bluuebunny/crossref_metadata_2025 huggingface dataset:
SGLT2 Inhibitor–Induced Low-Grade Ketonemia Ameliorates Retinal Hypoxia in Diabetic Retinopathy—A Novel Hypothesis
Authors: Mudaliar Sunder , Hupfeld Christopher , Chao Daniel L
Published: January 2021

Diabetic retinopathy (DR) is a well-recognized microvascular complication of diabetes. Growing evidence suggests that, in addition to retinal vascular damage, there is significant damage to retinal neural tissue in DR. Studies reveal neuronal damage before clinically evident vascular lesions and DR is now classified as a neurovascular complication. Hyperglycemia causes retinal damage through complex metabolic pathways leading to oxidative stress, inflammation, vascular damage, capillary ischemia, and retinal tissue hypoxia. Retinal hypoxia is further worsened by high oxygen consumption in the rods. Persistent hypoxia results in increases in vascular endothelial growth factor (VEGF) and other pro-angiogenic factors leading to proliferative DR/macular edema and progressive visual impairment. Optimal glucose control has favorable effects in DR. Other treatments for DR include laser photocoagulation, which improves retinal oxygenation by destroying the high oxygen consuming rods and their replacement by low oxygen consuming glial tissue. Hypoxia is a potent stimulator of VEGF, and intravitreal anti-VEGF antibodies are effective in regressing macular edema and in some studies, retinal neovascularization. In this review, we highlight the complex pathophysiology of DR with a focus on retinal oxygen/fuel consumption and hypoxic damage to retinal neurons. We discuss potential mechanisms through which sodium-glucose cotransporter 2 (SGLT2) inhibitors improve retinal hypoxia—through ketone bodies, which are energetically as efficient as glucose and yield more ATP per molecule of oxygen consumed than fat, with less oxidative stress. Retinal benefits would occur through improved fuel energetics, less hypoxia and through the anti-inflammatory/oxidative stress effects of ketone bodies. Well-designed studies are needed to explore this hypothesis.
Liability Insurance: Equilibrium Contracts under Monopoly and Competition
Authors: Lemus Jorge , Temnyalov Emil , Turner John L.
Published: January 2021

In liability lawsuits (e.g., patent infringement), a plaintiff demands compensation from a defendant, and the parties often negotiate a settlement to avoid a costly trial. Liability insurance creates bargaining leverage for the defendant in this settlement negotiation. We study the characteristics of monopoly and equilibrium contracts in settings where this leverage effect is a substantial source of value for insurance. Our results show that under adverse selection, a monopolist offers at most two contracts, which underinsure low-risk types and may inefficiently induce high-risk types to litigate. In a competitive market, only a pooling equilibrium with underinsurance may exist. (JEL D41, D42, D82, D86, G22, K13, K41)
Magnetic resonance neurography of the head and neck: state of the art, anatomy, pathology and future perspectives
Authors: Van der Cruyssen Fréderic , Croonenborghs Tomas-Marijn , Renton Tara , Hermans Robert , Politis Constantinus , Jacobs Reinhilde , Casselman Jan
Published: January 2021

Magnetic resonance neurography allows for the selective visualization of peripheral nerves and is increasingly being investigated. Whereas in the past, the imaging of the extracranial cranial and occipital nerve branches was inadequate, more and more techniques are now available that do allow nerve imaging. This basic review provides an overview of the literature with current state of the art, anatomical landmarks and future perspectives. Furthermore, we illustrate the possibilities of the three-dimensional CRAnial Nerve Imaging (3D CRANI) MR-sequence by means of a few case studies.
Run length encoding based wavelet features for COVID-19 detection in X-rays
Authors: Sarhan Ahmad
Published: January 2021

Objectives:

Introduced in his paper is a novel approach for the recognition of COVID-19 cases in chest X-rays.

Methods:

The discrete Wavelet transform (DWT) is employed in the proposed system to obtain highly discriminative features from the input chest X-ray image. The selected features are then classified by a support vector machine (SVM) classifier as either normal or COVID-19 cases. The DWT is well-known for its energy compression power. The proposed system uses the DWT to decompose the chest X-ray image into a group of approximation coefficients that contain a small number of high-energy (high-magnitude) coefficients. The proposed system introduces a novel coefficient selection scheme that employs hard thresholding combined with run-length encoding to extract only high-magnitude Wavelet approximation coefficients. These coefficients are utilized as features symbolizing the chest X-ray input image. After applying zero-padding to unify their lengths, the feature vectors are introduced to a SVM which classifies them as either normal or COVID-19 cases.

Results:

The proposed system yields promising results in terms of classification accuracy, which justifies further work in this direction.

Conclusion:

The DWT can produce a few features that are highly discriminative. By reducing the dimensionality of the feature space, the proposed system is able to reduce the number of required training images and diminish the space and time complexities of the system.

