bluuebunny/crossref_metadata_2025 huggingface dataset:
Gene Xpert a Promising Tool in Diagnosis of Extrapulmonary TB in Developing Countries
Authors: Akhter Jabin , Chowdhury MA Hassan
Published: March 2021

Introduction: Although Tuberculosis mostly affects lungs in about 85% cases, but can cause lesion almost in every part of the body. Extrapulmonary TB (EPTB) accounts for 15 to 20% which involves other parts of the body beside the lungs. There are several methods that can diagnose Pulmonary TB (PTB) conclusively , but extrapulmonary TB is very difficult to diagnose till now especially in resource limited settings. Though it is not communicable but diagnostic delay has made it significant cause of morbidity and mortality. The snidy was aimed to find out the Gene Xpert as one of the diagnostic tool for EPTB.

Methods: A laboratory based descriptive cross sectional study was conducted over a period of  17  months  from January 2017 to May 2018 to ascertain the performance of Gene Xpert technique as a diagnostic tool for EPTB. Data were collected through checklist and a total of 77 clinical samples were collected purposively with prior infom,ed consent from suspected EPTB patients following ethical issues. Laboratory investigations were  perfomed  at Rhodolphe Merieux Laboratory, Chittagong, Bangladesh with Gene Xpert MTB/Ri f assay, conventional culture (LJ media) and Microscopy (ZN stain) for the presence of Mycobacteium tuberculosis (MTB).

Results: Among the 77 samples from suspected cases, seven(9.09%) from CSF, one(!.29%) from pus and one(l .29%) from lymphnode specimens were positive by Gene Xpert MTB/Rif assay.Only one(1.29%) CSF specimen  was found to be culture and microscopy positive which was Gene Xpert positive also. Except one specimen from pus that is both Gene Xpert and microscopy positive but culture negative, no other specimens from EPTB cases were culture and microscopy positive.

Conclusion: Diagnosis of EPTB is challenging in worldwide. As it is paucibacillary, routine diagnostic test in detecting MTB is difficult. Gene X pert showed promising outcome in early detection of life threatening EPTB cases like TB meningitis which is common in developing countries.

JOPSOM 2020; 39(1): 26-30
Assessment of electronic gadgets use and its' effects on daily life and health of primary school children
Authors: Noor Saadia , Haseen Fariha , Tomal Lutful Ahsan , Noor Nadia
Published: March 2021

Background: Electronic devices are the latest exquisite invention of our modern life and  it makes our  life so easy and comfortable. Electronic gadgets are now used by the primary school children in a wider scale during the COVlD-19 pandemic. It is imperative to explore its effect of daily life and health of the school children. The objective of the study was to determine the technological interaction of the children and how it is  affecting  their daily routine, grades and physical health.

Methods: This is a cross-sectional study among the students of grade four. A total 340 students were selected by random sampling method from four schools. Data were collected by face to face interview with a structured pretested questionnaire. The study was conducted at Dhanmondi Govt. Boys' High School, Kamrunnessa Govt. Girls School, Dhanmondi, Bangladesh International School and College (BISC), Mohakhali and SOS Hermann Gmeiner College, Mirpur, Dhaka, Bangladesh. Data were collected from May to October, 2019. Data analysis, findings and results were prepared in November and December, 2019.

Results: Among 340 respondents of this study, maximum (78.2%) students  watch  TV daily, 55.9% of them  play with the mobile every day and half (50%) of the students use the tablet daily. Majority (79.7%) respondents have internet at their home and 36.5% of them use the net alone. The causes of usage are- 37.9% students use for entertainment purpose, 26.5% use for education purpose and 34.4% use for both entertainment and education purpose.

Conclusion: Children are the future generation of our country. So, it is a prime need to look into this problem and protect our children from the threat of electronic gadget use.

JOPSOM 2020; 39(1): 78-87
Life history through the eyes of a hogfish: trophic growth and differential juvenile habitat use from stable isotope analysis
Authors: Faletti ME , Stallings CD
Published: March 2021

Understanding ontogenetic linkages among fish habitats is critical for conservation of fish populations and the ecosystems on which they rely. Natural tags such as stable isotopes are effective for investigating ecological questions regarding fish movement and habitat use. We analyzed stable isotopes from sequentially deposited laminae of hogfish Lachnolaimus maximus eye lenses from the eastern Gulf of Mexico (eGOM) to investigate trophic and geographic changes across individual life histories. We documented evidence of 1 to 2 step trophic level increases through δ15N increases. We also observed depth separation at the juvenile stage, evidenced by δ13C variation early in life. These results suggest that adult hogfish in deeper habitats likely inhabited deeper juvenile habitats (i.e. nearshore reefs), while adult hogfish inhabiting shallower adult habitats likely used shallower juvenile habitats (i.e. estuaries). This novel finding for eGOM hogfish contradicts prior literature that solely discusses seagrass as juvenile habitat. We used muscle tissue isotopes to characterize juvenile hogfish habitats and linear discriminant function analysis (LDA) to determine the habitats previously inhabited by adults in this study. The LDA revealed Cedar Key as the most used juvenile hogfish habitat in this study, but more evidence is needed to determine its status as a nursery. This study provides the first evidence for ontogenetic migration of individual hogfish using natural tags as tracers and demonstrates a mechanism for identifying juvenile habitats based on eye lens stable isotope analysis. Identifying ontogenetic patterns and habitat use can help to better conserve stocks and essential fish habitats.
Association between duration of the sleep and body weight
Authors: Adámková V , Hubáček JA , Lánská V , Vrablík M , Králová Lesná I , Suchánek P , Zimmelová P , Veleminský M
Published: March 2021

