bluuebunny/crossref_metadata_2025 huggingface dataset:
CellTracker: an automated toolbox for single-cell segmentation and tracking of time-lapse microscopy images
Authors: Hu Tao , Xu Shixiong , Wei Lei , Zhang Xuegong , Wang Xiaowo
Published: December 2020

Recent advances of long-term time-lapse microscopy have made it easy for researchers to quantify cell behavior and molecular dynamics at single-cell resolution. However, the lack of easy-to-use software tools optimized for customized research is still a major challenge for quantitatively understanding biological processes through microscopy images. Here, we present CellTracker, a highly integrated graphical user interface software, for automated cell segmentation and tracking of time-lapse microscopy images. It covers essential steps in image analysis including project management, image pre-processing, cell segmentation, cell tracking, manually correction and statistical analysis such as the quantification of cell size and fluorescence intensity, etc. Furthermore, CellTracker provides an annotation tool and supports model training from scratch, thus proposing a flexible and scalable solution for customized dataset analysis.

Availability and implementation

CellTracker is an open-source software under the GPL-3.0 license. It is implemented in Python and provides an easy-to-use graphical user interface. The source code, instruction manual and demos can be found at https://github.com/WangLabTHU/CellTracker.

Supplementary information

Supplementary data are available at Bioinformatics online.
A Reliability Study: Strong Inter-Observer Agreement of an Expert Panel for Intestinal Ultrasound in Ulcerative Colitis
Authors: De Voogd Floris , Wilkens Rune , Gecse Krisztina , Allocca Mariangela , Novak Kerri , Lu Cathy , D’Haens Geert , Maaser Christian
Published: December 2020

Background

Intestinal ultrasound [IUS] is a promising and non-invasive cross-sectional imaging modality in the diagnosis and monitoring of ulcerative colitis [UC]. Unlike endoscopy, where standardized scoring for evaluation of disease activity is widely used, scoring for UC with IUS is currently unavailable. Therefore, we conducted a study to assess the reliability of IUS in UC among expert sonographists in order to identify robust parameters.

Methods

Thirty patients with both clinically active [25] and quiescent [five] UC were included. Six expert sonographers first agreed upon key IUS parameters and grading, including bowel wall thickness [BWT], colour Doppler signal [CDS], inflammatory fat [i-fat], loss of bowel wall stratification [BWS], loss of haustrations and presence of lymph nodes. Thirty video-recorded cases were blindly reviewed.

Results

Inter-observer agreement was almost perfect for BWT (intra-class correlation coefficient [ICC]: 0.96) and substantial for CDS [κ = 0.63]. Agreement was moderate for presence of lymph nodes [κ = 0.41] and fair for presence of i-fat [κ = 0.36], BWS [κ = 0.24] and loss of haustrations [κ = 0.26]. Furthermore, there was substantial agreement for presence of disease activity on IUS [κ = 0.77] and almost perfect agreement for disease severity [ICC: 0.93]. Most individual parameters showed a strong association with IUS disease activity as measured by the six readers.

Conclusion

IUS is a reliable imaging modality to assess disease activity and severity in UC. Important individual parameters such as BWT and CDS are reliable and could be incorporated in a future UC scoring index. Standardized acquisition and assessment of UC utilizing IUS with established reliability is important to expand the use of IUS globally.
Squat-to-stand provocation of dynamic left ventricular outflow tract obstruction in hypertrophic cardiomyopathy: a case report
Authors: Peng Lillian T , Newman D Brian , Geske Jeffrey B
Published: December 2020

Background

Left ventricular outflow tract (LVOT) obstruction is an important determinant of the management of hypertrophic cardiomyopathy (HCM). With a nationwide shortage of amyl nitrite in 2019, we implemented a ‘repetitive squat-to-stand’ manoeuvre to provoke LVOT obstruction during echocardiography.

Case summary

A 64-year-old female was referred with symptomatic HCM refractory to pharmacologic therapy. Transthoracic echocardiography showed minor LVOT obstruction with conventional imaging at rest and during Valsalva manoeuvre, but severe obstruction was confirmed with the repetitive squat-to-stand manoeuvre. Alcohol septal ablation via the first septal perforator was performed with subsequent resolution of symptoms.

Discussion

Due to the dynamic nature of LVOT obstruction, a series of provocative manoeuvres including Valsalva manoeuvre, inhalation of amyl nitrite, and exercise are often necessary to maximally augment ventricular obstruction. The recent unavailability of amyl nitrite during a nationwide shortage prompted the implementation of a protocol of repetitive squat-to-stand manoeuvre in our echocardiography laboratory. Rising from the squatting position decreases preload and afterload, both of which augment dynamic LVOT obstruction. Repetition of squatting and standing appears to enhance the sensitivity of the manoeuvre, particularly when exertional symptoms are reproduced. In this case, repetitive squat-to-stand manoeuvre led to the identification of severe LVOT obstruction which may not have been diagnosed otherwise, alteration of treatment to septal reduction therapy, and subsequent resolution of symptoms.
Unusual intracardiac thrombosis in two patients with coronavirus disease 2019 (COVID-19): case series
Authors: Calvi Emiliano , Bernardi Nicola , Cimino Giuliana , Pascariello Greta , Faggiano Pompilio , Gavazzi Emanuele , Vizzardi Enrico , Metra Marco
Published: December 2020

Background

COVID-19 may induce a coagulation dysregulation resulting in a prothrombotic state with a higher risk of arterial and venous thrombosis. This abnormal thrombotic diathesis can lead to pulmonary embolism, stroke, and intracardiac thrombosis.

