bluuebunny/crossref_metadata_2025 huggingface dataset:
Gestational Weight Gain and Long-term Maternal Obesity Risk: A Multiple-Bias Analysis
Authors: Hutchins Franya , Krafty Robert , El Khoudary Samar R. , Catov Janet , Colvin Alicia , Barinas-Mitchell Emma , Brooks Maria M.
Published: December 2020

Background:

Lifecourse research provides an important framework for chronic disease epidemiology. However, data collection to observe health characteristics over long periods is vulnerable to systematic error and statistical bias. We present a multiple-bias analysis using real-world data to estimate associations between excessive gestational weight gain and mid-life obesity, accounting for confounding, selection, and misclassification biases.

Methods:

Participants were from the multiethnic Study of Women’s Health Across the Nation. Obesity was defined by waist circumference measured in 1996–1997 when women were age 42–53. Gestational weight gain was measured retrospectively by self-recall and was missing for over 40% of participants. We estimated relative risk (RR) and 95% confidence intervals (CI) of obesity at mid-life for presence versus absence of excessive gestational weight gain in any pregnancy. We imputed missing data via multiple imputation and used weighted regression to account for misclassification.

Results:

Among the 2,339 women in this analysis, 937 (40%) experienced obesity in mid-life. In complete case analysis, women with excessive gestational weight gain had an estimated 39% greater risk of obesity (RR = 1.4, CI = 1.1, 1.7), covariate-adjusted. Imputing data, then weighting estimates at the guidepost values of sensitivity = 80% and specificity = 75%, increased the RR (95% CI) for obesity to 2.3 (2.0, 2.6). Only models assuming a 20-point difference in specificity between those with and without obesity decreased the RR.

Conclusions:

The inference of a positive association between excessive gestational weight gain and mid-life obesity is robust to methods accounting for selection and misclassification bias.
Descemetocele Management With Therapeutic Scleral Lens Wear
Authors: Gelles John D. , Bekerman Vladislav P. , Greenstein Steven A. , Shafiq Misbah , Hersh Peter S.
Published: December 2020

Objectives:

This case reports on the use of scleral lens therapy for a patient with a descemetocele secondary to exposure and neurotrophic keratopathy.

Methods:

Case report and literature review.

Results:

A 31-year-old man had undergone emergency surgery to repair a ruptured arteriovenous malformation resulting in left facial and trigeminal nerve palsies. The patient reported to our clinic with a central descemetocele secondary to exposure and neurotrophic keratopathy. Given the poor prognosis of a therapeutic penetrating keratoplasty in this case, the descemetocele was treated with therapeutic scleral lens wear. After 1 year, the patient has remained stable without corneal perforation.

Conclusions:

This case illustrates the use of extended scleral lens wear, followed by maintenance with daily scleral lens wear, to manage a descemetocele in a patient with neurotrophic and exposure keratopathy. For patients at high risk of postsurgical complications, therapeutic scleral lens wear may be used as an alternative or as a supplement to corneal transplantation and tarsorrhaphy in patients with descemetocele formation.
Genomics in nursing education
Authors: Seibert Diane
Published: December 2020

Genetics/Genomics is a relatively new science. The basic principles were formally described at the end of the 19th century, the physical structure of genes were described in the middle of the 20th century, and the first gene located in the early 1990s. Later, the human genome was sequenced. More and more genes have been located and described and some are now being manipulated. All health professions are struggling to infuse genomic content into the curriculum. This article traces the roots of the undergraduate and graduate nursing competencies and provides a brief review of the literature describing nursing genetic/genomics education.
Celebrating our history
Authors: Sheer Barbara
Published: December 2020

The year 2020 is an historic year on many accounts. It was to be an international year of celebration for nurses and midwives but turned into a year of turmoil with the emergence of the coronavirus pandemic and a call for justice and social awareness. Nurses were in the forefront and demonstrated courage and heroic efforts in the face of devastating events. Advanced practice nurses need to document their stories. This becomes our legacy. In an effort to preserve our legacy, the American Association of Nurse Practitioners history committee is in the process of identifying the existing historical documents for preservation.
A New CT Parameter for Predicting Residual Hearing Preservation in Cochlear Implantation: The “Basal Turn–Facial Ridge Angle”
Authors: Kim Hantai , Choo Oak-Sung , Ha Jungho , Jang Jeong Hun , Park Hun Yi , Choung Yun-Hoon
Published: December 2020

Objectives:

We suggest a simple measurement, called the “basal turn–facial ridge (BT–FR) angle,” for determining the electrode insertion axis using preoperative temporal bone computed tomography (CT) to predict hearing preservation (HP) in cochlear implantation (CI).

Study Design:

Retrospective chart review.

Setting:

Tertiary referral center.

Patients:

Eighty-two ears that underwent CI between 2010 and 2018 were included. Ears with preoperative thresholds less than or equal to 80 dB HL at 125, 250, and 500 Hz were enrolled and grouped using the criteria of Skarżyński et al.: Group 1, complete or partial HP; Group 2, minimal HP or complete hearing loss.

Intervention:

All subjects underwent CI with soft surgery techniques through the round window approach.

Main Outcome Measures:

The BT–FR angle is the angle between the basal turn line (BT-line), which is a straight line passing through the center of the longitudinal axis of the BT, and the facial ridge line, which is a straight line running from the endpoint of the BT-line to a point just above the facial ridge.