Some studies have suggested that there could be an association
between the duration of sleep in humans and development of the
obesity. We have analyzed the group of the probands (n = 3970,
2038 males and 1932 females, aged 18-65 years), with
permanent address in the Central or South Bohemia. We
ascertained the relationship between the duration of their sleep
(obtained per questionnaire) and body mass index, weight,
height, the value of systolic and diastolic blood pressure, heart
rate, waist and hip circumference, the values of total-, high
density- and low density- cholesterol, thyroid hormone and body
exercise performed. The optimal values of the body mass index
(and optimal body weight) were associated with the duration of
sleep 7 hours per night (P < 0.001). This association was found
both in males and females and in both districts. Other
anthropometrical and biochemical parameters were not
associated with the sleep duration.
Actigenetic of ACE gene polymorphism in Czech obese sedentary females
Authors: Suchánek P , Hubáček JA , Králová Lesná I , Pinekerová V , Adámková V
Published: March 2021

Obesity is a serious health problem worldwide and many genes
have been implicated in determination of obesity, but our
knowledge of the genes responsible for individual differences in
weight loss after physical intervention are poor. One of the
candidate genes is a gene for angiotensin-converting enzyme
(ACE) ant its insertion/deletion (I/D) polymorphism. We have
analyzed the association between the ACE gene variant in
intervened obese females. Twenty four unrelated healthy obese
(BMI > 29.9 kg/m2, with abdominal type of obesity) premenopausal (age between 25 and 45 years) Czech Caucasian sedentary and non-diabetic females, pre-selected according the ACE I/D polymorphism (twelve II and twelve DD homozygotes)
were studied in a medical research centre. They underwent 9
weeks intervention program (combination of the lowering of
dietary intake to optimal level for the age and 3 times a week
physical activity at fitness centre). The participants were
supervised to sustain a heart rate of 65 % of maximum.
Anthropometrical, biochemical parameters and body composition
(Bodystat 1500) were analyzed before and after the intervention.
Our study suggest, that in Czech Caucasian females I/D
polymorphism within the ACE gene will have no major effect on
weight loss. Interestingly, we have detected, that in obese
females II genotype was associated with higher increase in basal
metabolic rate (202 kcal per day) then in DD homozygotes
(p<0.05), thus at least under some circumstances, this genetic
variant may have an slight effect on BMI development.
Upregulation of Extracellular Vesicles-Encapsulated miR-132 Released From Mesenchymal Stem Cells Attenuates Ischemic Neuronal Injury by Inhibiting Smad2/c-jun Pathway via Acvr2b Suppression
Authors: Feng Bin , Meng Lei , Luan Liming , Fang Zhihao , Zhao Peng , Zhao Guangyu
Published: March 2021

Ischemic cerebrovascular disease is a significant and common public health issue worldwide. The emerging roles of mesenchymal stem cells (MSCs)-derived extracellular vesicles (EVs) in ischemic neuronal injury continue to be investigated. The current study aimed to investigate the role of EV-derived miR-132 from MSCs in ischemic neuronal injury. EVs were initially isolated from bone MSCs (BMSCs) and subsequently evaluated. A middle cerebral artery occlusion (MCAO) mouse model was constructed with the neurological function evaluated through a series of neurological scores, a pole test, and a foot fault test. Histopathological changes, neuron viability, and apoptosis, as well as cerebral infarction, were detected by hematoxylin and eosin (HE) staining and 2,3,5-triphenyltetrazolium hydrochloride (TTC) staining. The targeting relationship between microRNA (miR)-132 and Activin receptor type IIB (Acvr2b) was further confirmed based on dual-luciferase reporter gene assay results. Loss- and gain-of-function assays were conducted to elucidate the role of miR-132, EV-derived miR-132, Acvr2b, and Smad2 in oxygen-glucose deprivation (OGD)-treated neurons, and in mice models. Neuronal cell viability and apoptosis were evaluated via Cell Counting kit-8 (CCK-8) and flow cytometry. Our results indicated that Acvr2b was highly expressed, while miR-132 was poorly expressed in the MCAO mice and OGD-treated neurons. Acvr2b silencing or upregulation of miR-132 led to an elevation in neuronal activity, decreased neuronal apoptosis, reduced expression of Bax, and cleaved-caspase 3, as well as increased Bcl-2 expression. Acvr2b expression was targeted and inhibited by miR-132. EV-derived Acvr2b promoted activation of phosphorylated-Smad2 (p-Smad2)/c-jun signaling pathway, ultimately inducing neuronal injury. Our study provides evidence demonstrating that the overexpression of c-jun inhibits the protective role of MSCs-derived EV-miR-132 in neuronal injury. Upregulation of EV-derived miR-132 released from MSCs attenuates ischemic neuronal injury by inhibiting Smad2/c-jun pathways via the suppression of Acvr2b.
Autophagy Mediates Leptin-Induced Migration and ERK Activation in Breast Cancer Cells
Authors: García-Miranda Alin , Solano-Alcalá Karen Aylín , Montes-Alvarado José Benito , Rosas-Cruz Arely , Reyes-Leyva Julio , Navarro-Tito Napoleón , Maycotte Paola , Castañeda-Saucedo Eduardo
Published: March 2021

