bluuebunny/crossref_metadata_2025 huggingface dataset:
Management of retraction pockets: historic and novel approaches
Authors: Spinos D , Mallick S , Judd O
Published: January 2022

Background

Retraction pockets are collapsed segments of the tympanic membrane. Their formation is associated with a disruption in middle-ear ventilation pathways, leading to the loss of organised collagen of the tympanic membrane. There are several approaches in treating retraction pockets, which aim either to improve ventilation or repair the retraction pockets themselves.

Methods

A review of the literature regarding the classification and associated management of retraction pockets was conducted, using Medline and Cochrane Library databases, with the addition of our institution's experience in undertaking novel techniques.

Results

All the current classification systems fail to guide treatment or prognosticate the disease. Commonly, an initial conservative approach is suggested for early stages, with no clear indication regarding when a surgical solution should be offered. There are conflicting data concerning the effectiveness of these treatments in terms of disease prevention, recurrence and hearing outcomes.

Conclusion

Minimally invasive approaches utilising novel techniques may be key to reducing peri-operative morbidity and improving the overall patient experience.
An awareness and prevalence study of Irish cold-water athletes and external auditory canal exostoses
Authors: Boyle S , Keane R , Jinih M , McCarthy Deering E , Patil N , Choo M
Published: January 2022

Objective

This study aimed to determine the awareness, otological symptoms and prevalence of external auditory canal exostoses in Irish cold-water athletes.

Method

An online and in person cross-sectional survey was undertaken with Irish cold-water athletes to explore athletes' awareness, known prevalence of external auditory canal exostoses and attitudes towards preventive measures.

Results

Of the 926 participants surveyed, 67.5 per cent were aware of external auditory canal exostoses. Triathletes reported the lowest awareness (39.9 per cent) among water athletes. A total of 9.7 per cent (n = 90) had previously been diagnosed with external auditory canal exostoses and 46.7 per cent (n = 42) were non-surfers. Ear symptoms were reported in 76 per cent of athletes. Otoscopic examinations showed that 23.7 per cent had external auditory canal exostoses, 3.6 per cent of whom were aware of their diagnosis.

Conclusion

The majority of Irish surfing athletes are aware of external auditory canal exostoses. There is less awareness with regard to Ireland's newly emerging sports such as open water swimming and triathlons. Over 90 per cent of athletes surveyed had no idea they had external auditory canal exostoses, which highlights the need to increase public awareness.
Effects of mastoid and middle-ear volume on graft success and hearing outcomes in paediatric tympanoplasty
Authors: Baklaci D , Bilgin E , Çelik E K , Kılıç A , Erdem D , Eliçora S S
Published: January 2022

Objective

To examine the effects of mastoid and middle-ear volume on the anatomical and functional success of type 1 tympanoplasty in paediatric patients.

Methods

This study included 45 paediatric patients who underwent type 1 cartilage tympanoplasty. Patients’ demographic data, pre- and post-operative audiological evaluation results, and post-operative graft status were evaluated. Middle-ear and mastoid cavity volumes were calculated (in cubic centimetres) using temporal bone high-resolution computed tomography. Middle-ear and mastoid cavity volume values were compared between patients with and without post-operative anatomical and functional success.

Results

Anatomical success was achieved in 82.2 per cent of patients (n = 37), and functional success in 68.9 per cent (n = 31). When anatomical success and failure groups were compared, a statistically significant difference was found in mean mastoid volume (p = 0.037), while there was no significant difference in relation to mean middle-ear volume (p = 0.827). The comparison of functional success and failure groups revealed no significant difference in mean mastoid volume (p = 0.492) or middle-ear volume (p = 0.941).

Conclusion

The study showed that mastoid pneumatisation volume affects surgical success in paediatric tympanoplasty.
Topical treatment of eczematous external otitis involving the ear canal: long-term results of a trial comparing pimecrolimus 1 per cent versus clobetasone butyrate 0.05 per cent
Authors: Nemeth Z , Verga E , Verdolini R
Published: January 2022

Background

Eczematous external otitis is a common chronic condition that can have a significant impact on the life of sufferers, causing constant discomfort and pruritus, and leading to sleep deprivation. Treatment is based on the use of topical steroids, moisturisers and occasionally antibiotics. Results, however, can be disappointing, especially over the long term.

Methods

This study compared the long-term response to pimecrolimus, administered to a group of 11 patients, against clobetasone butyrate, administered to an equivalent number of patients. Response to the treatment was assessed and statistically analysed at 3 and 12 months.

Conclusion

Whereas the degree of improvement following the use of pimecrolimus and clobetasone butyrate was similar for the two groups at month 3, a highly statistically significant difference was documented at month 12, with a much greater and sustained improvement in the pimecrolimus group.
New record of bioluminescence inOdontosylliscf.australiensis(Annelida: Syllidae: Eusyllinae) in Japan
Authors: Kobayashi Genki , Sakamoto Tatsuya
Published: January 2022