Results:

The BT–FR angle was 2.5 ± 2.9 degrees in Group 1 and –0.3 ± 2.7 degrees in Group 2 (p = 0.003). The angle and hearing loss showed a significant negative correlation (r = –0.401, p = 0.002). In multiple linear regression, “age at operation” (β coefficient 0.260; p = 0.001) and the “BT–FR angle” (–1.967; p = 0.001) were significant variables affecting the degree of residual hearing loss.

Conclusions:

The BT–FR angle, which can be measured simply, may be useful to predict residual HP after CI.
Unusual suicide by a speargun shot
Authors: Barranco Rosario , Caputo Fiorella , Pinto Sara Lo , Drommi Martina , Ventura Francesco
Published: December 2020

Rationale:

Only a few cases of accidental deaths due to speargun injuries are reported in the literature. Murder or suicide cases are even rarer.

Patient concerns:

A 59-year-old male with a history of major depression and previous suicide attempts, was found, still alive and conscious, with a spear in his mouth and a fishing speargun a few meters away. The spear then penetrated the cranium and crossed the entire left cerebral hemisphere.

Diagnoses:

The patient underwent a retrograde removal of the spear. During the surgery, there was a massive encephalic bleeding. After about 2 days of coma, brain death was confirmed. An autopsy was performed to determine the cause of death.

Interventions:

The scalp presented hemorrhagic infiltrates in the left parieto-temporal region. There were an acute subdural hematoma and subarachnoid hemorrhage. At the opening of the lateral ventricles a massive fronto-parieto-temporal hematoma was evident. The skull base had a massive hemorrhagic infiltration and a circular fracture of about 0.5 cm in diameter, due to the penetration of the spear. The hard palate showed a circular solution of continuity with net margins whose diameter was consistent with the size of the spear.

Outcomes:

The cause of death was attributed to the traumatic cranial-encephalic lesions due to the speargun shot in the mouth.

Lessons:

The investigation into unusual cases of death constitutes a complex matter and requires a careful evaluation on the part of the forensic pathologist. A differential diagnosis may be necessary in order to rule out simulated suicide/homicide. In this particular case, the analysis of the scene of the self-suppression event and available circumstantial information, the evaluation of clinical data, the complete autopsy and the comparison between the injuries of the victim and the characteristics of the weapon used led to the confirmation of the suicidal nature of the death.
Diagnosis value preoperative localization of insulinoma by diffusion-weighted imaging
Authors: Chen Li-Jun , Han Yue-Dong , Zhang Ming
Published: December 2020

Insulinoma is the most common functional neuroendocrine tumor that originates from the islet of beta cells. Insulinoma is usually an isolated benign tumor and small in size (<2 cm). Due to the small size of the lesion, it often leads to difficulty in clinical preoperative localization diagnosis. However, we have unexpectedly discovered that the diffusion-weighted-imaging (DWI) adds great value in the preoperative localization diagnosis of insulinoma in non-invasive examination technique.

We verified using operative pathology data and retrospectively analyzed the clinical and imageology findings of 5 cases who reported to have an insulinoma. All the 5 cases underwent DWI examination, among non-contrast enhanced magnetic resonance imaging (MRI) in 1 case, contrast-enhanced MRI in 4 cases.

Five cases of DWI showed a nodular high signal <1.3 cm with pancreatic tail in 3 cases, pancreatic neck, and pancreatic head in 1 case each, respectively. Non-contrast enhanced MRI showed suspicious abnormal signals in the tail of the pancreas were detected in 1 case. MRI enhanced scans presented 2 cases with abnormal enhancement in the arterial phase and 2 cases without abnormal enhancement in arterial phase. Also, 3 cases showed mild persistence enhanced in the portal venous phase and delayed phase. However, 1 case remained normal in the portal venous phase and the delay period.

DWI examination has high clinical value in the localization diagnosis of insulinoma and thus it can be used as a routine examination for preoperative localization diagnosis.
Increased signal intensity of spinal cord on T2W magnetic resonance imaging for cervical spondylotic myelopathy patients
Authors: Yin Li-qiang , Zhang Jian , Wu Yong-gui , Li Jin-hui , Yang Qing
Published: December 2020

To investigate the risk factors for progression of increased signal intensity (ISI) on T2W magnetic resonance imaging (MRI) and its prognostic value in patients with cervical spondylotic myelopathy (CSM).

A total of 109 patients with CSM were included in this study. All the patients were treated with anterior cervical discectomy and fusion. MRI was performed for all 109 patients preoperatively and at the final follow-up. Radiological evaluation included ISI, anterior compression (AC) of dural and spinal cord, hyperintensity region (HR) at the involved level. Clinical data including Japanese Orthopedic Association (JOA) score, Neck Disability Index (NDI) score, and Visual Analogue Scale were collected and evaluated. Patients were divided into 2 groups according to ISI grades (Group A: no hyper-intensity; Group B: presence of ISI). Then all patients presented with ISI were divided into 2 subgroups based on the range of HR (Group B1: hyper-intensity diameter accounts for less than half of the spinal cord diameter at the involved level; Group B2, hyper-intensity diameter accounts for more than half of the spinal cord diameter at the involved level). AC, disease duration, age, and gender were analyzed as potential risk factors.

Significantly better JOA and NDI scores were observed in Group A preoperatively and at the final follow-up, compared to Group B (P < .05). Disease duration was found significantly longer in patients with ISI (P < .05). Notably better JOA and NDI scores were noticed in Group B1 rather than Group B2 (P < .05). Logistical regression showed that disease duration was the only factor that significantly correlated with the progress of ISI (P < .001).