Case summary

We present two cases of unusual intracardiac thrombosis in patients hospitalized for COVID-19. In both cases, imaging tests (such as transthoracic echocardiography (TTE), computed tomography scan of the chest, and cardiac magnetic resonance imaging) showed evidence of unusual intracardiac thrombosis with thrombi adherent to regularly contracting walls.

Discussion

This evidence confirms that COVID-19 induces a hypercoagulable state which can result in intracardiac thrombosis. Therefore, TTE is indicated in all COVID-19 patients for early diagnosis, and prompt anticoagulant therapy is to be considered as a thromboprophylaxis strategy.
A case report on transient cardiomyopathy with cytokine storm in SARS-CoV-2
Authors: Tarun Tushar , Kumar Senthil , Johnson Jeremy , Chockalingam Anand
Published: December 2020

Background

Cardiac manifestations during Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) pandemic have included acute coronary syndrome, arrhythmias, myocarditis, and stress cardiomyopathy. However, the combination of cardiomyopathy and negative cardiac biomarkers has not yet been reported.

Case summary

A 49-year-old man admitted for respiratory failure secondary to SARS-CoV-2 developed new-onset cardiomyopathy with negative cardiac biomarkers. Left ventricular ejection fraction and strain improved 7 days after the initial echocardiogram, after administration of Tocilizumab, coinciding with clinical recovery, and improvement in inflammatory markers.

Discussion

As experience of cardiovascular manifestations of SARS-CoV-2 increases, more patients will likely present with cardiovascular manifestations; the recognition and proper management of these may improve patient outcomes.
The power of optimal medical therapy using angiotensin receptor-neprilysin inhibitor in acute decompensated heart failure, sparing a critical patient open-heart surgery with a device therapy: a case report
Authors: Gerges Fady , Komaranchath Austin , Al Bakshy Faiz , Almaghraby Abdallah
Published: December 2020

Background

Timely use of Sacubitril/Valsartan has the potential to significantly improve cardiac function and dramatically reduce secondary mitral regurgitation (MR) severity even in patients presenting with acute decompensated heart failure (HF), not only in compensated chronic HF patients. The outstanding impact of echocardiography is obvious in monitoring improvement of cardiac function and MR severity in patients with HF with reduced ejection fraction (HFrEF).

Case summary

We report a relevant case of an elderly patient who presented with acute decompensated HF and severe MR. He was symptomatic despite being on maximally tolerated doses of ACEI, beta-blockers, and diuretics. Left ventricular ejection fraction (LVEF) improved from 15% to 35% 2 weeks following initiation of Sacubitril/Valsartan during second HF hospitalization. There was a dramatic improvement of patient’s symptoms from New York Heart Association (NYHA) Class IV to NYHA I. N-terminal pro B-type natriuretic peptide reduced from 9000 pg/mL to 800 pg/mL. Coronary angiography depicted three-vessel coronary artery disease. The patient was advised to undergo coronary artery bypass graft surgery with mitral valve repair, then followed by implantation of a cardiac resynchronization therapy-defibrillator device (CRT-D) if no LV function improvement is observed after revascularization. The electrocardiogram showed Q waves in inferior leads with QRSd ≥ 125 ms, hence a good candidate for CRT. Following an elective percutaneous coronary intervention, LVEF further improved to 50%. The patient became asymptomatic with preserved LVEF on follow-up for 18 months later.

Discussion

This case report documents the swift echocardiographic and symptom improvement in a decompensated end-stage HF patient when Sacubitril/Valsartan initiated during acute setting.
C-reactive protein and clinical outcomes in patients with COVID-19
Authors: Smilowitz Nathaniel R , Kunichoff Dennis , Garshick Michael , Shah Binita , Pillinger Michael , Hochman Judith S , Berger Jeffrey S
Published: December 2020

Background

A systemic inflammatory response is observed in coronavirus disease 2019 (COVID-19). Elevated serum levels of C-reactive protein (CRP), a marker of systemic inflammation, are associated with severe disease in bacterial or viral infections. We aimed to explore associations between CRP concentration at initial hospital presentation and clinical outcomes in patients with COVID-19.

Methods and results

Consecutive adults aged ≥18 years with COVID-19 admitted to a large New York healthcare system between 1 March and 8 April 2020 were identified. Patients with measurement of CRP were included. Venous thrombo-embolism (VTE), acute kidney injury (AKI), critical illness, and in-hospital mortality were determined for all patients. Among 2782 patients hospitalized with COVID-19, 2601 (93.5%) had a CRP measurement [median 108 mg/L, interquartile range (IQR) 53–169]. CRP concentrations above the median value were associated with VTE [8.3% vs. 3.4%; adjusted odds ratio (aOR) 2.33, 95% confidence interval (CI) 1.61–3.36], AKI (43.0% vs. 28.4%; aOR 2.11, 95% CI 1.76–2.52), critical illness (47.6% vs. 25.9%; aOR 2.83, 95% CI 2.37–3.37), and mortality (32.2% vs. 17.8%; aOR 2.59, 95% CI 2.11–3.18), compared with CRP below the median. A dose response was observed between CRP concentration and adverse outcomes. While the associations between CRP and adverse outcomes were consistent among patients with low and high D-dimer levels, patients with high D-dimer and high CRP have the greatest risk of adverse outcomes.

