bluuebunny/crossref_metadata_2025 huggingface dataset:
Large Intra-Abdominal Desmoid Tumor in a Deployed Soldier Initially Presented With Chronic Diarrhea
Authors: Perdue Matthew J , Umar Mohamad , Walker Jerimiah D , Kelly Martin
Published: April 2021

Diarrhea is a common condition seen among soldiers in both garrison and deployed environments. Although the vast majority of soldiers with diarrhea will recover uneventfully with supportive care, clinicians should also maintain suspicion for less common causes and perform a thorough physical exam. We report the case of a young, healthy soldier with chronic diarrhea and progressively worsening abdominal distention that began during his deployment to Honduras who was subsequently found to have a large intra-abdominal desmoid tumor. Desmoid tumor is a rare and benign neoplasm that typically appears on the extremity, abdominal wall, intra-abdominal space, and occasionally in the chest wall. This tumor may be associated with abdominal distension and gastrointestinal complaints. A large tumor can compress organs, causing local tissue damage and, in rare cases, death.
Analytic expressions for geometric cross-sections of fractal dust aggregates
Authors: Tazaki Ryo
Published: April 2021

In protoplanetary discs and planetary atmospheres, dust grains coagulate to form fractal dust aggregates. The geometric cross-section of these aggregates is a crucial parameter characterizing aerodynamical friction, collision rates, and opacities. However, numerical measurements of the cross-section are often time consuming as aggregates exhibit complex shapes. In this study, we derive a novel analytic expression for geometric cross-sections of fractal aggregates. If an aggregate consists of N monomers of radius R0, its geometric cross-section G is expressed as $G=AN\pi R_0^2/[1+(N-1)\tilde{\sigma }]$, where $\tilde{\sigma }$ is an overlapping efficiency, and A is a numerical factor connecting the analytic expression to the small non-fractal cluster limit. The overlapping efficiency depends on the fractal dimension, fractal prefactor, and N of the aggregate, and its analytic expression is derived as well. The analytic expressions successfully reproduce numerically measured cross-sections of aggregates. We also find that our expressions are compatible with the mean-field light scattering theory of aggregates in the geometrical optics limit. The analytic expressions greatly simplify an otherwise tedious calculation and will be useful in model calculations of fractal grain growth in protoplanetary discs and planetary atmospheres.
Gamma-rays from ultracompact minihaloes: effects on the Earth’s atmosphere and links to mass extinction events
Authors: Sarkis M , Beck G , Thomas B C
Published: April 2021

Recent studies of the effects on the Earth’s atmosphere by astrophysical sources, such as nearby gamma-ray bursts or supernovae, have shown that these events could lead to severe changes in atmospheric composition. Depletion of ozone, the most notable of these changes, is extremely dangerous to living organisms as any decrease in ozone levels leads to an increase in the irradiance of harmful solar radiation at the Earth’s surface. In this work, we consider dark matter as an astrophysical source of gamma-rays, by the annihilation and decay of weakly interacting massive particles found within dark compact halo objects known as ultracompact minihaloes (UCMHs). We calculate the fluence of gamma-rays produced in this way and simulate the resulting changes to terrestrial ozone levels using the Goddard Space Flight Center 2D Atmospheric Model. We then calculate the rate at which such events would occur, using estimates for the mass distribution of these haloes within the Milky Way. We find that the ozone depletion from UCMHs can be significant, and even of similar magnitude to the levels which have been linked to the cause of the Late-Ordovician mass extinction event. However, we also find that the rate of such extinction-level events due to UCMHs is markedly lower than for other astrophysical phenomena. This suggests that, while dark compact objects such as UCMHs could have had an impact on the Earth’s biosphere, events such as gamma-ray bursts or supernovae seem a more likely source of these effects.
A machine learning approach for GRB detection in AstroSat CZTI data
Authors: Abraham Sheelu , Mukund Nikhil , Vibhute Ajay , Sharma Vidushi , Iyyani Shabnam , Bhattacharya Dipankar , Rao A R , Vadawale Santosh , Bhalerao Varun
Published: April 2021

We present a machine learning (ML) based method for automated detection of Gamma-Ray Burst (GRB) candidate events in the range 60–250 keV from the AstroSat Cadmium Zinc Telluride Imager data. We use density-based spatial clustering to detect excess power and carry out an unsupervised hierarchical clustering across all such events to identify the different light curves present in the data. This representation helps us to understand the instrument’s sensitivity to the various GRB populations and identify the major non-astrophysical noise artefacts present in the data. We use Dynamic Time Warping (DTW) to carry out template matching, which ensures the morphological similarity of the detected events with known typical GRB light curves. DTW alleviates the need for a dense template repository often required in matched filtering like searches. The use of a similarity metric facilitates outlier detection suitable for capturing previously unmodelled events. We briefly discuss the characteristics of 35 long GRB candidates detected using the pipeline and show that with minor modifications such as adaptive binning, the method is also sensitive to short GRB events. Augmenting the existing data analysis pipeline with such ML capabilities alleviates the need for extensive manual inspection, enabling quicker response to alerts received from other observatories such as the gravitational-wave detectors.
Radio properties of 10 nearby ultraluminous infrared galaxies with signatures of luminous buried active galactic nuclei
Authors: Hayashi Takayuki J , Hagiwara Yoshiaki , Imanishi Masatoshi
Published: April 2021

