai Man Alexander , Davies Hywel , Epstein Ruth , Bassett Paul , Hogan Áine , Kabir Yusuf , Rubin John , Shin Gee Yen , Reid Jonathan P. , Torii Ryo , Tiwari Manish K. , Balachandran Ramanarayanan , Lovat Laurence B.
Published: July 2021

Background

COVID-19 has restricted singing in communal worship. We sought to understand variations in droplet transmission and the impact of wearing face masks.

Methods

Using rapid laser planar imaging, we measured droplets while participants exhaled, said ‘hello’ or ‘snake’, sang a note or ‘Happy Birthday’, with and without surgical face masks. We measured mean velocity magnitude (MVM), time averaged droplet number (TADN) and maximum droplet number (MDN). Multilevel regression models were used.

Results

In 20 participants, sound intensity was 71 Decibels (dB) for speaking and 85 dB for singing (p<0.001). MVM was similar for all tasks with no clear hierarchy between vocal tasks or people and >85% reduction wearing face masks. Droplet transmission varied widely, particularly for singing. Masks decreased TADN by 99% (p<0.001) and MDN by 98% (p<0.001) for singing and 86-97% for other tasks. Masks reduced variance by up to 48%. When wearing a mask, neither singing task transmitted more droplets than exhaling.

Conclusions

Wide variation exists for droplet production. This significantly reduced when wearing face masks. Singing during religious worship wearing a face mask appears as safe as exhaling or talking. This has implications for UK public health guidance during the COVID-19 pandemic.
Impacts of COVID-19 public measures on country-level trade flows: Global panel regression analysis
Authors: Szabo Sylvia , Srisawasdi Worawat , Tsusaka Takuji W , Kadigi Reuben M.J. , Vause James , Burgess Neil D.
Published: July 2021

As of 10 July 2021, there have been over 186 million cases of COVID-19 and more than four million died as a result of this disease. The COVID-19 outbreak has also contributed to tremendous global decline in trade flows. The rapid spread of COVID-19 and the measures implemented by governments to contain the pandemic have had serious consequences for the world’s economies. While the pandemic has affected the international movement of people, goods and services, there is still limited systematic research regarding the possible associations between the COVID-19 measures on countries’ international trade flows. To fill this gap, we conducted regression analysis based on country level time series data from the United Nations and World Bank datasets. The results of the random effects panel regression models show that, the country import and export values are positively affected by health-related policies, while there is a negative association between stringency measures and import and export values. More specifically, school closing, stay-at-home requirements, and testing policy measures were found to have significant negative effects on countries’ trade values. In contrast, facial covering policies were found to have significant positive effects on countries’ import, export and total trade values.
Suicidal Ideation in Dementia: Associations with Neuropsychiatric Symptoms and Subtype Diagnosis
Authors: Naismith Hamish , Howard Robert , Stewart Robert , Pitman Alexandra , Mueller Christoph
Published: July 2021

Objectives

To investigate factors associated with suicidal ideation around the time of dementia diagnosis. We hypothesised that relatively preserved cognition, co-occurring physical and psychiatric disorders, functional impairments and dementia diagnosis subtype would be associated with higher risk of suicidal ideation.

Design

Cross-sectional study using routinely collected electronic mental healthcare records.

Setting

National Health Service secondary mental healthcare services in South London, United Kingdom, which serve a population of over 1.36 million residents.

Participants

Patients who received a diagnosis of dementia (Alzheimer’s, vascular, mixed Alzheimer’s/vascular or dementia with Lewy bodies) between 1/1/2007-30/6/2016. 11,787 people with dementia were identified during the observation period.

Measurements

A natural language processing algorithm was used to identify recorded clinician statements about suicidal ideation around the time of dementia diagnosis.

Sociodemographic and clinical characteristics were also measured around the time of diagnosis. We compared people diagnosed with non-Alzheimer’s dementia to those with Alzheimer’s and used statistical models to adjust for putative confounders.

