bluuebunny/crossref_metadata_2025 huggingface dataset:
Adult Wilms Tumor
Authors: Argani Pedram , Tickoo Satish K. , Matoso Andres , Pratilas Christine A. , Mehra Rohit , Tretiakova Maria , Sibony Mathilde , Meeker Alan K. , Lin Ming-Tseh , Reuter Victor E. , Epstein Jonathan I. , Gagan Jeffrey , Palsgrove Doreen N.
Published: February 2022

The genetics of nephroblastoma (Wilms tumor) occurring in adults is largely unknown, as studies have largely been limited to isolated case reports. We, therefore, studied 14 adult Wilms tumors for genetic alterations, using expanded targeted sequencing on 11 cases. The patients ranged from 17 to 46 years of age (mean and median, 31 y), and there were 8 males and 6 females. Five Wilms tumors harbored BRAF V600E mutations. All of these had better-differentiated areas identical to metanephric adenoma, as has previously been described. In 3 such cases, microdissection studies revealed that the BRAF V600E mutation was present in both the metanephric adenoma and Wilms tumor areas; however, additional genetic alterations (including TERT promoter mutations in 2 cases, ASLX1/ATR mutations in 1 other case) were limited to the Wilms tumor component. These findings suggest that the Wilms tumor developed from the metanephric adenoma. Other adult Wilms tumors harbored genetic alterations previously reported in the more common pediatric Wilms tumors, including WT1 mutations (2 cases), ASLX1 mutations (3 additional cases), NSD2 mutation (1 additional case), and 11p loss (3 cases). In summary, a significant subset of adult Wilms tumors (specifically those of epithelial type with differentiated areas) harbor targetable BRAF V600E mutations and appear to arise from metanephric adenomas as a consequence of additional acquired genetic alterations. Other adult Wilms tumors often harbor genetic alterations found in their more common pediatric counterparts, suggesting at least some similarities in their pathogenesis.
Associations With Extubation Failure and Predictive Value of Risk Analytics Algorithms With Extubation Readiness Tests Following Congenital Cardiac Surgery
Authors: Hames Daniel L. , Sleeper Lynn A. , Bullock Kevin J. , Feins Eric N. , Mills Kimberly I. , Laussen Peter C. , Salvin Joshua W.
Published: February 2022

OBJECTIVES:

Extubation failure is associated with morbidity and mortality in children following cardiac surgery. Current extubation readiness tests (ERT) do not consider the nonrespiratory support provided by mechanical ventilation (MV) for children with congenital heart disease. We aimed to identify factors associated with extubation failure in children following cardiac surgery and assess the performance of two risk analytics algorithms for patients undergoing an ERT.

DESIGN:

Retrospective cohort study.

SETTING:

CICU at a tertiary-care children’s hospital.

PATIENTS:

Children receiving MV greater than 48 hours following cardiac surgery between January 1, 2017, and December 31, 2019.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Six hundred fifty encounters were analyzed with 49 occurrences (8%) of reintubation. Extubation failure occurred most frequently within 6 hours of extubation. On multivariable analysis, younger age (per each 3-mo decrease: odds ratio [OR], 1.06; 95% CI, 1.001–1.12), male sex (OR, 2.02; 95% CI, 1.03–3.97), Society of Thoracic Surgery-European Association for Cardiothoracic Surgery category 5 procedure (p equals to 0.005), and preoperative respiratory support (OR, 2.08; 95% CI, 1.09–3.95) were independently associated with unplanned reintubation. Our institutional ERT had low sensitivity to identify patients at risk for reintubation (23.8%; 95% CI, 9.7–47.6%). The addition of the inadequate delivery of oxygen (IDO2) index to the ERT increased the sensitivity by 19.0% (95% CI, –2.5 to 40.7%; p = 0.05), but the sensitivity remained low and the accuracy of the test dropped by 8.9% (95% CI, 4.7–13.1%; p < 0.01).

CONCLUSIONS:

Preoperative respiratory support, younger age, and more complex operations are associated with postoperative extubation failure. IDO2 and IVCO2 provide unique cardiorespiratory monitoring parameters during ERTs but require further investigation before being used in clinical evaluation for extubation failure.
Doctor of Physical Therapy Students' Perceptions of Engagement in Service Learning With Scouts: A Descriptive Study
Authors: Arena Sara K. , Heeg Samantha , Lewis Austin , Matero Erica
Published: February 2022

Purpose:

To describe doctor of physical therapy (DPT) students' perceptions following their engagement in a health promotion and wellness service-learning event (SLE) with boy scouts.

Methods:

A descriptive study using a sample of convenience examined engagement in an SLE with adolescents. Reflective journals summarized student experiences with the population, confidence in executing a fitness examination and motivational interviewing (MI), and anticipated challenges and benefits before and after the SLE. Journals were analyzed for themes and associated frequencies.

Results:

Pre-event themes included expected communication challenges, a mutually beneficial SLE, and increased competency with the population, fitness testing, and MI. Post-event themes included communication barriers not realized, unexpected challenges, and increased confidence with the population, fitness testing, and MI.