Autophagy is an intracellular recycling process active in eukaryotic cells that involves the formation of an autophagosome which delivers cytoplasmic components to the lysosome for degradation. This process occurs at low rates under basal conditions, but it can be induced by diverse types of stress such as starvation, hypoxia, metabolic disorders or in response to hormones, including leptin. Leptin is considered a pro-tumorigenic protein whose circulating levels have been related to bad prognosis in obese breast cancer patients. It has been recently demonstrated that leptin can induce autophagy in cancer cell lines from different tissues, suggesting that autophagy could modulate the pro-tumorigenic effects associated with leptin. In this study, the role of autophagy in leptin-induced proliferation, migration, apoptosis and ERK phosphorylation in breast cancer cell lines was evaluated. Although leptin differentially induced autophagy in the breast cancer cell lines tested, autophagy inhibition reduced leptin-induced cell proliferation in MCF7 cells and decreased cell migration, ERK activation, and impaired morphological changes in both cell lines. Our data demonstrates an important role for basal autophagy or leptin-induced autophagy in leptin-induced migration and ERK phosphorylation in breast cancer cell lines, suggesting a potential use for the inhibition of autophagy in breast cancer associated with obesity.
LMO7 as an Unrecognized Factor Promoting Pancreatic Cancer Progression and Metastasis
Authors: Liu Xinjian , Yuan Hao , Zhou Jing , Wang Qiongling , Qi Xiaoqiang , Bernal Catharine , Avella Diego , Kaifi Jussuf T. , Kimchi Eric T. , Timothy Parrett , Cheng Kun , Miao Yi , Jiang Kuirong , Li Guangfu
Published: March 2021

Pancreatic cancer (PC) is one of the most lethal human malignancies without effective treatment. In an effort to discover key genes and molecular pathways underlying PC growth, we have identified LIM domain only 7 (LMO7) as an under-investigated molecule, which highly expresses in primary and metastatic human and mouse PC with the potential of impacting PC tumorigenesis and metastasis. Using genetic methods with siRNA, shRNA, and CRISPR-Cas9, we have successfully generated stable mouse PC cells with LMO7 knockdown or knockout. Using these cells with loss of LMO7 function, we have demonstrated that intrinsic LMO7 defect significantly suppresses PC cell proliferation, anchorage-free colony formation, and mobilityin vitroand slows orthotopic PC tumor growth and metastasisin vivo. Mechanistic studies demonstrated that loss of LMO7 function causes PC cell-cycle arrest and apoptosis. These data indicate that LMO7 functions as an independent and unrecognized druggable factor significantly impacting PC growth and metastasis, which could be harnessed for developing a new targeted therapy for PC.
A Comparative Transcriptome Analysis of Human and Porcine Choroid Plexus Cells in Response to Streptococcus suis Serotype 2 Infection Points to a Role of Hypoxia
Authors: Lauer Alexa N. , Scholtysik Rene , Beineke Andreas , Baums Christoph Georg , Klose Kristin , Valentin-Weigand Peter , Ishikawa Hiroshi , Schroten Horst , Klein-Hitpass Ludger , Schwerk Christian
Published: March 2021

Streptococcus suis (S. suis) is an important opportunistic pathogen, which can cause septicemia and meningitis in pigs and humans. Previous in vivo observations in S. suis-infected pigs revealed lesions at the choroid plexus (CP). In vitro experiments with primary porcine CP epithelial cells (PCPEC) and human CP epithelial papilloma (HIBCPP) cells demonstrated that S. suis can invade and traverse the CP epithelium, and that the CP contributes to the inflammatory response via cytokine expression. Here, next generation sequencing (RNA-seq) was used to compare global transcriptome profiles of PCPEC and HIBCPP cells challenged with S. suis serotype (ST) 2 infected in vitro, and of pigs infected in vivo. Identified differentially expressed genes (DEGs) were, amongst others, involved in inflammatory responses and hypoxia. The RNA-seq data were validated via quantitative PCR of selected DEGs. Employing Gene Set Enrichment Analysis (GSEA), 18, 28, and 21 enriched hallmark gene sets (GSs) were identified for infected HIBCPP cells, PCPEC, and in the CP of pigs suffering from S. suis ST2 meningitis, respectively, of which eight GSs overlapped between the three different sample sets. The majority of these GSs are involved in cellular signaling and pathways, immune response, and development, including inflammatory response and hypoxia. In contrast, suppressed GSs observed during in vitro and in vivo S. suis ST2 infections included those, which were involved in cellular proliferation and metabolic processes. This study suggests that similar cellular processes occur in infected human and porcine CP epithelial cells, especially in terms of inflammatory response.
Unexpectedly High False-Positive Rates for Haemophilus influenzae Using a Meningoencephalitis Syndromic PCR Panel in Two Tertiary Centers
Authors: Zanella Marie-Céline , Cherkaoui Abdessalam , Hinic Vladimira , Renzi Gesuele , Goldenberger Daniel , Egli Adrian , Schrenzel Jacques
Published: March 2021