We present the results of our multifrequency observations for 10 ultraluminous infrared galaxies (ULIRGs) made by the Karl G. Jansky Very Large Array at 1.4, 5.5, 9.0, and 14.0 GHz. Our sample is selected from ULIRGs whose active galactic nuclei (AGNs) are not found at optical wavelengths (∼70 per cent of the total ULIRGs), but whose presence is suggested by mid-infrared or submillimetre observations (>50 per cent of the non-AGN ULIRGs at optical wavelengths). The statistical properties of the targets are similar to those of the entire ULIRG sample, which implies that ULIRGs have common radiative processes regardless of the presence of optical AGNs, and thus AGNs might equally contribute to the radio emission of every ULIRG. Although their spectra are mainly explained by starbursts and/or merger activity, some individual sources suggest contributions from AGNs. IRAS 00188−0856, whose optical morphology is not disturbed, shows a large non-thermal fraction and a spectral break at high frequency, which can be explained by synchrotron ageing of non-thermal plasma emitted from AGNs. In addition, we find 100-kpc-scale extended emission associated with IRAS 01004−2237. The two-sided morphology and absence of extended X-ray emission suggest that this system is not induced by a merger in a cluster but originates from AGN activity.
Effects of periodicity in observation scheduling on parameter estimation of pulsar glitches
Authors: Dunn L , Lower M E , Melatos A
Published: April 2021

In certain pulsar timing experiments, where observations are scheduled approximately periodically (e.g. daily), timing models with significantly different frequencies (including but not limited to glitch models with different frequency increments) return near-equivalent timing residuals. The average scheduling aperiodicity divided by the phase error due to time-of-arrival uncertainties is a useful indicator when the degeneracy is important. Synthetic data are used to explore the effect of this degeneracy systematically. It is found that phase-coherent tempo2 or temponest-based approaches are biased sometimes towards reporting small glitch sizes regardless of the true glitch size. Local estimates of the spin frequency alleviate this bias. A hidden Markov model is free from bias towards small glitches and announces explicitly the existence of multiple glitch solutions but sometimes fails to recover the correct glitch size. Two glitches in the UTMOST public data release are reassessed, one in PSR J1709−4429 at MJD 58178 and the other in PSR J1452−6036 at MJD 58600. The estimated fractional frequency jump in PSR J1709−4429 is revised upward from Δf/f = (54.6 ± 1.0) × 10−9 to (2432.2 ± 0.1) × 10−9 with the aid of additional data from the Parkes radio telescope. We find that the available UTMOST data for PSR J1452−6036 are consistent with Δf/f = 270 × 10−9 + N/(fT) with N = 0, 1, and 2, where $T \approx 1\, \text{sidereal day}$ is the observation scheduling period. Data from the Parkes radio telescope can be included, and the N = 0 case is selected unambiguously with a combined data set.
The Evolution of Calcification in Reef-Building Corals
Authors: Wang Xin , Zoccola Didier , Liew Yi Jin , Tambutte Eric , Cui Guoxin , Allemand Denis , Tambutte Sylvie , Aranda Manuel
Published: April 2021

Corals build the structural foundation of coral reefs, one of the most diverse and productive ecosystems on our planet. Although the process of coral calcification that allows corals to build these immense structures has been extensively investigated, we still know little about the evolutionary processes that allowed the soft-bodied ancestor of corals to become the ecosystem builders they are today. Using a combination of phylogenomics, proteomics, and immunohistochemistry, we show that scleractinian corals likely acquired the ability to calcify sometime between ∼308 and ∼265 Ma through a combination of lineage-specific gene duplications and the co-option of existing genes to the calcification process. Our results suggest that coral calcification did not require extensive evolutionary changes, but rather few coral-specific gene duplications and a series of small, gradual optimizations of ancestral proteins and their co-option to the calcification process.
ReFOLD3: refinement of 3D protein models with gradual restraints based on predicted local quality and residue contacts
Authors: Adiyaman Recep , McGuffin Liam J
Published: April 2021

ReFOLD3 is unique in its application of gradual restraints, calculated from local model quality estimates and contact predictions, which are used to guide the refinement of theoretical 3D protein models towards the native structures. ReFOLD3 achieves improved performance by using an iterative refinement protocol to fix incorrect residue contacts and local errors, including unusual bonds and angles, which are identified in the submitted models by our leading ModFOLD8 model quality assessment method. Following refinement, the likely resulting improvements to the submitted models are recognized by ModFOLD8, which produces both global and local quality estimates. During the CASP14 prediction season (May–Aug 2020), we used the ReFOLD3 protocol to refine hundreds of 3D models, for both the refinement and the main tertiary structure prediction categories. Our group improved the global and local quality scores for numerous starting models in the refinement category, where we ranked in the top 10 according to the official assessment. The ReFOLD3 protocol was also used for the refinement of the SARS-CoV-2 targets as a part of the CASP Commons COVID-19 initiative, and we provided a significant number of the top 10 models. The ReFOLD3 web server is freely available at https://www.reading.ac.uk/bioinf/ReFOLD/.
An integrative analysis of genome-wide 5-hydroxymethylcytosines in circulating cell-free DNA detects noninvasive diagnostic markers for gliomas
Authors: Cai Jiajun , Zeng Chang , Hua Wei , Qi Zengxin , Song Yanqun , Lu Xingyu , Li Dongdong , Zhang Zhou , Cui Xiaolong , Zhang Xin , Yang Zixiao , Zhang Jinsen , Quan Kai , Zhu Wei , Cai Jiabin , He Chuan , Cheng Shi-Yuan , Zhang Wei , Mao Ying
Published: April 2021

Background

Gliomas, especially the high-grade glioblastomas (GBM), are highly aggressive tumors in the central nervous system (CNS) with dismal clinical outcomes. Effective biomarkers, which are not currently available, may improve clinical outcomes through early detection. We sought to develop a noninvasive diagnostic approach for gliomas based on 5-hydroxymethylcytosines (5hmC) in circulating cell-free DNA (cfDNA).