Bioluminescence is widespread in the marine environment. The bioluminescence of some species of the firewormOdontosyllis(Annelida: Syllidae: Eusyllinae) has been well studied, although the presence or absence of bioluminescence in most species of this genus is yet to be revealed. The bioluminescent worms were observed after sunset around the new moon day in July and October 2020 and in July to October 2021 in Nagasaki Prefecture, Japan. Molecular phylogenetic analysis based on two mitochondrial and one nuclear gene sequence showed that the worms were closely related toOdontosyllis australiensis, but the partial 16S rRNA gene sequences differed by 2% between those of the Japanese and Australian material. Because only epitokes, i.e. morphologically modified sexually mature worms, were collected, further studies on morphological characters of atokes would be required in the future. We therefore tentatively refer to them asOdontosylliscf.australiensis. Molecular phylogenetic analysis also showed that known bioluminescentOdontosyllisspecies belong to various lineages.
Emotional intelligence: a comparison between patients after first episode mania and those suffering from chronic bipolar disorder type I
Authors: Varo Cristina , Amoretti Silvia , Sparacino Giulio , Jiménez Esther , Solé Brisa , Bonnin Caterina del Mar , Montejo Laura , Serra Maria , Torrent Carla , Salagre Estela , Benabarre Antoni , Salgado-Pineda Pilar , Montoro Salvatierra Irene , Sáiz Pilar A. , García-Portilla María Paz , Sánchez-Gistau Vanessa , Pomarol-Clotet Edith , Ramos-Quiroga Josep Antoni , Pacchiarotti Isabella , Garcia-Rizo Clemente , Undurraga Juan , Reinares María , Martinez-Aran Anabel , Vieta Eduard , Verdolini Norma
Published: January 2022

Background

Deficits in emotional intelligence (EI) were detected in patients with bipolar disorder (BD), but little is known about whether these deficits are already present in patients after presenting a first episode mania (FEM). We sought (i) to compare EI in patients after a FEM, chronic BD and healthy controls (HC); (ii) to examine the effect exerted on EI by socio-demographic, clinical and neurocognitive variables in FEM patients.

Methods

The Emotional Intelligence Quotient (EIQ) was calculated with the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT). Performance on MSCEIT was compared among the three groups using generalized linear models. In patients after a FEM, the influence of socio-demographic, clinical and neurocognitive variables on the EIQ was examined using a linear regression model.

Results

In total, 184 subjects were included (FEM n = 48, euthymic chronic BD type I n = 75, HC n = 61). BD patients performed significantly worse than HC on the EIQ [mean difference (MD) = 10.09, standard error (s.e.) = 3.14, p = 0.004] and on the understanding emotions branch (MD = 7.46, s.e. = 2.53, p = 0.010). FEM patients did not differ from HC and BD on other measures of MSCEIT. In patients after a FEM, EIQ was positively associated with female sex (β = −0.293, p = 0.034) and verbal memory performance (β = 0.374, p = 0.008). FEM patients performed worse than HC but better than BD on few neurocognitive domains.

Conclusions

Patients after a FEM showed preserved EI, while patients in later stages of BD presented lower EIQ, suggesting that impairments in EI might result from the burden of disease and neurocognitive decline, associated with the chronicity of the illness.
Rabies outbreak in black-backed jackals (Canis mesomelas), South Africa, 2016
Authors: Ngoepe E. , Chirima J. G. , Mohale D. , Mogano K. , Suzuki T. , Makita K. , Sabeta C. T.
Published: January 2022

Rabies, a fatal and vaccine-preventable disease, is endemic throughout Africa. In 2016, a rabies outbreak occurred in black-backed jackals (Canis mesomelas) along the western boundary of Gauteng Province, South Africa. We investigated the possible drivers of the 2016 outbreak and established its origin. Using spatio-temporal locations of cases, we applied logistic regression and Geographic Information System techniques to investigate environmental covariates driving occurrences of emerging rabies cases in Gauteng Province. About 53.8% of laboratory-confirmed lyssaviruses in Gauteng Province in 2016 originated from jackals. Phylogenetic trees reconstructed from a partial region of the glycoprotein gene of these and historical rabies viruses (RABVs) demonstrated the lyssaviruses to be of canid origin with 97.7% nucleotide sequence similarity. The major cluster comprised jackal RABVs from the 2012 KwaZulu/Natal outbreak and the 2016 outbreak in Gauteng Province. The second cluster was composed of both jackal and dog RABVs. Both clusters correlated with independent RABV introductions into Gauteng by dogs and jackals, respectively. This study demonstrated an expansion of a jackal rabies cycle from north-west Province into Gauteng Province during the 2016 dry period, as jackals ranged widely in search for food resources leading to increased jackal-dog interactions, reminiscent of the intricate links of domestic and wildlife rabies cycles in South Africa.
Why Bystanders Did Not Perform Cardiopulmonary Resuscitation on Out-of-Hospital Cardiac Arrest Patients: A Multi-Center Study in Hanoi (Vietnam)
Authors: Vu Dinh Hung , Hoang Bui Hai , Do Ngoc Son , Do Giang Phuc , Dao Xuan Dung , Nguyen Huu Huan , Luu Quang Thuy , Nguyen Lan Hieu , Nakahara Shinji
Published: January 2022

Aim:

The aim of this study was to determine why bystanders did not use formal Emergency Medical Services (EMS) or conduct cardiopulmonary resuscitation (CPR) on the scene for out-of-hospital cardiac arrest (OHCA) patients in Hanoi, Vietnam.

Methods:

This was a prospective, observational study of OHCA patients admitted to five tertiary hospitals in the Hanoi area from June 2018 through January 2019. The data were collected through interviews (using a structured questionnaire) with bystanders.

