bluuebunny/crossref_metadata_2025 huggingface dataset:
First-In-Asian Double-Blind Randomized Trial To Assess The Efficacy And Safety Of Insulin Sensitizer In Nonalcoholic Steatohepatitis Patients
Authors: Huang Jee-Fu , Dai Chia-Yen , Huang Chung-Feng , Tsai Pei-Chien , Yeh Ming-Lun , Hsu Po-Yau , Huang Shiu-Feng , Bair Ming-Jong , Hou Nai-Jen , Huang Ching-I , Liang Po-Cheng , Lin Yi-Hung , Wang Chih-Wen , Hsieh Ming-Yen , Chen Shinn-Chern , Lin Zu-Yau , Yu Ming-Lung , Chuang Wan-Long
Published: June 2021

Background: The efficacy and safety of insulin sensitizer in Asians with non-alcoholic steatohepatitis (NASH) remain elusive. Aims: The double-blind, randomized, placebo-controlled trial was conducted aiming to investigate the efficacy and safety of pioglitazone in NASH patients. Methods: A total of 90 NASH patients (66 males, age= 44.1 ± 12.7 years) were prospectively randomized into oral pioglitazone 30 mg/day (Arm A) or placebo (Arm B) for 24 weeks. The primary endpoint was the efficacy of pioglitazone in reducing inflammation and liver fat at end-of-treatment (EOT). NASH resolution/improvement without fibrosis worsening were also evaluated.Results: At EOT, there was a significantly decline of alanine aminotransferase (86.9 ± 34.3 to 45.7 ± 35.8 IU/L, P=0.003) level in Arm A patients. In intention-to-treat analysis among 66 patients who completed paired biopsies, The NAFLD activity score (NAS) of 30 Arm A patients significantly decreased from 4.27 ± 1.14 at baseline to 2.53 ± 1.63 at EOT (P< 0.0001), whereas there was no significant change in patients of Arm B (3.94 ± 1.41 vs 3.94 ± 1.51, P= 1.0). NASH improvement without worsening of fibrosis was achieved in 46.7% (14/30) patients in Arm A, compared to 11.1% (4/36) patients in Arm B (P= 0.002). Liver fat content reduced (20.2 ± 9.0 to 14.3 ± 6.9%, P<0.0001) on MRI-PDFF in Arm A compared to their counterparts. No significant difference of adverse events occurred between groups. Conclusions: A 24-weeks pioglitazone treatment was well-tolerated and effective in improving liver histology and reducing liver steatosis in Asian NASH patients. (ClinicalTrials.gov number: NCT01068444)
Semaphorin3A Promotes the Development of Nickel Allergy
Authors: Liu Lipei , Watanabe Megumi , Minami Norikazu , Yunizar Mohammad , Ichikawa Tetsuo
Published: June 2021

Metal allergy is one of the typical immune disorders encountered during the application of dental/medical materials and has a highly complex pathogenic mechanism. Semaphorin 3A (Sema3A), a member of the semaphorin family, is reported to be involved in various immune disorders. However, its role in metal allergy has not been clarified yet. Herein, we show that Sema3A promoted nickel (Ni) allergy by mediating tumor necrosis factor-alpha (TNF-α) production and mitogen-activated protein kinase (MAPK) activation in keratinocytes. Sema3A was upregulated in NiCl2-stimulated mouse keratinocytes and in Ni allergy-induced mouse ear tissue. TNF-α production and MAPK activation were altered when Sema3A was suppressed in keratinocytes. The specific deletion of Sema3A in keratinocytes alleviated Ni allergy and regulated the macrophage polarization towards an anti-inflammatory direction. Our results demonstrate that Sema3A promotes the development of metal allergy and should be explored as a potential target for the prevention and treatment of metal allergy.
Fifth fundamental force and unification of fundamental forces
Authors: Singh Raghvendra
Published: June 2021

There are four known fundamental forces of nature and there is a need to combine them into a unified theory. Progress has been made toward this goal but gravity remains an issue. However, the four forces are body forces that act on points. They together do not make the universe a closed system. Here, I identify a surface force, which acts outward normal to the surface of the universe. Further, using water drop hanging in a vacuum as a model, I provide a formula to find the magnitude of this force. The fifth force is generated by surface tension, a property of dark energy. On the other hand, matter particles interact with each other through cohesive forces and with dark matter through adhesive forces. I give a range of functional forms of all cohesive and adhesive forces and present an equation that unifies all the forces of nature.
Institutional “Paris Agreement Compatible” Mitigation Scenarios Evaluated Against the Paris Agreement 1.5°C Goal
Authors: Brecha Robert , Ganti Gaurav , Lamboll Robin , Nicholls Zebedee , Hare William , Lewis Jared , Meinshausen Malte , Schaeffer Michiel , Gidden Matthew
Published: June 2021

Scientifically rigorous guidance to policy makers on mitigation options for meeting the Paris Agreement long-term temperature goal requires an evaluation of long-term global-warming implications of greenhouse gas emissions pathways. Here we employ a uniform and transparent methodology to evaluate Paris Agreement compatibility of influential “institutional” emission scenarios from the grey literature. We compare a selection of these scenarios analyzed with this methodology to the Integrated Assessment Model scenarios assessed by the Intergovernmental Panel on Climate Change. We harmonize emissions to a consistent base-year and account for all greenhouse gases and aerosol precursor emissions, ensuring a self-consistent comparison of climate variables. An evaluation of peak and end-of-century temperatures is made, with both being relevant to the Paris Agreement goal. We find that few published scenarios that claim to be compatible with the Paris Agreement are so, and investigate root causes based on the underlying energy system transformation.
JUMPER Enables Discontinuous Transcript Assembly in Coronaviruses
Authors: Sashittal Palash , Zhang Chuanyi , Peng Jian , El-Kebir Mohammed
Published: June 2021