Methods

We obtained genome-wide 5hmC profiles using the 5hmC-Seal technique in cfDNA samples from 111 prospectively enrolled patients with gliomas and 111 age-, gender-matched healthy individuals, which were split into a training set and a validation set. Integrated models comprised 5hmC levels summarized for gene bodies, long noncoding RNAs (lncRNAs), cis-regulatory elements, and repetitive elements were developed using the elastic net regularization under a case–control design.

Results

The integrated 5hmC-based models differentiated healthy individuals from gliomas (area under the curve [AUC] = 84%; 95% confidence interval [CI], 74–93%), GBM patients (AUC = 84%; 95% CI, 74–94%), WHO II-III glioma patients (AUC = 86%; 95% CI, 76–96%), regardless of IDH1 (encoding isocitrate dehydrogenase) mutation status or other glioma-related pathological features such as TERT, TP53 in the validation set. Furthermore, the 5hmC biomarkers in cfDNA showed the potential as an independent indicator from IDH1 mutation status and worked in synergy with IDH1 mutation to distinguish GBM from WHO II-III gliomas. Exploration of the 5hmC biomarkers for gliomas revealed relevance to glioma biology.

Conclusions

The 5hmC-Seal in cfDNA offers the promise as a noninvasive approach for effective detection of gliomas in a screening program.
MR spectroscopic imaging predicts early response to anti-angiogenic therapy in recurrent glioblastoma
Authors: Talati Pratik , El-Abtah Mohamed , Kim Daniel , Dietrich Jorg , Fu Melanie , Wenke Michael , He Julian , Natheir Sharif N , Vangel Mark , Rapalino Otto , Vaynrub Anna , Arrillaga-Romany Isabel , Forst Deborah A , Yen Yi-Fen , Andronesi Ovidiu , Kalpathy-Cramer Jayashree , Rosen Bruce , Batchelor Tracy T , Gonzalez R Gilberto , Gerstner Elizabeth R , Ratai Eva-Maria
Published: April 2021

Background

Determining failure to anti-angiogenic therapy in recurrent glioblastoma (GBM) (rGBM) remains a challenge. The purpose of the study was to assess treatment response to bevacizumab-based therapy in patients with rGBM using MR spectroscopy (MRS).

Methods

We performed longitudinal MRI/MRS in 33 patients with rGBM to investigate whether changes in N-acetylaspartate (NAA)/Choline (Cho) and Lactate (Lac)/NAA from baseline to subsequent time points after treatment can predict early failures to bevacizumab-based therapies.

Results

After stratifying based on 9-month survival, longer-term survivors had increased NAA/Cho and decreased Lac/NAA levels compared to shorter-term survivors. ROC analyses for intratumoral NAA/Cho correlated with survival at 1 day, 2 weeks, 8 weeks, and 16 weeks. Intratumoral Lac/NAA ROC analyses were predictive of survival at all time points tested. At the 8-week time point, 88% of patients with decreased NAA/Cho did not survive 9 months; furthermore, 90% of individuals with an increased Lac/NAA from baseline did not survive at 9 months. No other metabolic ratios tested significantly predicted survival.

Conclusions

Changes in metabolic levels of tumoral NAA/Cho and Lac/NAA can serve as early biomarkers for predicting treatment failure to anti-angiogenic therapy as soon as 1 day after bevacizumab-based therapy. The addition of MRS to conventional MR methods can provide better insight into how anti-angiogenic therapy affects tumor microenvironment and predict patient outcomes.
Viral Load Kinetics of Severe Acute Respiratory Syndrome Coronavirus 2 in Hospitalized Individuals With Coronavirus Disease 2019
Authors: Regan James , Flynn James P , Rosenthal Alexandra , Jordan Hannah , Li Yijia , Chishti Rida , Giguel Francoise , Corry Heather , Coxen Kendyll , Fajnzylber Jesse , Gillespie Elizabeth , Kuritzkes Daniel R , Hacohen Nir , Goldberg Marcia B , Filbin Michael R , Yu Xu G , Baden Lindsey , Ribeiro Ruy M , Perelson Alan S , Conway Jessica M , Li Jonathan Z ,   MGH COVID-19 Collection & Processing Teams, Abayneh Betelihem A , Allen Patrick , Alter Galit , Antille Diane , Armstrong Katrina , Balazs Alejandro , Bals Julia , Barbash Max , Bartsch Yannic , Boucau Julie , Boyce Siobhan , Braley Joan , Branch Karen , Broderick Katherine , Carney Julia , Chan Andrew , Chevalier Josh , Chowdhury Fatema , Daley George , Davidson Susan , Dougan Michael , Drew David , Einkauf Kevin , Elliman Ashley , Fallon Jon , Fedirko Liz , Finn Kelsey , Flaherty Keith , Flannery Jeanne , Forde Pamela , Garcia-Broncano Pilar , Gettings Elise , Golan David , Griffin Amanda , Grimmel Sheila , Grinke Kathleen , Hall Kathryn , Hartana Ciputra , Healy Meg , Heller Howard , Henault Deborah , Holland Grace , Jiang Chenyang , Jilg Nikolaus , Kaplonek Paulina , Karpell Marshall , Kayitesi Chantal , Lam Evan C , LaValle Vlasta , Lefteri Kristina , Lian Xiaodong , Lichterfeld Mathias , Lingwood Daniel , Liu Hang , Liu Jinqing , Lu Yiting , Luthern Sarah , Ly Natasha , Marchewka Jordan , Martino Britanni , McNamara Roseann , Michell Ashlin , Millstrom Ilan , Miranda Noah , Nambu Christian , Nelson Susan , Noone Marjorie , O’Callaghan Claire , Ommerborn Christine , Osborn Mathew , Pacheco Lois Chris , Phan Nicole , Pillai Shiv , Porto Falisha A , Rassadkina Yelizaveta , Reissis Alexandra , Rosenthal Alex , Ruzicka Francis , Ryan Edward , Seiger Kyra , Selleck Kathleen , Sessa Libera , Sharpe Arlene , Sharr Christianne , Shin Sally , Singh Nishant , Slaughenhaupt Sue , Sheppard Kimberly Smith , Sun Weiwei , Sun Xiaoming , Suschana Elizabeth , Ticheli Hannah , Trocha-Piechocka Alicja , Wilson Vivine , Wong Colline , Worrall Daniel , Zhu Alex , Hill Zachary Manickas , Demers Edward , Judge Kelly , Walker Bruce , Lai Peggy , Li Jonathan , Ghebremichael Musie S
Published: April 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) kinetics remain understudied, including the impact of remdesivir. In hospitalized individuals, peak sputum viral load occurred in week 2 of symptoms, whereas viremia peaked within 1 week of symptom-onset, suggesting early systemic seeding of SARS-CoV-2. Remdesivir treatment was associated with faster viral decay.
Radial Artery Access for Cerebral Angiography: 2-Dimensional Operative Video
Authors: Chen Stephanie H , Suazo Roberto , Saini Vasu , Abecassis Isaac Josh , Yavagal Dileep , Starke Robert M , Peterson Eric C
Published: April 2021

