bluuebunny/crossref_metadata_2025 huggingface dataset:
Orbital dynamics of 2020 AV2: the first Vatira asteroid
Authors: Greenstreet Sarah
Published: February 2020

Vatira-class near-Earth objects (NEOs) have orbits entirely interior to the orbit of Venus with aphelia 0.307 < Q < 0.718 au. Recently discovered asteroid 2020 AV2 by the Zwicky Transient Facility on 2020 January 4 is the first known object on a Vatira orbit. Numerical integrations of 2020 AV2’s nominal orbit show it remaining in the Vatira region for the next few hundred kyr before coupling to Venus and evolving onto an Atira orbit (NEOs entirely interior to Earth’s orbit with 0.718 < Q < 0.983 au) and eventually scattering out to Earth-crossing. The numerical integrations of 9900 clones within 2020 AV2’s orbital uncertainty region show examples of Vatira orbits trapped in the 3:2 mean-motion resonance with Venus at semimajor axis a ≈ 0.552 au that can survive on the order of a few Myr. Possible 2020 AV2 orbits also include those on Vatira orbits between Mercury and Venus that only rarely cross that of a planet. Together, the 3:2 resonance and these rarely-planet-crossing orbits provide a meta-stable region of phase space that is stable on time-scales of several Myr. If 2020 AV2 is currently in this meta-stable region (or was in the past), that may explain its discovery as the first Vatira and may be where more are discovered.
Deep analysis of RNA N6-adenosine methylation (m6A) patterns in human cells
Authors: Wang Jun , Wang Liangjiang
Published: February 2020

N6-adenosine methylation (m6A) is the most abundant internal RNA modification in eukaryotes, and affects RNA metabolism and non-coding RNA function. Previous studies suggest that m6A modifications in mammals occur on the consensus sequence DRACH (D = A/G/U, R = A/G, H = A/C/U). However, only about 10% of such adenosines can be m6A-methylated, and the underlying sequence determinants are still unclear. Notably, the regulation of m6A modifications can be cell-type-specific. In this study, we have developed a deep learning model, called TDm6A, to predict RNA m6A modifications in human cells. For cell types with limited availability of m6A data, transfer learning may be used to enhance TDm6A model performance. We show that TDm6A can learn common and cell-type-specific motifs, some of which are associated with RNA-binding proteins previously reported to be m6A readers or anti-readers. In addition, we have used TDm6A to predict m6A sites on human long non-coding RNAs (lncRNAs) for selection of candidates with high levels of m6A modifications. The results provide new insights into m6A modifications on human protein-coding and non-coding transcripts.
Pulsed fraction of super-critical column accretion flows on to neutron stars: Modeling of ultraluminous X-ray pulsars
Authors: Inoue Akihiro , Ohsuga Ken , Kawashima Tomohisa
Published: February 2020

We calculate the pulsed fraction (PF) of the super-critical column accretion flows on to magnetized neutron stars (NSs), of which the magnetic axis is misaligned with the rotation axis, based on the simulation results by Kawashima et al. (2016, PASJ, 68, 83). Here, we solve the geodesic equation for light in the Schwarzschild spacetime in order to take into account the light-bending effect. The gravitational redshift and the relativistic Doppler effect from gas motions of the accretion columns are also incorporated. The pulsed emission appears since the observed luminosity, which exceeds the Eddington luminosity for the stellar-mass black holes, periodically changes via precession of the column caused by the rotation of the NS. The PF tends to increase as $\theta _{\rm obs}$ approaches to $\theta _{\rm B}$, where $\theta _{\rm obs}$ and $\theta _{\rm B}$ are the observer’s viewing angle and the polar angle of the magnetic axis measured from the rotation axis, respectively. The maximum PF is around 50%. Also, we find that the PF becomes less than 5% for $\theta _{\rm obs} \lesssim 5^\circ$ or for $\theta _{\rm B} \lesssim 5^\circ$. Our results are consistent with observations of ultraluminous X-ray pulsars (ULXPs) with few exceptions, since the ULXPs mostly exhibit the PF of $\lesssim 50$%. Our present study supports the hypothesis that the ULXPs are powered by the super-critical column accretion on to NSs.
dEMBF v2.0: An Updated Database of Enzymes for Microalgal Biofuel Feedstock
Authors: Sahoo Susrita , Mahapatra Soumya Ranjan , Parida Bikram Kumar , Narang Parminder Kaur , Rath Satyajit , Misra Namrata , Suar Mrutyunjay
Published: February 2020

In light of increasing algal genomics data and knowledge of biosynthetic pathways responsible for biofuel production, an integrated resource for easy access to all information is essential to improve our understanding of algal lipid metabolism. Against this backdrop, dEMBF v2.0, a significantly updated and improved version of our database of microalgae lipid biosynthetic enzymes for biofuel production, has been developed. dEMBF v2.0 now contains a comprehensive annotation of 2018 sequences encoding 35 enzymes, an increase of over 7-fold as compared with the first version. Other improved features include an increase in species coverage to 32 algal genomes, analysis of additional metabolic pathways, expanded annotation thoroughly detailing sequence and structural features, including enzyme–ligand interactions, and integration of supporting experimental evidence to demonstrate the role of enzymes in increasing lipid content. Along with a complete redesign of the interface, the updated database provides several inbuilt tools and user-friendly functionalities for more interactive and dynamic visualization of data.
Vaccination Policies: Between Best and Basic Interests of the Child, between Precaution and Proportionality
Authors: Pierik Roland
Published: February 2020