Results

4.8% of patients identified with dementia had recorded suicidal ideation. Recorded suicidal ideation was almost twice as common in dementia with Lewy bodies compared to other dementia diagnoses studied. After adjusting for sociodemographic and clinical factors, dementia with Lewy bodies, physical illnesses or disability and neuropsychiatric symptoms were significantly associated with suicidal ideation. Mini-Mental State Examination score at diagnosis was not associated with suicidal ideation.

Conclusions

Although completed suicide is rare, suicidal ideation is present in sufficient proportions of people with dementia to justify treatment of potentially modifiable risk factors within dementia care pathways.
Bias, precision and timeliness of historical (background) rate comparison methods for vaccine safety monitoring: an empirical multi-database analysis
Authors: Li Xintong , Lai Lana YH , Ostropolets Anna , Arshad Faaizah , Tan Eng Hooi , Casajust Paula , Alshammari Thamir M , Duarte-Salles Talita , Minty Evan P , Areia Carlos , Pratt Nicole , Ryan Patrick B , Hripcsak George , Suchard Marc A , Schuemie Martijn J , Prieto-Alhambra Daniel
Published: July 2021

Using real-world data and past vaccination data, we conducted a large-scale experiment to quantify bias, precision and timeliness of different study designs to estimate historical background (expected) compared to post-vaccination (observed) rates of safety events for several vaccines. We used negative (not causally related) and positive control outcomes. The latter were synthetically generated true safety signals with incident rate ratios ranging from 1.5 to 4.

Observed vs. expected analysis using within-database historical background rates is a sensitive but unspecific method for the identification of potential vaccine safety signals. Despite good discrimination, most analyses showed a tendency to overestimate risks, with 20%-100% type 1 error, but low (0% to 20%) type 2 error in the large databases included in our study. Efforts to improve the comparability of background and post-vaccine rates, including age-sex adjustment and anchoring background rates around a visit, reduced type 1 error and improved precision but residual systematic error persisted. Additionally, empirical calibration dramatically reduced type 1 to nominal but came at the cost of increasing type 2 error.

Our study found that within-database background rate comparison is a sensitive but unspecific method to identify vaccine safety signals. The method is positively biased, with low (<=20%) type 2 error, and 20% to 100% of negative control outcomes were incorrectly identified as safety signals due to type 1 error. Age-sex adjustment and anchoring background rate estimates around a healthcare visit are useful strategies to reduce false positives, with little impact on type 2 error.

Sufficient sensitivity was reached for the identification of safety signals by month 1-2 for vaccines with quick uptake (e.g., seasonal influenza), but much later (up to month 9) for vaccines with slower uptake (e.g., varicella-zoster or papillomavirus). Finally, we reported that empirical calibration using negative control outcomes reduces type 1 error to nominal at the cost of increasing type 2 error.
Metabolomic Profiles of Scleroderma-PAH are different than idiopathic PAH and associated with worse clinical outcomes
Authors: Alotaibi Mona , Shao Junzhe , Pauciulo Michael W. , Nichols William C. , Hemnes Anna R. , Malhotra Atul , Kim Nick H. , Yuan Jason X.-J. , Fernandes Timothy , Kerr Kim M. , Alshawabkeh Laith , Desai Ankit A. , Watrous Jeramie D. , Cheng Susan , Long Tao , Chan Stephen Y. , Jain Mohit
Published: July 2021

The molecular signature in patients with systemic sclerosis (SSc)-associated pulmonary arterial hypertension (SSc-PAH) relative to idiopathic pulmonary arterial hypertension (IPAH) remain unclear. We hypothesize that patients with SSc-PAH exhibit unfavorable bioactive metabolite derangements compared to IPAH that contribute to their poor prognosis and limited response to therapy. We sought to determine whether circulating bioactive metabolites are differentially altered in SSc-PAH versus IPAH.