Conclusion:

Engaging with adolescents in SLEs provides DPT students with skills and confidence for future clinical practice. See the Digital Abstract (available: at: http://links.lww.com/PPT/A347).
The Short-term Effects of Hippotherapy and Therapeutic Horseback Riding on Spasticity in Children With Cerebral Palsy: A Meta-analysis
Authors: Hyun Cheolhwan , Kim Kyungmin , Lee Soolim , Ko Nayeon , Lee In-Sik , Koh Seong-Eun
Published: February 2022

Purpose:

We systematically reviewed the short-term effects of hippotherapy and therapeutic horseback riding (THR) on lower-limb muscle spasticity in children with cerebral palsy (CP).

Methods:

PubMed, EMBASE, Cochrane Library, and Google Scholar databases were searched for relevant quantitative studies. Treatment effects were coded using the Ashworth scale (AS) or modified Ashworth scale (MAS) in pre- and posttreatment evaluations. Of the 73 studies identified initially, 7 met the inclusion criteria.

Results:

Treatment was associated with positive effects on lower-limb muscle spasticity, as supported by the AS or MAS scores. However, repeated trials did not show a statistically significant difference from a single trial (Q = 2.95, P = .086).

Conclusion:

Hippotherapy and THR can be used to treat lower-limb muscle spasticity in children with CP. However, repeated sessions did not show a better effect in reducing spasticity.

What this adds to the evidence:

This is the first meta-analysis to confirm that hippotherapy or THR can reduce lower-limb muscle spasticity in children with CP in the short term, but long-term effects on function still require further studies.
Facial Gender Confirmation Surgery: The Lower Jaw. Description of Surgical Techniques and Presentation of Results
Authors: Simon Daniel , Capitán Luis , Bailón Carlos , Bellinga Raúl J. , Gutiérrez-Santamaría Javier , Tenório Thiago , Sánchez-García Anabel , Capitán-Cañadas Fermín
Published: February 2022

Background:

Of the primary procedures associated with facial gender confirmation surgery, those involving the mentomandibular complex have received the least attention in the literature.

Methods:

The authors present their experience with 837 trans feminine patients operated on for facial gender confirmation surgery who underwent mandibular bone contouring procedures, including bone contouring, chin and mandibular body and angle ostectomies, and osteotomies to reposition the chin. The authors describe the surgical techniques and materials used, and present a customized lower border–supported cutting guide designed by their team and used with 205 patients. A femininity perception score was calculated preoperatively and 12 months postoperatively, and satisfaction with the results was measured 12 months postoperatively.

Results:

The postoperative follow-up ranged from 12 to 110 months. The mean femininity perception score increased from 47.86 preoperatively to 76.41 at 12 months postoperatively (p < 0.001). No emergency surgical operations were required. In no case was there any permanent damage to the mental or inferior dental nerve. The reoperation percentage because of problems detected during the postoperative period was 2.63 percent (22 patients).

Conclusions:

With facial gender confirmation surgery of the jawline and chin, it is possible to modify the transverse and vertical components of the jaw; soften the gonial angles; change the format, bone volume, and position of the chin; and harmonize the entire mandibular line. The facial feminization achieved high satisfaction scores regarding the results and feminine gender appearance 12 months after surgery. The future of mandibular bone contouring techniques includes planning with virtual software and surgical support with patient-specific cutting guides.
Automatic Real-Time Space Registration Application for Simulating Dental and Maxillofacial Surgery
Authors: Bai Sifan , Liao Shenghui , Han Fuchang , Peng Xinyu , Li Zhilin , Yang Weipeng , Wu Renzhong
Published: February 2022

Real-time surgical navigation systems are important for preoperative planning and intraoperative navigation. Automatic preoperative multimodal data registration and postoperative spatial registration are extremely crucial in such surgical navigation systems. However, existing automatic multimodal data registration methods have extremely limited application scope due to the lack of accuracy and speed. In addition, the registration results obtained by existing methods are practically lacking and are rarely applied in clinics. To address the above issues, this paper proposes a novel real-time teeth registration algorithm with computed tomography (CT) data and optical tracking scanning data. The proposed method is based on the weighted iterative closest point (ICP) algorithm with 3 improvements: (1) the multilayer spherical point set is generated inside the laser scanning marker sphere, (2) the weight decreases from inside to outside layer by layer, and (3) the weight of the voxel center point set is combined with the CT data of the marker sphere. Specifically, the proposed iCP registration method can overcome the limitation of surface point set registration and tackle the problem of high surface deformity of laser scanning marker spheres. For the registration result of CT and scanning data, the authors employ the real-time spatial registration algorithm based on optical tracking to complete the navigation of the simulated surgical instruments on the multimodal fusion image. The experimental results show that the proposed ICP algorithm reduces the mean square error by 1 order of magnitude and that our method has strong practical value.
Outcomes in Pediatric Maxillofacial Reconstruction With Vascularized Fibular Flaps: A Systematic Review
Authors: Cho Annie M. , Lopez Joseph , Teven Chad M. , Pourtaheri Navid , Do Nicholas T.K. , Jazayeri Hossein E. , Steinbacher Derek M. , Blackwell Keith E. , Ozaki Wayne , Yu Jason W.
Published: February 2022

Background:

The purpose of this study was to examine the complications and outcomes after maxillofacial reconstruction using the free fibular flap in the pediatric population.

Methods:

A systematic review and descriptive analysis were conducted using data variables, including study characteristics; patient characteristics; postoperative complications (major and minor); surgical revision; and dental rehabilitation.