How should liberal-democratic governments deal with emerging vaccination hesitancy when that leads to the resurgence of diseases that for decades were under control? This article argues that vaccination policies should be justified in terms of a proper weighing of the rights of children to be protected against vaccine-preventable diseases and the rights of parents to raise their children in ways that they see fit. The argument starts from the concept of the ‘best interests of the child involved’. The concept is elaborated for this context into the dual regime structure in which parents have fiduciary authority over what they consider to be best for their child, and the state has fiduciary authority over a child’s basic interests. This argument leads to conditional mandatory vaccination programs that should be informed by a correct balancing of the two legal principles of proportionality and precaution. This results in contextual childhood vaccination policies of upscaling interference: a three-tiered approach of increased intrusion, from voluntary program when possible and mandatory or even compulsory programs when necessary to protect the child’s basic interests.
Subomohyoid Anterior Suprascapular Block versus Interscalene Block for Arthroscopic Shoulder Surgery
Authors: Abdallah Faraj W. , Wijeysundera Duminda N. , Laupacis Andreas , Brull Richard , Mocon Aaron , Hussain Nasir , Thorpe Kevin E. , Chan Vincent W. S.
Published: February 2020

Background

Interscalene brachial plexus block, the pain relief standard for shoulder surgery, is an invasive technique associated with important complications. The subomohyoid anterior suprascapular block is a potential alternative, but evidence of its comparative analgesic effect is sparse. The authors tested the hypothesis that anterior suprascapular block is noninferior to interscalene block for improving pain control after shoulder surgery. As a secondary objective, the authors evaluated the success of superior trunk (C5–C6 dermatomes) block with suprascapular block.

Methods

In this multicenter double-blind noninferiority randomized trial, 140 patients undergoing shoulder surgery were randomized to either interscalene or anterior suprascapular block with 15 ml of ropivacaine 0.5% and epinephrine. The primary outcome was area under the curve of postoperative visual analog scale pain scores during the first 24 h postoperatively. The 90% CI for the difference (interscalene-suprascapular) was compared against a –4.4-U noninferiority margin. Secondary outcomes included presence of superior trunk blockade, pain scores at individual time points, opioid consumption, time to first analgesic request, opioid-related side-effects, and quality of recovery.

Results

A total of 136 patients were included in the analysis. The mean difference (90% CI) in area under the curve of pain scores for the (interscalene-suprascapular) comparison was –0.3 U (–0.8 to 0.12), exceeding the noninferiority margin of –4.4 U and demonstrating noninferiority of suprascapular block. The risk ratio (95% CI) of combined superior trunk (C5–C6 dermatomes) blockade was 0.98 (0.92 to 1.01), excluding any meaningful difference in superior trunk block success rates between the two groups. When differences in other analgesic outcomes existed, they were not clinically important.

Conclusions

The suprascapular block was noninferior to interscalene block with respect to improvement of postoperative pain control, and also for blockade of the superior trunk. These findings suggest that the suprascapular block consistently blocks the superior trunk and qualify it as an effective interscalene block alternative.

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What We Already Know about This Topic

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Epigenetic therapies in acute myeloid leukemia: the role of hypomethylating agents, histone deacetylase inhibitors and the combination of hypomethylating agents with histone deacetylase inhibitors
Authors: Xu Qing-Yu , Yu Li
Published: February 2020

Epigenetic regulation includes changes of DNA methylation and modifications of histone proteins and is essential for normal physiologic functions, especially for controlling gene expression. Epigenetic dysregulation plays a key role in disease pathogenesis and progression of some malignancies, including acute myeloid leukemia (AML). Epigenetic therapies, including hypomethylating agents (HMAs) and histone deacetylase (HDAC) inhibitors, were developed to reprogram the epigenetic abnormalities in AML. However, the molecular mechanisms and therapeutic effects of the two agents alone or their combination remain unknown. An overview of these epigenetic therapies is given here. A literature search was conducted through PubMed database, looking for important biological or clinical studies related to the epigenetic regimens in the treatment of AML until October 15th, 2019. Various types of articles, including original research and reviews, were assessed, identified, and eventually summarized as a collection of data pertaining the mechanisms and clinical effects of HMAs and HDAC inhibitors in AML patients. We provided here an overview of the current understanding of the mechanisms and clinical therapeutic effects involved in the treatment with HMAs and HDAC inhibitors alone, the combination of epigenetic therapies with intensive chemotherapy, and the combination of both types of epigenetic therapies. Relevant clinical trials were also discussed. Generally speaking, the large number of studies and their varied outcomes demonstrate that effects of epigenetic therapies are heterogeneous, and that HMAs combination regimens probably contribute to significant response rates. However, more research is needed to explore therapeutic effects of HDAC inhibitors and various combinations of HMAs and HDAC inhibitors.
Stem Cell Therapy for Acute Myocardial Infarctions
Authors: Rudman Joseph , Frishman William H.
Published: February 2020

Each year 790,000 people in the United States suffer from a myocardial infarction. This results in the permanent loss of cardiomyocytes and an irreversible loss of cardiac function. Current therapies lower mortality rates, but do not address the core pathology, which opens a pathway to step-wise heart failure. Utilizing stem cells to regenerate the dead tissue is a potential method to reverse these devastating effects. Several clinical trials have already demonstrated the safety of stem cell therapy. In this review, we highlight clinical trials, which have utilized various stem cell lineages, and discuss areas for future research.
Combined effects of mephedrone and cocaine on locomotor activity and conditioned place preference in male Sprague–Dawley rats
Authors: Kohler Robert J. , Cibelli Josefina , Baker Lisa E.
Published: February 2020

