bluuebunny/crossref_metadata_2025_split huggingface dataset:
When saliency goes off on a tangent: Interpreting Deep Neural Networks with nonlinear saliency maps
Authors: Rosenzweig Jan , Cvetkovic Zoran , Rosenzweig Ivana 
Published: February 2022

Abstract
A fundamental bottleneck in utilising complex machine learning systems for critical applications has been not knowing why they do and what they do, thus preventing the development of any crucial safety protocols. To date, no method exist that can provide full insight into the granularity of the neural network’s decision process. In past, saliency maps were an early attempt at resolving this problem through sensitivity calculations, whereby dimensions of a data point are selected based on how sensitive the output of the system is to them. However, the success of saliency maps has been at best limited, mainly due to the fact that they interpret the underlying learning system through a linear approximation.We present a novel class of methods for generating nonlinear saliency maps which fully account for the nonlinearity of the underlying learning system. While agreeing with linear saliency maps on simple problems where linear saliency maps are correct, they clearly identify more specific drivers of classification on complex examples where nonlinearities are more pronounced.
This new class of methods significantly aids interpretability of deep neural networks and related machine learning systems. Crucially, they provide a starting point for their more broad use in serious applications, where 'why' is equally important as 'what'.
Small RNA Sequencing and Bioinformatics Analysis of RAW264.7-Derived Exosomes after Mycobacterium Bovis Bacillus Calmette-Guérin Infection
Authors: Zhan Xuehua , Yuan Wenqi , Zhou Yueyong , Ma Rong , Ge Zhaohui 
Published: February 2022

Abstract
Background: The mechanisms through which Mycobacterium tuberculosis evades immune surveillance during tuberculosis (TB) infection remain complex. Previous studies have found that Mycobacteria can manipulate the miRNAs of host cells to promote their survival during host-pathogen interactions, and most of these effects occur at the cellular miRNA level. We at-tempted to investigate the possible related mechanisms at the exosomal miRNA level. Results: High-throughput sequencing revealed that Bacillus Calmette-Guérin (BCG) infection could alter the composition of the macrophage exosome content, and the expression levels of miRNAs in exosomes derived from the cell culture media of macrophages showed significant differences be-tween the BCG-infected and noninfected groups. Compared with the non-infection group, 20 exosomal miRNAs were up-regulated and 7 exosomal miRNAs were down-regulated in the infection group (p<0.05), of which mmu-miR-27b-3p, mmu-miR-93-5p, mmu-miR-25-3p, mmu-miR-1198-5p, mmu-let-7c-5p and let-7a-5p were significantly up-regulated. A bioinformatic analysis indicated that these differentially expressed exosomal miRNAs were involved in multiple biological processes and pathways. The target genes of top six miRNAs in up-regulated groups were positively correlated with the regulation of apoptosis.Conclusions: Our study provides relatively strong evidence for unravelling the complex pathophysiological processes of TB and the mechanisms of mycobacterial immune escape based on differential exosomal miRNA expression in host macrophages. Additionally, these exosomal miRNAs may serve as potential immunotherapy targets for the effective control of TB infection, but this probability requires further study.
Preparation of Gamma Poly-Glutamic Acid/Hydroxyapatite/Collagen Composite as the 3D-Printing Scaffold for Bone Tissue Engineering
Authors: Nguyen Thu-Trang , Hu Chih-Chien , Sakthivel Rajalakshmi , Nabilla Sasza Chyntara , Huang Yu-Wen , Yu Jiashing , Cheng Nai-Chen , Kuo Yi-Jie , Chung Ren-Jei 
Published: February 2022