Genes in SARS-CoV-2 and other viruses in the order of Nidovirales are expressed by a process of discontinuous transcription mediated by the viral RNA-dependent RNA polymerase. This process is distinct from alternative splicing in eukaryotes and produces subgenomic RNAs that express different viral genes. Here, we introduce the DISCONTINUOUS TRANSCRIPT ASSEMBLY problem of finding transcripts T and their abundances c given an alignment R of paired end short reads under a maximum likelihood model that accounts for varying transcript lengths. Underpinning our approach is the concept of a segment graph, a directed acyclic graph that, distinct from the splice graph used to characterize alternative splicing, has a unique Hamiltonian path. We provide a compact characterization of solutions as subsets of non-overlapping edges in this graph, enabling the formulation of an efficient progressive heuristic that uses mixed integer linear program. We show using simulations that our method, JUMPER, drastically outperforms existing methods for classical transcript assembly. On short-read data of SARS-CoV-1, SARS-CoV-2 and MERS-CoV samples, we find that JUMPER not only identifies canonical transcripts that are part of the reference transcriptome, but also predicts expression of non-canonical transcripts that are well supported by direct evidence from long-read data, presence in multiple, independent samples or a conserved core sequence. Moreover, application of JUMPER on samples with and without treatment reveals viral drug response at the transcript level. As such, JUMPER enables detailed analyses of Nidovirales transcriptomes under varying conditions.
Hydrogel tapes for fault-tolerant strong wet adhesion
Authors: Cao Yi , Xue Bin , Gu Jie , Yu Wenting , Li Lan , Qin Meng , Jiang Qing , Wang Wei
Published: June 2021

Fast and strong bio-adhesives are in high demand for many biomedical applications, including closing wounds in surgeries, fixing implantable devices, and haemostasis. However, most strong bio-adhesives rely on the instant formation of irreversible covalent crosslinks to provide strong surface binding. Repositioning misplaced adhesives during surgical operations may cause severe secondary damage to tissues. Here, we report hydrogel tapes that can form strong physical interactions with tissues in seconds and gradually form covalent bonds in hours. This timescale-dependent adhesion mechanism allows instant and robust wet adhesion to be combined with fault-tolerant convenient surgical operations. Specifically, inspired by the catechol chemistry discovered in mussel foot proteins, we develop an electrical oxidation approach to controllably oxidize catechol to catecholquinone, which reacts slowly with amino groups on the tissue surface. We demonstrate that the tapes show fast and reversible adhesion at the initial stage and ultrastrong adhesion after the formation of covalent linkages over hours for various tissues and electronic devices. Given that the hydrogel tapes are biocompatible, easy to use, and robust for bio-adhesion, we anticipate that they may find broad biomedical and clinical applications.
Wear and Friction Behavior of Gr/Sn Solid Lubricated Dual Reinforced AMCs
Authors: Singhal Varun , Pandey Om Prakash
Published: June 2021

The current work has been undertaken to see the effect of Gr/Sn as a solid lubricant for the development of hybrid aluminum metal matrix composite (HAMCs). HAMCs were fabricated by reinforcing 10 wt. % (sillimanite + ilmenite) minerals with or without 1 wt. % Sn/Gr/both solid via stir casting technique. Optical microscopy revealed a homogenous distribution of reinforced particles with the refinement of silicon. Vicker hardness of the HAMCs showed a good interfacial bonding of particles with the matrix. The wear rate and coefficient of friction of the HAMCs are reduced with a maximum of composite with tin and graphite as lubrication agents. The composite contained tin and graphite wear rate as lubrication agents were in tune with the cast-iron brake drum used in the automobile industries. Abrasive wear was dominant at low loads and adhesive wear at high load, as confirmed from SEM analysis.
The Effects of Propofol on Hypoxia- and TNF-α-Mediated Brain-Derived Neurotrophic Factor/Tyrosine Kinase Receptor B Pathway Dysregulation in Primary Rat Hippocampal Neurons and Astrocytes
Authors: Tao Weiping , Zhang Xuesong , Ding Juan , Yu Shijian , Ge Peiqing , Han Jingfeng , Luo Xing , Cui Wei , Chen Jiawei
Published: June 2021