Advances in knowledge:

Exploiting and reshaping the approximation coefficients can produce discriminative features representing the input image.
Η ανάπτυξη των απόψεων των εκ γενετής τυφλών παιδιών για το σχήμα της γης και την εναλλαγή της μέρας/νύχτας
Authors: Εικοσπεντάκη Καλλιόπη , Βοσνιάδου Στέλλα
Published: January 2021

An experiment is presented which investigated the conceptions of the earth in congenitally blind and sighted children. Twenty visually impaired and twenty sighted children attending first and third grade were interviewed individually in order to investigate their ideas about the earth. The children were asked questions about the shape andmovement of the Earth the Sun and the Moon and about the day/night cycle. They were also asked to construct models of the Earth, the Sun and the Moon using playdough. Τhe results showed that the visuallyimpaired children were capable of constructing models of the Earth similar in many respects to the models of the sighted children. These results were interpreted to indicate that the blind children, despite the lack of visual stimuli, received adequate information from their other senses and from their socio-cultural environment to create an adequate mental representation of the Earth. Nevertheless, the results also indicated that the visually impaired children had many more difficulties than the sighted children in understanding the normative model of a spherical earth in space, supporting the hypothesis that the blind children experience a developmental lag.
Θεραπευτικές παρεμβάσεις και σημαντικές ενδοσυνεδριακές στιγμές στη συστημική οικογενειακή ψυχοθεραπεία
Authors: Μπούσουλας Κωνσταντίνος , Μπούτρη Αλκμήνη , Στεργιάννη Χριστίνα , Σταλίκας Αναστάσιος
Published: January 2021

The purpose of this study was to investigate the psychotherapeutic process in family integrative systemic therapy that lead to therapeutic change. More specifically, the study investigated the relation between therapist interventions and in-session good moments at different phases of therapy. The sample consisted of five families with good therapeutic outcome at three different stages of therapy - beginning, middle, and ending. Results indicated the appearance of specific good moments and therapist’s interventions at different stages of therapy, as well as significant correlations between therapist interventions and client good moments. This study sheds light on the complex processes of systemic family therapy and the variables that contribute to good therapy outcome.
Ο μύθος της ανατροφής: Η σημασία της θεωρίας της ομαδικής κοινωνικοποίησης της Judith R. Harris στην κατανόηση και την αντιμετώπιση των διαταραχών προσωπικότητας σύμφωνα με το γνωσιακό-συμπεριφοριστικό μοντέλο
Authors: Ευσταθίου Γιώργος , Πέννα Υβόννη
Published: January 2021

This paper presents and examines the existing evidence for an alternative theory of child development. The theory of group socialization (TGS) suggests that, contrary to older evidence, socialization takes place in the peer groups of childhood and adolescence. Processes between those groups and among their members are responsible for the cultural transmission, personality shaping and for behavioural differentiation. Data that support the theory are presented, and the criticism that the theory has received is addressed. The usefulness of the theory in the context of the clinical understanding and treatment of personality disorders according to thecognitive behavioural model is discussed.
Τα ανατρεπτικά κείμενα και η πληροφορία κατηγοριοποίησης ως παράγοντες προώθησης της εννοιολογικής αλλαγής
Authors: Σκοπελίτη Ειρήνη , Βοσνιάδου Στέλλα
Published: January 2021

We present the results of two empirical studies which investigated the effect of the type of information included in refutational texts in 3rd grade students’ comprehension of the spherical shape of the earth. In the first study we compared three kinds of refutational texts: the first refuted only the belief that the earth is flat, the second refuted in addition the belief in up/down gravity, and the third refuted all of the above and in addition the belief that the earth is a physical and not an astronomical object. In Experiment 2, four texts were used to compare text type (refutation vs. non-refutation) and information type (categorical vs. non-categorical information). The results from the two experiments confirmed our hypothesis that refutational texts that include categorical information are the most effective in improving students’ understanding of scientific information about the earth.
Διερεύνηση εξελικτικών χαρακτηριστικών σχολικής και ψυχοκοινωνικής προσαρμογής παιδιών προσχολικής και σχολικής ηλικίας με βάση το σταθμισμένο τεστ Ψυχοκοινωνικής Προσαρμογής
Authors: Χατζηχρήστου Χρυσή , Πολυχρόνη Φωτεινή , Μπεζεβέγκης Ηλίας , Μυλωνάς Κώστας
Published: January 2021

Empirical evidence shows that specific psychosocial factors are linked to the learning process, school achievement and, in general, with students’ adjustment in the school and the family. The aim of the present study is to examine school, social and emotional adjustment of children attending Kindergarten and Elementary School and to identifygroups who are at risk of psychosocial adjustment difficulties. In order to achieve this aim, the teacher rating scales for preschool and school children were used from the standardized Test of Psychosocial Adjustment (Hatzichristou, Polychroni, Besevegis, & Mylonas, 2008). The sample consisted of teacher ratings for 432 Kindergarten children and 800 Elementary School children collected from different parts of Greece. Results showed more positive psychosocial adjustment for the younger age group in Elementary School, especially for the subscales “academic skills” and “problem behavior” and their relative dimensions. Moreover, gender differences were found especially in terms of the dimensions of school and emotional adjustment, with girls scoring higher while the reverse was found for problem behavior. Finally, similar profiles were found for the preschool and school age groups who were at risk for school and psychosocial adjustment difficulties. The results of this study contribute to our understanding of the risk and resilience factors of school and psychosocial adjustment of preschool and school aged children and have implications for the design and implementation of prevention and intervention programs in the school setting.
Επιλόχεια κατάθλιψη σε Ελληνίδες μητέρες: Επιδράσεις των στρεσογόνων γεγονότων ζωής, της κοινωνικής στήριξης και της συζυγικής σχέσης
Authors: Σταματίου Ευτυχία , Παπαληγούρα Ζαΐρα
Published: January 2021