Abstract
Background
Movement activities involving the role of articular cartilage and bones. The presence of cartilage enables bones to move over one another smoothly. However, repetitive microtrauma and ischemia as well as genetic effects can cause an osteochondral lesion. Numerous treatment methods such as microfracture, autograft, and allograft have been used, however, it possesses treatment challenges including extensive recovery time after surgery and financial burden on patients. Nowadays, tissue engineering approaches have been developed to repair bone and osteochondral defects using biomaterial implants to induce the regeneration of stem cells.
Methods
In this study, a collagen/γ-polyglutamate acid (PGA)/hydroxyapatite composite scaffold was fabricated using a 3D printing technique. A collagen/γ-PGA/hydroxyapatite 2D membrane was also fabricated for comparison. The scaffolds (4 layers) were designed with the size of 8 mm in diameter and 1.2 mm in thickness. The first layer was hydroxyapatite/γ-PGA and the second to fourth layers were collagen/γ-PGA. In addition, a 2D membrane was constructed from hydroxyapatite/γ-PGA and collagen/γ-PGA with a ratio of 1:3. The biocompatibility property and degradation activity were investigated for both scaffold and membrane samples. The rat bone marrow mesenchymal stem cells (rBMSCs) and human adipose stem cells (hADSCs) were cultured on the samples and were tested in-vitro to evaluate cell attachment, proliferation, and differentiation. The in-vivo experiments were performed in the rat and nude mice models.
Results
Finally, the in-vitro and in-vivo results show that the developed scaffold is of well biodegradation and biocompatible properties; the Col-HA scaffold enhances the mechanical properties for osteochondrogenesis in both in-vitro and animal trials.
Conclusions
It would be a great biomaterial application for bone and osteochondral regeneration.
Feasibility of Quantitative Sensory Testing in Juvenile Idiopathic Arthritis.
Authors: Mensink Maarten , Eijkelkamp Niels , Veldhuijzen Judy S. , Wulffraat Nico 
Published: February 2022

Abstract
Background Juvenile Idiopathic Arthritis (JIA) is a childhood-rheumatic disease with pain as a major complaint. Very few data exist on sensory thresholds changes at the knee in JIA, a location in which inflammation often manifest. We determined whether JIA is associated with sensory threshold changes at the knee by using Quantitative Sensory Testing (QST) and established reference values at the knee of children.Methods 16 JIA patients aged 9-18 years with one affected knee and a patient-reported pain (VAS)>10 on a 0-100 scale, and 16 healthy controls completed the study and were included for the analysis. QST was assessed in compliance with the DFNS standard. Disease severity was determined using JADAS. Perceived pain was assessed with a visual analogue scale(0-100). Feasibility of QST was tested in patients aged 5-9.Results JIA patients reported an average VAS pain score of 54.3. QST identified a significant reduction in PPT and increase in CDT compared to healthy controls. Under the age of 9, QST testing showed not to be feasible.Conclusion Sensory threshold changes at the knee are restricted to pressure pain and cold detection thresholds in JIA patients. This study shows that in a Dutch population, the extensive QST protocol is only feasible in the age group from 9 years and older, and a reduced set of QST tests containing at least pressure pain thresholds and cold detection thresholds could prove to be better suited to the pediatric setting with arthritis.
Chronic Recurrent Multifocal Osteomyelitis with an uncommon presentation and disabling features: A case report
Authors: Shahin Sarvenaz , Asnaashari Kosar , Zarei Mohammad , Faraji-Goodarzi Mojgan , Ziaee Vahid 
Published: February 2022

Abstract
Background: Chronic recurrent multifocal osteomyelitis (CRMO) is one of the auto-inflammatory bone disorders with yet to be determined etiology. Due to overlapping signs and symptoms with other bone involvements, the diagnosis of this disease might take a long period of time and the patients may develop deformities in long-term. Thus, increasing awareness about different presentations of the disease seems beneficial.Case presentation: A 12-year-old boy was referred to our center with severe back pain in his thoracic vertebrae from 18 months before referral. He had previously undergone two vertebroplasty surgeries due to his kyphosis and had received several courses of antibiotics, which resulted in no improvement in his disabling pain. His physical examination was unremarkable, except for severe thoracic vertebrae tenderness and a mild dextroscoliosis. MRI showed diffuse multiple hypo-signal lesions in thoracic vertebral bodies with slight enhancement, causing compression fractures of T8, T11 and T12 bodies. Bone scan revealed increased activity in thoracic region (T7-T8-T9-T12 vertebral bodies) and left clavicle. Other differentials were ruled out by bone marrow aspiration, bone biopsy and laboratory tests. His disease showed a favorable response to treatment with Pamidronate, Methotrexate and Indomethacin and he had no relapse in three years of follow-up.Conclusions: Uncommon presentations of CRMO can be misleading to the specialists and might result in prolonged diagnosis process. Increased awareness among different specialists about such presentations can potentially lead to earlier diagnosis, and timelier and more effective treatment of the CRMO patients.
Health System Barriers to the Variation of Caesarean Section Rates in Palestinian Governmental Hospitals
Authors: Shalash Aisha , Wahdan Yasmeen , Alsalman Hasan , Shehab Ala' , Afifi Tayseer , Nabaa’ Hendia , Sarsour Iman , Jarour Naheel , Hamed Ala'a , Abu-Rmeileh Niveen 
Published: February 2022