Background: BDNF/TrkB pathway dysregulation may be induced by hypoxia and inflammation, and play pivotal roles during the development of neurological disorders. Propofol is an anesthetic agent with neuro-protective properties. We aimed to verify whether propofol affected BDNF/TrkB pathway in neurons exposed to hypoxia or TNF-α.Methods: Primary rat hippocampal neurons and astrocytes were cultured and exposed to propofol followed by hypoxia or TNF-α treatment. The production of BDNF and the expression/truncation/phosphorylation of TrkB were measured. The underlying mechanisms such as ERK, CREB, p35 and Cdk5 were investigated.Results: In hippocampal neurons and astrocytes, hypoxia and TNF-α reduced the production of BDNF. Pretreatment of hippocampal neurons with 25μM propofol reversed the inhibitory effect of hypoxia or TNF-α on BDNF production. However, even 100μM propofol had no such effect in astrocytes. Further, we found that in hippocampal neurons hypoxia and TNF-α increased the phosphorylaion of ERK (p-ERK) and CREB at Ser142 (p-CREBSer142), while reduced the phosphorylation of CREB at Ser133 (p-CREBSer133), which were all reversed by 25μM propofol and 10μM ERK inhibitor. In addition, neither hypoxia nor TNF-α affected TrkB expression, truncation or phosphorylation in hippocampal neurons and astrocytes. However 50μM propofol induced TrkB phosphorylation without affecting its expression and truncation only in hippocampal neurons. Furthermore, we detected that in hippocampal neurons, 50μM propofol induced p35 expression and Cdk5 activation, and blockade of p35 or Cdk5 mitigated propofol-induced TrkB phosphorylation.Conclusions: Propofol, via ERK/CREB and p35/Cdk5, may modulate BDNF/TrkB pathway in hippocampal neurons that were exposed to hypoxia or TNF-α.
Changes In The Gut Microbiota After Hepatitis C Virus Eradication
Authors: Honda Takashi , Ishigami Masatoshi , Yamamoto Kenta , Takeyama Tomoaki , Ito Takanori , Ishizu Yoji , Kuzuya Teiji , Nakamura Masanao , Kawashima Hiroki , Miyahara Ryoji , Ishikawa Tetsuya , Hirooka Yoshiki , Fujishiro Mitsuhiro
Published: June 2021

The gut microbiota interacts with infectious diseases and affects host immunity. It has also been reported that liver disease is associated with changes in the gut microbiota. To investigate changes in the gut microbiota before and after eradication of hepatitis C virus (HCV) by direct-acting antiviral (DAA) treatment in patients with chronic hepatitis C (CHC), we investigated 42 samples from 14 CHC patients who received DAA therapy for HCV. Faecal samples were obtained before treatment (Pre), when treatment ended (EOT), and 24 weeks after treatment ended (Post24). The target V3–4 region of the 16S rRNA gene from faecal samples was amplified using the Illumina Miseq sequencing platform. The diversity of the gut microbiota did not differ significantly between Pre, EOT, and Post24. PCoA analysis showed that for each patient, the values at Pre, EOT, and Post 24 were concentrated within a small area. LEfSe analysis showed that the relative abundances of Faecalibacterium and Bacillus were increased at EOT and further increased at Post24, and these genera were significantly increased at Post24 compared to Pre. These results suggest that changes in the gut microbiota need to be considered as among the various effects on living organisms observed after HCV elimination.
Tolerance of Dosed Physical Loads in the Rehabilitation of Patients With a Recent Experience of Myocardial Infarction or Unstable Angina
Authors: Chenguang Mu , Ivanovna Kushakova Nadezhda , Evgenievich Bobyrev Vladimir
Published: June 2021

Objective: The study of reaction to dosed physical load of patient with recent experience of myocardial infarction or unstable angina to assess objectively physical condition and performance, to appoint an adequate individual program of physical rehabilitation and to optimize the effectiveness of the sanatorium stage of rehabilitation of this category of patients.Design: Study and observational analysis.Parameter: The subsidiary «Sanatorium-resort rehabilitation center «Slaviansk resort», the sanatorium «Yubileiny», Ukraine.Participants: Patients with recent experience of myocardial infarction or unstable angina who arrived at the sanatorium stage of rehabilitation from cardiological hospitals of Donetsk and Lugansk regions (Ukraine).Intervention: Non-invasive treatment (i.e. therapeutic exercise)Results: 3530 patients who arrived at the sanatorium stage of rehabilitation from cardiological hospitals of Donetsk and Lugansk regions (Ukraine) on 29,4 ±2,4 day of illness were examined. Men accounted for 64%, women - 36%. The average age of the patients was 54,4 ±1,8 years old. 1127 people (31,93 %) had a Q-positive myocardial infarction (MI), 388 people (10,99 %) – a Q-negative, 2015 people (57,08 %) – an unstable angina.When studying the tolerance to dosed physical activity, threshold or inadequate reactions were observed in 144 patients (12.78%) who had Q-positive myocardial infarction, 13 patients (3.35%) who had Q-negative myocardial infarction and 89 patients (4.42%) who had unstable angina. Threshold or inadequate responses in patients with recent experience of Q-positive myocardial infarction were recorded 3-4 times more often. The electrocardiographic examination revealed most often changes in the terminal part of the ventricular complex in the form of inversion or reversal of T waves, to a greater extent in patients who had Q-positive myocardial infarction.Conclusions: It was found in the course of study that patients with recent experience of Q-positive myocardial infarction master less physical activity at the sanatorium stage of rehabilitation than patients of other groups. Our study has shown that an insufficient level of physical activity does not give an optimal effect in increasing the functional reserves of the cardiovascular system and the body as a whole, and insufficient control of an increase in the level of physical activity is fraught with negative consequences.Careful selection of optimal physical activity for this category of patients allowed to prescribe adequate physical activity to patients and avoid possible complications.
A Low-Power and Low Cost Smart Streetlight System Based on Internet of Things Technology
Authors: Zhang Jingjing , Zeng Weihua , Hou Shengli , Chen Yuqi , Guo Linyan , Li Yanxing
Published: June 2021