Conclusions

Systemic inflammation, as measured by CRP, is strongly associated with VTE, AKI, critical illness, and mortality in COVID-19. CRP-based approaches to risk stratification and treatment should be tested.
Catheter ablation for non-paroxysmal atrial fibrillation accompanied by heart failure with preserved ejection fraction: feasibility and benefits in functions and B-type natriuretic peptide
Authors: Yamauchi Ryota , Morishima Itsuro , Okumura Kenji , Kanzaki Yasunori , Morita Yasuhiro , Takagi Kensuke , Nagai Hiroaki , Watanabe Naoki , Furui Koichi , Yoshioka Naoki , Miyazawa Hiroyuki , Shimojo Kazuki , Imaoka Takuro , Sakamoto Gaku , Murohara Toyoaki
Published: December 2020

Aims

We aimed to examine the benefits of catheter ablation in patients with non-paroxysmal atrial fibrillation (AF) accompanied by heart failure (HF) with preserved ejection fraction (HFpEF), in comparison with the benefits in patients with AF accompanied by HF with reduced ejection fraction (HFrEF) or patients with no HF.

Methods and results

From 1173 consecutive patients undergoing catheter ablation, 502 with non-paroxysmal AF were divided into three groups: no history of HF [plasma B-type natriuretic peptide (BNP) <100 pg/mL and no HF hospitalization; n = 125], HFpEF [left ventricular (LV) EF ≥50%; n = 293], and HF with midrange EF (HFmrEF) + HFrEF (LVEF <50%; n = 84) groups. The endpoints were AF recurrence at 1 year, changes in symptomatic and image-based functional status, and changes in BNP levels from baseline to 1 year. In the HFpEF group, AF recurred in 48 patients (16.4%) and 278 patients (94.8%) had sinus rhythm at 1 year; these values were comparable with those in the other groups. Significant improvement was observed in the left atrial diameter, LVEF, and New York Heart Association functional class in the HFpEF and HFmrEF + HFrEF groups. The BNP level significantly decreased irrespective of the index rate control status, and freedom from AF recurrence was an independent predictor of HF remission, defined as BNP <100 pg/mL at 1 year, in the HFpEF group.

Conclusion

Catheter ablation is highly feasible for restoring sinus rhythm in non-paroxysmal AF with coexisting HFpEF, thereby improving cardiac function and BNP levels. Catheter ablation for AF may be an optional management strategy.
Molecular cloning and biochemical characterization of a NAD-dependent sorbitol dehydrogenase from cold-adaptedPseudomonas mandelii
Authors: DangThu Quynh , Nguyen Thu-Thuy , Jang Sei-Heon , Lee ChangWoo
Published: December 2020

Sugar alcohols (polyols) have important roles as nutrients, anti-freezing agents and scavengers of free radicals in cold-adapted bacteria, but the characteristics of polyol dehydrogenases in cold-adapted bacteria remain largely unknown. In this study, based on the observation that a cold-adapted bacterium Pseudomonas mandelii JR-1 predominantly utilized d-sorbitol as its carbon source, among the four polyols examined (d-galactitol, d-mannitol, d-sorbitol and d-xylitol), we cloned and characterized a sorbitol dehydrogenase (SDH, EC 1.1.1.14) belonging to the short-chain dehydrogenase/reductase family from this bacterium (the SDH hereafter referred to as PmSDH). PmSDH contained Asn111, Ser140, Tyr153 and Lys157 as catalytic active site residues and existed as an ∼67-kDa dimer in size-exclusion chromatography. PmSDH converted d-sorbitol to d-fructose using nicotinamide adenine dinucleotide (NAD+) as a cofactor and, vice versa, d-fructose to d-sorbitol using nicotinamide adenine dinucleotide reduced (NADH) as a cofactor. PmSDH maintained its conformational flexibility, secondary and tertiary structures, and thermal stability at 4–25°C. These results indicate that PmSDH, which has a flexible structure and a high catalytic activity at colder temperatures, is well suited to sorbitol utilization in the cold-adapted bacterium P. mandelii JR-1.
Modern contraceptive availability and stockouts: a multi-country analysis of trends in supply and consumption
Authors: Muhoza Pierre , Koffi Alain K , Anglewicz Philip , Gichangi Peter , Guiella Georges , OlaOlorun Funmilola , Omoluabi Elizabeth , Sodani P R , Thiongo Mary , Akilimali Pierre , Tsui Amy , Radloff Scott
Published: December 2020

Approximately 214 million women of reproductive age lack adequate access to contraception for their family planning needs, yet patterns of contraceptive availability have seldom been examined. With growing demand for contraceptives in some areas, low contraceptive method availability and stockouts are thought to be major drivers of unmet need among women of reproductive age, though evidence for this is limited. In this research, we examined trends in stockouts, method availability and consumption of specific contraceptive methods in urban areas of four sub-Saharan African countries (Burkina Faso, Democratic Republic of Congo, Kenya and Nigeria) and India. We used representative survey data from the Performance Monitoring for Action Agile Project that were collected in quarterly intervals at service delivery points (SDP) stratified by sector (public vs private), with all countries having five to six quarters of surveys between 2017 and 2019. Among SDPs that offer family planning, we calculated the percentage offering at least one type of modern contraceptive method (MCM) for each country and quarter, and by sector. We examined trends in the percentage of SDPs with stockouts and which currently offer condoms, emergency contraception, oral pills, injectables, intrauterine devices and implants. We also examined trends of client visits for specific methods and the resulting estimated protection from pregnancy by quarter and country. Across all countries, the vast majority of SDPs had at least one type of MCM in-stock during the study period. We find that the frequency of stockouts varies by method and sector and is much more dynamic than previously thought. While the availability and distribution of long-acting reversible contraceptives (LARCs) were limited compared to other methods across countries, LARCs nonetheless consistently accounted for a larger portion of couple years of protection. We discuss findings that show the importance of engaging the private sector towards achieving global and national family planning goals.
Exclusion of bacterial co-infection in COVID-19 using baseline inflammatory markers and their response to antibiotics
Authors: Mason Claire Y , Kanitkar Tanmay , Richardson Charlotte J , Lanzman Marisa , Stone Zak , Mahungu Tabitha , Mack Damien , Wey Emmanuel Q , Lamb Lucy , Balakrishnan Indran , Pollara Gabriele
Published: December 2020