Results:

Of the 101 patients, 79% were aged <65 years, 71% were men, 79% were witnessed to collapse, 36% were transported to the hospital by formal EMS, and 16% received bystander CPR at the scene. The most frequently indicated reason for not using EMS by the attendants was “using a private vehicle or taxi is faster” (85%). The reasons bystanders did not conduct CPR at the scene included “not recognizing the ailment as cardiac arrest” (60%), “not knowing how to perform CPR” (33%), and “being afraid of doing harm to patients” (7%). Only seven percent of the bystanders had been trained in CPR.

Conclusion:

The information revealed in this study provides useful information to indicate what to do to increase EMS use and CPR provision. Spreading awareness and training among community members regarding EMS roles, recognition of cardiac arrest, CPR skills, and dispatcher training to assist bystanders are crucial to improve the outcomes of OHCA patients in Vietnam.
Triton Haze Analogs: The Role of Carbon Monoxide in Haze Formation
Authors: Moran Sarah E. , Hörst Sarah M. , He Chao , Radke Michael J. , Sebree Joshua A. , Izenberg Noam R. , Vuitton Véronique , Flandinet Laurène , Orthous‐Daunay François‐Régis , Wolters Cédric
Published: January 2022

Triton is the largest moon of the Neptune system and possesses a thin nitrogen atmosphere with trace amounts of carbon monoxide and methane, making it of similar composition to that of the dwarf planet Pluto. Like Pluto and Saturn's moon Titan, Triton has a haze layer thought to be composed of organics formed through photochemistry. Here, we perform atmospheric chamber experiments of 0.5% CO and 0.2% CH4 in N2 at 90 K and 1 mbar to generate Triton haze analogs. We then characterize the physical and chemical properties of these particles. We measure their production rate, their bulk composition with combustion analysis, their molecular composition with very high resolution mass spectrometry, and their transmission and reflectance from the optical to the near‐infrared with Fourier Transform Infrared (FTIR) Spectroscopy. We compare these properties to existing measurements of Triton's tenuous atmosphere and surface, as well as contextualize these results in view of all the small, hazy, nitrogen‐rich worlds of our solar system. We find that carbon monoxide present at greater mixing ratios than methane in the atmosphere can lead to significantly oxygen‐ and nitrogen‐rich haze materials. These Triton haze analogs have clear observable signatures in their near‐infrared spectra, which may help us differentiate the mechanisms behind haze formation processes across diverse solar system bodies.
DOA Estimation of Linear Dipole Array With Known Mutual Coupling Based on ESPRIT and MUSIC
Authors: Bensalem Mohamed , Barkat Ouarda
Published: January 2022

In this paper, multiple signal classification and estimation of signal parameters via rotational invariance technique (ESPRIT) algorithms are proposed to estimate the direction of arrival (DOA) of multiple incident signals under known mutual coupling among elements of the antenna array. These algorithms use the same subspace based techniques to achieve the separation of the eigenvectors into two subspaces: the signal space and the noise space. However, ESPRIT only uses the signal space. The performance of subspace based DOA estimation algorithm is evaluated using uniform linear arrays of dipole elements. The simulation results show the exact number of samples and elements, signal‐to‐noise ratio and spacing between the antennas elements used are the most important parameters in the algorithms, to sustain the accuracy of the DOA of the incident signals. The problem of calculating mutual coupling coefficient of the array elements is formed into a matrix has been considered. It is shown from the simulation results that the performance of the DOA estimation techniques considering the mutual coupling effect can be improved by the proposed compensation method. The different results obtained are in good agreement with those of the literature.
Contextualizing Inflow and Infiltration Within the Streamflow Regime of Urban Watersheds
Authors: Pangle Luke A. , Diem Jeremy E. , Milligan Richard , Adams Ellis , Murray Allison
Published: January 2022

Defects in sanitary‐sewer infrastructure enable exchange of large volumes of fluids to and from the environment. The intrusion of rainfall and groundwater into sanitary sewers is called inflow and infiltration (I&I). Though long recognized in the assessment of sewers, the impacts of I&I on streamflow within urban watersheds are unknown. We quantified rainfall‐derived I&I (RDI&I), groundwater infiltration (GI), and total I&I using measured flows within sanitary‐sewer pipes serving four watersheds near Atlanta, Georgia, USA. Flows were monitored in pipes that parallel local stream channels and compared with streamflow measured at nearby gauging sites. Freshwater diverted into the sewer system due to I&I ranged from 24% to 36% of the flow measured within individual pipes. The RDI&I was the smaller component of I&I, ranging from 4.2 to 9.8 mm per year among watersheds. The GI was typically an order of magnitude greater than RDI&I, ranging from 24 to 41 mm per year among watersheds with annual stream discharge of approximately 500 mm. The I&I occurring at specific moments in time commonly represented 0%–20% of the flow measured in the adjacent stream. The enhancement of low flows in streams that could be achievable if I&I were abated ranges from as much as 6%–36% across watersheds. Our discussion presents explanations for the seasonality of I&I and associated impacts on streamflow in urban watersheds, while identifying important sources of remaining uncertainty. Our results support the conclusion that I&I substantially reduces flows in urban streams, especially low flows during dry weather.
Oxygen saturation and heart rate in healthy term and late preterm infants with delayed cord clamping
Authors: Lara-Cantón Inmaculada , Badurdeen Shiraz , Dekker Janneke , Davis Peter , Roberts Calum , te Pas Arjan , Vento Máximo
Published: January 2022