A number of studies have demonstrated that the radial artery is a safer access site than the femoral artery for endovascular procedures.
1-4
In the prospective randomized studies comparing transradial and transfemoral approaches for cardiac procedures, there was a 60% reduction in access site complications as well as significant decreases in all-cause mortality with the transradial approach as compared to transfemoral, which has led to the adoption of a radial first strategy.
5-7
Neurointerventional studies have demonstrated similar safety benefits as well as improved patient preference.
8-14

In this video, a patient presented with an unruptured anterior communicating artery aneurysm and consented to a transradial artery diagnostic cerebral angiogram. This technical video demonstrates the key preprocedural preparation, room setup, patient positioning, steps for radial artery, and distal radial artery puncture and sheath placement. Distal transradial artery access is our preferred approach for diagnostic cerebral angiography because of an improved safety profile and procedural ergonomics. In cases in which a larger radial artery is advantageous such as for neurointerventions requiring larger systems, a standard transradial approach may be performed.
9
In this video, a full 6-vessel cerebral angiogram is performed, followed by our arteriotomy closure technique using our standard equipment including a 10-cm 5 French Glidesheath Slender (Terumo, Japan), 100-cm hydrophilic coated 5 French Simmons 1 catheter (Merit OEM), 0.035 hydrophilic coated guidewire, and SafeGuard closure device (Merit, Salt Lake City, Utah).
Repair of Giant Anterior Skull Base Encephalocele Containing Intralesional Eloquent Brain: Technical Note
Authors: Kobets Andrew J , Redett Richard J , Walsh Jonathan M , Lopez Joseph , Guryildirim Melike , Cohen Alan R
Published: April 2021

BACKGROUND

Encephaloceles are herniations of intracranial neural tissue and meninges through defects in the skull. Basal encephaloceles are rare anterior skull base defects incident in 1 in 35,000 live births. Sphenoethmoidal encephaloceles are even more uncommon, with an incidence of 1 in 700,000 live births. Anterior skull base encephaloceles may be life-threatening in infants, presenting as airway obstruction and respiratory compromise. They can also present with cerebrospinal fluid (CSF) rhinorrhea, purulent nasal drainage, or meningitis.

OBJECTIVE

To report a novel technique for repairing a giant sphenoethmoidal encephalocele containing eloquent neural tissue.

METHODS

A 16-mo-old girl presented with progressive airway obstruction from a giant sphenoethmoidal encephalocele that filled her oral cavity. She had multiple congenital anomalies including agenesis of the corpus callosum and cleft lip and palate. Computed tomography showed complete absence of the bony anterior cranial base, and magnetic resonance imaging demonstrated the presence of the pituitary gland and hypothalamus in the hernia sac.

RESULTS

We repaired the encephalocele using a combined microsurgical and endoscopic multidisciplinary approach working through transcranial, transnasal, and transpalatal corridors. The procedure was completed in a single stage, during which the midline cleft lip was also repaired. The child made an excellent neurological and aesthetic recovery with preservation of pituitary and hypothalamic function, without evidence of CSF fistula.

CONCLUSION

The authors describe a novel multidisciplinary technique for treating a giant sphenoethmoidal encephalocele containing eloquent brain. The cleft lip was also repaired at the same time. The ability to work through multiple corridors can enhance the safety and efficacy of an often-treacherous operative endeavor.
Microsurgical Anatomy of the Inferior Petroclival Vein and its Relation to Surrounding Structures: A Cadaveric and Radiological Study
Authors: Matsuo Satoshi , Komune Noritaka , Amano Toshiyuki , Nakamizo Akira
Published: April 2021

BACKGROUND

The inferior petroclival vein (IPV) courses along the extracranial surface of the petroclival fissure. It is occasionally involved in vascular diseases and has recently been used for vascular access to the cavernous sinus. However, detailed descriptions of its anatomy are currently lacking.

OBJECTIVE

To define the anatomic relationship between the IPV and its surrounding structures based on cadaveric dissection and radiological analysis.

METHODS

A dry skull and an injected cadaver head were examined to reveal the relationships between the IPV and its surrounding structures. The existence of the IPV and its relationships with other venous structures were also examined by contrast-enhanced, fat-suppressed T1-weighted magnetic resonance imaging in 26 patients (51 sides).