ABSTRACT IS AVAILABLE IN THE PDF
Οι επιστημολογικές πεποιθήσεις ως παράγοντες πρόβλεψης των ατομικών στόχων επίτευξης μαθητών και μαθητριών Γυμνασίου και Λυκείου
Authors: Μεταλλίδου Παναγιώτα , Μέγαρη Καλλιόπη , Κωνσταντινοπούλου Ελένη
Published: January 2021

ABSTRACT IS AVAILABLE IN THE PDF
Ντροπαλότητα και κοινωνικό άγχος σε μαθητές του Δημοτικού: συχνότητα εμφάνισης και ένα νέο ερωτηματολόγιο μέτρησης του παιδικού προσδοκητικού άγχους
Authors: Φ. Βασιλόπουλος Στέφανος
Published: January 2021

The abstract is available in the PDF
The use of ‘PICO for synthesis’ and methods for synthesis without meta-analysis: protocol for a survey of current practice in systematic reviews of health interventions
Authors: Cumpston Miranda S. , McKenzie Joanne E. , Thomas James , Brennan Sue E.
Published: January 2021

Introduction: Systematic reviews involve synthesis of research to inform decision making by clinicians, consumers, policy makers and researchers. While guidance for synthesis often focuses on meta-analysis, synthesis begins with specifying the ’PICO for each synthesis’ (i.e. the criteria for deciding which populations, interventions, comparators and outcomes are eligible for each analysis). Synthesis may also involve the use of statistical methods other than meta-analysis (e.g. vote counting based on the direction of effect, presenting the range of effects, combining P values) augmented by visual display, tables and text-based summaries. This study examines these two aspects of synthesis.

Objectives: To identify and describe current practice in systematic reviews of health interventions in relation to: (i) approaches to grouping and definition of PICO characteristics for synthesis; and (ii) methods of summary and synthesis when meta-analysis is not used.

Methods: We will randomly sample 100 systematic reviews of the quantitative effects of public health and health systems interventions published in 2018 and indexed in the Health Evidence and Health Systems Evidence databases. Two authors will independently screen citations for eligibility. Two authors will confirm eligibility based on full text, then extract data for 20% of reviews on the specification and use of PICO for synthesis, and the presentation and synthesis methods used (e.g. statistical synthesis methods, tabulation, visual displays, structured summary). The remaining reviews will be confirmed as eligible and data extracted by a single author. We will use descriptive statistics to summarise the specification of methods and their use in practice. We will compare how clearly the PICO for synthesis is specified in reviews that primarily use meta-analysis and those that do not.

Conclusion: This study will provide an understanding of current practice in two important aspects of the synthesis process, enabling future research to test the feasibility and impact of different approaches.
Smoldering subcutaneous polymicrobial infection concealed beneath a cast and a skin graft: Delayed wound healing due to recurring soft-tissue infections
Authors: Bharadia Deepak , Sturgeon Ashley , Baird Daniel , Aldrete Jonathan
Published: January 2021

Injury to soft-tissues secondary to trauma is common and may require surgical intervention depending on the extent of the injury and the structures involved. Motor vehicle accidents are a leading cause of traumatic injury and often require surgical irrigation and debridement (I&D) to remove damaged and necrotic tissue while preserving tissue integrity and function. Surgical intervention carries its own risks, however, with the introduction of pathogens to the surgical site being a potential complication. This case of an 18 yr. old woman with a chronic would due to recurring skin and soft tissue infections (SSTIs) highlights the complications of surgical intervention and the difficulty of dealing with recurring SSTIs. The patient suffered a left knee injury with patellar tendon laceration secondary to trauma from a motor vehicle accident. She initially underwent surgical irrigation and debridement, followed by patellar tendon repair with a rotational flap to close the open wound. Following the initial closure in December 2019, the patient underwent 6 more I&Ds and wound debridement over a 5-month period due to a chronic non-healing wound with recurring SSTIs.  Wound Healing was tentatively achieved with antibiotic coverage for both Staph Aureus and Pseudomonas Aeruginosa.
Utility of 3D printing of left atrial appendages for closure with Watchman Devices and comparison of computed tomography and transesophageal echocardiography based models
Authors: Galvan Bernardo , Ansari Mohammed , Arvandi Ali Akbar , Orozco Ronnie , Morales Carlos , Serralde Kate , Ochoa Ozman , Holder Katherine , Iskandir Marina , Shurmur Scott
Published: January 2021