Background

COVID-19 is infrequently complicated by bacterial co-infection, but antibiotic prescriptions are common. We used community-acquired pneumonia (CAP) as a benchmark to define the processes that occur in bacterial pulmonary infections, testing the hypothesis that baseline inflammatory markers and their response to antibiotic therapy could distinguish bacterial co-infection from COVID-19.

Methods

Retrospective cohort study of CAP (lobar consolidation on chest radiograph) and COVID-19 (PCR detection of SARS-CoV-2) patients admitted to Royal Free Hospital (RFH) and Barnet Hospital (BH), serving as independent discovery and validation cohorts. All CAP and >90% COVID-19 patients received antibiotics on hospital admission.

Results

We identified 106 CAP and 619 COVID-19 patients at RFH. Compared with COVID-19, CAP was characterized by elevated baseline white cell count (WCC) [median 12.48 (IQR 8.2–15.3) versus 6.78 (IQR 5.2–9.5) ×106 cells/mL, P < 0.0001], C-reactive protein (CRP) [median 133.5 (IQR 65–221) versus 86.0 (IQR 42–160) mg/L, P < 0.0001], and greater reduction in CRP 48–72 h into admission [median ΔCRP −33 (IQR −112 to +3.5) versus +14 (IQR −15.5 to +70.5) mg/L, P < 0.0001]. These observations were recapitulated in the independent validation cohort at BH (169 CAP and 181 COVID-19 patients). A multivariate logistic regression model incorporating WCC and ΔCRP discriminated CAP from COVID-19 with AUC 0.88 (95% CI 0.83–0.94). Baseline WCC >8.2 × 106 cells/mL or falling CRP identified 94% of CAP cases, and excluded bacterial co-infection in 46% of COVID-19 patients.

Conclusions

We propose that in COVID-19, absence of both elevated baseline WCC and antibiotic-related decrease in CRP can exclude bacterial co-infection and facilitate antibiotic stewardship efforts.
On filament fragmentation and the impact of ambient environment on it
Authors: Anathpindika S V , Francesco J Di
Published: December 2020

Filaments are crucial intermediaries in the star formation process. Recent observations of filaments show that (i) a number of them are non-singular entities, and rather a bundle of velocity coherent fibres, and (ii) while a majority of filaments spawn cores narrower than their natal filaments, some cores are broader. We explore these issues by developing hydrodynamic simulations of an initially sub-critical individual filament that is allowed to accrete gas from its neighbourhood and evolves under self-gravity. Results obtained here support the idea that fibres form naturally during the filament formation process. We further argue that the ambient environment, i.e. the magnitude of external pressure, and not the filament linemass alone, has bearing upon the morphology of its evolution. We observe that a filament is susceptible to the sausage-type instability irrespective of the external pressure. The fragments, however, are pinched in a filament experiencing pressure comparable to that in the Solar neighbourhood (∼104 K cm−3). By contrast, fragments are broad and spherical – having density profiles similar to that of a stable Bonnor–Ebert sphere – when the filament experiences a higher pressure, typically ≥105 K cm−3, but ≤106 K cm−3). The filament tends to rupture at even higher external pressure (≥107 K cm−3). These observations collectively mean that star formation is less efficient with increasing external pressure.
Ligand-dependent tRNA processing by a rationally designed RNase P riboswitch
Authors: Ender Anna , Etzel Maja , Hammer Stefan , Findeiß Sven , Stadler Peter , Mörl Mario
Published: December 2020

We describe a synthetic riboswitch element that implements a regulatory principle which directly addresses an essential tRNA maturation step. Constructed using a rational in silico design approach, this riboswitch regulates RNase P-catalyzed tRNA 5′-processing by either sequestering or exposing the single-stranded 5′-leader region of the tRNA precursor in response to a ligand. A single base pair in the 5′-leader defines the regulatory potential of the riboswitch both in vitro and in vivo. Our data provide proof for prior postulates on the importance of the structure of the leader region for tRNA maturation. We demonstrate that computational predictions of ligand-dependent structural rearrangements can address individual maturation steps of stable non-coding RNAs, thus making them amenable as promising target for regulatory devices that can be used as functional building blocks in synthetic biology.
Robust prediction of hourly PM2.5 from meteorological data using LightGBM
Authors: Zhong Junting , Zhang Xiaoye , Gui Ke , Wang Yaqiang , Che Huizheng , Shen Xiaojing , Zhang Lei , Zhang Yangmei , Sun Junying , Zhang Wenjie
Published: December 2020