RESULTS

The entire course of the IPV was shown via stepwise cadaver dissection from below. Its relationships with surrounding structures, such as the jugular bulb, sigmoid sinus, inferior petrosal sinus, petrosal venous confluence, and the posterior, lateral, and anterior condylar veins, were also shown. In the radiological analysis, the IPV was identified on all sides. The rostral end of the vein was connected to the venous plexus around the carotid artery on all sides. The vein drained into the caudal end of the inferior petrosal sinus (49/51 sides, 96.1%) or into the anterior condylar vein (2/51 sides, 3.9%).

CONCLUSION

A precise understanding of the anatomy of the IPV will enable endovascular and skull base surgeons to achieve diagnoses and gain safe access to lesions involving the IPV.
Coaxial Access for Microcatheter Stabilization During Aneurysm Coiling: 2-Dimensional Operative Video
Authors: Kim Miri , Shanker Rachyl , Kam Anthony , Reynolds Matthew , Serrone Joseph C
Published: April 2021

Coaxial support is a fundamental technique utilized by neurointerventionalists to optimize distal catheter control within the intracranial circulation. Here we present a 41-yr-old woman with a previously coiled ruptured anterior communicating artery aneurysm with progressive recurrence harboring tortuous internal carotid anatomy to demonstrate the utility of coaxial support. Raymond-Roy classification of initial aneurysm coiling of class 1 resulted as class 3b over the 21 mo from initial treatment.
1
The patient consented to stent-assisted coiling for retreatment of this aneurysm. Coaxial support was advanced as distally as possible in the proximal vasculature to improve catheter control, reducing dead space within which the microcatheter could move, decreasing angulations within proximal vasculature, limiting the movement of the native vessels, and providing a surface of lower friction than the endothelium. As the risk of recurrent subarachnoid hemorrhage in previously treated coiled aneurysms approaches 3%, retreatment occurs in 16.4% within 6 yr
2
and in 17.4% of patients within 10 yr.
3
Rerupture is slightly higher in patients who underwent coiling vs clipping, with the rerupture risk inversely proportional to the degree of aneurysm occlusion,
4
further substantiating that coaxial support provides technical advantage in selected patients where additional microcatheter control is necessary for optimal occlusion. Pitfalls of this technique include vasospasm and vascular injury, which can be ameliorated by pretreatment of the circulation with vasodilators to prevent catheter-induced vasospasm. This case and model demonstration illustrates the technique of coaxial access in the stent-assisted coiling of a recurrent anterior communicating artery aneurysm and identification and management of catheter-induced vasospasm.
Middle Cerebral Artery Thrombectomy: Clinical Findings and Technical Pearls: 2-Dimensional Operative Video
Authors: Rangwala Shivani D , Selvan Pradeep , Tenser Matthew , Mack William ,   Endovascular Neurosurgery Research Group (ENRG), Arthur Adam , Mark Bain , Bendock Bernard , Binning Mandy Jo , Boulos Alan S , Crowley Webster , Fessler Richard , Grande Andrew , Guterman Lee , Hanel Ricardo , Hoit Daniel , Hopkins L Nelson , Howington Jay , James Robert , Jankowitz Brian , Kan Peter , Khalessi Alex A , Kim Louis , Langer David , Lanzino Giuseppe , Levitt Michael , Levy Elad I , Lopes Demetrius , Mack William , Mericle Robert , Mocco J , Ogilvy Chris , Pandey Aditya , Replogle Robert , Riina Howard , Ringer Andrew , Rodriguez Rafael , Saugaveau Eric , Schirmer Clemens , Siddiqui Adnan H , Spiotta Alex , Sultan Ali , Tawk Rabih , Thomas Ajith , Turner Raymond , Veznedaroglu Erol , Welch Babu , White Jonathan
Published: April 2021

Mechanical thrombectomy as a treatment for large vessel occlusion to achieve rapid revascularization is supported in the literature.
1-3
The presenting symptoms will localize to functions of the ischemic area. The middle cerebral artery (MCA) supplies areas of the frontal, temporal, and parietal cortices, as well as the basal ganglia. Occlusion of the MCA will present with contralateral hemiplegia, sensory loss, and, if the dominant hemisphere is involved, language deficits.

We present a right-hand-dominant 79-yr-old female with right MCA syndrome—her last known well time was 1.5 h prior to presentation. Her NIH (National Institutes of Health) Stroke Scale was 16, most notable for left hemiplegia. Although the patient presented early in the clinical time course, as part of our institution protocol, a computed tomography (CT) head, CT perfusion, and CT angiogram (CTA) were performed. CT head did not demonstrate acute hemorrhage, so she received intravenous tissue plasminogen activator. CTA demonstrated a right MCA occlusion and CT perfusion suggested a large area of salvageable tissue, so she was taken to the angiography suite for mechanical thrombectomy. Angiography of the right internal carotid artery (ICA) showed MCA occlusion (insular segment). A thrombectomy device was deployed over the area of occlusion and allowed to engage for 5 min. An aspiration catheter was advanced over the stentriever up against the clot. The stentriever device was withdrawn under continuous aspiration and follow-up angiography showed complete reperfusion. The patient demonstrated improvement and was eventually discharged to an inpatient rehabilitation center.