Three dimensional (3D) printed cardiac models are useful for WATCHMAN device procedural planning, sizing, and complication reduction. These models also provide accurate representation of dynamic heart anatomy, helping practitioners determine their procedural approach and select proper device sizing. While the efficacy of 3D models obtained from Computed Tomography and Transesophageal Echocardiography over 2D Transesophageal Echocardiography imaging for WATCHMAN procedural planning has been demonstrated, this project aims to directly compare 3D Computed Tomography versus 3D Transesophageal Echocardiography and determine which is more favorable. Computed Tomography and Transesophageal Echocardiography 2D imaging studies from patients that underwent LAA WATCHMAN closure device implantation we used as templates for 3D cardiac models. These 3D models were scored using a 10-point Likert questionnaire. Scoring was conducted by a diverse team that included cardiologists, research specialists, medical students, and 3D printing technicians.  Three dimensional models developed using Computed Tomography demonstrated favorability over 3D models by all qualitative measures. Scoring indicates that Computed Tomography based 3D models are superior tools for WATCHMAN sizing, multi-level medical education, and physician preparedness. To our knowledge, this is the only study that compares 3D models crafted from each imaging modality, and we hope that it encourages future use of 3D modeling techniques based on Computed Tomography scans.
Survival following initiation of non-invasive ventilation during hospitalization for chronic hypercapnic respiratory failure
Authors: Daines Benjamin , Mittal Nitish , Ismail Amr , Berdine Gilbert
Published: January 2021

Patients hospitalized with chronic hypercapnic respiratory failure often have comorbidities and are at increased risk for mortality after discharge. Non-invasive ventilation (NIV) has become a common therapy for these patients to improve gas exchange both while hospitalized and after discharge. To understand the survival of hypercapnic respiratory failure patients started on home NIV therapy, a prospective study was conducted analyzing rate of survival and predictors of mortality. Patients had a significant one-year mortality rate of 16.7% ± 0.71%. Analysis of demographic and physiologic data revealed that the only significant predictor of mortality was hours of NIV use per day, with greater use associated with increased mortality. Although initial results indicate that NIV can be an effective long term therapy for chronic hypercapnic respiratory failure, these patients remain at high risk of mortality and require regular monitoring. Continued study will increase this cohort and follow it for longer periods of time to better understand the predictors of mortality in patients hospitalized with chronic hypercapnic respiratory failure.
Key words: Obesity hypoventilation syndrome, noninvasive ventilation, hypercapnic respiratory failure
Classic clinical descriptions of disease: curing medical education with a dose of the past
Authors: Choi Erin , Khan Sonia , Chintakayala Laxmi , Holder Katherine , Galvan Bernardo , Berk Steven
Published: January 2021

The importance of clinical skills, including obtaining patient history and performing physical examination, has been de-emphasized in the modern medical school curriculum. With advancements in diagnostic technologies, the clinical presentation of diseases in medical textbooks has been simplified, diminished, and largely replaced with detailed pathophysiology and laboratory findings. The implementation of the United States Medical Licensing Exam (USMLE) Step 1 has also contributed in pushing medical education toward classroom-based learning rather than emphasizing clinical experience. Clinical skills competency is crucial to accurately diagnose patients and simultaneously lowers health care costs by not relying on unneeded diagnostic tests. To address this gap in medical knowledge, a group of students at Texas Tech University Health Sciences Center, Lubbock, Texas, have created a website documenting classic clinical disease descriptions written by some of the renowned physicians from the 19th and 20th centuries, including Osler, Flint, Gowers, etc. This website will continue to grow and will be a useful tool for professors, physicians, and medical students.
COVID-19 vaccination: an attempt to control the pandemic
Authors: Armin Sabiha , Wakil Anisa , Tarbox James , Iwuji Kenneth
Published: January 2021

Background: Since the Severe Acute Respiratory Syndrome Coronavirus-2 was discovered in December 2019, there have been tireless efforts by the medical and scientific community to understand its pathophysiology, treatment, and prevention.
Discussion: In the last several months, several therapeutic treatments, including a corticosteroid, antiviral drugs, convalescent plasma, and several others, have been tried in the treatment of SARS-CoV-2 with varying results. Pfizer and Moderna COVID-19 vaccines recently received approval for Emergency Use Authorization. Although COVID-19 vaccine is the first hurdle in an attempt to control the pandemic, the following challenges still remain: adequate vaccine doses, issues with mass distribution, global access, proper storage, and sufficient vaccine compliance.
Summary: Vaccination, in addition to social distancing and wearing facemasks, will likely provide the best way to control the COVID pandemic. Healthcare professionals and government officials will need to address any concern or hesitancy the community has with the COVID vaccine to promote compliance.
Keywords: coronavirus therapeutics, herd immunity, coronavirus vaccine, vaccine targets, clinical trials
Degeneration grade of a femoropatellar joint and functional status of a knee joint
Authors: Olesiak Beata , Przedborska Agnieszka , Raczkowski Jan Wojciech
Published: January 2021

Aim of the paper: The aim of the study was to assess the impact of degeneration of femoropatellar joint cartilage on selected variables related with a knee joint function

Material and methods: The studied group consisted of 50 patients that were diagnosed, through ultrasonography, changes in femoropatellar joint cartilage according to the Outerbridge classification. The data was collected with usage of a self-designed questionnaire. The study included pain assessment according to the VAS scale, Zohlen’s test, rectus femoris muscle test.