Plasma biosamples from 415 patients with SSc-PAH (cases) and 1115 patients with IPAH (controls) were included in the study. Over 700 bioactive metabolites were assayed in plasma samples from independent discovery and validation cohorts using liquid chromatography - mass spectrometry (LC-MS) based approaches. Regression analyses were used to identify metabolites which exhibited differential levels between SSc-PAH and IPAH and associated with disease severity.

From among hundreds of circulating bioactive molecules, twelve metabolites were found to distinguish between SSc-PAH and IPAH, as well as associate with PAH disease severity. SSc-PAH patients had increased levels of fatty acid metabolites including lignoceric acid and nervonic acid, as well as kynurenine, polyamines, eicosanoids/oxylipins and sex hormone metabolites relative to IPAH. In conclusion, SSc-PAH patients are characterized by an unfavorable bioactive metabolic profile that may explain the poor and limited response to therapy. These data provide important metabolic insights into the pathogenesis of SSc-PAH.

Take Home Message

Among patients with PAH, those with SSc-PAH suffer disproportionately worse outcomes and disease course. This study represents the most comprehensive analysis of bioactive metabolites profiling comparing two subgroups of PAH. The findings shed light on key differences between SSc-PAH and IPAH that provide important metabolic insight into the disease pathogenesis.
The risk of drug resistance during long-acting antimicrobial therapy
Authors: Nande Anjalika , Hill Alison L.
Published: July 2021

The emergence of drug resistance during antimicrobial therapy is a major global health problem, especially for chronic infections like HIV, hepatitis B and C, and TB. Sub-optimal adherence to long-term treatment is an important contributor to resistance risk. New long-acting drugs are being developed for weekly, monthly, or less frequent dosing to improve adherence, but may lead to long-term exposure to intermediate drug levels. In this study we analyze the effect of dosing frequency on the risk of resistance evolving during time-varying drug levels. We find that long-acting therapies can increase, decrease, or have little effect on resistance, depending on the source (pre-existing or de novo) and degree of resistance, and rates of drug absorption and clearance. Long-acting therapies with rapid drug absorption, slow clearance, and strong WT inhibition tend to reduce resistance risks due to partially resistant strains in the early stages of treatment even if they don’t improve adherence. However, if subpopulations of microbes persist and can reactivate during suboptimal treatment, longer-acting therapies may substantially increase the resistance risk. Our results show that drug kinetics affect selection for resistance in a complicated manner, and that pathogen-specific models are needed to evaluate the benefits of new long-acting therapies.
Alterations to the gut microbiome after sport-related concussion and subconcussive impacts in a collegiate football players cohort
Authors: Soriano Sirena , Curry Kristen , Sadrameli Saeed , Wang Qi , Nute Michael , Reeves Elizabeth , Kabir Rasadul , Wiese Jonathan , Criswell Amber , Schodrof Sarah , Britz Gavin , Gadhia Rajan , Podell Kenneth , Treangen Todd , Villapol Sonia
Published: July 2021

Concussions, both single and repetitive, during contact sports cause brain and body alterations in athletes. The role of the brain-gut connection and changes in the microbiota have not been well established after a head injury or concussion-related health consequences. We recruited 33 Division I Collegiate football players and collected blood, stool, and saliva samples throughout the athletic season. Analysis of the gut microbiome reveals a decrease in abundance for two bacterial species, Eubacterium rectale, and Anaerostipes hadrus, after a diagnosed concussion. No significant differences were found regarding the salivary microbiome. Serum biomarker analysis shows an increase in GFAP blood levels in athletes during athletic activity. Additionally, S100β and SAA blood levels were positively correlated with the abundance of Eubacterium rectale species among athletes exposed to subconcussive impacts. These novel findings provide evidence that detecting changes in the gut microbiome may pave the way for improved concussion diagnosis following head injury.
Plasma P-selectin is an early marker of thromboembolism in COVID-19
Authors: Fenyves Bánk G. , Mehta Arnav , Kays Kyle R. ,   MGH COVID-19 Collection & Processing Team, Goldberg Marcia B. , Hacohen Nir , Filbin Michael R.
Published: July 2021