Blood oxygen in the fetus is substantially lower than in the newborn infant. In the minutes after birth, arterial oxygen saturation rises from around 50–60% to 90–95%. Initial respiratory efforts generate negative trans-thoracic pressures that drive liquid from the airways into the lung interstitium facilitating lung aeration, blood oxygenation, and pulmonary artery vasodilatation. Consequently, intra- (foramen ovale) and extra-cardiac (ductus arteriosus) shunting changes and the sequential circulation switches to a parallel pulmonary and systemic circulation. Delaying cord clamping preserves blood flow through the ascending vena cava, thus increasing right and left ventricular preload. Recently published reference ranges have suggested that delayed cord clamping positively influenced the fetal-to-neonatal transition. Oxygen saturation in babies with delayed cord clamping plateaus significantly earlier to values of 85–90% than in babies with immediate cord clamping. Delayed cord clamping may also contribute to fewer episodes of brady-or-tachycardia in the first minutes after birth, but data from randomized trials are awaited.

Impact

Delaying cord clamping during fetal to neonatal transition contributes to a significantly earlier plateauing of oxygen saturation and fewer episodes of brady-and/or-tachycardia in the first minutes after birth.

We provide updated information regarding the changes in SpO2 and HR during postnatal adaptation of term and late preterm infants receiving delayed compared with immediate cord clamping.

Nomograms in newborn infants with delayed cord clamping will provide valuable reference ranges to establish target SpO2 and HR in the first minutes after birth.
Temperature-sensitive hydrogel loaded with DNase I alleviates epidural fibrosis in a mouse model of laminectomy
Authors: Sun Jinpeng , Wang Gang , Wang Haoran , Hua Feng , Song Zeyuan , Jin Zhen , Liu Jun , Xin Hongliang , Zhang Mingshun
Published: January 2022

Excessive epidural fibrosis attached to the dura mater is the major cause of recurrent failed back surgery syndrome after spine surgery. Neutrophil extracellular traps (NETs) promote epidural fibrosis, raising the possibility that the DNA backbone of NETs may be a potential target in the therapy of epidural fibrosis. Human body temperature-sensitive hydroxypropyl chitin hydrogel solutions were prepared to encapsulate DNase I, which gradually decomposed in vivo. DNase I, which was released from temperature-sensitive hydrogels, destroyed the DNA backbone of NETs and dispersed the clustering of myeloperoxidase (MPO) in NETs. Evidence from MRI, H&E and Masson staining supported that hydroxypropyl chitin hydrogels loaded with DNase I were nontoxic and reduced epidural fibrosis. As expected, fibronectin in the wound was significantly abridged in the mice treated with hydrogels loaded with DNase I. Compared with the gelatin sponge absorbing DNase I, temperature-sensitive hydroxypropyl chitin hydrogels loaded with DNase I were more powerful in the therapy of epidural fibrosis. These results indicate that temperature-sensitive hydroxypropyl chitin hydrogels were effective in DNase I encapsulation and alleviation of epidural fibrosis in a mouse model of laminectomy.
Parametric estimation of gyrotactic microorganism hybrid nanofluid flow between the conical gap of spinning disk-cone apparatus
Authors: Alrabaiah Hussam , Bilal Muhammad , Khan Muhammad Altaf , Muhammad Taseer , Legas Endris Yimer
Published: January 2022

The silver, magnesium oxide and gyrotactic microorganism-based hybrid nanofluid flow inside the conical space between disc and cone is addressed in the perspective of thermal energy stabilization. Different cases have been discussed between the spinning of cone and disc in the same or counter wise directions. The hybrid nanofluid has been synthesized in the presence of silver Ag and magnesium oxide MgO nanoparticulate. The viscous dissipation and the magnetic field factors are introduced to the modeled equations. The parametric continuation method (PCM) is utilized to numerically handle the modeled problem. Magnesium oxide is chemically made up of Mg2+ and O2- ions that are bound by a strong ionic connection and can be made by pyrolyzing Mg(OH)2 (magnesium hydroxide) and MgCO3 (magnesium carbonate) at high temperature (700–1500 °C). For metallurgical, biomedical and electrical implementations, it is more efficient. Similarly, silver nanoparticle's antibacterial properties could be employed to control bacterial growth. It has been observed that a circulating disc with a stationary cone can achieve the optimum cooling of the cone-disk apparatus while the outer edge temperature remains fixed. The thermal energy profile remarkably upgraded with the magnetic effect, the addition of nanoparticulate in base fluid and Eckert number.
Contactless facial video recording with deep learning models for the detection of atrial fibrillation
Authors: Sun Yu , Yang Yin-Yin , Wu Bing-Jhang , Huang Po-Wei , Cheng Shao-En , Wu Bing-Fei , Chen Chun-Chang
Published: January 2022

Atrial fibrillation (AF) is often asymptomatic and paroxysmal. Screening and monitoring are needed especially for people at high risk. This study sought to use camera-based remote photoplethysmography (rPPG) with a deep convolutional neural network (DCNN) learning model for AF detection. All participants were classified into groups of AF, normal sinus rhythm (NSR) and other abnormality based on 12-lead ECG. They then underwent facial video recording for 10 min with rPPG signals extracted and segmented into 30-s clips as inputs of the training of DCNN models. Using voting algorithm, the participant would be predicted as AF if > 50% of their rPPG segments were determined as AF rhythm by the model. Of the 453 participants (mean age, 69.3 ± 13.0 years, women, 46%), a total of 7320 segments (1969 AF, 1604 NSR & 3747others) were analyzed by DCNN models. The accuracy rate of rPPG with deep learning model for discriminating AF from NSR and other abnormalities was 90.0% and 97.1% in 30-s and 10-min recording, respectively. This contactless, camera-based rPPG technique with a deep-learning model achieved significantly high accuracy to discriminate AF from non-AF and may enable a feasible way for a large-scale screening or monitoring in the future.
Electrical performance of efficient quad-crescent-shaped Si nanowire solar cell
Authors: El-Bashar Ramy , Hussein Mohamed , Hegazy Salem F. , Badr Yehia , Rahman B. M. A. , Grattan Kenneth T. V. , Hameed Mohamed Farhat. O. , Obayya Salah S. A.
Published: January 2022