CSM patients with ISI on T2W MR images had poorer surgical outcomes compared to others, while the increased range of HR may deteriorate preoperative neurological function. Moreover, patients with longer disease duration had greater risk of ISI in spinal cord.
Bisphosphonate for spontaneous osteonecrosis of the knee
Authors: Shen Zhen , Chen Zehua , Xie Zhuoting , Xu Yanfei , Wang Tao , Li Jiao , Yuan Changfei , Liu Jinqing , Shi Xiaodong , Ai Yuanliang , Dong Wei , Guo Ying
Published: December 2020

Background:

Bisphosphonates are commonly used to treat spontaneous osteonecrosis of the knee (SONK), while there are no relevant systematic review or meta-analysis designed to evaluate the effects of bisphosphonates on SONK.

Methods:

We will identify relevant randomized controlled trials from the PubMed, EMBASE, CINAHL and China National Knowledge Infrastructure, up to March 20, 2020. Data that meets the inclusion criteria will be extracted and analyzed using RevMan V.5.3 software. Two reviewers will assess quality of the included studies by using the Cochrane Collaboration risk of bias tool. Egger test and Begg test will be used to evaluate publication bias. And Grading of Recommendations Assessment, Development and Evaluation will be employed to assess the quality of evidence.

Results:

In this study, we will analyze the effect of bisphosphonates on pain intensity, physical function, biochemical including alkaline phosphatase, N-terminal propeptide of type I procollagen, and C-terminal type I collagen telopeptide, radiological outcome (evaluated by using Magnetic resonance imaging) and ratio of secondary surgery for patients with SONK.

Conclusion:

Our findings will provide evidence for the effectiveness and potential treatment prescriptions of bisphosphonates acupuncture for patients affected by SONK.
Henoch-Schönlein purpura in a patient with oesophageal cancer
Authors: Chen Haonan , Li Chao , Ye Wenli , Ye Wei , Xu Hui , Jiang Qingwei , Huo Zhen , Zhao Xinyan , Li Hang
Published: December 2020

Rationale:

Understanding the association between Henoch-Schönlein purpura (HSP) and malignancy is essential for early diagnosis and treatment of the potential lethal disease. To the best of our knowledge, there has been only one published case of HSP coexisting with oesophageal cancer. Here, we report another patient diagnosed with HSP and oesophageal squamous carcinoma simultaneously.

Patient concerns:

A 60-year-old Chinese male was referred to our hospital because of intermittent abdominal pain, abdominal distension, melena, lower extremities purpura. Positive laboratory values included pancytopenia, microscopic hematuria, nephrotic proteinuria, hematochezia, hypoalbuminemia, hyperlipidaemia, hypocomplementemia, and increased levels of hepatobiliary enzymes and immunoglobulin (Ig) A. Gastrocolonoscopy showed multiple erosion lesion on descending duodenum, terminal ileum, and ileal flap. Biopsy of these lesions suggested non-specific inflammation.

Diagnoses:

HSP (IIIb type) was diagnosed based on renal pathology examination in accordance with the International Study of Kidney Disease in Children (ISKDC) classification. Liver biopsy confirmed the diagnosis of nodular cirrhosis (Ishak 5). Gastroscopy unintentionally revealed three oesophagus lesions. Pathology study suggested intermediate differentiated squamous cell carcinoma (cTNM IB).

Interventions:

Before admission, he was administered intravenous Ig 10 g once daily(qd) for 10 days, methylprednisolone 40 mg qd for a week, followed by prednisolone 50 mg qd for almost 8 weeks. Endoscopic submucosal dissection (ESD) was performed to remove all lesions with negative margin after prednisolone was tapered (5 mg per week until 10 mg qd).

Outcomes:

Despite prednisone being tapered to 2.5 mg qd within 2 months, complete remission of HSP and esophageal malignancy was achieved after the resection of the esophagus lesions during 12 months follow-up.

Lessons:

We report a rare case of oesophageal squamous cell carcinoma initially presented as HSP. This case suggests the importance of evaluating adult patients with HSP for an underlying malignancy.
Long-Term Follow-Up of Tufting Enteropathy Caused by EPCAM Mutation p.Asp253Asn and Absent EPCAM Expression
Authors: Ozler Oğuz , Brunner-Véber Andrea , Fatih Parmis , Müller Thomas , Janecke Andreas R. , Arikan Cigdem
Published: December 2020

Tufting enteropathy (TE) is caused by recessive epithelial cell adhesion molecule (EPCAM) mutations, features congenital intractable diarrhea, growth retardation, and a characteristic disorganization of surface enterocytes. TE generally requires parenteral nutrition (PN) throughout childhood and into adulthood or a small bowel transplantation. We report 2 siblings with TE; a 3-year-old patient 1 intermittently receives partial PN, monthly somatostatin therapy, tolerates a normal diet and has a normal stool output. However, she is the sixth patient of 90 TE patients in literature, to develop a chronic arthritis. A 12-year-old patient 2 is on a normal diet, and did not require PN for the past 8 years. Duodenal biopsies showed characteristic tufts, and a complete lack of EPCAM staining. Both siblings were homozygous for EPCAM mutation c.757G>A (p.Asp253Asn). This observation shows that an overall favorable outcome can be obtained in TE, even with abrogated intestinal EPCAM expression.
ALK Immunohistochemistry and Molecular Analysis in Uterine Inflammatory Myofibroblastic Tumor: Proceedings of the ISGyP Companion Society Session at the 2020 USCAP Annual Meeting
Authors: Parra-Herran Carlos
Published: December 2020