Results:

The systematic review resulted in 1622 articles, 55 of which met inclusion criteria for this study. The 55 articles consisted of 17 case series and 38 case reports with level III/IV and level V of evidence, respectively. Of the 155 identified pediatric patients, the rate of major complications was 13.5% and minor complications was 24.5%. The most common complication was mild growth distortion (n = 7) at the recipient site. Complications at the donor site were less common. During follow-up, 29 patients (18.7%) underwent or awaited surgical revision, and 43 patients (27.7%) underwent or awaited dental rehabilitation.

Conclusions:

Our study suggests that the free fibular flap for pediatric maxillofacial reconstruction is safe and reliable. Additionally, surgical revision to correct the functional impairments resulting from primary reconstruction using the free fibular flap is relatively common.
Surgical Treatment of Parapharyngeal Space Salivary Gland Tumor
Authors: Shin Bong Jin , Lee Dong Hoon , Lee Joon Kyoo , Lim Sang Chul
Published: February 2022

Introduction:

Parapharyngeal space salivary gland tumors are very rare. The authors sought to examine the clinical features, treatment methods, and treatment results of parapharyngeal space salivary gland tumors in our hospital.

Methods:

The authors retrospectively enrolled 15 patients who were finally diagnosed as having parapharyngeal space salivary gland tumors from January 2010 to January 2021.

Results:

All parapharyngeal space salivary gland tumors arose from the prestyloid compartment. This study included 3 males and 12 females. The main symptoms were incidental diagnosis during imaging tests, followed by neck discomfort, oral mass, neck mass, and headache. Surgical methods for parapharyngeal space salivary gland tumors were performed in the following order: transcervical approach (n = 10), transcervical-parotid approach (n = 3), transoral approach (n = 1), and transparotid approach (n = 1). Pleomorphic adenoma was the most common tumor among parapharyngeal space salivary gland tumors.

Conclusions:

In the surgery of parapharyngeal space salivary gland tumors, a transcervical or transcervical-parotid approach was mainly used by predicting the origin site through radiologic examinations.
Medial Epicanthoplasty With the Classic and Modified Skin Redraping Method: A Retrospective Case Control Study
Authors: Huang Jiuzuo , Wang Hefei , Du Fengzhou , Long Xiao , Liu Zhigang
Published: February 2022

The skin redraping method for medial epicanthoplasty is characterized by some shortcomings which warrants modification. In this study, clinical data of 193 patients who underwent medial epichanthoplasty by the modified skin redraping technique or the classic skin redraping technique were reviewed retrospectively. The patients underwent operation between May 2018 and June 2020 and were followed up for not less than 6 months. Interepicanthal distance, interpupillary distance, patient satisfaction, and postoperative complications were evaluated. In terms of interepicanthal distance/inter-pupillary distance ratio (P > 0.05) and satisfaction score (P = 0.759), the modified skin redraping technique and the classic skin redraping technique were similar. In the classic skin redraping group, there were 3 cases of visible scarring in the lower eyelid, corresponding to significantly more cases than in the modified skin redraping group (n = 0, P < 0.001). There were more out-fold cases in the modified skin redraping group (76/90) than in the classic skin redraping group (17/88) (P < 0.001). Utilizing the modified skin redraping medial epicanthoplasty can prevent medial hooding of the upper eyelid, reduce the probability of visible scarring, and produce more out-fold with concurrent double eyelidplasty compared with classic skin redraping epicanthoplasty. Level of evidence: IV
Genotypic variation and plasticity in climate-adaptive traits after range expansion and fragmentation of red spruce (Picea rubensSarg.)
Authors: Prakash Anoob , DeYoung Sonia , Lachmuth Susanne , Adams Jacquelyne L. , Johnsen Kurt , Butnor John R. , Nelson David M. , Fitzpatrick Matthew C. , Keller Stephen R.
Published: February 2022

Shifting range limits are predicted for many species as the climate warms. However, the rapid pace of climate change will challenge the natural dispersal capacity of long-lived, sessile organisms such as forest trees. Adaptive responses of populations will, therefore, depend on levels of genetic variation and plasticity for climate-responsive traits, which likely vary across the range due to expansion history and current patterns of selection. Here, we study levels of genetic and plastic variation for phenology and growth traits in populations of red spruce (Picea rubens), from the range core to the highly fragmented trailing edge. We measured more than 5000 offspring sampled from three genetically distinct regions (core, margin and edge) grown in three common gardens replicated along a latitudinal gradient. Genetic variation in phenology and growth showed low to moderate heritability and differentiation among regions, suggesting some potential to respond to selection. Phenology traits were highly plastic, but this plasticity was generally neutral or maladaptive in the effect on growth, revealing a potential liability under warmer climates. These results suggest future climate adaptation will depend on the regional availability of genetic variation in red spruce and provide a resource for the design and management of assisted gene flow.