Patient provided consent for photography per university protocol. Institutional review board (IRB) approval was not needed for the single-patient data included in this report.
Endovascular Treatment of Basilar Bifurcation Aneurysms With PulseRider-Assisted Coiling: 2-Dimensional Operative Video
Authors: Sattur Mithun G , Al Kasab Sami , Porto Guilherme B , Spiotta Alejandro M ,   Endovascular Neurosurgery Research Group (ENRG), Arthur Adam , Mark Bain , Bendock Bernard , Binning Mandy Jo , Boulos Alan S , Crowley Webster , Fessler Richard , Grande Andrew , Guterman Lee , Hanel Ricardo , Hoit Daniel , Hopkins L Nelson , Howington Jay , James Robert , Jankowitz Brian , Kan Peter , Khalessi Alex A , Kim Louis , Langer David , Lanzino Giuseppe , Levitt Michael , Levy Elad , Lopes Demetrius , Mack William , Mericle Robert , Mocco J , Ogilvy Chris , Pandey Aditya , Replogle Robert , Riina Howard , Ringer Andrew , Rodriguez Rafael , Saugaveau Eric , Schirmer Clemens , Siddiqui Adnan , Spiotta Alex , Sultan Ali , Tawk Rabih , Thomas Ajith , Turner Raymond , Veznedaroglu Erol , Welch Babu , White Jonathan
Published: April 2021

Wide-necked bifurcation aneurysms pose technical and anatomical challenges to endovascular treatment, which make the simpler assisted (balloon or single stent) coiling techniques less effective.
1
Consequently, unique endovascular solutions to treat such aneurysms have been devised.
2,3
One such device is PulseRider (Cerenovus, New Brunswick, New Jersey), which is designed to provide neck support for a coil mass while protecting the bifurcation.
3
The device comprises a body or stem that is deployed in the parent artery and a saddle component that sits at the aneurysm neck to keep the coil mass away from the bifurcation. There are several technical nuances involved in successful use of the device during positioning, deployment, and detachment.
3
We present a surgical video detailing the steps of PulseRider-assisted coiling of unruptured basilar bifurcation (or basilar apex) aneurysms. The first case highlights index treatment at diagnosis and the second showcases treatment of a recurrent basilar apex aneurysm. Both patients provided informed consent to the procedure. We also briefly discuss the rationale for treating basilar apex aneurysms.
4,5
Management of an Uncommon Complication: Anterior Choroidal Artery Occlusion by Posterior Clinoid Process Detected Through Intraoperative Monitoring After Clipping of Paraclinoid Aneurysm: 2-Dimensional Operative Video
Authors: Marani Walter , Mannará Francisco , Noda Kosumo , Kondo Tomomasa , Ota Nakao , Perrini Paolo , Montemurro Nicola , Kinoshita Yu , Tsuji Shoichiro , Kamiyama Hiroyasu , Tanikawa Rokuya
Published: April 2021

Despite technological advances in endovascular therapy, surgical clipping of paraclinoid aneurysms remains an indispensable treatment option and has an acceptable profile risk. Intraoperative monitoring of motor and somatosensory evoked potentials has proven to be an effective tool in predicting and preventing postoperative motor deficits during aneurysm clipping.
1,2

We describe the case of a 61-yr-old Japanese woman with a history of hypertension and smoking. During follow-up for bilateral aneurysms of ophthalmic segment of the internal carotid artery (ICA), left-sided aneurysm growth was detected. A standard pterional approach with extradural clinoidectomy was used to approach the aneurysm. After clipping, a significant intraprocedural change in motor evoked potential (MEP) amplitude was observed despite native vessel patency was confirmed through micro-Doppler and indocyanine green video angiography.
3-5
After extensive dissection of the sylvian fissure and exposure of the communicating segment of ICA, the anterior choroidal artery was found to be compressed and occluded by the posterior clinoid because of an inadvertent shift of the ICA after clip application and removal of brain retractors. Posterior clinoidectomy was performed intradurally with microrongeur and MEP amplitude returned readily to baseline values.

Computed tomography (CT) angiogram demonstrated complete exclusion of the aneurysm, and magnetic resonance imaging (MRI) was negative for postoperative ischemic lesions on diffusion weighted images. The patient tolerated the procedure well and was discharged home on postoperative day 3 with modified Rankin Scale (mRS) 0. The patient signed the Institutional Consent Form to undergo the surgical procedure and to allow the use of her images and videos for any type of medical publications.
Species limits in birds: Australian perspectives on interrelated challenges of allopatry, introgression of mitochondrial DNA, recent speciation, and selection
Authors: Joseph Leo
Published: April 2021

Four main challenges that can underpin ongoing, intransigent debates about species limits in birds are reviewed: allopatry (population subdivision vs. speciation), geographically widespread introgression of mitochondrial DNA (mtDNA), recent speciation, and selection. Examples from birds of the Australian region show how these challenges, their interplay, and the molecular-phenotypic discordance they generate can clarify or mislead species limits. Examples of how phylogenetic frameworks help reject or retain hypotheses of species limits under these challenges are given. Although mtDNA’s strengths and limitations are well known, an underappreciated limitation of mtDNA is geographically widespread introgression that homogenizes mtDNA diversity across species, subspecies, or population boundaries and across hundreds of kilometers. The resulting discordance between mtDNA and phenotype can be profound. If undetected, the setting of species limits and evolutionarily significant units are misled. An example shows how recent genomic analyses can detect and solve the problem. Other examples concern legacy mtDNA-only datasets. These are often essentially unfinished studies leaving residual uncertainty in species limits. Examples illustrate when the possibility of large-scale introgression across species boundaries needs to be considered, and how genomic scale data offer solutions. Researchers must carefully parse 3 questions: has there been introgression of mtDNA and, if so, which population genetics-based driver has caused introgression, and do species limits need altering? Understanding of allopatry, mtDNA introgression, recent speciation, and selection must be properly integrated if species limits are to be robustly understood and applied with maximum benefit in downstream applications such as conservation and management.
Comparative phylogeographic analysis suggests a shared history among eastern North American boreal forest birds
Authors: Ralston Joel , FitzGerald Alyssa M , Burg Theresa M , Starkloff Naima C , Warkentin Ian G , Kirchman Jeremy J
Published: April 2021