Inflammatory myofibroblastic tumor of the uterus (uIMT) is rare. However, it has been increasingly recognized in recent years, largely due to more awareness of its occurrence in the gynecologic tract and the characterization of features that help distinguish it from more common lesions in the differential diagnosis, particularly smooth muscle neoplasms. One of these features is expression of anaplastic lymphoma kinase (ALK, also known as CD246), which has been documented in most uIMTs described in the literature. This review concentrates on the role of ALK testing in the diagnosis and management of uIMT. In terms of immunohistochemistry, an emphasis on antibody selection, sensitivity/specificity, interpretation and quality control is given. Regarding molecular analysis for ALK alterations, this review appraises fluorescence in situ hybridization and RNA sequencing technologies. Lastly, the role of tyrosine kinase inhibitor therapy in patients with uIMT is discussed, highlighting the importance of a correct diagnosis of this entity.
Immunotherapy Use in Patients With Lung Cancer and Comorbidities
Authors: von Itzstein Mitchell S. , Gonugunta Amrit S. , Mayo Helen G. , Minna John D. , Gerber David E.
Published: December 2020

Immune checkpoint inhibitor (ICI) therapy is now in widespread clinical use for the treatment of lung cancer. Although patients with autoimmune disease and other comorbidities were excluded from initial clinical trials, emerging real-world experience suggests that these promising treatments may be administered safely to individuals with inactive low-risk autoimmune disease such as rheumatoid arthritis or psoriasis, mild to moderate renal and hepatic dysfunction, and certain chronic viral infections. Considerations for ICI in autoimmune disease populations include exacerbations of the underlying autoimmune disease, increased risk of ICI-induced immune-related adverse events, and potential for compromised efficacy if patients are receiving chronic immunosuppression. Immune checkpoint inhibitor use in higher-risk autoimmune conditions, such as myasthenia gravis or multiple sclerosis, requires careful evaluation on a case-by-case basis. Immune checkpoint inhibitor use in individuals with solid organ transplant carries a substantial risk of organ rejection. Ongoing research into the prediction of ICI efficacy and toxicity may help in patient selection, treatment, and monitoring.
Immunotherapy for Lung Cancer—Improving Outcomes in Patients With Locally Advanced Non–Small Cell Lung Cancer With Immunotherapy
Authors: Sun Lova , Aggarwal Charu
Published: December 2020

Patients with locally advanced non–small cell lung cancer (NSCLC), a heterogenous group encompassing stage IIIA–IIIC disease, often have surgically unresectable cancer and are managed with concurrent chemoradiation. Since the establishment of platinum-based chemoradiation as standard of care for unresectable locally advanced NSCLC, various strategies including escalating radiation dose, targeted therapies, antiangiogenic agents, and induction or consolidation chemotherapy have failed to show improvement in outcomes. However, recently, use of consolidation immunotherapy with durvalumab following concurrent chemoradiation therapy has been associated with improvement in survival and has led to a paradigm shift. In this review, we will summarize results from trials of immunotherapy in locally advanced NSCLC and comment on ongoing trials and potential future investigations.
Overview of Lung Cancer Immunotherapy
Authors: Sanmamed Miguel F. , Eguren-Santamaria Iñaki , Schalper Kurt A.
Published: December 2020

Anti–PD-(L)1 therapy represents a turning point in lung cancer immunotherapy, moving from previously ineffective enhancer strategies to immune checkpoints as standard first- and second-line therapies. This unprecedented success highlights the importance of mechanisms to escape immune attack, such PD-1/PD-L1 axis, and emphasize the importance to better understand the tumor immune microenvironment. Analyzing the specifics of immune response against lung tumor cells and how malignant cells progressively adapt to this pressure may help to understand which are the key aspects to guide the development of new therapeutic strategies. Here we review the past and present of clinical lung cancer immunotherapy and give a perspective for the future development based on emerging biological insights.
Direct-drive laser fusion: status, plans and future
Authors: Campbell E. M. , Sangster T. C. , Goncharov V. N. , Zuegel J. D. , Morse S. F. B. , Sorce C. , Collins G. W. , Wei M. S. , Betti R. , Regan S. P. , Froula D. H. , Dorrer C.  , Harding D. R. , Gopalaswamy V. , Knauer J. P. , Shah R. , Mannion O. M. , Marozas J. A. , Radha P. B. , Rosenberg M. J. , Collins T. J. B. , Christopherson A. R. , Solodov A. A. , Cao D. , Palastro J. P. , Follett R. K. , Farrell M.
Published: December 2020

Laser-direct drive (LDD), along with laser indirect (X-ray) drive (LID) and magnetic drive with pulsed power, is one of the three viable inertial confinement fusion approaches to achieving fusion ignition and gain in the laboratory. The LDD programme is primarily being executed at both the Omega Laser Facility at the Laboratory for Laser Energetics and at the National Ignition Facility (NIF) at Lawrence Livermore National Laboratory. LDD research at Omega includes cryogenic implosions, fundamental physics including material properties, hydrodynamics and laser–plasma interaction physics. LDD research on the NIF is focused on energy coupling and laser–plasma interactions physics at ignition-scale plasmas. Limited implosions on the NIF in the ‘polar-drive’ configuration, where the irradiation geometry is configured for LID, are also a feature of LDD research. The ability to conduct research over a large range of energy, power and scale size using both Omega and the NIF is a major positive aspect of LDD research that reduces the risk in scaling from OMEGA to megajoule-class lasers. The paper will summarize the present status of LDD research and plans for the future with the goal of ultimately achieving a burning plasma in the laboratory.