This article is part of the theme issue ‘Species’ ranges in the face of changing environments (Part II)’.
The response of a metapopulation to a changing environment
Authors: Barton Nick , Olusanya Oluwafunmilola
Published: February 2022

A species distributed across diverse environments may adapt to local conditions. We ask how quickly such a species changes its range in response to changed conditions. Szép
et al.
(Szép E, Sachdeva H, Barton NH. 2021 Polygenic local adaptation in metapopulations: a stochastic eco-evolutionary model.
Evolution
75
, 1030–1045 (
doi:10.1111/evo.14210
)) used the infinite island model to find the stationary distribution of allele frequencies and deme sizes. We extend this to find how a metapopulation responds to changes in carrying capacity, selection strength, or migration rate when deme sizes are fixed. We further develop a ‘fixed-state’ approximation. Under this approximation, polymorphism is only possible for a narrow range of habitat proportions when selection is weak compared to drift, but for a much wider range otherwise. When rates of selection or migration relative to drift change in a single deme of the metapopulation, the population takes a time of order m
−1
to reach the new equilibrium. However, even with many loci, there can be substantial fluctuations in net adaptation, because at each locus, alleles randomly get lost or fixed. Thus, in a finite metapopulation, variation may gradually be lost by chance, even if it would persist in an infinite metapopulation. When conditions change across the whole metapopulation, there can be rapid change, which is predicted well by the fixed-state approximation. This work helps towards an understanding of how metapopulations extend their range across diverse environments.

This article is part of the theme issue ‘Species’ ranges in the face of changing environments (Part II)’.
The use of hippocampal grading as a biomarker for early MCI
Authors: Morrison Cassandra , Dadar Mahsa , Shafiee Neda , Collins D. Louis ,   Alzheimer’s Disease Neuroimaging Initiative
Published: February 2022

INTRODUCTION

Changes in the hippocampus are associated with both increased age and cognitive decline due to mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Most studies have examined the association between hippocampal changes and episodic memory, with many reporting a relationship between hippocampal measurements and global cognition. However, these studies often find associations only in the later stages of cognitive decline. The goal of this study was to examine if hippocampal grading is associated with global cognition in cognitively normal controls (NC), early MCI (eMCI), late (lMCI), and AD, and whether such associations differ across diagnostic cohorts.

METHODS

Data from 1620 Alzheimer’s Disease Neuroimaging Initiative older adults were examined in this study (495 NC, 262 eMCI, 545 lMCI, and 318 AD). Participants were included if they completed baseline MRI scans and the Alzheimer’s disease Assessment Scale (ADAS-13) and Clinical Dementia Rating – Sum of Boxes (CDR-SB) cognitive tests. Linear regressions examined the influence of hippocampal grading on cognitive scores.

RESULTS

Lower global cognition (i.e., increased ADAS-13 scores) was associated with hippocampal grading scores in all cohorts, including normal controls. Lower global cognition (i.e., increased CDR-SB scores) was associated with hippocampal grading scores in lMCI and AD, but not in eMCI or NC groups.

DISCUSSION

These findings suggest that hippocampal grading is associated with changes in global cognition in NC, eMCI, lMCI, and AD depending on the cognitive test. Thus, hippocampal grading may be a useful measure that is sensitive to progressive changes early in the disease course.
Clinical activity of MAPK targeted therapies in patients with non-V600 BRAF mutant tumors
Authors: Dankner Matthew , Wang Yifan , Fazelzad Rouhi , Johnson Benny , Nebhan Caroline A. , Dagogo-Jack Ibiayi , Myall Nathaniel J. , Richtig Georg , Bracht Jillian W. P , Gerlinger Marco , Shinozaki Eiji , Yoshino Takayuki , Kotani Daisuke , Fangusaro Jason R. , Gautschi Oliver , Mazieres Julien , Sosman Jeffrey A. , Kopetz Scott , Subbiah Vivek , Davies Michael A. , Groover Anna , Sullivan Ryan J. , Flaherty Keith T. , Johnson Douglas B. , Benedetti Andrea , Cescon David W. , Spreafico Anna , Zogopoulos George , Rose April A. N.
Published: February 2022

Purpose

Non-V600 mutations comprise approximately 35% of all BRAF mutations in cancer. Many of these mutations have been identified as oncogenic drivers in a wide array of cancer types and can be classified into three Classes according to molecular characteristics. Consensus treatment strategies for Class 2 and 3 BRAF mutations have not yet been established.

Methods

We performed a systematic review and meta-analysis of individual patient data to assess treatment outcomes with FDA-approved mitogen activated protein kinase pathway (MAPK) targeted therapy according to BRAF Class, cancer type and MAPK targeted therapy type. A search was conducted on literature from 2010-2021. Individual patient data was collected and analyzed from published reports of patients with cancer harboring Class 2 or 3 BRAF mutations and who received MAPK targeted therapy with available treatment response data. Co-primary outcomes were response rate (RR) and progression-free survival (PFS).

Results

18167 studies were screened, identifying 80 studies with 238 patients that met inclusion criteria. This included 167 patients with Class 2 and 71 patients with Class 3 BRAF mutations. Overall, 77 patients achieved a treatment response. In both univariate and multivariable analyses, RR and PFS were higher among patients with Class 2 compared to Class 3 mutations, findings that remain when analyses are restricted to patients with melanoma or lung primary cancers. MEK +/- BRAF inhibitors demonstrated greater clinical activity in Class 2 compared to Class 3 BRAF mutant tumors than BRAF or EGFR inhibitors.