Coagulopathy and thromboembolism are known complications of SARS-CoV-2 infection. The mechanisms of COVID-19-associated hematologic complications involve endothelial cell and platelet dysfunction and have been intensively studied. We leveraged a prospectively collected acute COVID-19 biorepository to study the association of plasma levels of a comprehensive list of coagulation proteins with the occurrence of venous thromboembolic events (VTE). We included in our analysis 305 subjects with confirmed SARS-CoV-2 infection who presented to an urban Emergency Department with acute respiratory distress during the first COVID-19 surge in 2020; 13 (4.2%) were subsequently diagnosed with venous thromboembolism during hospitalization. Serial samples were obtained and assays were performed on two highly-multiplexed proteomic platforms. Nine coagulation proteins were differentially expressed in patients with thromboembolic events. P-selectin, a cell adhesion molecule on the surface of activated endothelial cells, displayed the strongest association with the diagnosis of VTE, independent of disease severity (p=0.0025). This supports the importance of endothelial activation in the mechanistic pathway of venous thromboembolism in COVID-19. P-selectin together with D-dimer upon hospital presentation provided better discriminative ability for VTE diagnosis than D-dimer alone.
DeepOS: pan-cancer prognosis estimation from RNA-sequencing data
Authors: Pavageau M. , Rebaud L. , Morel D. , Christodoulidis S. , Deutsch E. , Massard C. , Vanacker H. , Verlingue L.
Published: July 2021

RNA-sequencing (RNA-seq) analysis offers a tumor-centered approach of growing interest for personalizing cancer care. However, existing methods – including deep learning models – struggle to reach satisfying performances on survival prediction based upon pan-cancer RNA-seq data. Here, we present DeepOS, a novel deep learning model that predicts overall survival (OS) from pan-cancer RNA-seq with a concordance-index of 0.715 and a survival AUC of 0.752 across 33 TCGA tumor types whilst tested on an unseen test cohort. DeepOS notably uses (i) prior biological knowledge to condense inputs dimensionality, (ii) transfer learning to enlarge its training capacity through pre-training on organ prediction, and (iii) mean squared error adapted to survival loss function; all of which contributed to improve the model performances. Interpretation showed that DeepOS learned biologically-relevant prognosis biomarkers. Altogether, DeepOS achieved unprecedented and consistent performances on pan-cancer prognosis estimation from individual RNA-seq data.
Understanding COVID-19 vaccine hesitancy in Pakistan: The paradigm of Confidence, Convenience, and Complacency; A Cross-sectional study
Authors: Sheikh Naveen Siddique , Touseef Mumtaz , Sultan Riddah , Cheema Kanwal Hassan , Cheema Sidra Shafiq , Sarwar Afia , Siddique Haniya Zainab
Published: July 2021

Background and objectives

Vaccine hesitancy is a big obstacle for vaccination programs, as is anticipated for the COVID-19 vaccination program, resulting in low uptake of vaccines thereby hindering the process of reaching herd immunity. Bearing this in mind the current study was aimed to explore the determinants of vaccine hesitancy amongst the Pakistani population.

Methodology

A cross-sectional study was carried out from November 2020 to March 2021. The conceptual framework of the study was based on the 3Cs (Confidence, Convenience, Complacency) model. The google-forms-based questionnaire was disseminated amongst the general population. Data collected were entered into SPSS version 26 and analyzed.