Street lighting, as the most essential and universal component of the urban lighting system, accounts for a large portion of public electricity usage. Therefore, improving street lamps working efficiency is vital for energy savings. This paper demonstrates the design of a smart street lighting system supported by the combination of NB-IoT and LoRa communication technology. By adopting an optimized street lamp control algorithm, the system can realize the automatic control of street lights according to the real-time traffic flow information. This system has been installed on Luyang Avenue, Lucheng City, Shanxi Province, China in May 2019. It managed to reduce the electricity consumption in this region significantly in June 2019, which was 18% lower than that in April 2019 and 19.7% lower than that in June 2018. By illustrating the unique advantages of this system in energy savings and cost reduction, this paper displays its potential for further application in the construction of smart cities on a large scale.
Efferent and Afferent Connections of the Supratrigeminal Neurons Conveying Orofacial Muscle Proprioception in Rats
Authors: Yoshida Atsushi , Inoue Misaki , Sato Fumihiko , Morita Yayoi , Tsutsumi Yumi , Furuta Takahiro , Uchino Katsuro , Akhter Fatema , Bae Yong Chul , Tachibana Yoshihisa , Inoue Tomio
Published: June 2021

The supratrigeminal nucleus (Su5) is a key structure for controlling jaw-movements since it receives proprioceptive sensation from jaw-closing muscle spindles (JCMSs) and sends projection to the trigeminal motor nucleus (Mo5). However, the central projection and regulation of JCMS proprioceptive sensation have not been fully understood. Therefore, we aimed to reveal the efferents and afferents of the Su5 by means of neuronal tract tracings. Anterograde tracer injections into the Su5 revealed that the Su5 sent contralateral projections (or bilateral projections with a contralateral predominance) to the Su5, basilar pontine nuclei, pontine reticular nucleus, deep mesencephalic nucleus, superior colliculus, caudo-ventromedial edge of ventral posteromedial thalamic nucleus, parafascicular thalamic nucleus, zona incerta, and lateral hypothalamus, and ipsilateral projections (or bilateral projections with an ipsilateral predominance) to the intertrigeminal region, trigeminal oral subnucleus, dorsal medullary reticular formation, and hypoglossal nucleus as well as the Mo5. Retrograde tracer injections into the Su5 demonstrated that the Su5 received bilateral projections with a contralateral predominance (or contralateral projections) from the primary and secondary somatosensory cortices, granular insular cortex and Su5, and ipsilateral projections (or bilateral projections with an ipsilateral predominance) from the dorsal peduncular cortex, bed nuclei of stria terminalis, central amygdaloid nucleus, lateral hypothalamus, parasubthalamic nucleus, trigeminal mesencephalic nucleus, parabrachial nucleus, juxtatrigeminal region, trigeminal oral and caudal subnuclei, and dorsal medullary reticular formation. These findings suggest that the Su5 receiving JCMS proprioceptive sensation has efferent and afferent connections with multiple brain regions, which are involved in emotional and autonomic functions as well as orofacial motor functions.
Dihydroartemisinin Exhibits Antitumor Activity Toward Human Gastric Cancer Cells Through the Endoplasmic Reticulum Stress Pathway
Authors: Chen Si , Wang Hanlin , Chen Tie , Deng Furong , Li Hongbin , Xia Lixin , Zhang Jian
Published: June 2021

Background: Gastric cancer is the most fatal digestive tract tumor. The current treatment of gastric cancer often causes adverse effects. Dihydroartemisinin (DHA), a first-line antimalarial drug, is a derivative of a compound from a well-known Chinese medicinal plant Artemisia annua. DHA demonstrates antitumor activities toward many different types of cancer while exerts no apparent adverse effects on normal cells, making it a promising lead compound for cancer treatment. DHA induces apoptosis in Gastric cancer cell line 7901 (SGC-7901). However, the exact mechanism of this antitumor activity remains not fully explored. Methods: A CCK-8 assay to detect cell viability with DHA treatment in gastric cancer SGC-7901. The colony formation was visualized by crystal violet staining. The DHA-treatment cells were stained by Annexin-V FITC/PI dye and then subject to cell flow cytometry. The apoptosis was further observed in the Hoechst staining assay. Real-time qPCR was conducted to detect apoptosis-related markers. Western blotting was conducted to detect the protein levels of the endoplasmic reticulum (ER) stress pathway-related proteins. KIRA6, an ER stress pathway inhibitor was applied to find out whether it could reverse the cell death. Results: DHA induced dose-dependent apoptosis in Gastric SGC-7901 cell with an IC50 of about 4 mg/ mL. It significantly increased the proportion of apoptotic cells in a dose-dependent pattern in the Annexin V/PI flow cytometry. Significantly higher percentages of cells with a more prominently stained nucleus were observed in the Hoechst staining assay. In qPCR assay, the mRNA level of Bcl-2 was significantly decreased while that of Bax was significantly increased in a dose-dependent manner after DHA treatment. In the western blot assay, increased Bax and Bim and decreased Caspase 9, Bcl-2 were observed. Consistently, the levels of pro-apoptotic proteins were increased while those of anti-apoptotic ones were decreased as shown in the Human Apoptosis Array assay after DHA treatment. DHA stimulated the expression of GRP78, ATF4, IRE1, CHOP, and phosphorylated c-Jun (p-c-Jun) as revealed in western blotting. The cell death caused by DHA treatment was reversed by KIRA6. Conclusions: DHA exerts its antitumor activity on SGC-7901 cells through the IRE1/c-Jun ER stress pathway.
Ctnna3 Deficiency Promotes Heart Regeneration by Enhancing Cardiomyocyte Proliferation in Neonatal Mice
Authors: zou sha , Dai Wuhou , Li Jifen , Wang Hongyan , Tao Wufan
Published: June 2021