The electrical characteristics of quad-crescent-shaped silicon nanowire (NW) solar cells (SCs) are numerically analyzed and as a result their performance optimized. The structure discussed consists of four crescents, forming a cavity that permits multiple light scattering with high trapping between the NWs. Additionally, new modes strongly coupled to the incident light are generated along the NWs. As a result, the optical absorption has been increased over a large portion of light wavelengths and hence the power conversion efficiency (PCE) has been improved. The electron–hole (e–h) generation rate in the design reported has been calculated using the 3D finite difference time domain method. Further, the electrical performance of the SC reported has been investigated through the finite element method, using the Lumerical charge software package. In this investigation, the axial and core–shell junctions were analyzed looking at the reported crescent and, as well, conventional NW designs. Additionally, the doping concentration and NW-junction position were studied in this design proposed, as well as the carrier-recombination-and-lifetime effects. This study has revealed that the high back surface field layer used improves the conversion efficiency by $$\sim$$
∼
80%. Moreover, conserving the NW radial shell as a low thickness layer can efficiently reduce the NW sidewall recombination effect. The PCE and short circuit current were determined to be equal to 18.5% and 33.8 mA$$/\hbox {cm}^2$$

/

cm
2

for the axial junction proposed. However, the core–shell junction shows figures of 19% and 34.9 mA$$/\hbox {cm}^2$$

/

cm
2

. The suggested crescent design offers an enhancement of 23% compared to the conventional NW, for both junctions. For a practical surface recombination velocity of $$10^{2}$$

10
2

cm/s, the PCE of the proposed design, in the axial junction, has been reduced to 16.6%, with a reduction of 11%. However, the core–shell junction achieves PCE of 18.7%, with a slight reduction of 1.6%. Therefore, the optoelectronic performance of the core–shell junction was marginally affected by the NW surface recombination, compared to the axial junction.
Characteristic parameters of photonic nanojets of single dielectric microspheres illuminated by focused broadband radiation
Authors: Mandal Amartya , Tiwari Pragya , Upputuri Paul K. , Dantham Venkata R.
Published: January 2022

Herein, we report the theoretical investigation on the photonic nanojets (PNJs) of single dielectric microspheres illuminated by focused broadband radiation (polychromatic light) from a Halogen lamp, supercontinuum source, light-emitting diode, and Hg arc lamp. The role of incident beam waist, refractive index of the surrounding medium, and radius of the microsphere on the characteristic parameters such as the electric field intensity enhancement, effective width, and length of the PNJ is studied. Interestingly, the characteristic parameters of the PNJs of solid microspheres obtained for the above-mentioned broadband radiation sources are found close to those observed for the focused monochromatic radiation of wavelengths which are near to the central wavelengths of the sources. Moreover, the characteristic parameters of PNJs of the core–shell microspheres of different thicknesses (t) illuminated by polychromatic radiation from most commonly used sources such as Halogen and Hg arc lamps are studied. For each t value, a suitable wavelength of monochromatic radiation has been found to generate the PNJ with characteristic parameters which are close to those obtained in the case of polychromatic radiation. We believe that the analytical theory and the theoretical simulations reported here would be useful for researchers who work in the fields such as PNJ assisted photoacoustic spectroscopy, white light nanoscopy, low-coherence phase-shifting interference microscopy, and Mirau interferometry.
Discovering cell types using manifold learning and enhanced visualization of single-cell RNA-Seq data
Authors: Vasighizaker Akram , Danda Saiteja , Rueda Luis
Published: January 2022

Identifying relevant disease modules such as target cell types is a significant step for studying diseases. High-throughput single-cell RNA-Seq (scRNA-seq) technologies have advanced in recent years, enabling researchers to investigate cells individually and understand their biological mechanisms. Computational techniques such as clustering, are the most suitable approach in scRNA-seq data analysis when the cell types have not been well-characterized. These techniques can be used to identify a group of genes that belong to a specific cell type based on their similar gene expression patterns. However, due to the sparsity and high-dimensionality of scRNA-seq data, classical clustering methods are not efficient. Therefore, the use of non-linear dimensionality reduction techniques to improve clustering results is crucial. We introduce a method that is used to identify representative clusters of different cell types by combining non-linear dimensionality reduction techniques and clustering algorithms. We assess the impact of different dimensionality reduction techniques combined with the clustering of thirteen publicly available scRNA-seq datasets of different tissues, sizes, and technologies. We further performed gene set enrichment analysis to evaluate the proposed method’s performance. As such, our results show that modified locally linear embedding combined with independent component analysis yields overall the best performance relative to the existing unsupervised methods across different datasets.
Calculating the force-dependent unbinding rate of biological macromolecular bonds from force-ramp optical trapping assays
Authors: Paul Apurba , Alper Joshua
Published: January 2022