Retrieving historical fine particulate matter (PM2.5) data is key for evaluating the long-term impacts of PM2.5 on the environment, human health and climate change. Satellite-based aerosol optical depth has been used to estimate PM2.5, but estimations have largely been undermined by massive missing values, low sampling frequency and weak predictive capability. Here, using a novel feature engineering approach to incorporate spatial effects from meteorological data, we developed a robust LightGBM model that predicts PM2.5 at an unprecedented predictive capacity on hourly (R2 = 0.75), daily (R2 = 0.84), monthly (R2 = 0.88) and annual (R2 = 0.87) timescales. By taking advantage of spatial features, our model can also construct hourly gridded networks of PM2.5. This capability would be further enhanced if meteorological observations from regional stations were incorporated. Our results show that this model has great potential in reconstructing historical PM2.5 datasets and real-time gridded networks at high spatial-temporal resolutions. The resulting datasets can be assimilated into models to produce long-term re-analysis that incorporates interactions between aerosols and physical processes.
The Glossopharyngo-Cochlear Triangle—Part I: Quantitative Anatomic Analysis of High-Riding Posterior Inferior Cerebellar Artery Aneurysms Exposed Through the Extended Retrosigmoid Approach
Authors: Zhao Xiaochun , Tayebi Meybodi Ali , Naeem Komal , Belykh Evgenii , Labib Mohamed A , Baranoski Jacob F , Catapano Joshua S , Mascitelli Justin R , Preul Mark C , Lawton Michael T
Published: December 2020

BACKGROUND

An extended retrosigmoid approach can offer sufficient space for clip reconstruction of some high-riding posterior inferior cerebellar artery (PICA) aneurysms.

OBJECTIVE

To quantitatively investigate the glossopharyngo-cochlear triangle (GCT) and anatomic structures within it.

METHODS

Extended retrosigmoid craniotomies were performed on 10 sides of cadaveric heads, and the GCT was identified in each specimen. The length of the base and the area of the GCT were measured. The depth of the vertebrobasilar system and the abducens nerve to the GCT were measured. The proximal and distal exposable and controllable points on the vertebrobasilar system were identified. Two imaging-based patient selection algorithms are provided using the lengths from those points to the vertebral artery dural entry point and the superoinferior distances from those points to the inferior edge of the foramen magnum. Other factors related to accessibility via the GCT were investigated.

RESULTS

The mean (standard deviation [SD]) area of the GCT was 45.7 (12.55) mm2. The mean (SD) depth of the abducens nerve was 14.3 (1.42) mm. The mean (SD) superoinferior distances from the foramen magnum to those points were 23.1 (7.39), 24.7 (8.25), 30.0 (9.56), and 32.6 (7.79) mm, respectively. The lower segment of the vertebrobasilar system was more superficial in the setting of a high-lying vertebrobasilar junction (VBJ) than a low-lying VBJ.

CONCLUSION

We describe the GCT in an extended retrosigmoid approach for high-riding PICA aneurysms and evaluate the spatial relationship of the neurovascular structures within it. Two potential algorithms are offered for preoperative patient selection.
Intraoperative Computed Tomography for Registration of Stereotactic Frame in Frame-Based Deep Brain Stimulation
Authors: Jones Michael R , Baskaran Archit B , Nolt Mark J , Rosenow Joshua M
Published: December 2020

BACKGROUND

Deep brain stimulation (DBS) electrode placement utilizing a frame-based technique requires registration of the stereotactic frame with computed tomography (CT) or magnetic resonance (MR) imaging. This traditionally has been accomplished with a conventional CT scanner. In recent years, intraoperative CT has become more prevalent.

OBJECTIVE

To compare the coordinates obtained with intraoperative CT and conventional CT for registration of the stereotactic frame for DBS.

METHODS

Patients undergoing DBS electrode placement between 2015 and 2017, who underwent both conventional and intraoperative CT for registration of the stereotactic frame, were included for analysis. The coordinates for the stereotactic target, anterior commissure, and posterior commissure for each CT method were recorded. The mean, maximum, minimum, and standard deviation of the absolute difference for each of the paired coordinates was calculated. Paired t-tests were performed to test for statistical significance of the difference. The directional difference as well as the vector error between the paired coordinates was also calculated.

RESULTS

The mean absolute difference between conventional and intraoperative CT for the coordinate pairs was less than 0.279 mm or 0.211 degrees for all coordinate pairs analyzed. This was not statistically significant for any of the coordinate pairs. Moreover, the maximum absolute difference between all coordinate pairs was 1.04 mm.

CONCLUSION

Intraoperative CT imaging provides stereotactic frame registration coordinates that are similar to those obtained by a standard CT scanner. This may save time and hospital resources by obviating the need for the patient to go to the radiology department for a CT scan.
C1-2 Pedicle Screw Fixation for Ponticulus Posticus and Duplication of Vertebral Artery: 2-Dimensional Operative Video
Authors: Jung Yoon Gyo , Lee Byung-Jou , Park Wonhyoung , Park Jin Hoon
Published: December 2020

We previously introduced C1 pedicle screw placement to treat C1-2 pathology in a patient with normal vertebral artery anatomy.
1
However, we should prepare to meet various anatomic variations. Ponticulus posticus is a bony prominence arising from the posterior arch or the superior articulating process of the atlas that completely or partially encircles the vertebral artery.
2
We herein report a 79-yr-old female who presented with myelopathy and was diagnosed with compressive myelopathy at the C1 level in magnetic resonance imaging. A computed tomography showed ponticulus posticus (complete type to the right side) with duplication of vertebral artery.