Heart regeneration requires renewal of lost cardiomyocytes. However, the mammalian heart loses its proliferative capacity soon after birth, and the molecular signaling underlying the loss of cardiac proliferation postnatally is not fully understood. Here we report that ablation of Ctnna3, coding for an αT-catenin protein and highly expressed in hearts, accelerated heart regeneration following heart apex resection in neonatal mice. Our results show that Ctnna3 deficiency enhances cardiomyocyte proliferation in hearts from P7 mice by upregulating Yap expression. Our study demonstrates that Ctnna3 deficiency is sufficient to promote heart regeneration and cardiomyocyte proliferation in neonatal mice and indicates that functional interference of α-catenins might help to stimulate myocardial regeneration after injury.
Matrine combined with Osthole inhibited the PERK apoptosis of splenic lymphocytes in PCV2-infected mice model
Authors: Xu Yinlan , Wan Shuangxiu , Sun Panpan , Khan Ajab , Guo Jianhua , Zheng Xiaozhong , Sun Yaogui , Fan Kuohai , Yin Wei , Li Hongquan , Sun Na
Published: June 2021

Background

PCV2 (Porcine circovirus type 2) is one of the major pathogens commonly in pigs, which can cause immunosuppression and apoptosis. Vaccinations and single drugs are not totally prevent and treat PCV2 diseases. We have previously reported that the synergistic anti-PCV2 effects of Matrine and Osthole were better than Matrine or Osthole alone in vitro, Matrine and Osthole were purchased with a clear content, chemical structure and plant origin. This study aimes to evaluate theirs synergistic anti-PCV2 effect and mechanism in Kunming (KM) mice model infected with PCV2. KM mice were randomly divided into 8 groups, namly: normal control group, PCV2 infected group, Matrine combined with Osthole high dose treatment group (40 mg/kg + 12 mg/kg), medium dose treatment group (20 mg/kg + 6 mg/kg), low dose treatment group (10 mg/kg + 3 mg/kg), Matrine treatment group (40 mg/kg), Osthole treatment group (12 mg/kg) and Ribavirin positive control group (40 mg/kg). PCV2 was intraperitoneally (i.p.) injected in all mice except the normal control group. At 5 days post-infection (dpi), mice in different treatment groups were injected i.p. with various doses of Matrine, Osthole and Ribavirin once daily for 5 consecutive days.
Results

The synergistic inhibition effect of Matrine and Osthole on PCV2 replication in mouse liver was significantly stronger than that of Matrine and Osthole alone. The protein expression of GRP78, p-PERK, p-eIF2α, ATF4, CHOP, cleaved caspase-3 and Bax were significantly reduced, but the protein expression of Bcl-2 was significantly increased in Matrine combined with Osthole groups, which alleviated the pathological change caused by PCV2, such as interstitial pneumonia, loss of spleen lymphocytes, infiltration of macrophages and eosinophils.
Conclusions

The synergistic effect of anti-apoptosis was better than that of Matrine and Osthole alone, although both of Matrine and Osthole could also directly inhibited the expression of PCV2 Cap and then inhibited the apoptosis of spleen cells induced by PCV2 Cap through the PERK pathway activated by endoplasmic reticulum (ER) GRP78. These results provide a new insight into controlling PCV2 infection and provide good component prescription candidate for the development of novel anti-PCV2 drugs.
To Explore the Effect of NLR and PLR on Prognosis of Rectal Cancer on the basis of T3 substage, and to draw the related nomogram
Authors: Li Donglin , Wang Shuang , Yang Yongping , Zhao Zeyun , Shang An , Guo Yu , Wang Min
Published: June 2021

Background: Approximately 50% of patients with rectal cancer are classified into T3 stage, and they are positioned as substage by various criteria. These patients with different neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) develop disparate outcomes. We sought to develop and validate nomograms to predict survival in patients with rectal cancer on the basis of T3 substage.Methods: We conducted a retrospective cohort study by collecting 170 cases from China. Individuals with rectal cancer after 2 or more years of follow up after surgery were eligible for inclusion. Candidate predictors consisted of NLR, PLR, T3 substage and clinical characteristics available at the time of rectal cancer diagnosis. The optimal cut-off values for NLR and PLR were determined using X-Tile (Version 3.6.1) software and were determined before statistical analyses. Variables with P values below 0.1 in the univariable analyses were further evaluated using Cox multivariate analysis. Model discrimination was assessed using receiver operating characteristic (ROC) curve and concordance index (C-index) analysis. Results were internally validated using related software.Results: We analyzed data from 170 patients with T3 rectal cancer. The optimal cut-off value of NLR in relation to overall and disease-free survival were 3.1 and 2.9, and that of PLR were 181.9 and 202.7. Among them, postoperative adjuvant chemotherapy, T3 substage, N stage, CA199 and NLR were independent risk factors affecting overall survival（OS）and disease-free survival (DFS). There was no significant difference in survival rate between T3a and T3b, or between T3c and T3d. The final nomograms of 2-year OS (area under the curve,0.886; The c-index,0.870) and 2-year DFS (area under the curve,0.895; The c-index,0.867) were developed according to independent risk factors analyzed by SPSS 26 (SPSS Inc., Chicago, IL, USA) software. The calibration curves showed negligible optimism.Conclusion: We developed nomograms based on postoperative adjuvant chemotherapy, T3 substage, N stage, CA199 and NLR to help identify patients with poor prognosis and to guide individualized therapy.
Repurposing the Combination Drug of Favipiravir, Hydroxychloroquine and Oseltamivir as a Potential Inhibitor Against SARS-CoV-2: A Computational Study
Authors: Yadav Pooja , CHOWDHURY PAPIA
Published: June 2021