This article is part of a discussion meeting issue ‘Prospects for high gain inertial fusion energy (part 2)’.
Factors influencing the commercialization of inertial fusion energy
Authors: Koepke M. E.
Published: December 2020

Managing the IFE pathway to fusion electricity will involve management of commericalization scope, schedule, cost and risk. The technology pathway to economical fusion power comprises the commercialization scope. Industry assumes commercialization risk in fielding its own pre-pilot plant research programme for this compact-fusion pathway without the benefit of a federally coordinated IFE research and development programme. The cost of commercializing the mass-production of inexpensive targets and insisting on high reliability, availability, maintainability and inspectability has a major impact on the economics of commercializing fusion power plants. Schedule vulnerability for inertial fusion energy arises from the sensitivity of time-based roadmap stages to uncertainties in the pace of scientific understanding and technology development, as well as to unexpected and inexplicable changes of the budgeting process. Rather than rely on a time-based roadmap, a milestone-based roadmap is maximally appropriate, especially for industry and investors who are particularly well-suited to taking the risks associated with reaching the target milestones provided by the government. Milestones must be identified and optimally sequenced and the necessary resources must be delineated. Progress on the above factors, since the outcomes of recent U.S., U.K. and EUROfusion roadmapping exercises were released, are reported.

This article is part of a discussion meeting issue ‘Prospects for high gain inertial fusion energy (part 2)’.
One-dimensional hydrodynamic simulations of low convergence ratio direct-drive inertial confinement fusion implosions
Authors: Paddock R. W. , Martin H. , Ruskov R. T. , Scott R. H. H. , Garbett W. , Haines B. M. , Zylstra A. B. , Aboushelbaya R. , Mayr M. W. , Spiers B. T. , Wang R. H. W. , Norreys P. A.
Published: December 2020

Indirect drive inertial confinement fusion experiments with convergence ratios below 17 have been previously shown to be less susceptible to Rayleigh–Taylor hydrodynamic instabilities, making this regime highly interesting for fusion science. Additional limitations imposed on the implosion velocity, in-flight aspect ratio and applied laser power aim to further reduce instability growth, resulting in a new regime where performance can be well represented by one-dimensional (1D) hydrodynamic simulations. A simulation campaign was performed using the 1D radiation-hydrodynamics code HYADES to investigate the performance that could be achieved using direct-drive implosions of liquid layer capsules, over a range of relevant energies. Results include potential gains of 0.19 on LMJ-scale systems and 0.75 on NIF-scale systems, and a reactor-level gain of 54 for an 8.5 MJ implosion. While the use of 1D simulations limits the accuracy of these results, they indicate a sufficiently high level of performance to warrant further investigations and verification of this new low-instability regime. This potentially suggests an attractive new approach to fusion energy.

This article is part of a discussion meeting issue ‘Prospects for high gain inertial fusion energy (part 2)’.
Neural correlates of sleep recovery following melatonin treatment for pediatric concussion: a randomized control trial
Authors: Iyer Kartik K. , Zalesky Andrew , Cocchi Luca , Barlow Karen M.
Published: December 2020

Evidence-based treatments for children with persistent post-concussion symptoms (PPCS) are few and limited. Common PPCS complaints such as sleep disturbance and fatigue could be ameliorated via the supplementation of melatonin, which has significant neuroprotective and anti-inflammatory properties. This study aims to identify neural correlates of melatonin treatment with changes in sleep disturbances and clinical recovery in a pediatric cohort with PPCS. We examined structural and functional neuroimaging (MRI) in 62 children with PPCS in a randomized, double-blind, placebo-controlled trial of 3mg or 10mg of melatonin (NCT01874847). The primary outcome was the total youth self-report Post-Concussion Symptom Inventory (PCSI) score after 28 days of treatment. Secondary outcomes included the change in the sleep domain PCSI score and sleep-wake behavior (assessed using wrist-worn actigraphy). Whole-brain analyses of (i) functional connectivity (FC) of resting-state fMRI, and (ii) structural grey matter (GM) volumes via voxel-based morphometry were assessed immediately before and after melatonin treatment and compared to placebo in order to identify neural effects of melatonin treatment. Increased FC of posterior default mode network (DMN) regions with visual, somatosensory and dorsal networks was detected in the melatonin groups over time. FC increases also corresponded with reduced wake periods (r=−0.27,p=0.01). Children who did not recover (n=39) demonstrated significant FC increases within anterior DMN and limbic regions compared to those that did recover (i.e. PCSI scores returned to pre-injury leveln=23) over time, (p=0.026). Increases in GM volume within the posterior cingulate cortex were found to correlate with reduced wakefulness after sleep onset (r=−0.32,p=0.001) and sleep symptom improvement (r=0.29,p=0.02). Although the melatonin treatment trial was negative and did not result in PPCS recovery (with or without sleep problems), the relationship between melatonin and improvement in sleep parameters were linked to changes in function-structure within and between brain regions interacting with the DMN.
Kinetic sequencing (k-Seq) as a massively parallel assay for ribozyme kinetics: utility and critical parameters
Authors: Shen Yuning , Pressman Abe , Janzen Evan , Chen Irene
Published: December 2020