False-positive results in the diagnostic of meningitis and encephalitis pose important challenges. This study aimed to determine false-positive rates for Haemophilus influenzae in cerebrospinal fluids evaluated by the BioFire FilmArray® Meningitis/Encephalitis Panel. We conducted a retrospective study of all H. influenzae-positive FilmArray®. Meningitis/Encephalitis Panel results from June 2016 to October 2019 in two Swiss university hospitals. Cases were classified as true positive, likely true-positive, and likely false-positive results according to cerebrospinal fluid culture, H. influenzae-specific quantitative real-time PCR (qPCR), and Gram staining, as well as culture of other materials. We performed 3,082 panels corresponding to 2,895 patients: 0.6% of the samples (18/3,082) were positive for H. influenzae. Culture and H. influenzae-specific qPCR were performed on 17/18 (94.4%) and 3/18 (16.7%) cerebrospinal fluid samples, respectively; qPCR was negative in all cases. Among 17 samples sent for culture, 10 concerned patients were not treated with antibiotics prior to lumbar puncture. Only 1/17 revealed growth of H. influenzae and was classified as a true positive. We further classified 3/18 (16.7%) cases with the identification of Gram-negative rods in the cerebrospinal fluid or positive blood cultures for H. influenzae as likely true-positive and 14/18 (77.8%) cases as likely false-positive. Diagnostic results should always be interpreted together with the clinical presentation, cerebrospinal fluid analysis, and other available microbiological results. All H. influenzae-positive results should be viewed with special caution and a H. influenzae-specific qPCR should be systematically considered.
Survival Sounds in Insects: Diversity, Function, and Evolution
Authors: Low Melanie L. , Naranjo Mairelys , Yack Jayne E.
Published: March 2021

Insect defense sounds have been reported for centuries. Yet, aside from the well-studied anti-bat sounds of tiger moths, little is understood about the occurrence, function, and evolution of these sounds. We define a defense sound as an acoustic signal (air- or solid-borne vibration) produced in response to attack or threat of attack by a predator or parasitoid and that promotes survival. Defense sounds have been described in 12 insect orders, across different developmental stages, and between sexes. The mechanisms of defensive sound production include stridulation, percussion, tymbalation, tremulation, and forced air. Signal characteristics vary between species, and we discuss how morphology, the intended receiver, and specific functions of the sounds could explain this variation. Sounds can be directed at predators or non-predators, and proposed functions include startle, aposematism, jamming, and alarm, although experimental evidence for these hypotheses remains scant for many insects. The evolutionary origins of defense sounds in insects have not been rigorously investigated using phylogenetic methodology, but in most cases it is hypothesized that they evolved from incidental sounds associated with non-signaling behaviors such as flight or ventilatory movements. Compared to our understanding of visual defenses in insects, sonic defenses are poorly understood. We recommend that future investigations focus on testing hypotheses explaining the functions and evolution of these survival sounds using predator-prey experiments and comparative phylogenetics.
Whole Genome Interpretation for a Family of Five
Authors: Corpas Manuel , Megy Karyn , Mistry Vanisha , Metastasio Antonio , Lehmann Edmund
Published: March 2021

Although best practices have emerged on how to analyse and interpret personal genomes, the utility of whole genome screening remains underdeveloped. A large amount of information can be gathered from various types of analyses via whole genome sequencing including pathogenicity screening, genetic risk scoring, fitness, nutrition, and pharmacogenomic analysis. We recognize different levels of confidence when assessing the validity of genetic markers and apply rigorous standards for evaluation of phenotype associations. We illustrate the application of this approach on a family of five. By applying analyses of whole genomes from different methodological perspectives, we are able to build a more comprehensive picture to assist decision making in preventative healthcare and well-being management. Our interpretation and reporting outputs provide input for a clinician to develop a healthcare plan for the individual, based on genetic and other healthcare data.
Impacts of Whale-Watching on the Short-Term Behavior of Fin Whales (Balaenoptera physalus) in a Marine Protected Area in the Southeastern Pacific
Authors: Santos-Carvallo Macarena , Barilari Fernanda , Pérez-Alvarez María José , Gutiérrez Laura , Pavez Guido , Araya Héctor , Anguita Cristobal , Cerda Claudia , Sepúlveda Maritza
Published: March 2021

Whale-watching (WW) is an activity which has been increasing worldwide due to the great interest of tourists and the economic benefits it provides to local communities. However, it has been reported that this activity affects the behavioral patterns of some cetaceans, although for some species such as the fin whale (Balaenoptera physalus) this has not been extensively studied. To identify the effects of WW on the behavioral patterns of this species, we studied its traveling and resting behaviors in a locality of north-central Chile from 2015 to 2018. Using a theodolite, we calculated the response variables of swim speed, directness index, and reorientation for each behavior. We used the number of WW boats and the WW scenarios of “before”, “during”, and “after” the presence of boats as possible factors to explain the differences in the response variables of the whales, along with the factors of year, month, group size, and distance from the observation point. Reorientation increased significantly and the directness index decreased significantly for both traveling and resting behaviors from “before” to “during” WW scenarios, indicating more erratic and sinuous movements in the presence of boats. These changes in movement patterns are a commonly reported evasion response of cetaceans to the presence of WW boats. For traveling behavior, the swimming speed significantly increased, and trends showed increased reorientation and a decrease in the directness index in the “after” WW scenario, which suggests perturbation of the whales potentially associated with the speed and the direction in which the boats left. During resting behavior, the trajectories of the fin whales became straighter (decrease in reorientation) as the number of boats increased, thus evasion (more erratic and sinuous movements) is a behavior used less by fin whales as the number of boats increases. Notwithstanding the fact that tourism development in the study area is small in scale, we found that WW generates adverse effects that are reflected in changes in the whales’ movement patterns. This kind of information is valuable to the adjustment and/or design of management strategies for the species, which is fundamental for WW to continue to be a sustainable activity.
Circular RNA Microarray Analyses in Hepatic Ischemia-Reperfusion Injury With Ischemic Preconditioning Prevention
Authors: Tian Xinyao , Hu Yan , Liu Yuanxing , Yang Zhe , Xie Haiyang , Zhou Lin , Zheng Shusen
Published: March 2021