The virus SARS-CoV-2 has created a situation of global emergency all over the world from the last few months. We are witnessing a helpless situation due to COVID-19 as no vaccine or drug is effective against the disease. In the present study, we have tested the repurposing efficacy of some currently used combination drugs against COVID-19. We have tried to understand the mechanism of action of some repurposed drugs:Favipiravir (F), Hydroxychloroquine (H) and Oseltamivir (O). The ADME analysis have suggested strong inhibitory possibility of F, H, O combination towards receptor protein of 3CLpro of SARS-CoV-2 virus. The strong binding affinity, number of hydrogen bond interaction between inhibitor, receptor and lower inhibition constant computed from molecular docking validated the better complexation possibility of F + H + O:3CLprocombination. Various thermodynamical output from Molecular dynamics (MD) simulations like potential energy (Eg), temperature (T), density, pressure, SASA energy, interaction energies, Gibbs free energy (ΔGbind) etc., also favored the complexation between F + H + O and CoV-2 protease. Our in-silico results have recommended the strong candidature of combination drugs Favipiravir, Hydroxychloroquine and Oseltamivir as a potential lead inhibitor for targeting SARS-CoV-2 infections.
Prevalence and Time-Course of Diaphragmatic Dysfunction Following Lung Resection: A Repeated Ultrasonic Assessment
Authors: Daniel Matthieu , Lang Elodie , Huynh Thi Mum , Martin Julien , Brebion Myriam , Guessous Karim , Zlotnik Diane , Gouzien Laura , Chaouch Oussama , Delval Paul , Ferraris Arnaud , Pimpec-Barthes Françoise Le , Cholley Bernard
Published: June 2021

BACKGROUND: There is little information regarding diaphragmatic dysfunction (DD) following thoracic surgery. Ultrasound allows for non-invasive repeated assessments of diaphragmatic excursion (DE) and thickening fraction (DTF) at the bedside, reflecting DD. We aimed at determining the prevalence of DD and the time-course of DE and DTF following elective thoracic surgery. Secondary endpoints included the association between DD and postoperative complications. METHODS: We led a prospective, single center, observational study in consecutive patients undergoing thoracic surgery. DE and DTF were measured by two observers blinded to each other at 3 different time-points: prior to surgery (D-1), immediately after extubation (D0) and on postoperative day 3 (D3). The changes in excursion and thickening fraction of both hemi-diaphragms over time were compared according to the side (operated or non-operated) using a two-way ANOVA. The association with postoperative complications was assessed using logistic regression.RESULTS: Fifty patients, 60% males, aged 60±15 years were included. Surgical procedures included lobectomy (n=30), wedge-resection (n=17) or pneumonectomy (n=3). DD was highly prevalent after thoracic surgery and was observed on the operated side (or both sides) in, at least, 68% of patients immediately after surgery (D0). Among those patients, 46% still had this DD on the operated side on D3. On the operated side, we observed a decrease in DE and DTF at D0 (-0.71±0.12mm, P<0.05; -44±30%, P<0.05) and D3 (-0.82±0.19mm, P<0.05; -39±19%, P<0.05) with respect to values at D-1. On the non-operated side, mean values for DE and DTF did not change significantly over the study period. Persistent DD on the operated side, defined by a DD present at the two postoperative time-points, was associated with an increased risk of lung infection (P=0.001), ICU-admission (P=0.04) according to univariate analysis and a prolonged length in hospital (OR:1.3, 95% CI [1.1-1.7], P=0.016) according to multivariate analysis.CONCLUSIONS: Diaphragmatic Dysfunction (DD) was very common after thoracic surgery, mainly concerned the operated side and was associated with an increase in the diaphragmatic excursion on the non-operated side. When this dysfunction failed to regress within 72 hours, it was associated with a significant increase in the length of hospital stay.
Clinical effect of individualized 3D printing guide assisted placement of upper cervical pedicle screw
Authors: Niu Guoqi , Li Chao , Bai Jianzhong , Zhou Gong , Liu Lutan , Zhou Qiankun , Chen Hui , Nie Hu , Liu Tao , Jiang Weili , Cheng Jiawei , Zhao Baoyin , Zhu Jun , Yu Ruochen
Published: June 2021

Objective
To investigate the clinical effect of individualized 3D printing guide assisted upper cervical pedicle screw placement.
Methods
Eighteen patients with upper cervical spine injury requiring surgical treatment were included in our hospital from May 2010 to May 2019. These patients were divided into guide plate assisted screw implantation group (Group A, N = 10) and traditional operation group (Group B, N = 8). All patients were followed up for more than 6 months. Screw implant accuracy, cervical spine JOA score, ASIA score, VAS score, operation time, intraoperative blood loss were compared between the two groups.
Result
A total of 72 atlantoaxial pedicle screws were implanted, 40 in group A and 32 in group B. The accuracy rate of nail implantation was 97.50% in group A and 81.25% in group B (P < 0.05). The operation time in group A (189.7 ± 16.1 mins) and group B (242.1 ± 23.2 mins), P < 0.05. The intraoperative blood loss in group A (216.0 ± 49.7 ml) and group B (385.0 ± 23.5 ml), P < 0.05. The intraoperative fluoroscopic times was 8.7 ± 1.1 in group A and 30.0 ± 3.3 in group B (P < 0.05). Besides, the JOA, Asia and VAS scores of the two groups at one week after operation and the last follow-up were significantly different from those before operation. One week after operation, the JOA, Asia and VAS scores of group A were significantly better than those of group B, but there was no significant difference between the two groups at the last follow-up.
Conclusions
individualized 3D printing guide assisted placement of upper cervical pedicle screw can significantly improve the accuracy of screw implantation and postoperative function of patients, reduce the times of X-ray fluoroscopy, operation time, and intraoperative blood loss, which is a safe and effective approach and worthy of clinical promotion.
Assessment on the Progressive Collapse Resistance of a Long-Span Curved Spatial Grid Structure With Main Trusses
Authors: Zhou Guangpan , Song Qianen , Li Aiqun , Shen Shungao , Zhou Qing , Wang Bin , Zhang Yuye
Published: June 2021