Conclusions

This meta-analysis suggests that MAPK targeted therapies have clinical activity in some Class 2 and 3 BRAF mutant cancers. BRAF Class may dictate responsiveness to current and emerging treatment strategies, particularly in metastatic melanoma and lung cancers. Together, this analysis provides clinical validation of predictions made based on a mutation classification system established in the preclinical literature. Further evaluation with prospective clinical trials is needed for this population.
Whole Exome Sequencing of Nigerian Prostate Tumors from the Prostate Cancer Transatlantic Consortium (CaPTC) Reveals DNA Repair Genes Associated with African Ancestry
Authors: White Jason , Kaninjing Ernest T , Adeniji Kayode A , Jibrin Paul , Obafunwa John O , Ogo Chidiebere N , Faruk Mohammed , Popoola Ademola , Fatiregun Omolara A , Oluwole Olabode P , Karanam Balasubramanyam , Elhussin Isra , Ambs Stefan , Tang Wei , Davis Melissa , Polak Paz , Campbell Moray J , Francis Damian K , Gibbs Denise Y , Brignole Kathryn R , Rotimi Solomon , Odedina Folake T , Martin Damali N , Yates Clayton
Published: February 2022

In this study, we used whole-exome sequencing of a cohort of 45 advanced-stage, treatment-naïve Nigerian (NG) primary prostate cancer (PCa) tumors and 11 unmatched non-tumor tissues to compare genomic alterations with African American (AA) and European American (EA) TCGA PCa. NG samples were collected from 6 sites in central and southwest Nigeria. After whole-exome sequencing, samples were processed using GATK best practices. BRCA1 (100%), BARD1 (45%), BRCA2 (27%), and PMS2(18%) had germline alterations in at least two NG non-tumor samples. Across 111 germline variants, the AA cohort reflected a pattern [BRCA1 (68%), BARD1 (34%), BRCA2 (28%), and PMS2 (16%)] similar to NG samples. Of the most frequently mutated genes, BRCA1 showed a statistically (p ≤ 0.05) higher germline mutation frequency in men of African ancestry (MAA) and increasing variant frequency with increased African ancestry. Disaggregating gene level mutation frequencies by variants revealed both ancestry-linked and NG-specific germline variant patterns. Driven by rs799917 (T>C), BRCA1 showed an increasing mutation frequency as African admixture increased. BRCA2_rs11571831 was present only in MAAs, and BRCA2_rs766173 was elevated in NG men. 133 somatic variants were present in 26 PCa-associated genes within the NG tumor cohort. BRCA2 (27%), APC (20%), ATM (20%), BRCA1 (13%), DNAJC6 (13%), EGFR (13%), MAD1L1 (13%), MLH1 (11%), and PMS2 (11%) showed mutation frequencies > 10%. Compared to TCGA cohorts, NG tumors showed statistically significant elevated frequencies of BRCA2, APC, and BRCA1. The NG cohort variant pattern shared similarities (cosign similarities ≥ 0.734) with COSMIC signatures 5 and 6, and mutated genes showed significant (q < 0.001) GO and functional enrichment in mismatch repair and non-homologous repair deficiency pathways. Here, we showed that alterations in DNA damage response (DDR) genes were higher in NG PCa samples and that a portion of those alterations correlate with African ancestry. Moreover, we identified variants of unknown significance that may contribute to population-specific routes of tumorigenesis and treatment. These results present the most comprehensive characterization of the NG PCa exome to date and highlight the need to increase diversity of study populations.
Quantitative Radiomic Features from Computed Tomography Can Predict Pancreatic Cancer up to 36 Months Before Diagnosis
Authors: Chen Wansu , Zhou Yichen , Asadpour Vahid , Parker Rex A , Lustigova Eva , Puttock Eric J. , Wu Bechien U
Published: February 2022

Objectives

Pancreatic cancer (PC) is the 3rdleading cause of cancer deaths. We aimed to detect early changes on computed tomography (CT) images associated with pancreatic ductal adenocarcinoma (PDAC) based on quantitative imaging features (QIF).

Methods

Adults 18+ years of age diagnosed with PDAC in 2008-2018 were identified. Their CT scans 3 months-3 years prior to the diagnosis date were matched to up to two scans of controls. Pancreas was automatically segmented using a previously developed algorithm. 111 QIF were extracted. The dataset was randomly split for training/validation. Neighborhood and principal component analyses were applied to select the most important features. Conditional support vector machine was used to develop prediction algorithms. The computer labels were compared with manually reviewed CT images 2-3 years prior to the index date in 19 cases and 19 controls.

Results

227 scans from cases (stages: 35% I-II, 44% III-IV, 21% unknown) and 554 matched scans of healthy controls were included (average age 71 years; 51% females). In the validation dataset, accuracy measures were 94%-95%, and area under the curve (AUC) measures were 0.98-0.99. Sensitivity, specificity, positive predictive value, and negative predictive values were in the ranges of 88-91%, 96-98%, 91-95%, and 94-96%. QIF on CT examinations within 2-3 years prior to index date also had very high predictive accuracy (accuracy 95-98%; AUC 0.99-1.00). The QIF-based algorithm outperformed manual re-review of images for determination of PDAC-risk.

Conclusions

QIF can accurately predict PDAC on CT imaging and represent promising biomarkers for early detection of pancreatic cancer.

WHAT IS KNOWN

Pancreatic cancer is the 3rdleading cause of cancer deaths.

Early detection of pancreatic ductal adenocarcinoma (PDAC) is difficult owing to lack of specific symptoms or established screening.

WHAT IS NEW HERE

Quantitative imaging features (QIF) of pre-diagnostic CT scans can accurately predict PDAC in 3-36 months prior to diagnosis (accuracy 94-95% and AUC 0.98-0.99).

QIF on CT examinations within 2-3 years prior to cancer diagnosis also had very high predictive accuracy (accuracy 95-98%; AUC 0.99-1.00).