Mephedrone (MEPH) is one of several synthetic cathinone derivatives and a common constituent of illicit ‘bath salts’. Concomitant use of MEPH with other psychostimulants is common among recreational users, but their combined effects have not been evaluated rigorously. In experiment 1, 56 male Sprague-Dawley rats were administered saline, MEPH (1 or 5 mg/kg), COC (5 mg/kg), or a mixture of MEPH (1 or 5 mg/kg) + COC (5 mg/kg) for seven consecutive days. Following a 10-day drug washout, rats were given a challenge injection of COC (5 mg/kg). Locomotor activity was recorded for 60 minutes immediately before and for 60 minutes immediately after injections on days 1, 7, and 17. In experiment 2, an unbiased conditioned place preference procedure was implemented over a 10-day period with a separate group of 66 male Sprague-Dawley rats randomly assigned to similar drug treatments used in experiment. Results of experiment 1 indicated significant increases in horizontal activity after repeated treatment with MEPH+COC mixtures, but not with either drug alone. Additionally, rats pretreated with MEPH + COC mixtures exhibited an augmented response to cocaine following drug abstinence. Evidence for CPP was established in rats treated with 5 mg/kg MEPH, 5 mg/kg COC and the 5 mg/kg MEPH + 5 mg/kg COC mixture. In conclusion, cocaine and mephedrone may have additive locomotor stimulant effects, although further assessment with a wider range of dose combinations must be evaluated. As a precautionary note, concurrent use of these substances may pose an enhanced risk for abuse.
CASE OF TORPEDO MACULOPATHY WITH TWO DISTINCT ZONES OF THE RETINAL PIGMENT EPITHELIUM
Authors: Brill Daniel A. , Lin Xihui , Garcia Armando L. , Hou Andrew C. , Le Kim H.
Published: February 2020

Background/Purpose:

To report a case of torpedo maculopathy with two distinct zones of the retinal pigment epithelium visualized on optical coherence tomography.

Methods:

Observational case report.

Results:

A 6-year-old female presented for a routine examination. Visual acuity was 20/20 bilaterally. Dilated fundus examination was normal in the right eye. Dilated fundus examination of the left eye showed a wedge-shaped area of hypopigmentation in the temporal macula. Optical coherence tomography macula of the left eye showed outer retinal cavitation with segmentation of the foveal retinal pigment epithelium into a superficial fluffy zone and a deeper hyperreflective zone.

Conclusion:

This case helps contribute to the growing body of the torpedo maculopathy literature that may reveal different stages of the same disease evolving over time.
Immunogenicity of Diphtheria Booster Vaccination in Adolescents With Inflammatory Bowel Disease
Authors: Dembiński Łukasz , Krzesiek Elżbieta , Klincewicz Beata , Grzybowska-Chlebowczyk Urszula , Demkow Urszula , Banaszkiewicz Aleksandra , Radzikowski Andrzej
Published: February 2020

The aim of this prospective study was to assess the immunogenicity and safety of booster vaccine against diphtheria in children with inflammatory bowel disease on and without immunosuppression treatment. Immunoprotection was achieved in 93% of the children. No significant differences depending on the treatment used and no serious adverse events or flares of inflammatory bowel disease were observed.
New Strategy Is Needed to Prevent Pneumococcal Meningitis
Authors: Mukerji Reshmi , Briles David E
Published: February 2020

Background:

Polysaccharide conjugate vaccines (PCVs) target the pneumococcal capsular types that most commonly cause fatal pneumonia and sepsis. Because these types were eliminated by the vaccines, it became apparent that in immunized populations, most invasive pneumococcal diseases, including bacteremia, sepsis and complicated pneumonia, were greatly reduced. However, the protective effects of PCVs against another invasive disease, meningitis, has shown much less or no decrease in disease incidence.

Methods:

References were identified through searches of PubMed for articles published from January 1930 to the present by use of specific search terms. Relevant articles were also identified through searches in Google and Google Scholar. Relevant references cited in those articles were also reviewed.

Results:

Even in the presence of the PCVs, meningitis rates in children have been reported globally to be as high as 13 per 100,000 annually. Widespread use of vaccines resulted in the emergence of a broad diversity of replacement non-PCV type strains. These strains generally failed to cause sepsis, but caused meningitis of comparable severity and levels similar to, or in excess of, prior pneumococcal meningitis rates. This is probably because these non-PCV type strains do not survive well in the blood, therefore possibly entering the brain through nonhematogenous routes.

Conclusions:

Because virtually all cases of pneumococcal meningitis lead to either permanent neurologic sequelae or death, it would be well worth the effort to develop a new vaccine capable of preventing pneumococcal meningitis regardless of capsular type. Such a vaccine would need to protect against colonization with most, if not all, pneumococci.
Ceftolozane/Tazobactam Treatment of Multidrug-resistant Pseudomonas aeruginosa Infections in Children
Authors: Molloy Leah , Abdulhamid Ibrahim , Srivastava Ruma , Ang Jocelyn Y.
Published: February 2020

The clinical use, safety and effectiveness of ceftolozane/tazobactam among 13 patients 3 months to 19 years of age infected with multidrug-resistant Pseudomonas aeruginosa are described. All but one patient achieved clinical cure after initial treatment. Adverse drug events attributed to treatment included transaminitis and neutropenia which occurred in 2 patients and resolved upon dose reduction.
A review of the incidence and risk factors for fibromyalgia and chronic widespread pain in population-based studies
Authors: Creed Francis
Published: February 2020