Results: There is statistically significant correlation between the grade of degenerative changes and age (p
‘It’s a real fine balancing act’: directly employed care workers’ experiences of engaging with health services
Authors: Wilcock Jane , Manthorpe Jill , Moriarty Jo , Iliffe Steve
Published: January 2021

Little is known of the experiences of directly employed care workers communicating with healthcare providers about the situations of their employers. We report findings from 30 in-depth semi-structured interviews with directly employed care workers in England undertaken in 2018–19. Findings relate to role content, communication with healthcare professionals and their own well-being. Directly employed care workers need to be flexible about the tasks they perform and the changing needs of those whom they support. Having to take on health liaison roles can be problematic, and the impact of care work on directly employed workers’ own health and well-being needs further investigation.
Design and optimization of line-field optical coherence tomography at visible wavebands
Authors: Xing Fangjian , Lee Jang-Hoon , Polucha Collin , Lee Jonghwan
Published: January 2021

Parallel line-field Fourier-domain optical coherence tomography (LF-FDOCT) has emerged to enable relatively higher speeds than the conventional FDOCT system. In the LF-FDOCT, one B-scan is captured at a time instead of scanning the beam to acquire hundreds of A-scans. On the other hand, spectroscopic OCT using the visible waveband provides absorption information over multiple wavelengths at each voxel. This information of spectral absorption enables quantitative measurement of blood oxygenation, voxel by voxel. Here, we presented the design and optimization of a LF-FDOCT system at the visible waveband (520–620 nm), especially using a generic Camera Link area sensor (2048 × 1088 pixels). To optimize the axial resolution and depth of imaging volume, we simulated various parameters and found that two Nyquist optima can exist, the origin and implication of which has been discussed. As a result, our system acquired 1088 A-scans in parallel at the camera’s frame rate of 281 frame per second, achieving an equivalent rate of over 300,000 A-scan/s, while minimizing sacrifice in the point spread function (2.8 × 3.1 × 3.2 µm3, x × y × z) and the field of view (750 × 750 × 750 µm3). As an example of application, we presented high-speed imaging of blood oxygenation in the rodent brain cortex.
Fast, multiplane line-scan confocal microscopy using axially distributed slits
Authors: Tsang Jean-Marc , Gritton Howard J. , Das Shoshana L. , Weber Timothy D. , Chen Christopher S. , Han Xue , Mertz Jerome
Published: January 2021

The inherent constraints on resolution, speed and field of view have hindered the development of high-speed, three-dimensional microscopy techniques over large scales. Here, we present a multiplane line-scan imaging strategy, which uses a series of axially distributed reflecting slits to probe different depths within a sample volume. Our technique enables the simultaneous imaging of an optically sectioned image stack with a single camera at frame rates of hundreds of hertz, without the need for axial scanning. We demonstrate the applicability of our system to monitor fast dynamics in biological samples by performing calcium imaging of neuronal activity in mouse brains and voltage imaging of cardiomyocytes in cardiac samples.
Phase-change reconfigurable metasurface for broadband, wide-angle, continuously tunable and switchable cloaking
Authors: Tian Ximin , Xu Junwei , Xu Kun , Qian Yanhong , Ma Xiaolong , Yang Peng , Duan Xiangyang , Ding Pei , Li Zhi-Yuan
Published: January 2021

Being invisible at will has fascinated humanity for centuries and it has become more tangible with the development of metasurfaces, which have demonstrated the extraordinary ability of wavefront manipulation. However, state-of-the-art invisibility cloaks typically work in a deterministic system with a limited bandwidth and small incident angle ranges. Here, by integrating the phase-change material of Ge2Sb2Te5 and the wavefront tailoring functionality of a reflective metasurface, we have achieved a unique carpet cloak that is endowed with broadband invisibility from 6920 to 8220 nm, fully concealing objects over a wide angular span of ±25° and a prominent radar cross-section reduction. Furthermore, the central cloaking wavelength can be continuously tuned with Ge2Sb2Te5 film under different intermediate phases by precisely controlling external stimuli, which will provide a flexible and encouraging way to achieve active features once fabricated. Simulation results also show that the cloaking bandwidth can be significantly extended by triggering Ge2Sb2Te5 from the amorphous to crystalline states. Importantly, the hybrid metasurface can realize switching of “ON” and “OFF” states in terms of cloaking features by converting Ge2Sb2Te5 from the amorphous to the crystalline state. To the best of our knowledge, this is the first metasurface carpet cloak that utilizes the phase-change material of Ge2Sb2Te5 to achieve ultra-broadband, wide-angle, continuously tunable and switchable cloaking with low profiles, light weights, and easy access. This design of a reconfigurable cloak is expected to find potential applications in various areas such as vehicle cloaking, illusions and so on.
Intense emission at ∼3.3  µm from Er3+-doped fluoroindate glass fiber
Authors: He Huiyu , Jia Zhixu , Wang Tao , Ohishi Yasutake , Qin Weiping , Qin Guanshi
Published: January 2021

Fluoroindate glass fibers with an

E
r

3
+

doping concentration of

∼

0.5

m
o
l

%

were fabricated by using a rod-in-tube method. Pumped by a 976 nm laser diode, intense emission at