Abstract
Background
Globally, the increased use of cesarean sections has become prevalent in high-income and low and middle-income countries. In Palestine, the rate had risen from 20.3% in 2014 to 25.1% in 2018. The difference is that we have rates as high as 35.8 % in some public hospitals and some as low as 15%. This study aimed to understand better why there is a variation in cesarean rates in public hospitals that use the same protocol.
Methods
A qualitative approach was used. In-depth interviews with 27 specialists, obstetrics and gynecologists, and midwives in five government hospitals were performed. The hospitals were selected based on the 2017 Annual Health Report reported cesarean section rates. The interview guide was created with the support of specialists and researchers and was piloted. Questions focused mainly on adherence to the obstetric guidelines and barriers to the use, sources of information, training for healthcare providers, the hospital system, and the factors that affect decision making.
Results
The results indicated that each public hospital at the system level had a different policy on cesarean sections. One specialist decided for a cesarean section at high-rate hospitals, while low-rate hospitals used collective decision-making with empowered midwives. At the professional level, all hospitals urged for the importance of a continuous training program to refresh the medical team knowledge, in-house training of new members joining the hospital, and to discuss cases that are subjective to obstetrician-gynecologists interpretations.
Conclusion
We recommend strengthening the implementation of support for staff to meet the standards in the national obstetric protocol. Encourage collective decision-making between obstetrician-gynecologists and midwives and use a second opinion. The Robson classification implementation in hospitals will allow medical teams to evaluate delivery management processes and provide a standardized method for reporting and comparison between hospitals, regions, and countries.
What is the impact of COVID-19 pandemic years on Deliveries and Home Based New Born Care in India? A cross-sectional comparative research study, Jan 2018-2021Dec
Authors: Kumar Piyush 
Published: February 2022

Abstract
The COVID-19 pandemic caused by SARS-CoV-2 has led to disruption of health services globally. I assessed the effect of the ongoing pandemic on the Deliveries and Home Based New Born Care (HBNC) in India. The author is curious and suspects a rise in maternal and neonatal mortality due to possible negative effects of COVID-19 on maternal institutional delivery and HBNC. Hence author decided to find out answer to the research question mentioned as title above. I conducted a retrospective cross-sectional comparative study among total numbers of women and newborn who have received delivery and HBNC care at different health facilities in 36 states and union territories across India during the pandemic years with pre-pandemic years (comparing 2020 and 2021(forecasted up to December 2021 with available data from January2021 to May 2021) with previous two years of pre-pandemic era i.e. 2018–2019). The data for the research study is extracted from electronic records of HMIS (health management information system) of MoHFW (ministry of health and family welfare), Govt. of India and analysed with stata and Microsoft office. The mean number of home deliveries attended by SBA [(Skill Birth Attendant) (Doctor/Nurse/ANM/ Midwife)] during the pandemic year 2021 with total number of observation of 5 months of 2021(January to May) forecasted up to December 2021 across India was 13370.27938, for years 2020, 2019, 2018 it was 16429.25, 19006.58, 21317.83 respectively with total number of observation of 12 months across India for these three years. This research study revealed that pandemic years have negative impact on number of home deliveries attended by SBA [(Skill Birth Attendant) (Doctor/Nurse/ANM/ Midwife)]. This research study revealed that pandemic years have negative impact on number of home deliveries attended by SBA [(Skill Birth Attendant) (Doctor/Nurse/ANM/ Midwife)]. There is a (projected) decrease of 37.28% in mean number of home deliveries attended by SBA in 2021 as compared to 2018. This novel research study revealed that during pandemic years 2020 and 2021 all the variables reduced quantitatively except Number of PW given Tablet Misoprostol during HD which increased in 2020 (first pandemic year).The ongoing COVID-19 pandemic has had negative effects on Deliveries and Home Based New Born Care (HBNC) in India. More research is required to investigate the direct and indirect consequence of the pandemic on birth and provision of HBNC as well as the health facility type which are not performing well in providing respectful maternity care and newborn services during pandemic period. The facility based research analysis is under process by the author which will be available in next version of this article.
Relating SARS-CoV-2 Variants Using Cellular Automata Imaging
Authors: de Souza Luryane Ferreira , Filho Tarcísio Marciano da Rocha , Moret Marcelo Albano 
Published: February 2022