Ischemic preconditioning (IPC) represents an effective intervention to relieve hepatic ischemia-reperfusion injury (IRI). Systematic detection of circRNA expression revealing the protection effect of IPC still remains to be elucidated. Here, we applied a microarray to detect circRNA and mRNA expression in ischemic liver with and without IPC (n = 3 in each group). Compared with the sham group, there were 39 circRNAs and 432 mRNAs increased and 38 circRNAs and 254 mRNAs decreased (fold change ≥1.5, P < 0.05) in the group of hepatic IRI. As the result of IPC intervention, 43 circRNAs and 64 mRNAs were increased, and 7 circRNAs and 31 mRNAs were decreased in the IPC group when compared with IRI. We then identified circRNA_017753 as the most possible target that may closely relate to IPC protective signaling and predicted Jade1 as the target related to circRNA_017753. Three possible circRNA–miRNA–mRNA axes were constructed that may play a vital role in protective mechanisms in IPC. The study for the first time systematically detects the dysregulated circRNAs and mRNAs in response to hepatic IRI and IPC intervention. Our profile and bioinformatic analysis provide numerous novel clues to understanding the pathophysiologic mechanism of IPC protection against hepatic IRI.
Extensively Drug-Resistant Hypervirulent Klebsiella pneumoniae From a Series of Neonatal Sepsis in a Tertiary Care Hospital, India
Authors: Banerjee Tuhina , Wangkheimayum Jayalaxmi , Sharma Swati , Kumar Ashok , Bhattacharjee Amitabha
Published: March 2021

The recent emergence of multidrug-resistant (MDR) Klebsiella pneumoniae with hypervirulent traits causing severe infections and considerable mortality is a global cause for concern. The challenges posed by these hypermucoviscous strains of K. pneumoniae with regard to their optimal treatment, management, and control policies are yet to be answered. We studied a series of extensively drug-resistant (XDR) and hypervirulent K. pneumoniae ST5235 isolates with resistance to carbapenems and polymyxins causing neonatal sepsis in a tertiary care hospital in India. A total of 9 K. pneumoniae isolates from 9 cases of neonatal sepsis were studied with respect to their clinical relevance, antimicrobial susceptibility profile, presence of extended spectrum β lactamase (ESBL) production, and responsible genes, carbapenemases (classes A, B, and D), and aminoglycoside-resistant genes. Hypervirulence genes encoding hypermucoid nature, iron uptake, and siderophores were detected by multiplex PCR. The plasmid profile was studied by replicon typing. Isolates were typed by multilocus sequence typing (MLST) and enterobacterial repetitive intergenic consensus (ERIC) PCR to study the sequence types (STs) and clonal relation, respectively. The neonates in the studied cases had history of pre-maturity or low birth weight with maternal complications. All the cases were empirically treated with piperacillin–tazobactam and amikacin followed by imipenem/meropenem and vancomycin and polymyxin B as a last resort. However, all the neonates finally succumbed to the condition (100%). The studied isolates were XDR including resistance to polymyxins harboring multiple ESBL genes and carbapenemase genes (blaNDM and blaOXA−48). Hypervirulence genes were present in various combinations with rmpA/A2 genes present in all the isolates. IncFI plasmids were detected in these isolates. All belonged to ST5235. In ERIC PCR, 6 different clusters were seen. The study highlighted the emergence and burden of XDR hypervirulent isolates of K. pneumoniae causing neonatal sepsis in a tertiary care hospital.
Mitochondrial Behavior in Axon Degeneration and Regeneration
Authors: Wang Biyao , Huang Minghao , Shang Dehao , Yan Xu , Zhao Baohong , Zhang Xinwen
Published: March 2021

Mitochondria are organelles responsible for bioenergetic metabolism, calcium homeostasis, and signal transmission essential for neurons due to their high energy consumption. Accumulating evidence has demonstrated that mitochondria play a key role in axon degeneration and regeneration under physiological and pathological conditions. Mitochondrial dysfunction occurs at an early stage of axon degeneration and involves oxidative stress, energy deficiency, imbalance of mitochondrial dynamics, defects in mitochondrial transport, and mitophagy dysregulation. The restoration of these defective mitochondria by enhancing mitochondrial transport, clearance of reactive oxidative species (ROS), and improving bioenergetic can greatly contribute to axon regeneration. In this paper, we focus on the biological behavior of axonal mitochondria in aging, injury (e.g., traumatic brain and spinal cord injury), and neurodegenerative diseases (Alzheimer's disease, AD; Parkinson's disease, PD; Amyotrophic lateral sclerosis, ALS) and consider the role of mitochondria in axon regeneration. We also compare the behavior of mitochondria in different diseases and outline novel therapeutic strategies for addressing abnormal mitochondrial biological behavior to promote axonal regeneration in neurological diseases and injuries.
Failure Handling of Robotic Pick and Place Tasks With Multimodal Cues Under Partial Object Occlusion
Authors: Zhu Fan , Wang Liangliang , Wen Yilin , Yang Lei , Pan Jia , Wang Zheng , Wang Wenping
Published: March 2021