Results

Of the 421 participants, 68.4% were women. Non-healthcare workers were 55.8% of respondents. Of vaccine-hesitant individuals, 26.13% reported they were very unlikely to get vaccinated. The vaccine was not safe as it came out too fast was agreed upon by 12.6% of individuals, 50.6% were worried about experiencing side-effects, 18% believed the vaccine will not offer protection and 5.9% believed the vaccine would cause death. Low Practice of SOP in non-Healthcare workers was the strongest contributor to vaccine hesitancy (OR: 5.338, p=0.040, 95% CI: 1.082-26.330) followed by High complacency (p=0.026) and Moderate Complacency (OR: 0.212, p=0.007, 95% CI: 0.069-0.654) towards COVID-19 vaccination. In Healthcare workers the strongest contributor to vaccine hesitancy was having a Moderate Confidence (OR: 0.323, p=0.042, 95% CI: 0.109-0.958) in the vaccine followed by Moderate Convenience (OR: 0.304, p=0.049, 95% CI: 0.093-0.993) for vaccination

Conclusion

Campaigning and communication strategies to reaffirm confidence in the COVID-19 vaccine and educating the general population about the vaccine could lead to increased perception of vaccine safety and effectiveness thereby restoring confidence in vaccine and decreasing vaccine hesitancy. Likewise, working to increase vaccine convenience and decreasing complacency towards the COVID-19 vaccine would translate into high vaccine uptake.
Making Strides in Doctoral-Level Career Outcomes Reporting: Surveying the Landscape of Classification and Visualization Methodologies and Creating a Crosswalk Tool
Authors: Collins Tammy , Ramadoss Deepti , Layton Rebekah L. , MacDonald Jennifer , Wheeler Ryan , Bankston Adriana , Stayart Abigail , Hao Yi , Robinson-Hamm Jacqueline N , Sinche Melanie , Burghart Scott , Carlsen-Bryan Aleshia , Eswara Pallavi , Krasna Heather , Xu Hong , Sullivan Mackenzie
Published: July 2021

The recent movement underscoring the importance of career taxonomies has helped usher in a new era of transparency in PhD career outcomes. The convergence of discipline-specific organizational movements, interdisciplinary collaborations, and federal initiatives have all helped to increase PhD career outcomes tracking and reporting. Transparent and publicly available PhD career outcomes are being used by institutions to attract top applicants, as prospective graduate students are factoring these in when deciding on the program and institution in which to enroll for their PhD studies. Given the increasing trend to track PhD career outcomes, the number of institutional efforts and supporting offices for these studies have increased, as has the variety of methods being used to classify and report/visualize outcomes. This report identifies and summarizes currently available PhD career taxonomy tools, resources, and visualization options to help catalyze and empower institutions to develop and publish their own PhD career outcomes. Similar fields between taxonomies were mapped to create a new crosswalk tool. This work serves as an empirical review of the career outcome tracking systems available and highlights organizations, consortia, and funding agencies that are impacting policy change toward greater transparency in PhD career outcomes reporting.
Bidirectionally connected cores in a mouse connectome: Towards extracting the brain subnetworks essential for consciousness
Authors: Kitazono Jun , Aoki Yuma , Oizumi Masafumi
Published: July 2021

Where in the brain consciousness resides remains unclear. It has been suggested that the subnetworks supporting consciousness should be bidirectionally (recurrently) connected because both feed-forward and feedback processing are necessary for conscious experience. Accordingly, evaluating which subnetworks are bidirectionally connected and the strength of these connections would likely aid the identification of regions essential to consciousness. Here, we propose a method for hierarchically decomposing a network into cores with different strengths of bidirectional connection, as a means of revealing the structure of the complex brain network. We applied the method to a whole-brain mouse connectome. We found that cores with strong bidirectional connections consisted of regions presumably essential to consciousness (e.g., the isocortical and thalamic regions, and claustrum) and did not include regions presumably irrelevant to consciousness (e.g., cerebellum). Contrarily, we could not find such correspondence between cores and consciousness when we applied other simple methods which ignored bidirectionality. These findings suggest that our method provides a novel insight into the relation between bidirectional brain network structures and consciousness.
Detecting the state of drowsiness induced by propofol by spatial filter and machine learning algorithm on EEG recording
Authors: Zhou Zhibin , Srinivasan Ramesh
Published: July 2021