Characterization of genotype-phenotype relationships of genetically encoded molecules (e.g., ribozymes) requires accurate quantification of activity for a large set of molecules. Kinetic measurement using high-throughput sequencing (e.g.,k-Seq) is an emerging assay applicable in various domains that potentially scales up measurement throughput to 105~ 106unique sequences. However, technical challenges introduced by sequence heterogeneity and DNA sequencing must be understood to realize the utility and limitations of such assays. We characterized thek-Seq method in terms of model identifiability, effects of sequencing error, accuracy and precision using simulated datasets and experimental data from a variant pool constructed from previously identified ribozymes. Relative abundance, kinetic coefficients, and measurement noise were found to affect the measurement of each sequence. We introduced bootstrapping to robustly quantify the uncertainty in estimating model parameters and proposed interpretable metrics to quantify model identifiability. These efforts enabled the rigorous reporting of data quality for individual sequences ink-Seq experiments. Critical experimental factors were examined, and general guidelines are proposed to maximize the number of sequences having precisely estimated and identifiable kinetic coefficients fromk-Seq data. Practices analogous to those laid out here could be applied to improve the rigor of similar sequencing-based assays.
Cingulate prediction of response to antidepressant and cognitive behavioral therapies for depression: Theory, meta-analysis, and empirical application
Authors: Strege Marlene V. , Siegle Greg J. , Young Kymberly
Published: December 2020

Objective

In the interest of precision medicine, we sought to derive preclinical markers of neural mechanisms associated with treatment response in unipolar depression, separated by treatment type.

Methods

We conducted separate neuroimaging meta-analyses of neural predictors for response to Cognitive Behavioral Therapy (CBT) and Selective Serotonin Reuptake Inhibitors (SSRIs). We assessed whether reactivity of derived regions predicted clinical change in a preference trial of patients with major depressive disorder (MDD) who received CBT (n = 61) or SSRIs (n = 19).

Results

The meta-analyses yielded regions within the perigenual (pgACC) and subgenual anterior cingulate cortex (sgACC) associated with SSRI and CBT response, respectively. In our sample, reactivity of the sgACC region was prognostic for response to CBT, but neither cingulate region was prognostic for response to SSRIs using a linguistic task; most prognostic SSRI studies used images. An exploratory analysis revealed a pgACC region for which reactivity to images was prognostic for response to SSRIs.

Conclusions

Results suggest that neural reactivity of the sgACC and pgACC are associated with CBT and SSRI response for unipolar depression. Further research incorporating methodological considerations is necessary for translation.
SARS-CoV-2 in Brazil: analysis of molecular variance and genetic diversity in viral haplotypes found in the states of Rio de Janeiro, São Paulo, Paraná and Tocantins
Authors: de Albuquerque Rosane Maria , Da Silva Eduarda Doralice Alves Braz , Venâncio Dallynne Bárbara Ramos , da Silva Ramos Robson , Felix Pierre Teodósio
Published: December 2020

In this work, 18 sequences of the SARS-CoV-2 virus were used, from four Brazilian states (Rio de Janeiro, São Paulo, Paraná and Tocantins) with 09, 04, 04, 8 and 01 haplotypes, respectively, with lengths ranging from 234 to 29,903 bp. All sequences were publicly available on the National Biotechnology Information Center (NCBI) platform and were previously aligned with the MEGA X software, where all gaps and ambiguous sites were extracted for the construction of the phylogenetic tree. Of the 301 sites analyzed, 68% varied, 131 of which were parsimonium-informative sites. Phylogenetic analyses revealed the presence of two distinct subgroups, corroborated by the high FST(80%). The high degree of polymorphism found among these samples helped to establish a clear pattern of non-genetic structuring, based on the time of divergence between the groups. All molecular variance estimators confirmed that there was no consensus in the conservation of the studied sequences, also indicating a high variation for the protein products of the virus. In a highly miscegenational and diverse population such as the Brazilian population, this observation draws our attention to the need for an urgent increase in public health actions, awareness strategies, hygiene and distancing practices and not the other way around.
Sca1+cells as direct isolate (ex vivo) versusin vitrocultured exhibit differential proteomic signatures in murine skeletal muscle
Authors: Kapoor Saketh , Subba Pratigya , Shenoy P Sudheer , Bose Bipasha
Published: December 2020

Stem cell antigen-1 (Sca-1) is a glycosyl-phosphatidylinositol-anchored membrane protein that is expressed in a sub-population of muscle stem and progenitor cell types. Reportedly, Sca-1 regulates the myogenic property of myoblasts andSca-1-/-mice exhibited defective muscle regeneration. Although the role of Sca-1 in muscle development and maintenance is well-acknowledged, molecular composition of muscle derived Sca-1+cells is not characterized. Here, we applied a high-resolution mass spectrometry-based workflow to characterize the proteomic landscape of mouse hindlimb skeletal muscle derived Sca-1+cells. Furthermore, we characterized the impact of the cellular microenvironments on the proteomes of Sca-1+cells. The proteome component of freshly isolated (ex vivo) Sca-1+cells was compared with that of Sca-1+cells expanded in cell culture (in vitro). The analysis revealed significant differences in the protein abundances in the two conditions reflective of their functional variations. The identified proteins were enriched in various biological pathways. Notably, we identified proteins related to myotube differentiation, myotube cell development and myoblast fusion. We also identified a panel of cell surface marker proteins that can be leveraged in future to enrich Sca-1+cells using combinatorial strategies. Comparative analysis implicated the activation of various pathways leading to increased protein synthesis underin vitrocondition. We report here the most comprehensive proteome map of Sca-1+cells that provides insights into the molecular networks operative in Sca-1+cells. Importantly, through our work we generated the proteomic blueprint of protein abundances significantly altered in Sca-1+cells underex vivoandin vitroconditions.
Absence-like epileptic spike-wave discharges in adult Lister Hooded rats and their pharmacological modulation
Authors: Nyitrai Gabriella , Diószegi Pálma , Somogyi Gergely , Czurkó András
Published: December 2020