∼

3.3

µ

m

was obtained from a 40 cm long

E
r

3
+

-doped fiber, which could be attributed to the transition

4

S

3

/

2

→

4

F

9

/

2

of

E
r

3
+

ions. The calculated emission cross section at

∼

3.3

µ

m

was

∼

3

×

10

−
26

m

2

, which was

∼

1.5

times larger than that of transitions

E
r

3
+

:

4

F

9

/

2

→

4

I

9

/

2

and

D
y

3
+

:

6

H

13

/

2

→

6

H

15

/

2

. In addition, broad emissions ranging from 3.1 µm to 3.85 µm were obtained in the

E
r

3
+

-doped fiber under a 976 nm/1973 nm dual-wavelength pumping scheme. Our results indicated that

E
r

3
+

-doped fluoroindate glass fibers had the potential for constructing efficient

∼

3.3

µ

m

fiber lasers.
Deep-learning based denoising and reconstruction of super-resolution structured illumination microscopy images
Authors: Shah Zafran Hussain , Müller Marcel , Wang Tung-Cheng , Scheidig Philip Maurice , Schneider Axel , Schüttpelz Mark , Huser Thomas , Schenck Wolfram
Published: January 2021

Super-resolution structured illumination microscopy (SR-SIM) provides an up to twofold enhanced spatial resolution of fluorescently labeled samples. The reconstruction of high-quality SR-SIM images critically depends on patterned illumination with high modulation contrast. Noisy raw image data (e.g., as a result of low excitation power or low exposure time), result in reconstruction artifacts. Here, we demonstrate deep-learning based SR-SIM image denoising that results in high-quality reconstructed images. A residual encoding–decoding convolutional neural network (RED-Net) was used to successfully denoise computationally reconstructed noisy SR-SIM images. We also demonstrate the end-to-end deep-learning based denoising and reconstruction of raw SIM images into high-resolution SR-SIM images. Both image reconstruction methods prove to be very robust against image reconstruction artifacts and generalize very well across various noise levels. The combination of computational image reconstruction and subsequent denoising via RED-Net shows very robust performance during inference after training even if the microscope settings change.
HippoUnit: A software tool for the automated testing and systematic comparison of detailed models of hippocampal neurons based on electrophysiological data
Authors: Sáray Sára , Rössert Christian A. , Appukuttan Shailesh , Migliore Rosanna , Vitale Paola , Lupascu Carmen A. , Bologna Luca L. , Van Geit Werner , Romani Armando , Davison Andrew P. , Muller Eilif , Freund Tamás F. , Káli Szabolcs
Published: January 2021

Anatomically and biophysically detailed data-driven neuronal models have become widely used tools for understanding and predicting the behavior and function of neurons. Due to the increasing availability of experimental data from anatomical and electrophysiological measurements as well as the growing number of computational and software tools that enable accurate neuronal modeling, there are now a large number of different models of many cell types available in the literature. These models were usually built to capture a few important or interesting properties of the given neuron type, and it is often unknown how they would behave outside their original context. In addition, there is currently no simple way of quantitatively comparing different models regarding how closely they match specific experimental observations. This limits the evaluation, re-use and further development of the existing models. Further, the development of new models could also be significantly facilitated by the ability to rapidly test the behavior of model candidates against the relevant collection of experimental data. We address these problems for the representative case of the CA1 pyramidal cell of the rat hippocampus by developing an open-source Python test suite, which makes it possible to automatically and systematically test multiple properties of models by making quantitative comparisons between the models and electrophysiological data. The tests cover various aspects of somatic behavior, and signal propagation and integration in apical dendrites. To demonstrate the utility of our approach, we applied our tests to compare the behavior of several different rat hippocampal CA1 pyramidal cell models from the ModelDB database against electrophysiological data available in the literature, and evaluated how well these models match experimental observations in different domains. We also show how we employed the test suite to aid the development of models within the European Human Brain Project (HBP), and describe the integration of the tests into the validation framework developed in the HBP, with the aim of facilitating more reproducible and transparent model building in the neuroscience community.
CTD: An information-theoretic algorithm to interpret sets of metabolomic and transcriptomic perturbations in the context of graphical models
Authors: Thistlethwaite Lillian R. , Petrosyan Varduhi , Li Xiqi , Miller Marcus J. , Elsea Sarah H. , Milosavljevic Aleksandar
Published: January 2021

We consider the following general family of algorithmic problems that arises in transcriptomics, metabolomics and other fields: given a weighted graph G and a subset of its nodes S, find subsets of S that show significant connectedness within G. A specific solution to this problem may be defined by devising a scoring function, the Maximum Clique problem being a classic example, where S includes all nodes in G and where the score is defined by the size of the largest subset of S fully connected within G. Major practical obstacles for the plethora of algorithms addressing this type of problem include computational efficiency and, particularly for more complex scores which take edge weights into account, the computational cost of permutation testing, a statistical procedure required to obtain a bound on the p-value for a connectedness score. To address these problems, we developed CTD, “Connect the Dots”, a fast algorithm based on data compression that detects highly connected subsets within S. CTD provides information-theoretic upper bounds on p-values when S contains a small fraction of nodes in G without requiring computationally costly permutation testing. We apply the CTD algorithm to interpret multi-metabolite perturbations due to inborn errors of metabolism and multi-transcript perturbations associated with breast cancer in the context of disease-specific Gaussian Markov Random Field networks learned directly from respective molecular profiling data.
Estimating the time-varying reproduction number of COVID-19 with a state-space method
Authors: Koyama Shinsuke , Horie Taiki , Shinomoto Shigeru
Published: January 2021