 She underwent surgical treatment of C1-2 pedicle screw placement and reduction of C1 vertebra under a microscopic view. After C1 laminectomy, both-side vertebral arteries were dissected with a microscissor. The mobilization of upper divisions of vertebral artery was identified to secure the entry point and pedicle to insert a C1 pedicle screw. After complete protection of the upper and lower divisions of vertebral artery and identification of pedicle, a C1 pedicle screw was inserted by a freehand technique. We inserted autologous bone chips in the distracted C1-2 facet joint for facet joint fusion, and the C1 vertebra was pulled out by a rod reducer.

 After surgery, the patient's symptoms disappeared, and no vertebral artery injury was identified in postoperative 3-dimensional computed tomography angiography.

 Patient consent was obtained prior to performing the procedure.
Lateral Myelotomy for Resection of a Ruptured Intramedullary Cervico-Thoracic Cavernous Malformation
Authors: Ginalis Elizabeth E , Herschman Yehuda , Patel Nitesh V , Jumah Fareed , Xiong Zhenggang , Hanft Simon J
Published: December 2020

BACKGROUND AND IMPORTANCE

Intramedullary spinal cord cavernous malformations represent 5% to 12% of spinal vascular disease. Most patients present with acute or progressive neurological symptoms, including motor weakness or sensory loss. Surgical resection is the only definitive management and is recommended for symptomatic lesions that are surgically accessible.

CLINICAL PRESENTATION

A 35-yr-old woman presented with a sudden onset of pain and temperature sensation loss in the left lower extremity. Magnetic resonance imaging of the spine showed a hemorrhage located ventral and slightly lateral to the right of the midline of the spinal cord from C7 through T3. Ultimately, a right lateral myelotomy between the ventral and dorsal roots was performed, and the cavernous malformation was removed. Postoperative imaging confirmed gross total resection of the cavernous malformation.

CONCLUSION

In this article, we report a highly unusual case of a multisegment, ruptured intramedullary cavernous malformation that was ultimately resected through a lateral myelotomy approach. This case demonstrates that a lateral approach to the spinal cord substance can be utilized for ruptured cavernous malformation, especially if there is hemorrhage at the surface of the spinal cord. This can be used as an entry into the anterolateral compartment of the spinal cord, which would otherwise be regarded as a highly morbid approach due to the sensory deficits induced. We believe this entry point to the spinal cord is feasible in highly select cases such as this.
Sterile Gelatin Film Reduces Cortical Injury Associated With Brain Tumor Re-Resection
Authors: Przybylowski Colin J , So Veronica , DeTranaltes Kaylee , Walker Corey , Baranoski Jacob F , Chapple Kristina , Sanai Nader
Published: December 2020

BACKGROUND

Recurrent intracranial tumors frequently require re-resection. Dural adhesions to the cortex increase the morbidity and duration of these revision craniotomies.

OBJECTIVE

To describe the use of commercially available sterile gelatin film to prevent meningocerebral adhesions and decrease the rate of surgically induced ischemia from revision craniotomy.

METHODS

This retrospective cohort study examined patients with recurrent glioma, meningioma, and metastasis who underwent re-resection at least 30 d following their initial tumor resection. Cortical surface tissue ischemia after re-resection on diffusion-weighted magnetic resonance imaging was compared for patients with (gelatin film group) and without (nongelatin film group) a history of gelatin film placement at the conclusion of their initial tumor resection.

RESULTS

A total of 84 patients in the gelatin film group were compared to 86 patients in the nongelatin film group. Patient age, sex, tumor pathology, tumor volume, tumor eloquence, laterality of surgical approach, history of radiotherapy, and time interval between resections did not differ between groups. Radiographic evidence of cortical ischemia following reoperation was less prevalent in the gelatin film group (13.1% vs 32.6%; P < .01). In multivariate logistic regression analysis, no gelatin film (P < .01) and larger tumor size (P = .02) predicted cortical surface ischemia following revision craniotomy. Postoperative complications in the gelatin film and nongelatin film group otherwise did not differ.

CONCLUSION

Routine placement of commercially available sterile gelatin film on the cortex prior to dural closure is associated with decreased surgically induced tissue ischemia at the time of revision tumor craniotomy.
Nipping Diseases in the Bud? Ethical and Social Considerations of the Concept of ‘Disease Interception’
Authors: Narchi Jonas , Winkler Eva C
Published: December 2020

‘Disease interception’ describes the treatment of a disease in its clinically inapparent phase and is increasingly used in medical literature. However, no precise definition, much less an ethical evaluation, has been developed yet. This article starts with a definition of ‘disease interception’ by distinguishing it from other preventions. It then analyses the ethical and social implications of the concept in light of the four principles of medical ethics by Beauchamp and Childress. The term ‘disease interception’ refers to a form of secondary prevention applied in a short interception window intended to prevent a preclinical disease from developing further. We propose the definition ‘early and targeted secondary prevention by treatment’. The ethical evaluation of the concept shows that while it promises to be beneficial, it raises a number of ethical and social challenges regarding patient autonomy and justice. In order to ensure decision-making that respects patient autonomy, commercially motivated metaphors such as ‘disease interception’ should make way for precise definitions. Future research should not only focus on how to detect clinically inapparent diseases but also on the ethical question, when this is justifiable and what consequences it has for the individual and society as a whole.
Evaluation of on-farm indicators of gilt reproductive performance potential at 21 days of age1
Authors: Mills Kayla M , Schinckel Allan P , Stevens Jebadiah G , Casey Theresa M , Stewart Kara R
Published: December 2020