The present work is aimed at studying the progressive collapse resistance of the terminal building of Zhongchuan Airport in Lanzhou, China, which is a long-span curved spatial grid structure with main trusses. Firstly, the finite element model was built using MSC.Marc software. The alternate load path method (AP method) was used to simulate the initial failure of component. An improved method of zoned concept judgment and sensitivity analysis was proposed to determine the key components. Then, the initial failure components were removed individually on the course of analyzing. The responses of remaining structure were calculated using nonlinear dynamic analysis method. According to the results, the structure has a strong ability of resisting progressive collapse, though the structural responses are significant when removing the concrete filled steel tubular column directly supporting the roof at cantilever end. The maximum vertical displacement reaches 10 m. Moreover, the proposed method can avoid omitting the key components having significant influence on structural progressive collapse resistance. In addition, the influences brought by the cross-sectional sizes of chord and web members were investigated through conducting parametric analysis. The research can provide references for the structural optimization and safety control of similar long-span spatial structures.
Post-traumatic Growth in Psychosis: A Systematic Review and Narrative Synthesis
Authors: Ng Fiona , Ibrahim Nashwa , Franklin Donna , Jordan Gerald , Lewandowski Felix , Fang Fan , Roe David , Rennick-Egglestone Stefan , Newby Christopher , Hare-Duke Laurie , Llewelyn-Beardsley Joy , Yeo Caroline , Slade Mike
Published: June 2021

Background and Objective: People with psychosis report experiences of highly traumatic events. Positive change or post-traumatic growth (PTG) can occur as a result of traumatic experiences. Yet there is limited attention on PTG in psychosis, possibly due to the negative impact of psychotic symptoms on functioning and quality of life. The aim of this review was to identify relationships between PTG and psychosis and to develop a conceptual framework synthesising facilitators of PTG in psychosis.Method: Ten electronic databases were searched in seven languages, whilst five journals and grey literature were searched in English. Quantitative studies were eligible if examining the association or temporal relationship between PTG and one or more variables. Qualitative studies were eligible if describing PTG arising from experiences of psychosis. Findings from quantitative papers were grouped by their analysis method, whilst a narrative synthesis was conducted of findings in qualitative papers.Results: 37 papers were included. Mediators of PTG in psychosis included meaning in life, coping self-efficacy, core beliefs, and self-reported recovery. Seven facilitators of PTG in psychosis were identified: Personal identity and strength, Receiving support, Opportunities and possibilities, Strategies for coping, Perspective shift, Emotional experience, and Relationships, giving the acronym PROSPER.Conclusions: Individuals with psychosis can grow from traumatic experiences. Clinicians can support PTG through the provision of trauma-informed care that supports positively valued identity changes. For researchers, the findings provide an evidence-based theoretical framework for conceptualising PTG, which can be validated through longitudinal cohort studies and underpin the development of new clinical interventions.
Generalized Probabilistic Theories in a New Light
Authors: Shaiia Raed
Published: June 2021

In this paper we will present a modified formulation of generalized probabilistic theories that will always give rise to the structure of Hilbert space of quantum mechanics,
in any finite outcome space, and give the guidelines to how to extend this work to
infinite dimensional Hilbert spaces. Moreover, this new formulation which we will call
extended operational-probabilistic theories, applies not only to quantum systems, but
also equally well to classical systems, without violating Bell’s theorem, and at the same
time solves the measurement problem. This is why we will see that the question of
why our universe is quantum mechanical rather than classical is misplaced. The only
difference that exists between a classical universe and a quantum mechanical one lies
merely in which observables are compatible and which are not. Besides, this extended
probability theory which we present in this paper shows that it is non-determinacy,
or to be more precise, the non-deterministic description of the universe, that makes
the laws of physics the way they are. In addition, this paper shows us that what used
to be considered as purely classical systems and to be treated that way are in fact
able to be manipulated according to the rules of quantum mechanics –with this new
understanding of these rules- and that there is still a possibility that there might be a
deterministic level from which our universe emerges, which if understood correctly, may
open the door wide to applications in areas such as quantum computing. In addition
to all that, this paper shows that without the use of complex vector spaces, we cannot
have any kind of continuous evolution of the states of any system.
Mycobacterium species on the cutaneous microbiome of very preterm neonates
Authors: Shah Pritik A , Govindarajan Varun , Rangaiah Ambica , Diggikar Shivshankar , Devadas Sahana , Chunchanur Sneha K , Shankar Sathyanarayan Muthur
Published: June 2021

The neonatal skin microbiome consists of all the genomes and genetic products of microorganisms harbouring on the skin of babies. Host and the microbiota develop a harmonious environment resulting in symbiosis. Any disruption of this environment could lead to pathological disease. We conducted this study to understand the neonatal skin microbiome of very preterm neonates admitted to NICU at a tertiary health care setting before and after Kangaroo Mother Care. Next Generation sequencing showed relative abundance for Mycobacterium tuberculosis in 83.33% & 66.67% (p0.285) and Mycobacteroides abscessus in 100% & 93.33%( p0.303) of the very preterm neonates on the skin microbiome before and after KMC respectively. The mere presence of Mycobcaterium species as commensals or as potential pathogens, is alarming due to the risk of early exposure and incidence of tuberculosis right from birth. These findings, in our view, are the first findings to be established in such a setting.
A straightforward and Lagrangian proof of the Einsteinian equivalence between the mass and the inernal energy (i.e. rest energy)
Authors: Berké Özgür
Published: June 2021