The success of a robotic pick and place task depends on the success of the entire procedure: from the grasp planning phase, to the grasp establishment phase, then the lifting and moving phase, and finally the releasing and placing phase. Being able to detect and recover from grasping failures throughout the entire process is therefore a critical requirement for both the robotic manipulator and the gripper, especially when considering the almost inevitable object occlusion by the gripper itself during the robotic pick and place task. With the rapid rising of soft grippers, which rely heavily on their under-actuated body and compliant, open-loop control, less information is available from the gripper for effective overall system control. Tackling on the effectiveness of robotic grasping, this work proposes a hybrid policy by combining visual cues and proprioception of our gripper for the effective failure detection and recovery in grasping, especially using a proprioceptive self-developed soft robotic gripper that is capable of contact sensing. We solved failure handling of robotic pick and place tasks and proposed (1) more accurate pose estimation of a known object by considering the edge-based cost besides the image-based cost; (2) robust object tracking techniques that work even when the object is partially occluded in the system and achieve mean overlap precision up to 80%; (3) contact and contact loss detection between the object and the gripper by analyzing internal pressure signals of our gripper; (4) robust failure handling with the combination of visual cues under partial occlusion and proprioceptive cues from our soft gripper to effectively detect and recover from different accidental grasping failures. The proposed system was experimentally validated with the proprioceptive soft robotic gripper mounted on a collaborative robotic manipulator, and a consumer-grade RGB camera, showing that combining visual cues and proprioception from our soft actuator robotic gripper was effective in improving the detection and recovery from the major grasping failures in different stages for the compliant and robust grasping.
Hardware Design for Autonomous Bayesian Networks
Authors: Faria Rafatul , Kaiser Jan , Camsari Kerem Y. , Datta Supriyo
Published: March 2021

Directed acyclic graphs or Bayesian networks that are popular in many AI-related sectors for probabilistic inference and causal reasoning can be mapped to probabilistic circuits built out of probabilistic bits (p-bits), analogous to binary stochastic neurons of stochastic artificial neural networks. In order to satisfy standard statistical results, individual p-bits not only need to be updated sequentially but also in order from the parent to the child nodes, necessitating the use of sequencers in software implementations. In this article, we first use SPICE simulations to show that an autonomous hardware Bayesian network can operate correctly without any clocks or sequencers, but only if the individual p-bits are appropriately designed. We then present a simple behavioral model of the autonomous hardware illustrating the essential characteristics needed for correct sequencer-free operation. This model is also benchmarked against SPICE simulations and can be used to simulate large-scale networks. Our results could be useful in the design of hardware accelerators that use energy-efficient building blocks suited for low-level implementations of Bayesian networks. The autonomous massively parallel operation of our proposed stochastic hardware has biological relevance since neural dynamics in brain is also stochastic and autonomous by nature.
Roles of Selenoproteins in Brain Function and the Potential Mechanism of Selenium in Alzheimer’s Disease
Authors: Zhang Zhong-Hao , Song Guo-Li
Published: March 2021

Selenium (Se) and its compounds have been reported to have great potential in the prevention and treatment of Alzheimer’s disease (AD). However, little is known about the functional mechanism of Se in these processes, limiting its further clinical application. Se exerts its biological functions mainly through selenoproteins, which play vital roles in maintaining optimal brain function. Therefore, selenoproteins, especially brain function-associated selenoproteins, may be involved in the pathogenesis of AD. Here, we analyze the expression and distribution of 25 selenoproteins in the brain and summarize the relationships between selenoproteins and brain function by reviewing recent literature and information contained in relevant databases to identify selenoproteins (GPX4, SELENOP, SELENOK, SELENOT, GPX1, SELENOM, SELENOS, and SELENOW) that are highly expressed specifically in AD-related brain regions and closely associated with brain function. Finally, the potential functions of these selenoproteins in AD are discussed, for example, the function of GPX4 in ferroptosis and the effects of the endoplasmic reticulum (ER)-resident protein SELENOK on Ca2+homeostasis and receptor-mediated synaptic functions. This review discusses selenoproteins that are closely associated with brain function and the relevant pathways of their involvement in AD pathology to provide new directions for research on the mechanism of Se in AD.
Is There an Exercise-Intensity Threshold Capable of Avoiding the Leaky Gut?
Authors: Ribeiro Filipe M. , Petriz Bernardo , Marques Gabriel , Kamilla Lima H. , Franco Octavio L.
Published: March 2021