The non-covalent biological bonds that constitute protein–protein or protein–ligand interactions play crucial roles in many cellular functions, including mitosis, motility, and cell–cell adhesion. The effect of external force ($$F$$
F
) on the unbinding rate ($${k}_{\text{off}}\left(F\right)$$

k
off

F

) of macromolecular interactions is a crucial parameter to understanding the mechanisms behind these functions. Optical tweezer-based single-molecule force spectroscopy is frequently used to obtain quantitative force-dependent dissociation data on slip, catch, and ideal bonds. However, analyses of this data using dissociation time or dissociation force histograms often quantitatively compare bonds without fully characterizing their underlying biophysical properties. Additionally, the results of histogram-based analyses can depend on the rate at which force was applied during the experiment and the experiment’s sensitivity. Here, we present an analytically derived cumulative distribution function-like approach to analyzing force-dependent dissociation force spectroscopy data. We demonstrate the benefits and limitations of the technique using stochastic simulations of various bond types. We show that it can be used to obtain the detachment rate and force sensitivity of biological macromolecular bonds from force spectroscopy experiments by explicitly accounting for loading rate and noisy data. We also discuss the implications of our results on using optical tweezers to collect force-dependent dissociation data.
Soluble programmed cell death-1 predicts hepatocellular carcinoma development during nucleoside analogue treatment
Authors: Kozuka Ritsuzo , Enomoto Masaru , Dong Minh Phuong , Hai Hoang , Thuy Le Thi Thanh , Odagiri Naoshi , Yoshida Kanako , Kotani Kohei , Motoyama Hiroyuki , Kawamura Etsushi , Hagihara Atsushi , Fujii Hideki , Uchida-Kobayashi Sawako , Tamori Akihiro , Kawada Norifumi
Published: January 2022

Soluble immune checkpoint molecules are emerging novel mediators of immune regulation. However, it is unclear whether soluble immune checkpoint proteins affect the development of hepatocellular carcinoma (HCC) during nucleos(t)ide analogue (NA) treatment in patients with chronic hepatitis B virus infection. This study included 122 NA-naïve patients who received NA therapy. We assessed the associations of clinical factors, including soluble immune checkpoint proteins, with HCC development during NA treatment. The baseline serum concentrations of 16 soluble immune checkpoint proteins were measured using multiplexed fluorescent bead-based immunoassay. In total, 13 patients developed HCC during the follow-up period (median duration, 4.3 years). Of the 16 proteins, soluble inducible T-cell co-stimulator (≥ 164.71 pg/mL; p = 0.014), soluble programmed cell death-1 (sPD-1) (≤ 447.27 pg/mL; p = 0.031), soluble CD40 (≤ 493.68 pg/mL; p = 0.032), and soluble herpes virus entry mediator (≤ 2470.83 pg/mL; p = 0.038) were significantly associated with HCC development (log-rank test). In multivariate analysis, an sPD-1 level ≤ 447.27 pg/mL (p = 0.014; hazard ratio [HR], 4.537) and α-fetoprotein level ≥ 6.4 ng/mL (p = 0.040; HR, 5.524) were independently and significantly associated with HCC development. Pre-treatment sPD-1 is a novel predictive biomarker for HCC development during NA treatment.
Midbrain injury in patients with subarachnoid hemorrhage: a diffusion tensor imaging study
Authors: Jang Sung Ho , Kwon Young Hyeon
Published: January 2022

We investigated the characteristics of midbrain injuries in patients with spontaneous subarachnoid hemorrhage (SAH) by using diffusion tensor imaging (DTI). Twenty-seven patients with SAH and 25 healthy control subjects were recruited for this study. Fractional anisotropy (FA) and mean diffusivity (MD) data were obtained for four regions of the midbrain (the anterior ventral midbrain, posterior ventral midbrain, tegmentum area, and tectum) in 27 hemispheres that did not show any pathology other than SAH. The mean FA and MD values of the four regions of the midbrain (anterior ventral midbrain, posterior ventral midbrain, tegmentum, and tectum) of the patient group were significantly lower and higher than those of the control group, respectively (p < 0.05). The mean FA values of the patient group were significantly different among the anterior ventral midbrain, posterior ventral midbrain, tegmentum, and tectum regions (ANOVA; F = 3.22, p < 0.05). Post hoc testing showed that the mean FA value of the anterior ventral midbrain was significantly lower than those of the posterior ventral midbrain, tegmentum, and tectum (p < 0.05); in contrast, there were no differences in mean FA values of the posterior ventral midbrain, tegmentum, and tectum (p > 0.05). However, differences were not observed among four regions of the midbrain (anterior ventral midbrain, posterior ventral midbrain, tegmentum, and tectum) in the mean MD values. We detected evidence of neural injury in all four regions of the midbrain of patients with SAH, and the anterior ventral midbrain was the most severely injured among four regions of the midbrain. Our results suggest that a pathophysiological mechanism of these neural injuries might be related to the occurrence of a subarachnoid hematoma.
Frequency and component analysis of contaminants generated in preparation of anticancer agents using closed system drug transfer devices (CSTDs)
Authors: Sumikawa Satomi , Yakushijin Yoshihiro , Aogi Kenjiro , Yano Takuya , Hiroki  , Hashimoto  , Tsukui Chiyuki , Noguchi Tadashi , Shiraishi Taro , Horikawa Yasuhiro , Yasuoka Yasuo , Tanaka Akihiro , Hidaka Noriaki , Tanaka Mamoru
Published: January 2022