After slowing down the spread of the novel coronavirus COVID-19, many countries have started to relax their confinement measures in the face of critical damage to socioeconomic structures. At this stage, it is desirable to monitor the degree to which political measures or social affairs have exerted influence on the spread of disease. Though it is difficult to trace back individual transmission of infections whose incubation periods are long and highly variable, estimating the average spreading rate is possible if a proper mathematical model can be devised to analyze daily event-occurrences. To render an accurate assessment, we have devised a state-space method for fitting a discrete-time variant of the Hawkes process to a given dataset of daily confirmed cases. The proposed method detects changes occurring in each country and assesses the impact of social events in terms of the temporally varying reproduction number, which corresponds to the average number of cases directly caused by a single infected case. Moreover, the proposed method can be used to predict the possible consequences of alternative political measures. This information can serve as a reference for behavioral guidelines that should be adopted according to the varying risk of infection.
Genome-scale CRISPR screening for modifiers of cellular LDL uptake
Authors: Emmer Brian T. , Sherman Emily J. , Lascuna Paul J. , Graham Sarah E. , Willer Cristen J. , Ginsburg David
Published: January 2021

Hypercholesterolemia is a causal and modifiable risk factor for atherosclerotic cardiovascular disease. A critical pathway regulating cholesterol homeostasis involves the receptor-mediated endocytosis of low-density lipoproteins into hepatocytes, mediated by the LDL receptor. We applied genome-scale CRISPR screening to query the genetic determinants of cellular LDL uptake in HuH7 cells cultured under either lipoprotein-rich or lipoprotein-starved conditions. Candidate LDL uptake regulators were validated through the synthesis and secondary screening of a customized library of gRNA at greater depth of coverage. This secondary screen yielded significantly improved performance relative to the primary genome-wide screen, with better discrimination of internal positive controls, no identification of negative controls, and improved concordance between screen hits at both the gene and gRNA level. We then applied our customized gRNA library to orthogonal screens that tested for the specificity of each candidate regulator for LDL versus transferrin endocytosis, the presence or absence of genetic epistasis withLDLRdeletion, the impact of each perturbation on LDLR expression and trafficking, and the generalizability of LDL uptake modifiers across multiple cell types. These findings identified several previously unrecognized genes with putative roles in LDL uptake and suggest mechanisms for their functional interaction with LDLR.
Regulating the expression of gene drives is key to increasing their invasive potential and the mitigation of resistance
Authors: Hammond Andrew , Karlsson Xenia , Morianou Ioanna , Kyrou Kyros , Beaghton Andrea , Gribble Matthew , Kranjc Nace , Galizi Roberto , Burt Austin , Crisanti Andrea , Nolan Tony
Published: January 2021

Homing-based gene drives use a germline source of nuclease to copy themselves at specific target sites in a genome and bias their inheritance. Such gene drives can be designed to spread and deliberately suppress populations of malaria mosquitoes by impairing female fertility. However, strong unintended fitness costs of the drive and a propensity to generate resistant mutations can limit a gene drive’s potential to spread.

Alternative germline regulatory sequences in the drive element confer improved fecundity of carrier individuals and reduced propensity for target site resistance. This is explained by reduced rates of end-joining repair of DNA breaks from parentally deposited nuclease in the embryo, which can produce heritable mutations that reduce gene drive penetrance.

We tracked the generation and selection of resistant mutations over the course of a gene drive invasion of a population. Improved gene drives show faster invasion dynamics, increased suppressive effect and later onset of target site resistance. Our results show that regulation of nuclease expression is as important as the choice of target site when developing a robust homing-based gene drive for population suppression.
How social capital helps communities weather the COVID-19 pandemic
Authors: Makridis Christos A. , Wu Cary
Published: January 2021

Why have the effects of COVID-19 been so unevenly geographically distributed in the United States? This paper investigates the role of social capital as a mediating factor for the spread of the virus. Because social capital is associated with greater trust and relationships within a community, it could endow individuals with a greater concern for others, thereby leading to more hygienic practices and social distancing. Using data for over 2,700 US counties, we investigate how social capital explains the level and growth rate of infections. We find that moving a county from the 25thto the 75thpercentile of the distribution of social capital would lead to a 18% and 5.7% decline in the cumulative number of infections and deaths, as well as suggestive evidence of a lower spread of the virus. Our results are robust to many demographic characteristics, controls, and alternative measures of social capital.
An open prospective study on the efficacy of Navina Smart, an electronic system for transanal irrigation, in neurogenic bowel dysfunction
Authors: Emmanuel Anton , Kurze Ines , Krogh Klaus , Ferreiro Velasco Maria Elena , Christensen Peter , Del Popolo Giuilio , Bazzocchi Gabriele , Hultling Claes , Perrouin Verbe Brigitte , Bothig Ralf , Glott Thomas , Gonzalez Viejo Miguel Angel
Published: January 2021

Background

Transanal irrigation (TAI) has emerged as a key option when more conservative bowel management does not help spinal cord injured (SCI) individuals with neurogenic bowel dysfunction (NBD).