The QIF-based algorithm outperformed manual re-review of images for determination of PDAC risk.
Insights on Telemedicine Use by Physiatrists Before, During, and Beyond the COVID-19 Pandemic
Authors: Sobrepera M. J. , Weseloh A. , Chaudhri D. , Johnson M. J.
Published: February 2022

Purpose

To determine if physiatrists increased their use of telemedicine during the first 11 months of the COVID-19 pandemic and if changes are expected to persist post-pandemic. And to identify key tasks which require video for telemedicine.

Materials and Methods

A survey containing questions about the telemedicine tools used before, during, and after (planned) the COVID-19 pandemic was distributed to physiatrists. Analysis was conducted to evaluate the change in usage of telemedicine due to the pandemic and predict whether the pandemic will lead to a durable change in usage. Tasks which physiatrists have/believe they can complete with different modes of interaction were explored.

Results

Responses from 56 physiatrists showed a 105% increase in video-based telemedicine use during the pandemic. The use of phone and video communications for care delivery significantly increased. 79% of respondents planned to use video-based telemedicine post-pandemic, a significant increase from pre-pandemic use. Motor assessments, cognitive assessments, stretching, strength building, and orthotics assessment and prescription were identified as key tasks that require video for telemedicine.

Conclusion

This study confirms increased use of telemedicine by physiatrists during the pandemic and suggests this shift will be durable. Key tasks where video is necessary for telemedicine were identified.
Oral ingestion of the environmental toxicant trichloroethylene in rats induces alterations in the gut microbiome: relevance to idiopathic Parkinson’s disease
Authors: Ilieva Neda M. , Wallen Zachary D. , De Miranda Briana R.
Published: February 2022

Microbial alterations within the gut microbiome appear to be a common feature of individuals with Parkinson’s disease (PD), providing further evidence for the role of the gut-brain axis in PD development. As a major site of contact with the environment, questions have emerged surrounding the cause and effect of alterations to the gut microbiome by environmental contaminants associated with PD risk, such as pesticides, metals, and organic solvents. Recent data from our lab shows that ingestion of the industrial byproduct and environmental pollutant trichloroethylene (TCE) induces key Parkinsonian pathology within aged rats, including the degeneration of dopaminergic neurons, α-synuclein accumulation, neuroinflammation, and endolysosomal deficits. As TCE is the most common organic contaminant within drinking water, we postulated that ingestion of TCE associated with PD-related neurodegeneration may alter the gut microbiome to a similar extent as observed in persons with PD. To assess this, we collected fecal samples from adult rats treated with 200 mg/kg TCE over 6 weeks via oral gavage – the dose that produced nigrostriatal neurodegeneration – and analyzed the gut microbiome via whole genome shotgun sequencing. Our results showed changes in gut microorganisms reflective of the microbial signatures observed in individuals with idiopathic PD, such as decreased abundance of short-chain fatty acid producing Blautia and elevated lactic-acid producing Bifidobacteria, as well as genera who contain species previously reported as opportunistic pathogens such as Clostridium. From these experimental data, we postulate that TCE exposure within contaminated drinking water could induce alterations of the gut microbiome that contributes to chronic disease risk, including idiopathic PD.
Post-COVID-19 tele-survey for persistent symptoms in a single center hospital cohort in India along with a parallel country-wide web-survey
Authors: Chaudhuri Kausik , Sarkar Jit , Das Tirthankar , Paul Shekhar Ranjan , Basu Rajita , Gangopadhyay Supratik , Gangopadhyay Devyani , Manna Asis , Haldar Anima , Ray Yogiraj , Banerjee Sayantan , Ganguly Dipyaman
Published: February 2022

Introduction

A major concern amidst the ongoing coronavirus pandemic has been the longer term persistence of morbidities in individuals recovering from COVID-19 disease, called ‘long COVID’. We aimed at documenting the prevalence and key associations of post-COVID symptoms (PCS) in India in telephonic survey among recovered patients in a single hospital in eastern India as well as a parallel web-survey covering a wider population of the country.

Methods

Self-reported PCS, ranging up to one year since the original COVID-19 diagnosis, were documented in a telephonic survey of subjects (analyzed N=986), treated for acute COVID-19 in Infectious Diseases and Beleghata General Hospital, Kolkata, between April 1, 2020 and April 13, 2021. In parallel, we ran a web-based survey (analyzed N=580), to evaluate concordance.

Results

Shortness of breath, fatigue and insomnia were identified to be the most commonly reported PCS in both the surveys, with higher prevalence in females. In the telephonic survey, a 3.65% post-discharge mortality was registered within a median of 39 days since COVID diagnosis. Intensive care during acute disease and hypertension were more often associated with PCS, while fatigue was more often reported by the 20-40 years age-group. The web-survey revealed a gradual decline in PCS with time since COVID-19 diagnosis and type 2 diabetes to be associated with higher prevalence of these symptoms.

