bluuebunny/crossref_metadata_2025 huggingface dataset:
Variation of the silicon optical parameters after rapid heat treatment
Authors: Anishchik Victor M. , Harushka Valiantzina A. , Pilipenka Uladzimir A. , Ponariadov Vladimir V. , Saladukha Vitali A. , Omelchenko Anna A. Omelchenko
Published: November 2021

The results of the effect of rapid heat treatment on the optical characteristics of a silicon wafer surface in the region of the G-point in the Brillouin zone are presented for different types of silicon wafers conductivity, their doping level, the covalent radii of dopants and the crystallographic orientation of the wafer surface. The absorption coefficient and refractive index of the initial 100 mm diameter samples KDB-12 <100>, KDB-10 <111>, KDB-0.005 <100> and KES-0.015 <100>, underwent standard chemical-mechanical polishing, was measured on a Uvisel 2 ellipsometer (Horiba Scientific, France) in the spectral range 0.6–6.0 eV (200–2100 nm) before and after rapid heat treatment. The incidence angle of the light beam was 70° relative to the sample plane. It is shown that the changes in the optical characteristics of the silicon surface in the spectral region of the location of the G-point in the Brillouin zone after rapid heat treatment is due to a decrease in the surface deformation potential due to solid-phase recrystallisation of the mechanically damaged layer. It has been established that carrying out the rapid heat treatment of silicon samples with a high boron concentration leads to a more significant decrease in the refractive index and absorption compared with silicon with a low boron concentration, due to an increase in the depletion of the silicon surface with boron as a result of diffusion processes at the silicon – silicon dioxide interface.
SYNTHESIS AND SPECTRAL CHARACTERISTICS OF Cu(II), Ni(II) AND Fe(III) NANOSIZED COM­PLEXES ON THE SURFACE OF CARBON QUANTUM DOT
Authors: Ogenko Volodymyr , Orysyk Svitlana , Kharkova Ljudmila , Yanko Oleg , Chen Dongchu
Published: November 2021

Processes of interaction between carbon quantum dots (CQDs) and solutions of Cu(II) Ni(II) and Fe(III) chlorides in the surface layer have been investigated by electron and IR spectroscopy.

When hydrochloric acid is added to the aqueous suspension of CQDs, there is a signi­ficant batochromic shift of the average absorption band (AB) by 1285 cm-1 with a decrease in its intensity to ε = 23.39. The presence of copper in the suspension of CQDs at room temperature leads to a decrease in the intensity of this AB (ε = 21.80), which indicates the interaction of CQDs with metal ions.

After heating the suspension for 1 and 3 hours, the gypsochromic shift of this ABs (by 335 cm-1) to 27790 cm-1 with a decrease in intensity depending on the heating time was recorded. Such changes in the UV–Vis Spectrum are due to the redistribution of the electron density of electron transitions n → π *due to the coordination of functional groups with metal ions and the appearance of transitions with charge transfer from ligand to metal (CQD→Cu2+).

When heating the suspensions significantly increases the absorption intensity of the AB at 22070 cm-1: from ε = 4.59 to ε = 6.75, which indicates the formation of transitions with charge transfer from ligand to metal (ChTLM) due to the coordination of copper ions with CQD.

In the absorption spectra of CQD suspensions with NiCl2 before heating, a hypsochromic shift of AB at 27305 cm-1 by 150 cm-1 and an increase in the intensity of its to ε = 4.95 were registered. That is, Ni(II) ions also form coordination bonds with functional groups on the periphery of the CQD.

After heating hydrochloric acid suspensions of CQD with FeCl3, in contrast to the chlorides of previous metals, in the UV-region registered shoulder-shaped AB at 31545 cm-1, the intensity of which increases with heating time (from ε = 9.59 to ε = 12.10), and in the visible region, a weakly intense shoulder-shaped AB at 19345 cm-1 (ε = 3.71 and 4.58), associated with the presence of dd-electron transitions in the metal ion.

Such changes in the absorption spectra are explained by the fact that iron may interact with CQD in different ways (in addition to coordination with functional donor groups, the formation of coordination bonds with the π-electron system of conjugated CQDs bonds), which leads to additional weak shoulder-like AB at 31545 cm-1.