Aim

To investigate the short-term efficacy and safety of an electronic TAI system (Navina Smart) in subjects with NBD.

Design

We present an open, prospective efficacy study on Navina Smart, in individuals with NBD secondary to SCI, studied at three months.

Population

Eighty-nine consecutive consenting established SCI individuals (61 male; mean age 48, range 18–77) naïve to TAI treatment were recruited from ten centres in seven countries. Subjects had confirmed NBD of at least moderate severity (NBD score ≥10).

Methods

Subjects were taught how to use the device at baseline assisted by the Navina Smart app, and treatment was tailored during phone calls until optimal TAI regime was achieved. The NBD score was measured at baseline and at three months follow up (mean 98 days). Safety analysis was performed on the complete population while per protocol (PP) analysis was performed on 52 subjects.

Results

PP analysis showed a significant decrease in mean NBD score (17.8 to 10, p<0.00001). In subjects with severe symptoms (defined as NBD score ≥14), mean NBD scores decreased (19.4 to 10.9, p<0.0001). The number of subjects with severe symptoms decreased from 41 (79%) subjects at baseline to 16 (31%) at three months follow-up. Device failure accounted for the commonest cause for loss of data. Side effects possibly related to the device developed in 11 subjects (12%). Discontinuation due to failure of therapy to relieve symptoms was reported by 5 subjects (6%).

Conclusion

Navina Smart is effective for individuals with NBD, even those with severe symptoms; long-term data will follow. Whilst there were some device problems (addressed by the later stages of subject recruitment) the treatment was generally safe.

Clinical trial

(ClinicalTrials.gov number NCT02979808)
The Gender Gap Tracker: Using Natural Language Processing to measure gender bias in media
Authors: Asr Fatemeh Torabi , Mazraeh Mohammad , Lopes Alexandre , Gautam Vagrant , Gonzales Junette , Rao Prashanth , Taboada Maite
Published: January 2021

We examine gender bias in media by tallying the number of men and women quoted in news text, using the Gender Gap Tracker, a software system we developed specifically for this purpose. The Gender Gap Tracker downloads and analyzes the online daily publication of seven English-language Canadian news outlets and enhances the data with multiple layers of linguistic information. We describe the Natural Language Processing technology behind this system, the curation of off-the-shelf tools and resources that we used to build it, and the parts that we developed. We evaluate the system in each language processing task and report errors using real-world examples. Finally, by applying the Tracker to the data, we provide valuable insights about the proportion of people mentioned and quoted, by gender, news organization, and author gender. Data collected between October 1, 2018 and September 30, 2020 shows that, in general, men are quoted about three times as frequently as women. While this proportion varies across news outlets and time intervals, the general pattern is consistent. We believe that, in a world with about 50% women, this should not be the case. Although journalists naturally need to quote newsmakers who are men, they also have a certain amount of control over who they approach as sources. The Gender Gap Tracker relies on the same principles as fitness or goal-setting trackers: By quantifying and measuring regular progress, we hope to motivate news organizations to provide a more diverse set of voices in their reporting.
Maternal prenatal stress exposure and sex-specific risk of severe infection in offspring
Authors: Robinson Monique , Carter Kim W. , Pennell Craig E. , Jacoby Peter , Moore Hannah C. , Zubrick Stephen R. , Burgner David
Published: January 2021

Background

Maternal stressful life events during pregnancy have been associated with immune dysregulation and increased risk for asthma and atopy in offspring. Few studies have investigated whether prenatal stress is associated with increased overall or specific infectious diseases in childhood, nor explored sex differences. We sought to examine the relationship between the nature and timing of maternal stress in pregnancy and hospitalisation with infection in offspring.

Methods

Between 1989 and 1992, exposure data on stressful life events were collected from pregnant women (Gen1) in the Raine Study at 18 and 34 weeks’ gestation and linked to statutory state-wide hospital morbidity data. We examined associations between the number, category and timing of maternal prenatal stress events and overall and clinical groups of offspring (Gen2) infection-related hospitalisation until age 16 years, adjusting for maternal age, education, and smoking in pregnancy in addition to the presence of siblings at birth.

Results

Of 2,141 offspring with complete stress in pregnancy data available, 1,089 had at least one infection-related hospitalisation, with upper respiratory tract infections the most common (n = 556). Each additional stressful life event during pregnancy was associated with increased risk in male offspring for hospitalisation with all infection types. There was little evidence of these associations in girls.

Conclusions

Increased exposure to stressful life events in utero is associated with sex-specific infection-related hospitalisations in childhood. Prenatal stress may adversely affect early immune development for boys and increase the risk of more severe infections. Mechanistic understanding would inform preventative interventions.