Conclusions

We assessed the predominant PCS among Indian COVID-19 patients and identified key demographic and clinical associations in our surveys, which warrants deeper epidemiological and mechanistic studies for guiding management of long-COVID in the country.
Conformational Ensemble of Monomeric α-Synuclein in Aqueous and Crowded Environments as revealed by Markov State Model
Authors: Menon Sneha , Mondal Jagannath
Published: February 2022

140-residue intrinsically disordered protein α-synuclein (αS) is known to be susceptible to environmental cues/crowders and adopts conformations that are vastly variable in the extent of secondary structure and tertiary interactions. Depending upon the nature of these interactions, some of the conformations may be suitable for its physiological functions while some may be predisposed to aggregate with other partners into higher ordered species or to phase separate. However, the inherently heterogenous and dynamic nature of αS has precluded a clear demarcation of its monomeric precursor between aggregation-prone and functionally relevant aggregation-resistant states. Here, we optimally characterise a set of metastable conformations of αS by developing a comprehensive Markov state model (MSM) using cumulative 108 µs-long all-atom MD simulation trajectories of monomeric αS. Notably, the dimension of the most populated metastable (85%) state (Rg ∼ 2.59 (±0.45) nm) corroborates PRENMR studies of αS monomer and undergoes kinetic transition at 0.1-150 µs time-scale with weakly populated (0.06%) random-coil like ensemble (Rg ∼ 5.85 (±0.43) nm) and globular protein-like state (14%) (Rg ∼ 1.95 (±0.08) nm). The inter-residue contact maps identify a set of mutually interconverting aggregation-prone β-sheet networks in the NAC region and aggregation-resistant long-range interactions between N- and C-terminus or helical conformations. The presence of crowding agents compacts the MSM-derived metastable conformations in a non-monotonic fashion and skews the ensemble by either introducing new tertiary contacts or reinforcing the innate contacts to adjust to the excluded-volume effects of such environments. These observations of crucial monomeric states would serve as important steps towards rationalising routes that trigger αS-associated pathologies.

Significance statement

α-synuclein, a neuronal protein, is often associated with neurogenerative diseases due to its tendency to self-assemble into higher ordered aggregates. While the monomeric precursor of this protein is intrinsically disordered, it is also known to be susceptible to biological environmental cues and adopts a wide range of conformations that are either primed for aggregation or remain in auto-inhibitory states. However, the inherently heterogenous nature of the monomeric form has prevented a clear dissection of aggregation-prone and functionally relevant aggregation-resistant states. Here, we resolve this via an atomistic characterisation of an optimal set of crucial metastable monomeric conformations via statistical modelling of computer simulated data. The investigation also sheds light on crowding-induced modulation of the ensemble and eventual fibrillation pathways.
Quantitative sequence basis for the E. coli transcriptional regulatory network
Authors: Qiu Sizhe , Lamoureux Cameron , Akbari Amir , Palsson Bernhard O. , Zielinski Daniel C.
Published: February 2022

The transcriptional regulatory network (TRN) of E. coli consists of thousands of interactions between regulators and DNA sequences. Inherently the DNA sequence is the primary determinant of the TRN; however, it is well established that the presence of a DNA binding motif does not guarantee a functional regulatory protein binding site. Thus, the extent to which the TRN architecture can be predicted by the genome DNA sequence alone remains unclear. Here, we developed machine learning models that predict the TRN structure of E. coli based on genome sequence. Models were constructed successfully (cross-validation AUROC >= 0.8) for 84% (57/68) of valid E. coli regulons identified from top-down analysis of RNA-seq data. We found that: 1) While regulatory motif strength is the most important sequence feature for determining regulon membership, additional features such as DNA shape substantially influence membership; 2) complex regulons involving multiple interacting regulators could be unraveled by machine learning; 3) investigating regulons where initial ML models failed revealed new regulator-specific sequence features that improved model accuracy. Finally, while regulon structure can appear to be variable across estimation methods and strains, we found that strong regulatory sequence features underlie both the genes that appear most consistently in regulons across estimation methods as well as the core regulon genes in the Fur pan-regulon. This work develops a quantitative understanding of the sequence basis of the TRN and suggests a path towards computationally-guided control of transcriptional regulation for synthetic biology applications.
Fast fragment- and compound-screening pipeline at the Swiss Light Source
Authors: Kaminski Jakub W. , Vera Laura , Stegmann Dennis P. , Vering Jonatan , Eris Deniz , Smith Kate M. L. , Huang Chia-Ying , Meier Nathalie , Steuber Julia , Wang Meitian , Fritz Günter , Wojdyla Justyna A. , Sharpe May E.
Published: February 2022

Over the last two decades, fragment-based drug discovery (FBDD) has emerged as an effective and efficient method to identify new chemical scaffolds for the development of lead compounds. X-ray crystallography can be used in FBDD as a tool to validate and develop fragments identified as binders by other methods. However, it is also often used with great success as a primary screening technique. In recent years, technological advances at macromolecular crystallography beamlines in terms of instrumentation, beam intensity and robotics have enabled the development of dedicated platforms at synchrotron sources for FBDD using X-ray crystallography. Here, the development of the Fast Fragment and Compound Screening (FFCS) platform, an integrated next-generation pipeline for crystal soaking, handling and data collection which allows crystallography-based screening of protein crystals against hundreds of fragments and compounds, at the Swiss Light Source is reported.
Structural basis for substrate recognition in the Phytolacca americana glycosyltransferase PaGT3
Authors: Maharjan Rakesh , Fukuda Yohta , Nakayama Taisuke , Nakayama Toru , Hamada Hiroki , Ozaki Shin-ichi , Inoue Tsuyoshi
Published: February 2022