This review identified prospective cohort studies in the general population, which showed incidence (23 papers) and risk factors (37 papers) for fibromyalgia and chronic widespread pain. Median incidence of physician diagnosed fibromyalgia in the general population was 4.3 per 1000 person-years (range = 0.33-18.8) but 14.0 (1.2-32.7) if medical illness was present. Median incidence of chronic widespread pain was 12.5 per 1000 person-years (7.2-81.6) but 67 per 1000 person years (14.8-124) for those with pre-existing pain. Risk factors included various childhood difficulties, female sex (except with pre-existing medical disorders), older/middle age, smoking, high body mass index, alcohol abstinence, and pre-existing medical disorders in adulthood. The strongest associations were with sleep disorders, headaches and other pains, depression, and illness behaviour. These data suggest strongly that there are many aetiological routes into fibromyalgia, and future research could be enhanced by studying the underlying mechanisms relating to these risk factors.
A Qualitative Exploration of Shift Work and Employee Well-Being in the US Manufacturing Environment
Authors: McHugh Megan , Farley Diane , Rivera Adovich S.
Published: February 2020

Objective:

Describe manufacturing workers’ perceptions of the effect of shift work, following the Framework for Worker Well-Being.

Methods:

Eight focus groups and 43 interviews were conducted across four large manufacturing plants. Thematic analysis was used to analyze the data within each of the five domains of the Framework: physical environment and safety climate; workplace policies and culture; health status; work evaluation and experience; and home, community, and society.

Results:

Respondents described shift work as detrimental to well-being across four of the five Framework domains. The exception was in the workplace policies and culture domain, where some respondents described shift work as necessary, fair, and financially beneficial.

Conclusions:

Shift work negatively influences worker well-being in a holistic way. Employers could consider reconfiguring workplace wellness benefits to transcend the boundaries of the workplace and better support workers and their families.
Identification of Knee Effusions With Ultrasound: A Comparison of Three Methods
Authors: Cushman Daniel M. , Ross Brendon , Teramoto Masaru , English Joy , Joyner James R. , Bosley Justin
Published: February 2020

Objectives:

To determine whether simple methods can improve identification of suprapatellar joint fluid during sonographic evaluation of the knee.

Design:

Prospective cohort study.

Setting:

Outpatient orthopaedic clinic.

Patients:

Fifty-two patients were sequentially recruited from an orthopaedic clinic.

Interventions:

Bilateral sonographic evaluation of the suprapatellar recess with static scanning, parapatellar pressure, or patient-initiated quadriceps contraction.

Main Outcome Measures:

Identification of fluid in the suprapatellar recess.

Results:

Fifty-two patients (104 knees), consisting of 57 (54.8%) painful knees, were examined. Static scanning identified 45 effusions, parapatellar pressure identified 58 effusions, and quadriceps contraction identified 77 effusions. Quadriceps contraction was superior to parapatellar pressure for identifying an effusion {P < 0.001, proportion ratio [PR] = 1.33 [95% confidence interval (CI) = 1.16, 1.52]}, painful knee effusions [P = 0.036, PR = 1.24 (95% CI = 1.06-1.44)], and painless knee effusions (P = 0.006, PR = 1.50 [95% CI = 1.16-1.93]). Both methods were superior to static scanning. Parapatellar pressure identified effusions in 16.9% of knees not seen on static scanning, whereas quadriceps contraction identified effusions in 54.2% of knees not seen on static scanning. Inter-rater reliability kappa values were 0.771 for static scanning (95% CI = 0.605-0.937), 0.686 for parapatellar pressure (95% CI = 0.531-0.840), and 0.846 for quadriceps contraction (95% CI = 0.703-0.990).

Conclusions:

Parapatellar pressure and patient-initiated quadriceps contraction both improve sonographic detection of suprapatellar joint fluid with high inter-rater reliability; however, quadriceps contraction was superior to parapatellar pressure when assessing for grade 1 or occult effusions.
Religion and Psychiatry in the Age of Neuroscience
Authors: Phillips James , El-Gabalawi Fayez , Fallon Brian A. , Majeed Salman , Merlino Joseph P. , Nields Jenifer A. , Saunders David , Norko Michael A.
Published: February 2020

In recent decades, an evolving conversation among religion, psychiatry, and neuroscience has been taking place, transforming how we conceptualize religion and how that conceptualization affects its relation to psychiatry. In this article, we review several dimensions of the dialogue, beginning with its history and the phenomenology of religious experience. We then turn to neuroscientific studies to see how they explain religious experience, and we follow that with two related areas: the benefits of religious beliefs and practices, and the evolutionary foundation of those benefits. A final section addresses neuroscientific and evolutionary accounts of the transcendent, that is, what these fields make of the claim that religious experience connects to a transcendent reality. We conclude with a brief summary, along with the unresolved questions we have encountered.
Clinical, Histologic, and Molecular Characteristics of Anaplastic Lymphoma Kinase-positive Primary Cutaneous Anaplastic Large Cell Lymphoma
Authors: Melchers Rutger C. , Willemze Rein , van de Loo Merel , van Doorn Remco , Jansen Patty M. , Cleven Arjen H.G. , Solleveld Nienke , Bekkenk Marcel W. , van Kester Marloes S. , Diercks Gillis F.H. , Vermeer Maarten H. , Quint Koen D.
Published: February 2020