Phylogeographic structure within high-latitude North American birds is likely shaped by a history of isolation in refugia during Pleistocene glaciations. Previous studies of individual species have come to diverse conclusions regarding the number and location of likely refugia, but no studies have explicitly tested for biogeographic concordance in a comparative phylogeographic framework. Here we use a hierarchical approximate Bayesian computation analysis of mitochondrial DNA sequences from 653 individuals of 6 bird species that are currently co-distributed in the boreal forest of North America to test for biogeographic congruence. We find support for congruent phylogeographic patterns across species, with shallow divergence dating to the Holocene within each species. Combining genetic results with paleodistribution modeling, we propose that these species shared a single Pleistocene refugium south of the ice sheets in eastern North America. Additionally, we assess modern geographic genetic structure within species, focusing on Newfoundland and disjunct high-elevation populations at the southern periphery of ranges. We find evidence for a “periphery effect” in some species with significant genetic structure among peripheral populations and between peripheral and central populations. Our results suggest that reduced gene flow among peripheral populations, rather than discordant biogeographic histories, can explain the small differences in genetic structure and levels of genetic diversity among co-distributed boreal forest birds.
The fourth scientific discovery paradigm for precision medicine and healthcare: Challenges ahead
Authors: Shen Li , Bai Jinwei , Wang Jiao , Shen Bairong
Published: April 2021

With the progression of modern information techniques, such as next generation sequencing (NGS), Internet of Everything (IoE) based smart sensors, and artificial intelligence algorithms, data-intensive research and applications are emerging as the fourth paradigm for scientific discovery. However, we face many challenges to practical application of this paradigm. In this article, 10 challenges to data-intensive discovery and applications in precision medicine and healthcare are summarized and the future perspectives on next generation medicine are discussed.
Long-term tolerability and efficacy of golimumab in active non-radiographic axial spondyloarthritis: results from open-label extension
Authors: van der Heijde Désirée , Dougados Maxime , Maksymowych Walter P , Bergman Gina , Curtis Sean P , Tzontcheva Anjela , Huyck Susan , Philip George , Sieper Joachim
Published: April 2021

Objectives

We report the open-label extension (OLE) of the GO-AHEAD study evaluating the long-term efficacy and safety of golimumab (GLM) in patients with non-radiographic axial spondyloarthritis (nr-axSpA).

Methods

Patients [both GLM- and placebo (PBO)-treated in the double-blind phase] received GLM 50 mg every 4 weeks during the OLE (36-week treatment; additional 8-week safety follow-up; GLM/GLM and PBO/GLM groups). All patients who entered and received ≥1 dose of study treatment in the OLE were included in the efficacy and safety analyses. The primary efficacy evaluations were the proportions of patients achieving 20% and 40% improvement in the ASAS criteria (ASAS20 and ASAS40, respectively). Responders’ analyses were calculated using a non-responder imputation approach.

Results

Of 198 patients randomised, 189/198 (95.5%) entered the OLE; 174/198 patients (87.9%) completed all visits. Although the proportion of responders increased from week 16 to week 52 in the OLE in both GLM/GLM and PBO/GLM groups, the GLM/GLM group had a higher proportion of responders than the PBO/GLM group throughout the OLE from week 16 to week 52 (ASAS20: 71.1% to 83.9% vs 40.0% to 75.0%, respectively; ASAS40: 56.7% to 76.3% vs 23.0% to 59.4%, respectively; ASAS partial remission: 33.0% to 53.8% and 18.0% to 45.8%). In the OLE, the overall incidence of AEs was lower in the GLM/GLM vs PBO/GLM groups (41.9% and 54.2%).

Conclusions

Sustained improvement in clinical efficacy was observed at 52 weeks in patients with nr-axSpA following GLM treatment. GLM was well tolerated and provided substantial long-term benefits to patients with nr-axSpA.

Trial registration

NCT01453725; United States National Library of Medicine clinical trials database; www.clinicaltrials.gov.
Mortality in patients with primary Sjögren’s syndrome: a systematic review and meta-analysis
Authors: Huang Hong , Xie Wenhui , Geng Yan , Fan Yong , Zhang Zhuoli
Published: April 2021

Objective

It remains debated whether patients with primary Sjögren’s syndrome (pSS) are at greater risk of mortality. We aimed to determine the magnitude of all-cause mortality risk in patients with pSS compared with the general population through a systematic review and meta-analysis.

Methods

We searched PubMed, EMBASE and Cochrane Library for studies published from inception to October 2020. Stata meta-analysis software was used to calculate the pooled risk estimates for mortality (standardized mortality ratio, SMR).

Results

Our search identified 2796 articles, of which 14 studies with 14 584 patients were eventually included for the analysis. A total of 902 deaths were observed. Overall, we found a 1.46-fold increased risk of death in pSS patients when compared with the general population [meta-standardized mortality ratio (SMR): 1.46, 95% CI: 1.10, 1.93]. Subgroup analyses showed that mortality risks were higher in European countries (meta-SMR: 1.55, 95% CI: 1.04, 2.33), in retrospective studies (meta-SMR: 1.50, 95% CI: 1.09, 2.05), in studies based on referral cohorts (meta-SMR: 1.55, 95% CI: 1.04, 2.30), in studies that enrolled >500 patients (meta-SMR: 1.70, 95% CI: 1.11, 2.61) and in studies with follow-up time longer than 8 years (meta-SMR: 1.55, 95% CI: 0.87, 2.77). Significantly greater mortality risk was found in patients with older age, male gender, vasculitis, interstitial lung disease, low complements, positive anti-La/SSB and cryoglobulinaemia.