Capsaicinoids are phenolic compounds that have health benefits. However, the pungency and poor water solubility of these compounds limit their exploitation. Glycosylation is a powerful method to improve water solubility and reduce pungency while preserving bioactivity. PaGT3, a uridine diphosphate glycosyltransferase (UGT) from Phytolacca americana, is known for its ability to glycosylate capsaicinoids and other phenolic compounds. While structural information on several UGTs is available, structures of UGTs that can glycosylate a range of phenolic compounds are rare. To fill this gap, crystal structures of PaGT3 with a sugar-donor analogue (UDP-2-fluoroglucose) and the acceptors capsaicin and kaempferol were determined. PaGT3 adopts a GT-B-fold structure that is highly conserved among UGTs. However, the acceptor-binding pocket in PaGT3 is hydrophobic and large, and is surrounded by longer loops. The larger acceptor-binding pocket in PaGT3 allows the enzyme to bind a range of compounds, while the flexibility of the longer loops possibly plays a role in accommodating the acceptors in the binding pocket according to their shape and size. This structural information provides insights into the acceptor-binding mechanism in UGTs that bind multiple substrates.
Directing from the shadows: Women’s experiences of male relative suicide bereavement
Authors: Gordon Evelyn , McElvaney Rosaleen
Published: February 2022

Suicide bereavement evokes particular emotions that can hamper recovery processes, if neglected. This Interpretative Phenomenological Analysis (IPA) study explored five women’s experiences of bereavement following the death by suicide of a male relative. One superordinate theme, directing from the shadows, and three interrelated subordinate themes: roller coasting, speaking the unspeakable, and finding meaning and living with suicide were identified. This study highlights that women bereaved by suicide may occupy a complex position in the family when trying to balance caring for themselves and others, sometimes leading them to negate their own support and therapeutic needs. However, women in this study felt supported by timely, flexible and sensitive professional responses and found a proactive outreach approach, peer support groups and counselling helpful at different stages in their bereavement process.
Daily appraisal of commercial real estate a new mixed frequency approach
Authors: Francke Marc , Van De Minne Alex
Published: February 2022

We present a mixed frequency repeat sales model for commercial real estate, taking into account changes in net operating income between the date of buying and selling the property. Moreover, we relate monthly private market index asset returns to lags, up to 1 year, of daily (REIT) index returns. The underlying daily model enables us to interpolate the monthly private market index returns on a daily basis, and to predict the private market index asset returns going forward. The mixed frequency repeat sales model facilitates daily appraisal of commercial real estate portfolios. We apply the model on sale prices (all property types, and apartments only) in the period January 2006–July 2020. We find that the mixed frequency repeat sales model reduces 1‐month‐ahead forecasts errors and index revisions, compared to a benchmark model without daily returns.
What is the best approach for preventing recruitment to terrorism? Findings from ABM experiments in social and situational prevention
Authors: Weisburd David , Wolfowicz Michael , Hasisi Badi , Paolucci Mario , Andrighetto Giulia
Published: February 2022

Research Summary

This study uses agent‐based models (ABMs) to compare the impacts of three different types of interventions targeting recruitment to terrorism—community workers at community centers; community‐oriented policing; and an employment program for high‐risk agents. The first two programs are social interventions that focus on de‐radicalization and changing the dispositions of agents in the model, whereas the employment program focuses on “deflection” and represents a situational/opportunity reducing approach to prevention. The results show significant impacts of the community worker and community policing interventions on radicalization but no significant impact on recruitment. In contrast, the employment intervention had a strong and significant impact on recruitment, but little impact on radicalization.

Policy Implications

Our ABM simulations challenge the reliance of existing programs to reduce recruitment to terrorism on counter and de‐radicalization approaches. Instead they suggest that policy makers should focus more attention on deflection and opportunity reduction. At the same time, our ABMs point to the salience of social interventions focusing on risk and protective factors for reducing radicalization in society.
Effect of different alfalfa cultivars on growth and development of the spotted alfalfa aphid, Therioaphis trifolii (Monell)
Authors: Yu Liang‐bin , Lin Ke‐Jian , Xu Lin‐bo , Wang Hui , Cui Jin , Zhang Quan‐yi , Wang Ya‐ping , Yan Li‐ying
Published: February 2022

Therioaphis trifolii (Monell) is a well‐known pest in alfalfa cultivation in China. Individuals of T. trifolii were allowed to feed on 10 alfalfa cultivars and their growth, reproduction, and population life table parameters were estimated. Nymphs that fed on Hunter River had the longest development time, whereas nymphs that fed on Defu had the shortest development time. Adults that fed on Debao, Zhongmu No. 2, and Defu had the shortest development time, whereas adults that fed on Golden Empress and Hunter River had the longest development times. Individuals that fed on Zhungeer produced the greatest number of offspring (13.950), and those that fed on Hunter River produced the fewest offspring (6.000). The survival rate of T. trifolii was the highest on Algonquin and lowest on Hunter River, whereas the survival time was the longest on Golden Empress and shortest on Debao. The population that fed on Algonquin had the highest intrinsic growth rate (0.560) and shortest population doubling time (1.237 days), whereas those that fed on Hunter River had the lowest intrinsic growth rate (0.217) and longest population doubling time (3.194 days). The life table parameters of the experimental T. trifolii population were used to quantify the resistance strengths of the cultivars. Results indicate that the Hunter River cultivar may effectively resist damage from T. trifolii. This study provides a theoretical basis for breeding aphid‐resistant alfalfa cultivars, enabling further research into the prevention and control of aphid infestation.