Unlike systemic anaplastic large cell lymphoma, the vast majority of primary cutaneous anaplastic large cell lymphomas (C-ALCL) do not carry translocations involving the ALK gene and do not express ALK. Expression of ALK protein therefore strongly suggests secondary cutaneous involvement of a systemic anaplastic large cell lymphoma. Recent studies described a small subgroup of ALK-positive C-ALCL, but information on frequency, prognosis, and translocation partners is virtually lacking. A total of 6/309 (2%) C-ALCL patients included in the Dutch registry for cutaneous lymphomas between 1993 and 2019 showed immunohistochemical ALK expression. Clinical and histopathologic characteristics, immunophenotype and disease course were evaluated. Underlying ALK translocations were analyzed with anchored multiplex polymerase chain reaction-based targeted next-generation sequencing. Median age at diagnosis was 39 years (range: 16 to 53 y). All patients presented with a solitary lesion. Treatment with radiotherapy (n=5) or anthracycline-based chemotherapy (n=1) resulted in complete responses in all 6 patients. Three patients developed a relapse, of whom 2 extracutaneous. After a median follow-up of 41 months, 5 patients were alive without disease and 1 patient died of lymphoma. Immunohistochemically, 3 cases (50%) showed combined nuclear and cytoplasmic ALK expression with underlying NPM1-ALK fusions, while 3 cases (50%) showed solely cytoplasmic ALK expression with variant ALK fusion partners (TRAF1, ATIC, TPM3). ALK-positive C-ALCL is extremely uncommon, has a comparable favorable prognosis to ALK-negative C-ALCL, and should be treated in the same way with radiotherapy as first-line treatment.
Dual-energy Subtraction Chest Radiography
Authors: Ansari-Gilani Kianoush , Tandon Yasmeen K. , Jordan David W. , Ciancibello Leslie , Wilson David L. , Gilkeson Robert C.
Published: February 2020

The chest radiograph is the most frequently performed imaging in radiology and by including the heart and central vessels can suggest the presence of cardiovascular disease. Dual-energy subtraction radiography of the chest provides improved detection of a wide variety of cardiovascular pathologies including coronary artery disease, valvular pathologies, and pericardial disease given the presence of calcification in many subtypes of these diseases. We review the principles of dual-energy subtraction radiography and demonstrate its added value in the assessment of cardiovascular disease.
Signs of Increased Intrapericardial Pressure on Chest Computed Tomography
Authors: Rojas Carlos A. , Livingston David , Padilla Gary , Feldhaus Jacob , Rajan Celin , Bowman Andrew W. , Shapiro Brian P. , Mergo Patricia J.
Published: February 2020

We sought to describe incidental imaging features of increased intrapericardial pressure due to pericardial effusion on chest computed tomography (CT) and correlate them with cardiac CT, cardiac magnetic resonance imaging, and echocardiography. It is important for the radiologist to become familiar with imaging findings of increased intrapericardial pressure in the setting of pericardial effusion when identified on chest CT. Recognizing the imaging findings of increased intrapericardial pressure can better guide the care of these patients.
Risk of Permanent Hypoparathyroidism After Total Thyroidectomy for Benign Disease
Authors: Annebäck Matilda , Hedberg Jakob , Almquist Martin , Stålberg Peter , Norlén Olov
Published: February 2020

Objective:

To investigate the prevalence and risk factors for permanent hypoparathyroidism after total thyroidectomy for benign disease in a population-based setting with data independent of input of complication data.

Summary of Background Data:

The reported rate of permanent hypoparathyroidism is highly variable and mostly rely on reported complication data from national or institutional registries.

Methods:

All patients who underwent total thyroidectomy in Sweden from 2005 to 2015 were identified through Scandinavian Quality Register for Thyroid, Parathyroid and Adrenal Surgery and the Swedish National Patient Register. Patients were matched to outcome data from the Swedish Prescribed Drug Register. Permanent hypoparathyroidism was defined as treatment with calcium and/or active vitamin D more than 1 year after surgery.

Results:

Seven thousand eight hundred fifty-two patients were included and 938 (12.5%) developed permanent hypoparathyroidism. The risk was lower in patients registered in the quality register (11.0% vs 16%, P < 0.001). In a multivariable analysis there was a higher risk of permanent hypoparathyroidism in patients with parathyroid autotransplantation [Odds ratio (OR) 1.72; 95% confidence interval 1.47–2.01], center-volume <100 thyroidectomies per year (OR 1.22; 1.03–1.44), age above 60 year (OR 1.64; 1.36–1.98) and female sex (OR 1.27; 1.05–1.54). Reported data from the quality register only identified 178 of all 938 patients with permanent hypoparathyroidism.

Conclusion:

The risk of permanent hypoparathyroidism after total thyroidectomy was high and associated with parathyroid autotransplantation, higher age, female sex and surgery at a low volume center. Reported follow-up data might underestimate the rate of permanent hypoparathyroidism.
Postoperative Opioid Utilization in Older Women Undergoing Pelvic Organ Prolapse Surgery
Authors: Ackenbom Mary F. , Dong Shirley , Romanova Anna , Baranski Lindsey , Butters Meryl A. , Davis Esa M. , Zyczynski Halina M.
Published: February 2020

Objectives

The objective of this study was to determine total postoperative opioid consumption by women 60 years and older during the first week after pelvic organ prolapse surgery. We secondarily aimed to describe opioid prescribing patterns in this cohort.