Endurance-sport athletes have a high incidence of gastrointestinal disorders, compromising performance and impacting overall health status. An increase in several proinflammatory cytokines and proteins (LPS, I-FABP, IL-6, IL-1β, TNF-α, IFN-γ, C-reactive protein) has been observed in ultramarathoners and triathlon athletes. One of the most common effects of this type of physical activity is the increase in intestinal permeability, known as leaky gut. The intestinal mucosa's degradation can be identified and analyzed by a series of molecular biomarkers, including the lactulose/rhamnose ratio, occludin and claudin (tight junctions), lipopolysaccharides, and I-FABP. Identifying the molecular mechanisms involved in the induction of leaky gut by physical exercise can assist in the determination of safe exercise thresholds for the preservation of the gastrointestinal tract. It was recently shown that 60 min of vigorous endurance training at 70% of the maximum work capacity led to the characteristic responses of leaky gut. It is believed that other factors may contribute to this effect, such as altitude, environmental temperature, fluid restriction, age and trainability. On the other hand, moderate physical training and dietary interventions such as probiotics and prebiotics can improve intestinal health and gut microbiota composition. This review seeks to discuss the molecular mechanisms involved in the intestinal mucosa's adaptation and response to exercise and discuss the role of the intestinal microbiota in mitigating these effects.
Novel Nutrition-Based Nomograms to Assess the Outcomes of Lung Cancer Patients Treated With Anlotinib or Apatinib
Authors: Zheng Hui , Pan Qin , Zhu Wenchao , Li Hongsen , Niu Zhongfeng , Fang Yong , Li Da , Lou Haizhou , Hu Hong , Shou Jiawei , Pan Hongming
Published: March 2021

Background

Previous studies have indicated that the changes in body composition during treatment are prognostic in lung cancer. The question which follows is it may be too late to identify vulnerable patients after treatment and to improve outcomes for these patients. In our study, we sought to explore the alterations of body composition and weight before the outset of the antiangiogenic treatment and its role in predicting clinical response and outcomes.

Methods

In this retrospective study, 122 patients with advanced lung cancer treated with anlotinib or apatinib were analyzed. The changes in weight and body composition including skeletal muscle index (SMI), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) for 3 months before the outset of antiangiogenic treatment and other clinical characteristics were evaluated with LASSO Cox regression and multivariate Cox regression analysis, which were applied to construct nomograms. The performance of the nomograms was validated internally by using bootstrap method with 1,000 resamples models and was assessed by the concordance index (C-index), calibration plots, decision curve analysis (DCA).

Results

The median progression-free survival (PFS) and overall survival (OS) were 128 (95% CI 103.2–152.8) days and 292 (95% CI 270.9–313.1) days. Eastern Cooperative Oncology Group performance status (ECOG PS), brain metastases, the Glasgow Prognostic Score (GPS), clinical response, therapeutic regimen, and ΔL1SMI per 90 days were significantly associated with PFS, while ECOG PS, GPS, clinical response, therapeutic regimen, ΔL1SMI per 90 days were identified for OS. The C-index for the nomograms of PFS and OS were 0.763 and 0.748, respectively. The calibration curves indicated excellent agreement between the predicted and actual survival outcomes of 3- and 4-month PFS and 7- and 8-month OS. DCA showed the considerable value of the model.

Conclusion

Nomograms were developed from clinical features and nutritional indicators to predict the probability of achieving 3-month and 4-month PFS and 7-month and 8-month OS with antiangiogenic therapy for advanced lung cancer. Dynamic changes in body composition before the initiation of treatment contributed to early detection of poor outcome.
Potential Association Between Asthma, Helicobacter pylori Infection, and Gastric Cancer
Authors: Wu Fengxia , Chen Cai , Peng Fulai
Published: March 2021

Background: The prevalence of Helicobacter pylori infection (HPI) is still high around the world, which induces gastric diseases, such as gastric cancer (GC). The epidemiological investigation showed that there was an association between HPI and asthma (AST). Coptidis rhizoma (CR) has been reported as an herbal medicine with anti-inflammatory and anti-bacterial effects.

Purpose: The present study was aimed to investigate the protective mechanism of HPI on AST and its adverse effects on the development of GC. Coptis chinensis was used to neutralize the damage of HPI in GC and to hopefully intensify certain protective pathways for AST.

Method: The information about HPI was obtained from the public database Comparative Toxicogenomics Database (CTD). The related targets in AST and GC were obtained from the public database GeneCards. The ingredients of CR were obtained from the public database Traditional Chinese Medicine Systems Pharmacology (TCMSP). The network pharmacology including gene ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and molecular docking were utilized. Protein–protein interaction was constructed to analyze the functional link of target genes. The molecular docking was employed to study the potential effects of active ingredients from CR on key target genes.

Result: The top 10 key targets of HPI for AST were CXCL9, CX3CL1, CCL20, CCL4, PF4, CCL27, C5AR1, PPBP, KNG1, and ADORA1. The GO biological process involved mainly leukocyte migration, which responded to bacterium. The (R)-canadine and quercetin were selected from C. chinensis, which were employed to explore if they inhibited the HPI synchronously and protect against AST. The targets of (R)-canadine were SLC6A4 and OPRM1. For ingredient quercetin, the targets were AKR1B1 and VCAM1.

Conclusion: CXCL9 and VCAM1 were the common targets of AST and HPI, which might be one of the imported targets of HPI for AST. Quercetin could be an effective ingredient to suppress HPI and help prevent AST.
Comparison of Sutureless and Conventional Laparoscopic Partial Nephrectomy: A Propensity Score-Matching Analysis
Authors: Zhang Feng , Gao Shuang , Zhao Yiqiao , Wu Bin , Chen Xiaonan
Published: March 2021

Objective: To compare the functional outcome, safety and efficacy of sutureless and conventional laparoscopic partial nephrectomy.