Conclusion

The existing data indicated ∼50% increase of mortality among patients with pSS compared with the general population. More attention should be paid to those patients with poor prognostic factors.
Patients with early-onset primary Sjögren’s syndrome have distinctive clinical manifestations and circulating lymphocyte profiles
Authors: Wei Lin , Zhifei Xin , Xiaoran Ning , Meilu Liu , Yang Li , Yixuan Liu , Xiuying Ren , Yashuang Su , Jingjing Cao , Shaoying Guo , Liu Yang , Lijun Sun , Fengxiao Zhang , Wen Zhang
Published: April 2021

Objectives

To further investigate the clinical characteristics and circulating lymphocyte profiles of patients with early-onset primary Sjögren’s syndrome (pSS).

Method

Data of 333 patients with pSS were analysed retrospectively. Early onset was defined as a pSS diagnosis at an age of 35 years or younger. The clinical, laboratory and immunophenotypic profiles of peripheral blood lymphocyte subsets were compared between early- and later-onset pSS.

Results

Thirty-six (10.81%) patients matched the definition of early-onset pSS, with age at disease onset being 28.97  (5.53) years. Elevated serum IgG level (77.14% vs 31.16%, P <0.001), low C3 (41.67% vs 20.20%, P =0.004) and C4 levels (27.78% vs 6.40%, P <0.001), anti-SSA positivity (91.67% vs 51.85%, P <0.001) and anti-SSB positivity (50% vs 20.54%, P <0.001) were more frequent in early-onset patients. The frequencies of hematological (80.56% vs 52.53%, P =0.001), renal (19.44% vs 5.05%, P =0.005) and mucocutaneous involvement (50% vs 22.56%, P <0.001) were significantly higher in the early-onset pSS group, which showed a higher 2010 EULAR SS Disease Activity Index (ESSDAI) [11(6.25–17) vs 7(3–12); P =0.003], compared with the later-onset group. In addition, profound CD4+ T-cell lymphopenia was found in patients with early-onset.

Conclusions

Patients with early-onset pSS have distinctive clinical manifestations and greater activation of the cellular immune system, present with more severe clinical symptoms and immunological features, have increased activation of circulating T cells and have an unfavourable prognosis. Thus, they require more positive treatment with glucocorticoids and/or immunosuppressants and merit closer follow-up and regular monitoring.
Sleep spindles comprise a subset of a broader class of electroencephalogram events
Authors: Dimitrov Tanya , He Mingjian , Stickgold Robert , Prerau Michael J
Published: April 2021

Study Objectives

Sleep spindles are defined based on expert observations of waveform features in the electroencephalogram (EEG) traces. This is a potentially limiting characterization, as transient oscillatory bursts like spindles are easily obscured in the time domain by higher amplitude activity at other frequencies or by noise. It is therefore highly plausible that many relevant events are missed by current approaches based on traditionally defined spindles. Given their oscillatory structure, we reexamine spindle activity from first principles, using time-frequency activity in comparison to scored spindles.

Methods

Using multitaper spectral analysis, we observe clear time-frequency peaks in the sigma (10–16 Hz) range (TFσ peaks). While nearly every scored spindle coincides with a TFσ peak, numerous similar TFσ peaks remain undetected. We therefore perform statistical analyses of spindles and TFσ peaks using manual and automated detection methods, comparing event cooccurrence, morphological similarities, and night-to-night consistency across multiple datasets.

Results

On average, TFσ peaks have more than three times the rate of spindles (mean rate: 9.8 vs. 3.1 events/minute). Moreover, spindles subsample the most prominent TFσ peaks with otherwise identical spectral morphology. We further demonstrate that detected TFσ peaks have stronger night-to-night rate stability (ρ = 0.98) than spindles (ρ = 0.67), while covarying with spindle rates across subjects (ρ = 0.72).

Conclusions

These results provide compelling evidence that traditionally defined spindles constitute a subset of a more generalized class of EEG events. TFσ peaks are therefore a more complete representation of the underlying phenomenon, providing a more consistent and robust basis for future experiments and analyses.
Measuring sleep regularity: theoretical properties and practical usage of existing metrics
Authors: Fischer Dorothee , Klerman Elizabeth B , Phillips Andrew J K
Published: April 2021

Study Objectives

Sleep regularity predicts many health-related outcomes. Currently, however, there is no systematic approach to measuring sleep regularity. Traditionally, metrics have assessed deviations in sleep patterns from an individual’s average; these traditional metrics include intra-individual standard deviation (StDev), interdaily stability (IS), and social jet lag (SJL). Two metrics were recently proposed that instead measure variability between consecutive days: composite phase deviation (CPD) and sleep regularity index (SRI). Using large-scale simulations, we investigated the theoretical properties of these five metrics.

Methods

Multiple sleep–wake patterns were systematically simulated, including variability in daily sleep timing and/or duration. Average estimates and 95% confidence intervals were calculated for six scenarios that affect the measurement of sleep regularity: “scrambling” the order of days; daily vs. weekly variation; naps; awakenings; “all-nighters”; and length of study.

Results

SJL measured weekly but not daily changes. Scrambling did not affect StDev or IS, but did affect CPD and SRI; these metrics, therefore, measure sleep regularity on multi-day and day-to-day timescales, respectively. StDev and CPD did not capture sleep fragmentation. IS and SRI behaved similarly in response to naps and awakenings but differed markedly for all-nighters. StDev and IS required over a week of sleep–wake data for unbiased estimates, whereas CPD and SRI required larger sample sizes to detect group differences.

Conclusions

Deciding which sleep regularity metric is most appropriate for a given study depends on a combination of the type of data gathered, the study length and sample size, and which aspects of sleep regularity are most pertinent to the research question.