Selection of replacements for the sow herd is one of the most important facets in swine production. Although our current methods of selection are effective, there is still a large amount of variation in sow reproductive performance traits such as pigs per sow per year (PSY). Therefore, the objective of this study was to determine if on-farm phenotypic traits at 21 d postnatal (PN) or perinatal environmental factors could predict sow reproductive performance. Data were prospectively collected from 2,146 gilts born on a commercial sow production facility and included birth and weaning weights, vulva length and width at 21 d PN, birth and nursing litter size, days nursed, average daily gain from birth to weaning, and age at first estrus. Of the initial animals, 400 (17%) were selected for the sow herd, 353 remained after removal of animals culled for non-reproductive reasons. Animals were assigned to 1 of 5 reproductive performance categories based on observation of estrus or pigs per sow per year (PSY) across two farrowings: High Fertility (HF; 23%; n = 82; ≥26 PSY), Middle Fertility (MF2; 12%; n = 43; 20–25 PSY), Low Fertility (MF3; 15%; n = 54; <20 PSY), Infertile-Estrus (IFe; 10%; n = 36; estrus, no pregnancy), and Infertile-No Estrus (IFno; 39%; n = 138; no estrus, no pregnancy). Generalized linear model analysis indicated vulva width (P = 0.03) was related to PSY, however, it only explained 1.5% of the total variation in PSY. To determine if preweaning variables were predictive of gilt fertility outcome, animals were grouped as those that became pregnant (n = 179) or not (n = 174). Vulva width tended to be greater in fertile animals versus infertile (P = 0.07). Binomial regression analysis revealed a positive relationship between vulva width and gilt fertility, however, this relationship is not strong enough to make sow herd selection decisions.
Phylogenetic, Morphological, and Pathogenic Characterization of Alternaria Species Associated With Fruit Rot of Mandarin in California
Authors: Wang Fei , Saito Seiya , Michailides Themis J. , Xiao Chang-Lin
Published: December 2020

Alternaria rot caused by Alternaria species is one of the major postharvest diseases of mandarin fruit in California. The aims of this study were to identify these Alternaria species via phylogenetic analyses and morphological characteristics and test their pathogenicity on mandarin. Decayed mandarin fruits exhibiting Alternaria rot symptoms were collected from three citrus fruit packinghouses in the Central Valley of California. In total, 177 Alternaria isolates were obtained from decayed fruit and preliminarily separated into three groups representing three species (A. alternata, A. tenuissima, and A. arborescens) based on the colony characterization and sporulation patterns. To further identify these isolates, phylogenetic analysis was conducted based on DNA sequences of the second largest subunit of RNA polymerase II (RPB2), plasma membrane ATPase (ATPase), and Calmodulin gene regions in combination with morphological characters. Of the 177 isolates, 124 (70.1%) were identified as A. alternata, and 53 (29.9%) were A. arborescens. The isolates initially identified as A. tenuissima based on the morphological characteristics could not be separated from those of A. alternata in phylogenetic analysis and thus considered A. alternata. Pathogenicity tests showed that both Alternaria species were pathogenic on mandarin fruit at both 5°C and 20°C. Our results indicated that two Alternaria species, A. alternata and A. arborescens, were responsible for Alternaria rot of mandarin fruit in California, with A. arborescens causing fruit rot on mandarin being reported for the first time.
An Isolated Presentation of Ischemic Retinal Vasculitis by the Great Masquerader
Authors: Lim Yi Wen , Lott Pooi Wah , Mohamad Nor Fadhilah , Samsudin Amir , Singh Sujaya , Iqbal Tajunisah
Published: December 2020

Ischemic retinal vasculitis is a sight-threatening inflammatory ocular condition that involves the retinal blood vessels. It is often associated with vascular occlusion and retinal hypoperfusion that may lead to neovascularization and subsequently preretinal and vitreous hemorrhages. It can be idiopathic or secondary to infection, neoplasia, or any other systemic diseases. Although it is rare, tuberculosis, which is an airborne disease caused by Mycobacterium tuberculosis, can manifest as retinal vasculitis without any evidence of pulmonary or other ocular structures involvement.

We present a case of a 16-year-old girl with sudden blurred vision in the right eye. Based on fundoscopic examination and fluorescein fundus angiography, the right eye had severe bilateral ischemic vasculitis and neovascularization. Both Mantoux and tuberculosis spot test (T-Spot) further supported the presumptive clinical diagnosis of ocular tuberculous ischemic retinal vasculitis. Subsequently, pan-retinal photocoagulation sessions were commenced together with antituberculosis therapy and resulted in improved vision. We also include a literature review of similar reported cases where occlusive retinal vasculitis is the only presentation of ocular tuberculosis. Although this case highlights the possibility of ischemic retinal vasculitis as the only feature of ocular tuberculosis, a high degree of suspicion is necessary when dealing with this great masquerader.
Generalization of placebo pain relief
Authors: Kampermann Lea , Tinnermann Alexandra , Büchel Christian
Published: December 2020

Efficacy of treatment is heavily dependent on experience and expectations. Moreover, humans can generalize from one experience to a perceptually similar but novel situation. We investigated whether and how this applies to pain relief, using ecologically valid tonic pain stimuli treated by surreptitiously lowering the applied temperature. Using different face cues, participants experienced better treatment from one physician than another. Participants were then tested on 6 additional face cues perceptually lying between both faces. Our data from 2 independent samples (N = 18 and N = 39) show a treatment experience effect, ie, for physically identical treatments, the initially superior physician was reported to deliver stronger pain relief. More importantly, the other faces on the perceptual continuum showed a graded effect of pain relief, indicating placebo generalization. Introducing a paradigm feasible to induce placebo pain relief, we show that the generic learning principle of generalization can explain carryover effects between learned and novel treatment situations.
Beyond botulinum neurotoxin A for chemodenervation of the bladder
Authors: Thaker Hatim , Zhang Sicai , Diamond David A. , Dong Min
Published: December 2020

Purpose of review

Botulinum neurotoxin A (BoNT/A), or Botox, is a popular option for overactive bladder (OAB) and neurogenic bladder (NGB) with or without incontinence. This review aims to discuss the clinical outcomes of BoNT in adult and pediatric bladder conditions, and introduces the potential benefit of novel, engineered neurotoxins beyond BoNT/A.