To accurately measure the depth of anesthesia has been a challenge for both anesthesiologists and engineers who work on developing tools of measurements. This study aims to use a machine-learning algorithm to predict the drowsy state, a transitional depth of sedation during propofol anesthesia. The data used in this study were scalp EEG (electroencephalogram) recordings selected from the University of Cambridge Repository. Raw EEG recordings were preprocessed into power spectrum matrices one second per sample. A total of 170 samples (110 awake samples and 60 drowsy samples) were used. A CNN (Convolutional Neural Network) for the MNIST (Modified National Institute of Standards and Technology) dataset was applied on these EEG power spectrum matrices. Due to the small dataset volume, Leave-One-Out cross-validation was used to train the data. Results of the training accuracy reached 99.69%. And test accuracy averaged 96.47%. Overall, the model is able to predict the state of drowsiness during propofol anesthesia. This provides the potential to develop EEG monitoring devices with closed-loop feedback of such a machine learning algorithm that controls the titration of the dosage of anesthetic administration and the depth of anesthesia.
In vitro determinants of e-cig aerosol condensate bioavailability and toxicity: Influence of cell culture parameters and utility of a normalized dose metric in e-cigarette studies
Authors: Obodo Udochukwu C. , O’Connor Timothy R.
Published: July 2021

Electronic cigarettes (e-cigs) have a strong foothold in the marketplace as a product to replace tobacco cigarette usage. Despite many researchers investigating the use of e-cigs and possible health issues, there is still controversy concerning how to evaluate and use e-cig condensates. Therefore, to identify factors that influence in vitro e-cig studies, we examined parameters that can impact experimental outcomes. We generated high wattage e-cig aerosol condensate (ECAC) to determine reproducible conditions to evaluate ECAC with respect to cellular survival. Cytotoxicity of ECAC was independent of serum conditions. However, cytotoxicity of ECAC is altered by treatment duration and by physical factors, including cell seeding density and volume of ECAC used. In addition, interactions between ECAC components and cells, as well as the culture vessel surface, diminish the bioavailability of ECAC components in vitro and altered the results obtained. Moreover, the cell seeding density changes reactive oxygen species production in response to ECAC exposure. Our data indicated that normalized ECAC doses (ECAC weight per cell) better reflect the toxicity of ECAC than nominal doses (ECAC percentage). These results provide factors for researchers to consider in the design of in vitro experiments using ECAC.
Genetic, bioacoustic and morphological analyses reveal cryptic speciation in the warbling vireo complex (Vireo gilvus: Vireonidae: Passeriformes)
Authors: Carpenter AM , Graham BA , Spellman GM , Klicka J , Burg TM
Published: July 2021

Cryptic species are closely related taxa that are difficult to separate morphologically, but are reproductively isolated. Here we examine the warbling vireo complex (Vireo gilvus), a widespread songbird speculated to be comprised of more than one cryptic species. We included three taxa within the complex: two of the western (Vireo gilvus swainsonii and V. g. brewsteri) subspecies and the single eastern (V. g. gilvus) subspecies. We used mtDNA and microsatellite loci to assess the congruence of genetic data to the current subspecies boundaries. We then incorporated bioacoustic, morphometric, and ecological niche modeling analyses to further examine differences. We found two genetic groups with mtDNA analysis. Microsatellite analyses revealed four genetic groups: an eastern group, a Black Hills group and two western groups that do not agree with current western subspecies boundaries based on phenotypic data. Our results suggest that eastern and western warbling vireos have been reproductively isolated for a long period of time and therefore, may be best treated as separate species; however, more research into areas of contact to examine the presence of hybridization is advised before making a taxonomic revision. Differences between the two western genetic groups appear less clear, requiring additional research.