I propose a Lagrangian proof of Einstein's well-known law that the mass of any system is its internal energy. The interest of this proof is to show how the distinction between internal degrees of freedom and the center of mass appears in the Lagrangian formalism. Considering that the Lagrangian depends on a particular set of variables for the internal degree of freedom, I show in a standard Lagrangian way how one can naturally find the desired law. This proof does not use the tensors of energy-momentum and can be easily used by students familiar with Lagrangian mechanics and the basis of Special Relativity. I apply the method for the particles and for the field, using the scalar field for simplification but it is easy to generalize for other fields (containing only the first derivative in Lagrangian). I give the example for the gravitation field. The method permits us to observe a strong relation between the Einstein’s E=mc² law and his other famous law of the time dilation. I carefully analyze the meaning of the particular choice of the variable and showing a sort of a modified speed addition formula without contradicting, of course, the one of Einstein (& Poincaré). I also try to untangle, with this point of view, the relation between the mass and the origin of the energy scale. Finally I analyze the reason why in Newtonian mechanic we don’t have a such law. In the annex I give some elements of the Hamiltonian analysis checking again the coherence of the particular set of variables and I apply this way of thinking to the old Lorentz-Poincaré model of the electron (useful for an explicit classical renormalization of the mass).
SPC212 Human Mesothelioma Cell Underwent Apoptosis, Oxidative Stress, Morhological Deformation Following Astaxanthin Treatment
Authors: Kacar Sedat , Sevimli Tuğba S. , Sahinturk Varol
Published: June 2021

Although astaxanthin (ASX) is one type of caretonoids, it is more bioactive compound than other carotenoids. Despite its utilization against different cancer types, effect of ASX on mesothelioma has yet to be well-studied. In this study, our goal is to ascertain how ASX will affect SPC212 human mesothelioma cells. First, the effective doses of ASX against SPC212 cells was uncovered by MTT test. Thereafter, with flow cytometry analysis, Annexin-V and caspase 3/7 assay was implemented for the evaluation of apoptotic cell death and oxidative stress test was carried out to determine how the free radicals changed. Ultimately, the cells’ morphology was examined under light microscope. The effective doses of ASX were found as 50,100 and 200 µM. In Annexin V assay, the total apoptosis increased to around 12%, 30% and %45 with increasing doses of ASX. In caspase 3/7 assay, the total apoptosis was around %25 and %38 at 100 and 200 µM. In oxidative stress analysis, ROS positive cells rose from 4.54 at the lowest dose to 86.95 at the highest dose. In morphological analysis, cellular shrinkage, decrease in cell density, swelling and vacuolations in some cells, membrane blebbing and apoptotic bodies are observed in ASX-treated cells. To conclude, the current study provided insights into the efficacy and effects of ASX against SPC212 mesothelioma cells regarding morphology, proliferation and cell death for the future studies.
Analysis of the stability of alanine aminotransferase (ALT) levels in donor samples
Authors: Todoroff S.S.
Published: June 2021

This study was designed to 1) analyze the stability of serum alanine aminotransferase (ALT) activity in nonseparated donor samples stored at room temperature (RT) over 72 hours and 2) compare ALT levels of paired samples stored at RT and 4 ° C over the same time period. The study showed that mean ALT activities for samples stored at RT increased at all assay times and that those stored at 4 ° C decreased (0.54 IU/L over 72 hours). Although the mean increase in activity of the RT samples over 72 hours (1.45 IU/L) was statistically significant, it was of little practical significance. For example, based on the frequency distribution of the 311 RT samples from this study, and using a cut-off value of 69 IU/L, only one unit of blood would have been eliminated based on the difference between time zero and 72 hours. It was concluded that RT would be the storage of choice for 72 hours, since the tendency of ALT levels to decrease during storage at 4 ° C could make possible the inclusion of borderline donor units in the blood supply.
A case report: unusual Gerbich antibody in a patient with sickle cell anemia
Authors: Gorman M. , Woody B.
Published: June 2021

A patient whose red blood cells (RBCs) typed as Ge:2,3 produced an alloantibody to a high-frequency antigen in the Gerbich system. This antibody was shown to be nonreactive with Ge: −2, −3 RBCs using adsorption-elution studies. A monocyte monolayer assay (MMA) suggested that transfusion of Ge:2,3 RBCs to this patient would have reduced in vivo survival.
Auberger red cell antigens are not part of the Kell, Colton, or Dombrock blood group systems
Authors: Tippett P. , Daniels G.L. , Lomas C. , Green C.A.
Published: June 2021

Since 1981, red cell samples from families were tested with anti-Aua and, since 1986, with both anti-Aua and anti-Aub in an attempt to elevate Auberger to a blood group system status. The results show that Auberger is not part of the Kell (five families), Colton (three families), or Dombrock (two families) blood group systems. Exclusion from four more systems (Di, Yt, LW, Ch;Rg) is required before system status may be claimed.
Recovery of costs for special procedures done in reference laboratories
Authors: Rolih S.
Published: June 2021

In recent years, blood bank laboratories have been encouraged to look at special procedures that might generate needed revenues. Laboratories that elect to offer special procedures to recover costs or to generate revenue should evaluate each test carefully. Areas to be considered are the projected demand tor the test, proficiency of present laboratory staff, cost of reagents and equipment, and assay time relative to labor cost.