Efforts to advance translation through pre-clinical behavioural and pharmacological tests prompted attention to rat strain differences. Particularly the use of touchscreen technology for cognitive testing initiated the widespread use of Lister Hooded and Long Evans rats and they differed in pharmacological sensitivity to certain drugs. One possible reason for this rat strain difference could be that Long Evans rats produce high-amplitude spike-wave discharges (SWDs) in their cortical EEG recordings, while no information available about Lister Hooded rats in this regard. As a serendipitous observation, we noticed the presence of SWDs during the EEG recordings of Lister Hooded rats. In this study, therefore, we examined these spontaneous SWDs in two groups of Lister Hooded rats. The number and sum duration of the SWDs were similar to that was observed in other rat strains. We found SWDs during wakefulness, slow-wave sleep (SWS) and rapid eye movement (REM) sleep, their duration was the longest during wakefulness, but their number and sum duration were also high during REM. The GABA-B receptor agonist baclofen exacerbated, while the GABA-B antagonist SCH50911 reduced the occurrence of the recorded SWDs. Typical anti-seizure medications, valproate and diazepam, decreased the number and sum duration of SWDs. Although the two rat strains typically used in touchscreen experiments are similar in term of SWDs, the occurrence and possible pharmacological modulation of SWDs are considerable during their use in behavioural experiments.
Cicada timetree by BEAST v1.X verified the recently and exponentially increasing base substitution rates
Authors: Osozawa Soichi , Wakabayashi John
Published: December 2020

Following the recent publication of global cicada phylogenetic trees by Marshall et al. (2018), Łukasik et al. (2018), and Simon et al. (2019), we developed a new dated tree incorporating mostly endemic east Asian cicada data for totally 113 specimens, using the mostly advanced BEAST v1.X software applied the relaxed clock model. Fossil calibrations as old as Triassic were adopted after Moulds (2018), and a Quaternary geological event calibration was adopted following Osozawa et al. (2012), applying the calibration function of BEAST. Our timetree suggests that Tettigarctidae had cicada basal lineage as old as 200 Ma, and Derotettiginae was next as old as 100 Ma. Tibicininae was a sister of the resting Cicadidae, and Tettigomyiinae, Cicadettinae, and Cicadina started simultaneous branching and radiation around 40 Ma. We made a base substitution rate vs age diagram based on the timetree using the BEAST function, and it strongly suggested an exponential increase of base substitution rate approaching the present. The consequent increased cicada biodiversity including generation of cryptic species might have been driven by the generation and spreading of C4 grasses and the following Quaternary glaciations and severe environmental change.
Adaptation ofBacillus thuringiensisto plant colonization affects differentiation and toxicity
Authors: Lin Yicen , Alstrup Monica , Pang Janet Ka Yan , Maróti Gergely , Er-Rafik Mériem , Tourasse Nicolas , Økstad Ole Andreas , Kovács Ákos T.
Published: December 2020

Bacillus cereusgroup (Bacillus cereus sensu lato) has a diverse ecology, including various species that are vertebrate or invertebrate pathogens. Few isolates from theB. cereusgroup have however been demonstrated to benefit plant growth. Therefore, it is crucial to explore how bacterial development and toxicity evolves during plant colonization. Herein, we investigatedBacillus thuringiensis(Cry-) adaptation to the colonization ofArabidopsis thalianaroots, and monitored changes in cellular differentiation in experimentally evolved isolates. Isolates from two populations displayed improved iterative ecesis on roots and increased toxicity against insect larvae. Molecular dissection and recreation of a causative mutation revealed the importance of a non-sense mutation in therhotranscription terminator gene. Transcriptome analysis revealed how Rho impacts variousB. thuringiensisgenes involved in carbohydrate metabolism and virulence. Our work suggests that evolved multicellular aggregates have a fitness advantage over single cells when colonizing plants, creating a trade-off between swimming and multicellularity in evolved lineages, in addition to unrelated alterations in pathogenicity.

Importance

Biologicals-based plant protection relies on the use of safe microbial strains. During application of biologicals to the rhizosphere, microbes adapt to the niche, including genetic mutations shaping the physiology of the cells. Here, the experimental evolution ofBacillus thuringiensislacking the insecticide crystal toxins was examined on the plant root to reveal how adaptation shapes the differentiation of this bacterium. Interestingly, evolution of certain linages led to increased emetic toxin production, hemolysis and insect larvae pathogenesis inB. thuringiensisdriven by transcriptional rewiring. Further, our detailed study reveals how inactivation of the transcription termination protein Rho promotes aggregation on the plant root in addition to altered differentiation and pathogenesis inB. thuringiensis.
Horizontal gene transfer and recombination analysis of SARS-CoV-2 genes helps discover its close relatives and shed light on its origin
Authors: Makarenkov Vladimir , Mazoure Bogdan , Rabusseau Guillaume , Legendre Pierre
Published: December 2020

Background

The SARS-CoV-2 pandemic is among the most dangerous infectious diseases that have emerged in recent history. Human CoV strains discovered during previous SARS outbreaks have been hypothesized to pass from bats to humans using intermediate hosts, e.g. civets for SARS-CoV and camels for MERS-CoV. The discovery of an intermediate host of SARS-CoV-2 and the identification of specific mechanism of its emergence in humans are topics of primary evolutionary importance. In this study we investigate the evolutionary patterns of 11 main genes of SARS-CoV-2. Previous studies suggested that the genome of SARS-CoV-2 is highly similar to the horseshoe bat coronavirus RaTG13 for most of the genes and to some Malayan pangolin coronavirus (CoV) strains for the receptor binding (RB) domain of the spike protein.