Methods: After the inclusion and exclusion criteria were applied, our study reviewed 379 patients with T1 stage renal tumors. We applied propensity score matching (PSM) to limit potential baseline confusion. Perioperative and functional outcomes between sutureless laparoscopic partial nephrectomy (sLPN) and conventional laparoscopic partial nephrectomy (cLPN) groups were compared and analyzed before and after PSM.

Results: Of our 379 patients with T1 stage renal tumors, 199 and 180 were identified in the cLPN and sLPN groups, respectively. After applying PSM with preoperative features, 116 patients in the cLNP group were paired to 116 patients in the sLNP group. We found that all differences in preoperative baseline characteristics disappeared. All the preoperative characteristics (age, gender, tumor diameter, RENAL nephrometry score, side, preoperative eGFR, hypertension, diabetes mellitus, ASA score) were not statistically different between the two groups. The operative time (OT) (p < 0.001) and warm ischemia time (WIT) (p < 0.001) of the sLPN group were of shorter duration than that of the cLPN group. The eGFR baseline was almost equal, but there was a statistically smaller decrease in eGFR in the sLPN than in the cLPN group 1 week after surgery (14.3 vs. 7.4, p < 0.001) and after 6 months (11.9 vs. 5.0, p < 0.001). After both preoperative features and WIT were included in PSM, fifty-one pairs of patients were identified between the groups, the WIT difference between them disappeared, while the decrease in eGFR between the groups remained as it was previously at 1 week (15.4 vs. 8.6, p < 0.001) and at 6 months (13.0 vs. 6.2, p < 0.001).

Conclusion: Sutureless laparoscopic partial nephrectomy is as safe and effective as conventional laparoscopic partial nephrectomy, and compared to cLPN, sLPN can effectively reduce the WIT, retain more renal parenchyma and protect renal function.
Biejiajian Pill Inhibits Carcinogenesis and Metastasis via the Akt/GSK-3β/Snail Signaling Pathway in Hepatocellular Carcinoma
Authors: Sun Jialing , Chen Weicong , Wen Bin , Zhang Mingjia , Sun Haitao , Yang Xuemei , Zhao Wenting , La Lei , An Haiyan , Pang Jie , Gao Lei , He Songqi
Published: March 2021

Hepatocellular carcinoma (HCC) is among the most usual cancers globally. In China, Biejiajian pill (BJJP), Traditional Chinese Medicine clinical prescription, is broadly utilized for the prevention and therapy of HCC. However, the mechanisms by which BJJP exerts its effects on the prevention of tumor invasion and metastasis are still largely unknown. In this study, in vitro multiple hepatic cancer cell lines and an in vivo xenograft mice model were used to validate the preventive effects and molecular mechanisms of BJJP in HCC. We established that BJJP significantly repressed the proliferation, metastasis and infiltration of HCC cells. Furthermore, BJJP remarkably suppressed HCC cell migration, as well as invasion via epithelial-mesenchymal transition (EMT) by modulating Snail expression, which was associated with the repression of Akt/GSK-3β/Snail signaling axis activation. In vivo HCC xenograft results indicated that BJJP delayed HCC development and efficiently inhibited lung metastasis. Taken together, BJJP was shown to be an effective therapeutic agent against HCC through repression of the Akt/GSK-3β/Snail signaling cascade and EMT.
Vancomycin Associated Acute Kidney Injury: A Longitudinal Study in China
Authors: Kunming Pan , Can Chen , Zhangzhang Chen , Wei Wu , Qing Xu , Xiaoqiang Ding , Xiaoyu Li , Qianzhou Lv
Published: March 2021

Background: Vancomycin-associated acute kidney injury (VA-AKI) is a recognizable condition with known risk factors. However, the use of vancomycin in clinical practices in China is distinct from other countries. We conducted this longitudinal study to show the characteristics of VA-AKI and how to manage it in clinical practice.

Patients and Methods: We included patients admitted to hospital, who received vancomycin therapy between January 1, 2016 and June 2019. VA-AKI was defined as a patient having developed AKI during vancomycin therapy or within 48 h following the withdrawal of vancomycin therapy.

Results: A total of 3719 patients from 7058 possible participants were included in the study. 998 patients were excluded because of lacking of serum creatinine measurement. The incidence of VA-AKI was 14.3%. Only 32.3% (963/2990) of recommended patients performed therapeutic drug monitoring of vancomycin. Patients with VA-AKI were more likely to concomitant administration of cephalosporin (OR 1.55, 95% CI 1.08–2.21, p = 0.017), carbapenems (OR 1.46, 95% CI 1.11–1.91, p = 0.006) and piperacillin-tazobactam (OR 3.12, 95% CI 1.50–6.49, p = 0.002). Full renal recovery (OR 0.208, p = 0.005) was independent protective factors for mortality. Compared with acute kidney injury stage 1, AKI stage 2 (OR 2.174, p = 0.005) and AKI stage 3 (OR 2.210, p = 0.005) were independent risk factors for fail to full renal recovery.

Conclusion: Lack of a serum creatinine measurement for the diagnosis of AKI and lack of standardization of vancomycin therapeutic drug monitoring should be improved. Patient concomitant with piperacillin-tazobactam are at higher risk. Full renal recovery was associated with a significantly reduced morality.