Methods

This is a secondary analysis of a prospective cohort study assessing changes in cognition in women 60 years and older undergoing prolapse surgery. Postoperative opioid use at home during the first week was collected through daily self-reported diary entries. Total postoperative opioid consumption was calculated by adding opioid administration in the postoperative anesthesia recovery unit, inpatient setting, and home opioid use (as documented in diary). Regression models were used to identify demographic and clinical factors associated with total postoperative opioid consumption in the top quartile of this cohort and home opioid use.

Results

Data from 80 women were analyzed. Mean ± SD age was 71.78 ± 6.14 years (range, 60–88 years). Fifty women (62.5%) underwent vaginal surgery, and 30 (7.5%) underwent laparoscopic/robotic surgery, with concomitant hysterectomy in 47 (58.8%). The median (interquartile range) total morphine milligram equivalents used during the first week after surgery was 30 (7.5–65.75). The median (interquartile range) total morphine milligram equivalents prescribed was 225 (150–225).

Conclusions

Opioid consumption after prolapse surgery in older women is very modest and equates to a median (interquartile range) of 4 (1–9) oxycodone (5 mg) tablets. Opioid prescribing patterns should be adjusted accordingly.
Aberrant sorting of hippocampal complex pyramidal cells in Type I Lissencephaly alters topological innervation
Authors: D’Amour James A. , Ekins Tyler G. , Ghanatra Stuti , Yuan Xiaoqing , McBain Chris J.
Published: February 2020

Layering has been a long-appreciated feature of higher order mammalian brain structures but the extent to which it plays an instructive role in synaptic specification remains unknown. Here we examine the formation of synaptic circuitry under cellular heterotopia in hippocampal CA1, using a mouse model of the human neurodevelopmental disorder Type I Lissencephaly. We identify calbindin-expressing principal cells which are mispositioned under cellular heterotopia. Ectopic calbindin-expressing principal cells develop relatively normal morphological features and stunted intrinsic physiological features. Regarding network development, a connectivity preference for cholecystokinin-expressing interneurons to target calbindin expressing principal cells is diminished. Moreover, in vitro gamma oscillatory activity is less synchronous across heterotopic bands and mutants are less responsive to pharmacological antagonism of cholecystokinin-containing interneurons. This study will aid not only in our understanding of how cellular networks form but highlight vulnerable cellular circuit motifs that might be generalized across disease states.
Conserved small nucleotidic elements at the origin of concerted piRNA biogenesis from genes and lncRNAs
Authors: Jensen Silke , Brasset Emilie , Parey Elise , Roest-Crollius Hugues , Sharakhov Igor V. , Vaury Chantal
Published: February 2020

PIWI-interacting RNAs (piRNAs) target transcripts by sequence complementarity serving as guides for RNA slicing in animal germ cells. The piRNA pathway is increasingly recognized as critical for essential cellular functions such as germline development and reproduction. In theAnopheles gambiaeovary, as much as 11% of piRNAs map to protein-coding genes. Here we show that ovarian mRNAs and long non-coding RNAs (lncRNAs) are processed into piRNAs that can direct other transcripts into the piRNA biogenesis pathway. Targeting piRNAs fuel transcripts either into the ping-pong cycle of piRNA amplification or into the machinery of phased piRNA biogenesis, thereby creating networks of inter-regulating transcripts. RNAs of the same network share related genomic repeats. These repeats give rise to piRNAs, which target other transcripts and lead to a cascade of concerted RNA slicing. While ping-pong networks are based on repeats of several hundred nucleotides, networks that rely on phased piRNA biogenesis operate through short ∼40-nucleotides long repeats, which we named snetDNAs. Interestingly, snetDNAs are recurring in evolution from insects to mammals. Our study brings to light a new type of a conserved regulatory pathway, the snetDNA-pathway, by which short sequences can include independent genes and lncRNAs in the same biological pathway.

AUTHOR SUMMARY

Small RNA molecules are essential actors in silencing mobile genetic elements in animal germ cells. The 24-29-nucleotide-long Piwi-interacting RNAs (piRNAs) target transcripts by sequence complementarity serving as guides for RNA slicing. Mosquitoes of theAnopheles gambiaespecies complex are the principal vectors of malaria, and research on their germline is essential to develop new strategies of vector control by acting on reproduction. In theAnopheles gambiaeovary as much as 11% of piRNAs originate from protein-coding genes. We identified piRNAs which are able to target transcripts from several distinct genes or long non-coding RNAs (lncRNAs), bringing together genic transcripts and lncRNAs in a same regulation network. piRNA targeting induces transcript slicing and production of novel piRNAs, which then target other mRNAs and lncRNAs leading again to piRNA processing, thus resulting in a cascade of RNA slicing and piRNA production. Each network relies on piRNAs originating from repeated genetic elements, present in all transcripts of the same network. Some of these repeats are very short, only ∼40-nucleotides long. We identified similar repeats in all 43 animal species that we analysed, including mosquitoes, flies, arachnidae, snail, mouse, rat and human, suggesting that such regulation networks are recurrent, possibly conserved, in evolutionary history.
Persistent increases of PKMζ in memory-activated neurons trace LTP maintenance during spatial long-term memory storage
Authors: Hsieh Changchi , Tsokas Panayiotis , Grau-Perales Alejandro , Lesburguères Edith , Bukai Joseph , Khanna Kunal , Chorny Joelle , Chung Ain , Jou Claudia , Burghardt Nesha S. , Denny Christine A. , Flores-Obando Rafael E. , Hartley Benjamin Rush , Rodríguez Valencia Laura Melissa , Hernández A. Iván , Bergold Peter J. , Cottrell James E. , Alarcon Juan Marcos , Fenton André Antonio , Sacktor Todd Charlton
Published: February 2020