Occupational exposure of anticancer agents during their preparation has been recognized as a serious hazard. Closed system drug transfer devices (CSTDs) enable “safe” preparation of agents for medical personnel and ensure a safe hospital environment. However, artificial particles of infusion materials have been reported during CSTD use. Here, the incidence of insoluble fine particles during preparation of anticancer agents using CSTDs was examined. Visible insoluble fine particles were found in 465 (9.4%) of 4948 treatment cases at Ehime University Hospital with CSTD use. Contaminants occurred more frequently during preparation of monoclonal antibodies than cytotoxic anticancer agents (19.4% vs. 4.1%, respectively, P < 0.01). A similar survey was conducted at nine hospitals to investigate the incidence of insoluble fine particles with or without CSTDs. Insoluble fine particles were detected in 113 (15.4%) of 732 treatment cases during preparation of monoclonal antibodies with CSTD use. In contrast, the occurrence of insoluble fine particles without CSTDs was found in only 3 (0.073%) of 4113 treatment cases. Contamination with CSTDs might cause harmful effects on patients during cancer therapy. We strongly recommend the use of in-line filters combined with infusion routes after CSTD use to avoid contamination-associated adverse events.
Decrease of Pdzrn3 is required for heart maturation and protects against heart failure
Authors: Pernot Mathieu , Jaspard-vinassa Béatrice , Abelanet Alice , Rubin Sebastien , Forfar Isabelle , Jeanningros Sylvie , Cetran Laura , Yu Murielle Han-Yee , Balse Elise , Hatem Stéphane , Dufourcq Pascale , Couffinhal Thierry , Duplàa Cécile
Published: January 2022

Heart failure is the final common stage of most cardiopathies. Cardiomyocytes (CM) connect with others via their extremities by intercalated disk protein complexes. This planar and directional organization of myocytes is crucial for mechanical coupling and anisotropic conduction of the electric signal in the heart. One of the hallmarks of heart failure is alterations in the contact sites between CM. Yet no factor on its own is known to coordinate CM polarized organization. We have previously shown that PDZRN3, an ubiquitine ligase E3 expressed in various tissues including the heart, mediates a branch of the Planar cell polarity (PCP) signaling involved in tissue patterning, instructing cell polarity and cell polar organization within a tissue. PDZRN3 is expressed in the embryonic mouse heart then its expression dropped significantly postnatally corresponding with heart maturation and CM polarized elongation. A moderate CM overexpression of Pdzrn3 (Pdzrn3 OE) during the first week of life, induced a severe eccentric hypertrophic phenotype with heart failure. In models of pressure-overload stress heart failure, CM-specific Pdzrn3 knockout showed complete protection against degradation of heart function. We reported that Pdzrn3 signaling induced PKC ζ expression, c-Jun nuclear translocation and a reduced nuclear ß catenin level, consistent markers of the planar non-canonical Wnt signaling in CM. We then show that subcellular localization (intercalated disk) of junction proteins as Cx43, ZO1 and Desmoglein 2 was altered in Pdzrn3 OE mice, which provides a molecular explanation for impaired CM polarization in these mice. Our results reveal a novel signaling pathway that controls a genetic program essential for heart maturation and maintenance of overall geometry, as well as the contractile function of CM, and implicates PDZRN3 as a potential therapeutic target for the prevention of human heart failure.
Inappropriate sinus tachycardia in post-COVID-19 syndrome
Authors: Aranyó Júlia , Bazan Victor , Lladós Gemma , Dominguez Maria Jesús , Bisbal Felipe , Massanella Marta , Sarrias Axel , Adeliño Raquel , Riverola Ariadna , Paredes Roger , Clotet Bonaventura , Bayés-Genís Antoni , Mateu Lourdes , Villuendas Roger
Published: January 2022

Inappropriate sinus tachycardia (IST) is a common observation in patients with post-COVID-19 syndrome (PCS) but has not yet been fully described to date. To investigate the prevalence and the mechanisms underlying IST in a prospective population of PCS patients. Consecutive patients admitted to the PCS Unit between June and December 2020 with a resting sinus rhythm rate ≥ 100 bpm were prospectively enrolled in this study and further examined by an orthostatic test, 2D echocardiography, 24-h ECG monitoring (heart rate variability was a surrogate for cardiac autonomic activity), quality-of-life and exercise capacity testing, and blood sampling. To assess cardiac autonomic function, a 2:1:1 comparative sub-analysis was conducted against both fully recovered patients with previous SARS-CoV-2 infection and individuals without prior SARS-CoV-2 infection. Among 200 PCS patients, 40 (20%) fulfilled the diagnostic criteria for IST (average age of 40.1 ± 10 years, 85% women, 83% mild COVID-19). No underlying structural heart disease, pro-inflammatory state, myocyte injury, or hypoxia were identified. IST was accompanied by a decrease in most heart rate variability parameters, especially those related to cardiovagal tone: pNN50 (cases 3.2 ± 3 vs. recovered 10.5 ± 8 vs. non-infected 17.3 ± 10; p < 0.001) and HF band (246 ± 179 vs. 463 ± 295 vs. 1048 ± 570, respectively; p < 0.001). IST is prevalent condition among PCS patients. Cardiac autonomic nervous system imbalance with decreased parasympathetic activity may explain this phenomenon.
Country-specific optimization strategy for testing through contact tracing can help maintain a low reproduction number ($$R_{0}$$) during unlock
Authors: Sarma Uddipan , Ghosh Bhaswar
Published: January 2022