Abstract
We classify the main variants of the SARS-CoV-2 virus representing a given biological sequence represented as a symbolic sequence of digital codes and its evolution by a cellular automata with a properly chosen rule.The spike protein, common to all variants of the SARS-CoV-2 virus, is then represented by an image of the cellular automaton evolution which represents in a more visible way important features of the protein. We use information theory Hamming distance between different stages of the evolution of the cellular automaton representing seven variants with respect to the original Wuhan/China virus. We show that our approach allows to classify together variants with common ancestors and same mutations. Although being a much simpler method, it can be used as an alternative for building phylogenetic trees.
The effect of different bands of LED exposure on vitreous metabolites and retinal architecture.
Authors: TN Nagarajan , Joshi Manjunath B , Valiathan Manna , Rao Shonraj BG , Bhat Shailaja , Surendran Sudarshan 
Published: February 2022

Abstract
The accumulating experimental evidence indicates that exposure to blue and white LED light leads to damage in the visual system against short-term exposure. Chronic exposure, adaptive responses to light and self-protective mechanisms against LED light exposures need to be explored and would be essential to know the repercussions of LED radiations on vitreous metabolites. A total of 24 male Wistar rats were used in our study, which was divided into four groups (n = 6 in each group). Three groups were exposed to either blue, white, or yellow LED light for 90 days (12:12 light-dark cycle routine) with uniform illumination (450–500 lux). Control rats were maintained under standard laboratory conditions. Post-exposure the vitreous was removed for mass spectrometry and retinal tissues for immunofluorescence and H&E staining. The thickness of the retina decreased in blue and white light exposure animals compared with controls, whereas the yellow light exposure group showed an increase in thickness (p < 0.001). The number of apoptotic cells was significantly lower in controls compared to light-exposed groups (p < 0.001) and (p < 0.001). Altered metabolites were observed in light exposure groups particularly in D-alanine, taurine, D-serin (p < 0.05 and lysine (p < 0.001). The self-protective or reworking system in the chronic light exposure could be dazed and drop the ability to compensate for the defending mechanism. This might fail to maintain the metabolomic structural integrity of the vitreous and retina.
Surface Plasmon Resonance Based Refractive Index Biosensor: A External Sensing Approach
Authors: Mitu Sumaiya Akhtar , Aktar Mst. Nargis , Ibrahim Sobhy Mohamed , Ahmed Kawsar 
Published: February 2022

Abstract
A surface plasmon resonance (SPR) based sensor founded on Photonic crystal fiber (PCF) is suggested and numerically analyzed in the manuscript. The refractive index (RI) detecting SPR based sensor has the ability to identify the analyte range from 1.33 to 1.4. Pure silica is used as a base material and it has high RI value than the analyte RI. Furthermore, an analyte layer and chemically stable gold (Au) layer are also placed at the sensor design. The simulations are done based on the Finite Element Method (FEM). Here, the scaled-down approach has the necessity to increase phase matching point within the core mode and surface plasmon polariton (SPP) mode which tends to the sensor to reach high sensitivity response. At the intersect point of core and SPP mode, the loss curve shows a maximum peak value. The suggested sensor shows the highest wavelength sensitivity (WS) response of 35,943.22 nm/RIU, amplitude sensitivity (AS) response of 2321.36 RIU−1, sensor resolution of 9.04×10−6 RIU, and Figure of merit (FOM) value of 600. It is noted that all the optical parameters show better performance analysis. Furthermore, an external sensing approach provides more fabrication feasibility which marks the offered sensor more suitable for practical experimentation. Besides, the investigated sensor provides the maximum and rapid sensing performance that will be helpful for microfluidic analyte detection, detection of biomolecules, medical diagnostics, virus detection, security, and bio-imaging.
Necroptosis-related Prognostic Gene Signature to Aid Therapy in Lung Adenocarcinoma
Authors: Song Yuqi , Zhang Jinming , Fang Linan , Liu Wei 
Published: February 2022