PKMζ is an autonomously active PKC isoform crucial for the maintenance of synaptic long-term potentiation (LTP) and long-term memory. Unlike other protein kinases that are transiently stimulated by second messengers, PKMζ is persistently activated through sustained increases in kinase protein expression. Therefore, visualizing increases in PKMζ expression during long-term memory storage might reveal the sites of its persistent action and thus the location of memory-associated LTP maintenance in the brain. Using quantitative immunohistochemistry validated by the lack of staining in PKMζ-null mice, we examined the amount and distribution of PKMζ in subregions of the hippocampal formation of wild-type mice during LTP maintenance and spatial long-term memory storage. During LTP maintenance in hippocampal slices, PKMζ increases in the pyramidal cell body and stimulated dendritic layers of CA1 for at least 2 h. During spatial memory storage, PKMζ increases in CA1 pyramidal cells for at least 1 month, paralleling the persistence of the memory. The subset of CA1 pyramidal cells that are tagged by immediate early geneArc-driven transcription of fluorescent proteins, whose expression increases during initial memory formation, also expresses the persistent increase of PKMζ during memory storage. In the memory-tagged cells, the increased PKMζ expression persists in dendritic compartments withinstratum radiatumfor 1 month, indicating the long-term storage of information in the CA3-to-CA1 pathway during remote spatial memory. We conclude that persistent increases in PKMζ trace the molecular mechanism of LTP maintenance and thus the sites of information storage within brain circuitry during long-term memory.
Functionalin vivocharacterization of zebrafishsox10enhancers in melanoma and neural crest
Authors: Cunningham Rebecca L. , Kramer Eva T. , DeGeorgia Sophia K. , Seneviratne Shayana , Grigura Vadim , Kaufman Charles K.
Published: February 2020

The re-emergence of a neural crest transcriptional program, including Sox10 upregulation, is a key step in melanoma initiation in humans and zebrafish. We hypothesize that epigenetic regulation ofsox10modulates melanoma initiation. ATAC-Seq analysis of zebrafish melanoma tumors identifies recurrently open chromatin domains nearsox10. Reporter constructs for each putativesox10enhancer were examined in zebrafish embryos for neural crest activity and in stable transgenic lines for melanoma activity. One element,peak5(23 kilobases upstream ofsox10), drivesEGFPreporter expression in a subset of neural crest cells, Kolmer-Agduhr neurons, and early melanoma patches and tumors with high specificity. A ∼200 bp region, conserved across theCyprinidaefamily (fish), is required forpeak5activity in neural crest and melanoma, and contains dimeric SoxE binding sites essential for neural crest activity. Our work identifies a novel melanoma transcriptional enhancer, expanding our knowledge of epigenetic regulation of neural crest identity in melanoma.
Exploratory Factor Analysis with Structured Residuals for Brain Imaging Data
Authors: van Kesteren Erik-Jan , Kievit Rogier A.
Published: February 2020

Dimension reduction is widely used and often necessary to reduce high dimensional data to a small number of underlying variables, making subsequent analyses and their interpretation tractable. One popular technique is Exploratory Factor Analysis (EFA), used by cognitive neuroscientists to reduce measurements from a large number of brain regions to a tractable number of factors. However, dimension reduction often ignores relevant a priori knowledge about the structure of the data. For example, it is well established that the brain is highly symmetric. In this paper, we (a) show the adverse consequences of ignoring a priori structure in factor analysis, (b) propose a technique to accommodate structure in EFA using structured residuals (EFAST), and (c) apply this technique to three large and varied brain imaging datasets, demonstrating the superior fit and interpretability of our approach. We provide an R software package to enable researchers to apply EFAST to other suitable datasets.
Targeting serine hydroxymethyltransferases 1 and 2 for T-cell acute lymphoblastic leukemia therapy
Authors: Pikman Yana , Ocasio-Martinez Nicole , Alexe Gabriela , Kitara Samuel , Diehl Frances F. , Robichaud Amanda L. , Conway Amy Saur , Su Angela , Qi Jun , Roti Giovanni , Lewis Caroline A. , Puissant Alexandre , Heiden Matthew G. Vander , Stegmaier Kimberly
Published: February 2020

Despite progress in the treatment of acute lymphoblastic leukemia (ALL), T-cell ALL (T-ALL) has limited treatment options particularly in the setting of relapsed/refractory disease. Using an unbiased genome-scale CRISPR-Cas9 screen we sought to identify pathway dependencies for T-ALL which could be harnessed for therapy development. Disruption of the one-carbon folate, purine and pyrimidine pathways scored as the top metabolic pathways required for T-ALL proliferation. We used a recently developed inhibitor of SHMT1 and SHMT2, RZ-2994, to characterize the effect of inhibiting these enzymes of the one-carbon folate pathway in T-ALL and found that T-ALL cell lines were differentially sensitive to RZ-2994, with a S/G2 cell cycle arrest. The effects of SHMT1/2 inhibition were rescued by formate supplementation. Loss of both SHMT1 and SHMT2 was necessary for impaired growth and cell cycle arrest, with suppression of both SHMT1 and SHMT2 impairing leukemia progressionin vivo. RZ-2994 decreased leukemia burdenin vivoand remained effective in the setting of methotrexate resistancein vitro. This study highlights the significance of the one-carbon folate pathway in T-ALL and supports further development of SHMT inhibitors for treatment of T-ALL and other cancers.
Population dynamics in pre-Inca human groups from the Osmore Valley, the Azapa Valley and the coast of the south central Andes
Authors: Coppa A. , Candilio F. , Arganini C. , de la Vega E. , Terrazas E.G. Moreno , Lucci M. , Cucina A.
Published: February 2020