In response to the COVID19 pandemic, many countries have implemented lockdowns in multiple phases to ensure social distancing and quarantining of the infected subjects. Subsequent unlocks to reopen the economies started next waves of infection and imposed an extra burden on quarantine to keep the reproduction number ($$R_{0}$$

R
0

) < 1. However, most countries could not effectively contain the infection spread, suggesting identification of the potential sources weakening the effect of lockdowns could help design better informed lockdown-unlock cycles in the future. Here, through building quantitative epidemic models and analyzing the metadata of 50 countries from across the continents we first found that the estimated value of $$R_{0}$$

R
0

, adjusted w.r.t the distribution of medical facilities and virus clades correlates strongly with the testing rates in a country. Since the testing capacity of a country is limited by its medical resources, we investigated if a cost–benefit trade-off can be designed connecting testing rate and extent of unlocking. We present a strategy to optimize this trade-off in a country specific manner by providing a quantitative estimate of testing and quarantine rates required to allow different extents of unlocks while aiming to maintain $$R_{0} < 1$$

R
0

<
1

. We further show that a small fraction of superspreaders can dramatically increase the number of infected individuals even during strict lockdowns by strengthening the positive feedback loop driving infection spread. Harnessing the benefit of optimized country-specific testing rates would critically require minimizing the movement of these superspreaders via strict social distancing norms, such that the positive feedback driven switch-like exponential spread phase of infection can be avoided/delayed.
A computational modeling approach for dosing endoscopic intratumoral chemotherapy for advanced non-small cell lung cancer
Authors: Mori Vitor , Bates Jason H. T. , Jantz Michael , Mehta Hiren J. , Kinsey C. Matthew
Published: January 2022

We recently developed a computational model of cisplatin pharmacodynamics in an endobronchial lung tumor following ultrasound-guided transbronchial needle injection (EBUS-TBNI). The model suggests that it is more efficacious to apportion the cisplatin dose between injections at different sites rather than giving it all in a single central injection, but the model was calibrated only on blood cisplatin data from a single patient. Accordingly, we applied a modified version of our original model in a set of 32 patients undergoing EBUS-TBNI for non-small cell lung cancer (NSCLC). We used the model to predict clinical responses and compared them retrospectively to actual patient outcomes. The model correctly predicted the clinical response in 72% of cases, with 80% accuracy for adenocarcinomas and 62.5% accuracy for squamous-cell lung cancer. We also found a power-law relationship between tumor volume and the minimal dose needed to induce a response, with the power-law exponent depending on the number of injections administered. Our results suggest that current injection strategies may be significantly over- or under-dosing the agent depending on tumor size, and that computational modeling can be a useful planning tool for EBUS-TBNI of cisplatin in lung cancer.
Session interest model for CTR prediction based on self-attention mechanism
Authors: Wang Qianqian , Liu Fang’ai , Zhao Xiaohui , Tan Qiaoqiao
Published: January 2022

Click-through rate prediction, which aims to predict the probability of the user clicking on an item, is critical to online advertising. How to capture the user evolving interests from the user behavior sequence is an important issue in CTR prediction. However, most existing models ignore the factor that the sequence is composed of sessions, and user behavior can be divided into different sessions according to the occurring time. The user behaviors are highly correlated in each session and are not relevant across sessions. We propose an effective model for CTR prediction, named Session Interest Model via Self-Attention (SISA). First, we divide the user sequential behavior into session layer. A self-attention mechanism with bias coding is used to model each session. Since different session interest may be related to each other or follow a sequential pattern, next, we utilize gated recurrent unit (GRU) to capture the interaction and evolution of user different historical session interests in session interest extractor module. Then, we use the local activation and GRU to aggregate their target ad to form the final representation of the behavior sequence in session interest interacting module. Experimental results show that the SISA model performs better than other models.
Robust LC3B lipidation analysis by precisely adjusting autophagic flux
Authors: Liebl Martina P. , Meister Sarah C. , Frey Lisa , Hendrich Kristina , Klemmer Anja , Wohlfart Bettina , Untucht Christopher , Nuber Judith , Pohl Christian , Lakics Viktor
Published: January 2022

Autophagic flux can be quantified based on the accumulation of lipidated LC3B in the presence of late-stage autophagy inhibitors. This method has been widely applied to identify novel compounds that activate autophagy. Here we scrutinize this approach and show that bafilomycin A1 (BafA) but not chloroquine is suitable for flux quantification due to the stimulating effect of chloroquine on non-canonical LC3B-lipidation. Significant autophagic flux increase by rapamycin could only be observed when combining it with BafA concentrations not affecting basal flux, a condition which created a bottleneck, rather than fully blocking autophagosome-lysosome fusion, concomitant with autophagy stimulation. When rapamycin was combined with saturating concentrations of BafA, no significant further increase of LC3B lipidation could be detected over the levels induced by the late-stage inhibitor. The large assay window obtained by this approach enables an effective discrimination of autophagy activators based on their cellular potency. To demonstrate the validity of this approach, we show that a novel inhibitor of the acetyltransferase EP300 activates autophagy in a mTORC1-dependent manner. We propose that the creation of a sensitized background rather than a full block of autophagosome progression is required to quantitatively capture changes in autophagic flux.