Abstract
Lung adenocarcinoma (LUAD) is the most common type of non-small cell lung cancer (NSCLC), which is also the most important cause of cancer-related deaths. Necroptosis is a phenomenon of cellular necrosis resulting from cell membrane rupture by the corresponding activation of Receptor Interacting Protein Kinase 3 (RIPK3) and Mixed Lineage Kinase domain-Like protein (MLKL) under programmed regulation. It is reported that necroptosis is closely related to the development of tumor, but the prognostic role and biological functions of necroptosis in LUAD are still obscure. In this study, we constructed a prognostic Necroptosis-related gene (NRG) signature based on the RNA transcription data of LUAD patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases as well as the corresponding clinical characteristics information. Next, Kaplan-Meier analysis, receiver operating characteristic (ROC), univariate Cox and multivariate Cox regression were made to validate and evaluate the model. We also accurately and quantitatively predicted the prognosis of LUAD patients using our nomogram, which includes age, gender, stage and risk score. To improve patients’ prognosis and achieve personalized precision medicine, we analyzed the immune landscape in LUAD and predicted the sensitivity of LUAD patients with different risk scores to immunotherapeutic regimens and chemotherapeutic regimens. In conclusion, our study provides a reference for in-depth mechanistic exploration of necroptosis in LUAD.
Hamilton-Jacobi and Lagrange formulation of relativistic quantum mechanics wave equations with solutions with only-positive and only-negative kinetic energies
Authors: de Peralta Luis Grave , Ruiz-Columbie Arquimedes 
Published: February 2022

Abstract
Using the Hamilton-Jacobi and the Lagrange formalisms, a pair of relativistic quantum mechanics equations are obtained. These equations, in contrast with the Klein-Gordon and other relativistic quantum mechanics equations, have no solutions with both positive and negative kinetic energies. The equation with solutions with only positive kinetic energy values describes a spin-0 particle of mass m, which is moving at relativistic speeds in a scalar potential. The wavefunctions and the energies corresponding to the associated antiparticle can be obtained by solving the other equation, which only has solutions with negative kinetic energy values.
Gene Network Analysis Reveals Candidate Genes Related with the Hair Follicle Development in Sheep
Authors: He Junmin , Zhao Bingru , Huang Xixia , Fu Xuefeng , Liu Guifen , Tian Yuezhen , Wu Cuiling , Mao Jingyi , Liu Jing , Gun Shuangbao , Tian Kechuan 
Published: February 2022

Abstract
Background: Merino sheep is the most famous fine wool sheep in the world. It has high wool production and excellent wool quality, which has attracted worldwide attention. The fleece of the Merino sheep is composed predominantly of wool fibres grown from secondary wool follicles. Therefore, it is very necessary to study the development of hair follicle in order to understand the mechanism of wool. The hair follicle is a complex biological system involved in a dynamic process governed by gene regulation. The development process of hair follicle is very complex and unclear. The purpose of our research is to find candidate genes related to hair follicle development, provide molecular breeding theoretical basis for the cultivation of fine wool sheep, and provide side reference for the problems of hair loss and alopecia areata that perplex human beings.Results: We analyzed 18 mRNA data of skin tissues of 18 Merino sheep at 4 days (E65, E85, E105 and E135) and 2 days after birth (D7 and D30). We identified 7879 differentially expressed genes (DEGs) and 12623 novel-DEGs, revealed different expression patterns of these DEGs at six stages of hair follicle development, and proved their complex interactions. DEGs with stage-specific expression were significantly enriched in epidermal differentiation and development, hair follicle development and hair follicle morphogenesis, and enriched in many pathways related to hair follicle development. The key genes (LAMA5, WNT10A, KRT25, SOSTDC1, ZDHHC21, FZD1, BMP7, LRP4, TGFβ2, TMEM79, SOX10, ITGB4, ITGA6, GLI2) affecting hair follicle morphogenesis was identified by network analysis. Conclusion: This study provides a new reference of the molecular basis of hair follicle development and lays a foundation for further improving sheep hair follicle breeding. Candidate genes related to hair follicular development were found, which provided a theoretical basis of molecular breeding for the culture of fine wool sheet. These results are a valuable resource for biological investigation of fleece evolvement in animals and also supply some potential clues for understanding the molecular mechanisms of human hair development.