Results

We provide a detailed list of statistically significant horizontal gene transfer and recombination events (both intergenic and intragenic) inferred for each of 11 main genes of the SARS-Cov-2 genome. Our analysis reveals that two continuous regions of genes S and N of SARS-CoV-2 may result from intragenic recombination between RaTG13 and Guangdong (GD) Pangolin CoVs. Statistically significant gene transfer-recombination events between RaTG13 and GD Pangolin CoV have been identified in region [1215-1425] of gene S and region [534-727] of gene N. Moreover, some significant recombination events between the ancestors of SARS-CoV-2, RaTG13, GD Pangolin CoV and bat CoV ZC45-ZXC21 coronaviruses have been identified in genes ORF1ab, S, ORF3a, ORF7a, ORF8 and N. Furthermore, topology-based clustering of gene trees inferred for 25 CoV organisms revealed a three-way evolution of coronavirus genes, with gene phylogenies of ORF1ab, S and N forming the first cluster, gene phylogenies of ORF3a, E, M, ORF6, ORF7a, ORF7b and ORF8 forming the second cluster, and phylogeny of gene ORF10 forming the third cluster.

Conclusions

The results of our horizontal gene transfer and recombination analysis suggest that SARS-Cov-2 could not only be a chimera resulting from recombination of the bat RaTG13 and Guangdong pangolin coronaviruses but also a close relative of the bat CoV ZC45 and ZXC21 strains. They also indicate that a GD pangolin may be an intermediate host of SARS-CoV-2.
Six 1-halobenzoyl-4-(2-methoxyphenyl)piperazines having Z′ values of one, two or four; disorder, pseudosymmetry, twinning and supramolecular assembly in one, two or three dimensions
Authors: Harish Chinthal Chayanna , Kavitha Channappa N. , Yathirajan Hemmige S. , Foro Sabine , Glidewell Christopher
Published: December 2020

Six 1-halobenzoyl-4-(2-methoxyphenyl)piperazines have been prepared using carbodiimide-mediated coupling reactions between halobenzoic acids and N-(2-methoxyphenyl)piperazine. The molecules of 1-(4-fluorobenzoyl)-4-(2-methoxyphenyl)piperazine, C18H19FN2O2 (I), are linked into a chain of rings by a combination of C—H...O and C—H...π(arene) hydrogen bonds. 1-(4-Chlorobenzoyl)-4-(2-methoxyphenyl)piperazine, C18H19ClN2O2 (II), crystallizes in the space group Pca21 with Z′ = 4 and it exhibits both pseudosymmetry and inversion twinning: a combination of six C—H...O and two C—H...π(arene) hydrogen bonds generate a three-dimensional assembly. In 1-(4-bromobenzoyl)-4-(2-methoxyphenyl)piperazine, C18H19BrN2O2 (III), which also crystallizes in space group Pca21 but with Z′ = 2, the bromobenzoyl unit in one of the molecules is disordered. Pseudosymmetry and inversion twinning are again present, and a combination of three C—H...O and one C—H...π(arene) hydrogen bonds generate a two-dimensional assembly. A single C—H...O hydrogen bond links the molecules of 1-(4-iodobenzoyl)-4-(2-methoxyphenyl)piperazine, C18H19IN2O2 (IV), into simple chains but in the isomeric 3-iodobenzoyl analogue (V), which crystallizes in space group P212121 with Z′ = 2, a two-dimensional assembly is generated by a combination of four C—H...O and two C—H...π(arene) hydrogen bonds; pseudosymmetry and inversion twinning are again present. A single C—H...O hydrogen bond links the molecules of 1-(2-fluorobenzoyl)-4-(2-methoxyphenyl)piperazine, C18H19FN2O2 (VI), into simple chains. Comparisons are made with the structures of some related compounds.
Integrating technology subjects with design studio teaching: comparing curriculum of architecture education in Australia and Iran
Authors: Saghafi Mahmoud Reza , Crowther Philip
Published: December 2020

Purpose

Design studio and technology subjects are two dominant parts of the architecture curriculum. How to integrate these different parts of the curriculum is one of the important challenges in architecture education around the world. With increasing internationalisation of both the profession and higher education, an understanding of similarities and differences across the globe is important. This paper illustrates two different approaches to such integration in two very different contexts: case studies at the Queensland University of Technology (QUT) in Australia and the University of Tehran (UT) in Iran.

Design/methodology/approach

The study implemented a case study approach based on document analysis methods. This paper explores the integrated role of technology subjects in architecture education, followed by a critique of the teaching of technology within the design studio. The analysis is conducted across four significant features of the curriculum.

Findings

Overall, in both programmes, the aim is for students to develop architectural knowledge and skills; although the Iranian programme has a stronger focus on knowledge, the Australian programme has a stronger focus on the application of knowledge and skills, particularly within the design studio projects.

Originality/value

The comparative analysis of architectural education in these two different contexts offers an insight into alternative approaches to teaching technology. Such an insight may offer guidance in curriculum development to support the exploration of new hybrid approaches as well as supporting international student mobility.