The present study applies a dental morphological perspective to the understanding of the complex population history of pre-contact South-Central Andes, the detection of the underlying dynamics, and the assessment of the biological ties among groups. It takes into account 1665 individuals from 16 sites that date from the Archaic to the Late Intermediate located along the coast, on thealtiplano, and in the coastal valleys of both Chile and Peru. The results obtained highlight the need for wider perspectives capable of taking into account both the different micro-regional realities and the region in its ensemble. The population dynamics and mobility patterns detected indicate the widely accepted interpretations and distinctions based on cultural affiliations might be insufficient to comprehend the complex population history of the region, especially because the results obtained in the present study indicate the presence of a general and widespread common morphological background for the inhabitants of some of these cultures (i.e., Moche and Wari) and that the interactions they had throughout time must have been far from inconsequential.
A VTA GABAergic computational model of dissociated reward prediction error computation in classical conditioning
Authors: Kaushik Pramod , Naudé Jérémie , Raju Surampudi Bapi , Alexandre Frédéric
Published: February 2020

Classical Conditioning is a fundamental learning mechanism where the Ventral Striatum is generally thought to be the source of inhibition to Ventral Tegmental Area (VTA) Dopamine neurons when a reward is expected. However, recent evidences point to a new candidate in VTA GABA encoding expectation for computing the reward prediction error in the VTA. In this system-level computational model, the VTA GABA signal is hypothesised to be a combination of magnitude and timing computed in the Peduncolopontine and Ventral Striatum respectively. This dissociation enables the model to explain recent results wherein Ventral Striatum lesions affected the temporal expectation of the reward but the magnitude of the reward was intact. This model also exhibits other features in classical conditioning namely, progressively decreasing firing for early rewards closer to the actual reward, twin peaks of VTA dopamine during training and cancellation of US dopamine after training.
Kinetics ofPlasmodium midgutinvasion in Anopheles mosquitoes
Authors: Volohonsky Gloria , Paul-Gilloteaux Perrine , Štáfková Jitka , Soichot Julien , Salamero Jean , Levashina Elena A.
Published: February 2020

Malaria-causingPlasmodiumparasites traverse the mosquito midgut cells to establish infection at the basal side of the midgut. This dynamic process is a determinant of mosquito vector competence, yet the kinetics of the parasite migration is not well understood. Here we used transgenic mosquitoes of twoAnophelesspecies and aPlasmodium bergheifluorescence reporter line to track parasite passage through the mosquito tissues at high spatial resolution. We provide new quantitative insight into malaria parasite invasion in African and IndianAnophelesspecies and demonstrate that species-specific kinetics ofPlasmodiuminvasion is shaped by the mosquito complement-like system.

Author Summary

The traversal of the mosquito midgut cells is one of the critical stages in the life cycle of malaria parasites. Motile parasite forms, called ookinetes, traverse the midgut epithelium in a dynamic process which is not fully understood.

Here, we harnessed transgenic reporters to track invasion ofPlasmodiumparasites in African and Indian mosquito species. We found important differences in parasite dynamics between the two anopheline species and demonstrated an unexpected role of mosquito complement-like system in regulation of parasite invasion.
Optimal Binning of Peri-Event Time Histograms Using Akaike Information Criterion
Authors: Ghazizadeh Ali , Ambroggi Frederic
Published: February 2020

Peri-event time histograms (PETH) are widely used to study correlations between experimental events and neuronal firing. The accuracy of firing rate estimate using a PETH depends on the choice of binsize. We show that the optimal binsize for a PETH depends on factors such as the number of trials and the temporal dynamics of the firing rate. These factors argue against the use of a one-size-fits-all binsize when making PETHs for an inhomogeneous population of neurons. Here we propose a binsize selection method by adapting the Akaike Information Criterion (AIC). Simulations show that optimal binsizes estimated by AIC closely match the optimal binsizes using mean squared error (MSE). Furthermore, using real data, we find that optimal binning improves detection of responses and their dynamics. Together our analysis strongly supports optimal binning of PETHs and proposes a computationally efficient method for this optimization based on AIC approach to model selection.
Structure determination of a new cocrystal of carbamazepine and DL-tartaric acid by synchrotron powder X-ray diffraction
Authors: Guerain Mathieu , Derollez Patrick , Roca-Paixão Luisa , Dejoie Catherine , Correia Natália T. , Affouard Frédéric
Published: February 2020

The crystal structure of a new cocrystal of carbamazepine (systematic name: 5H-dibenzo[b,f]azepine-5-carboxamide, C15H12N2O) and DL-tartaric acid (C4H6O6), obtained by liquid-assisted grinding, was solved by powder X-ray diffraction (PXRD). The high-resolution PXRD pattern of this new phase was recorded at room temperature thanks to synchrotron experiments at the European Synchrotron Radiation Facility (Grenoble, France). The starting structural model was generated by a Monte-Carlo simulated annealing method. The final structure was obtained through Rietveld refinement and an energy minimization simulation was used to estimate the H-atom positions. The stability of the proposed structure as a function of temperature was also assessed from molecular dynamics simulations. The symmetry is monoclinic (space group P21/c) and contains eight molecules per unit cell, namely, four DL-tartaric acid and four carbamazepine molecules.