Recent findings

A large volume of evidence supports the use of Botox for OAB (to reduce urgency, frequency and incontinence episodes), and for NGB (to decrease incontinence and improve bladder capacity and detrusor pressures). Botox is now also Food & Drug Administration (FDA)-approved for pediatric neurogenic detrusor overactivity. However, urinary retention, diminished response over time and treatment failures are prevalent issues with Botox. Modifying natural BoNTs or forming chimeric toxins are alternatives to BoNT/A that may have higher efficacy and lower side-effect profile. One example is BoNT/BMY-WW. This novel engineered toxin binds to a more commonly expressed synaptotagmin receptor, with potentially more potent paralytic effect and less capacity for systemic diffusion.

Novel engineered neurotoxins may be the next frontier in OAB and NGB therapy.
Placing a Central Vascular Access Device in a Patient With Substance Use Disorder
Authors: Chapple Helen Stanton
Published: December 2020

When infusion nurses place central vascular access devices in patients with substance use disorder (SUD), they are both enabling treatment and making the patient more vulnerable to his or her addictive illness. Using the lens of rescue enables an exploration of the ethical position of the infusion nurse regarding these patients, even though rescue, per se, is inadequate to the complexity of the situation. Suggestions are offered to both the infusion nurse and the health care team for improving their ethical stance, as well as their care of patients with SUD.
Meta-Analysis of Allergy Genome-Wide Association Studies
Authors: Sharma Ronin
Published: December 2020

Allergies are complex conditions involving both environmental and genetic factors. The genetic basis underlying allergic disease is investigated through genetic association studies. Genome-wide association studies (GWAS) leverage sequenced data to identify genetic mutations, such as single-nucleotide polymorphisms (SNPs), associated with phenotypes of interest. Machine learning can be used to analyze large datasets and generate predictive models. In this study, several classification models were created to predict the significance level of SNPs associated with allergies. Summary statistics were obtained from the GWAS Catalog and combined from several studies. Biological features such as chromosomal location, base pair location, effect allele, and odds ratio were used to train the models. The models ranged from simple linear regressions to multi-layer neural networks. The final models reached accuracies of 80% and reflect the features that have the largest impact on a SNP’s association level.
MHC-II constrains the natural neutralizing antibody response to the SARS-CoV-2 spike RBM in humans
Authors: Castro Andrea , Ozturk Kivilcim , Zanetti Maurizio , Carter Hannah
Published: December 2020

SARS-CoV-2 antibodies develop within two weeks of infection, but wane relatively rapidly post-infection, raising concerns about whether antibody responses will provide protection upon re-exposure. Here we revisit T-B cooperation as a prerequisite for effective and durable neutralizing antibody responses centered on a mutationally constrained RBM B cell epitope. T-B cooperation requires co-processing of B and T cell epitopes by the same B cell and is subject to MHC-II restriction. We evaluated MHC-II constraints relevant to the neutralizing antibody response to a mutationally-constrained B cell epitope in the receptor binding motif (RBM) of the spike protein. Examining common MHC-II alleles, we found that peptides surrounding this key B cell epitope are predicted to bind poorly, suggesting a lack MHC-II support in T-B cooperation, impacting generation of high-potency neutralizing antibodies in the general population. Additionally, we found that multiple microbial peptides had potential for RBM cross-reactivity, supporting previous exposures as a possible source of T cell memory.

Graphical abstract
Functional MRI based simulations of ECoG grid configurations for optimal measurement of spatially distributed hand-gesture information
Authors: van den Boom Max , Miller Kai J. , Ramsey Nick F. , Hermes Dora
Published: December 2020

In electrocorticography (ECoG), the physical characteristics of the electrode grid determine which aspect of the neurophysiology is measured. For particular cases, the ECoG grid may be tailored to capture specific features, such as in the development and use of brain-computer-interfaces (BCI). Neural representations of hand movement are increasingly used to control ECoG based BCIs. However, it remains unclear which grid configurations are the most optimal to capture the dynamics of hand gesture information. Here, we investigate how the design and surgical placement of grids would affect the usability of ECoG measurements. High resolution 7T functional MRI was used as a proxy for neural activity in ten healthy participants to simulate various grid configurations, and evaluated the performance of each configuration for decoding hand gestures. The grid configurations varied in number of electrodes, electrode distance and electrode size. Optimal decoding of hand gestures occurred in grid configurations with a higher number of densely-packed, large-size, electrodes up to a grid of~5×5 electrodes. When restricting the grid placement to a highly informative region of primary sensorimotor cortex, optimal parameters converged to about 3×3 electrodes, an inter-electrode distance of 8mm, and an electrode size of 3mm radius (performing at~70% 3-class classification accuracy). Our approach might be used to identify the most informative region, find the optimal grid configuration and assist in positioning of the grid to achieve high BCI performance for the decoding of hand-gestures prior to surgical implantation.