The IR-spectra data of CQDs showed the presence of a number of characteristic ABs for functionalized CQDs: ν(N–H) at 3260 сm1, (C=O) at 1830, 1840 and 1850 сm1, –С=O(NH) at 1770 сm1, ν(C=N) at 1680 and δ(N–H) at 1640 сm1 and 320-360 см-1 СП ν(Cu–Cl, Ni–Cl, Fe–Cl), which confirms the coordination of metals on the surface of CQDs.
Communicating Climate Risk: A Toolkit
Authors: Walton Jo Lindsay , Levontin Polina , Barons Martine J. , Workman Mark , Mackie Erik , Kleineberg Jana
Published: November 2021

The Communicating Climate Risk toolkit draws together best practice on the effective communication of climate information from across STEM, social sciences, and arts and humanities. It provides users with insights, recommendations, and tools for all forms of climate-related communication and decision-making, and identifies open problems.
Perspiration modelling of the human foot
Authors: Breward Chris , Lacey Andrew
Published: November 2021

SATRA Technology wishes to use an “artificial foot” to replace those of live volunteers in comfort tests for shoes. The artificial foot has the size and shape of a real foot and is made of a heated aluminium core surrounded by a polyurethane and a porous-rubber layer. The tests involve equipping the artificial foot with socks and the shoes or boots to be tested, and subjecting it to controlled environments for periods of up to several hours. In this report, we build simple models for heat and moisture flow in an idealised foot. We consider two cases: “hot and sticky” (sweat layer present) and “cool and dry”. We then build simple models for the wicking of liquid and temperature distribution in a sock. We find that wicking tends to lead to a uniform level of saturation across the sock.
The Influence Of The Leadership And Character Of A Pastor On The Spiritual Growth Of The Congregation At The GPdI Alfa Omega Church.
Authors: Purnomo Setya Hari , Wibowo Daniel Ari
Published: November 2021

Leadership is a task given by Jesus Christ to Christians through His Church. Leaders are needed by every human being to achieve happiness and prosperity in all fields. Thus the Church has an important role in improving leadership for the spiritual growth of God's congregation because through qualified leaders people can understand correctly how to actually follow God. With this quality leader, people can understand who and for what God created them. Seeing the existence of a congregation that always needs guidance in spiritual growth, and that requires someone who can accompany The congregation is a leader or shepherd who is often referred to as the Pastor of the congregation. And not many Christian ministers or often referred to as Congregational Pastors have these criteria. So that they cannot be an example in the lives of the people they lead. So there are criteria set out in the Bible to become a Christian leader with quality and character. A leader is someone who deserves to be a role model for others because the leader has good character and becomes a leader blessing for the church he leads.
Innate Lymphoid Cells and Natural Killer Cells in Bacterial Infections: Function, Dysregulation, and Therapeutic Targets
Authors: Elemam Noha Mousaad , Ramakrishnan Rakhee K. , Hundt Jennifer E. , Halwani Rabih , Maghazachi Azzam A. , Hamid Qutayba
Published: November 2021

Infectious diseases represent one of the largest medical challenges worldwide. Bacterial infections, in particular, remain a pertinent health challenge and burden. Moreover, such infections increase over time due to the continuous use of various antibiotics without medical need, thus leading to several side effects and bacterial resistance. Our innate immune system represents our first line of defense against any foreign pathogens. This system comprises the innate lymphoid cells (ILCs), including natural killer (NK) cells that are critical players in establishing homeostasis and immunity against infections. ILCs are a group of functionally heterogenous but potent innate immune effector cells that constitute tissue-resident sentinels against intracellular and extracellular bacterial infections. Being a nascent subset of innate lymphocytes, their role in bacterial infections is not clearly understood. Furthermore, these pathogens have developed methods to evade the host immune system, and hence permit infection spread and tissue damage. In this review, we highlight the role of the different ILC populations in various bacterial infections and the possible ways of immune evasion. Additionally, potential immunotherapies to manipulate ILC responses will be briefly discussed.
MFAP4 Deficiency Attenuates Angiotensin II-Induced Abdominal Aortic Aneurysm Formation Through Regulation of Macrophage Infiltration and Activity
Authors: Pilecki Bartosz , de Carvalho Paulo V. S. D. , Kirketerp-Møller Katrine L. , Schlosser Anders , Kejling Karin , Dubik Magdalena , Madsen Nicklas P. , Stubbe Jane , Hansen Pernille B. L. , Andersen Thomas L. , Moeller Jesper B. , Marcussen Niels , Azevedo Vasco , Hvidsten Svend , Baun Christina , Shi Guo-Ping , Lindholt Jes S. , Sorensen Grith L.
Published: November 2021

Objective: Abdominal aortic aneurysm (AAA) is a common age-related vascular disease characterized by progressive weakening and dilatation of the aortic wall. Microfibrillar-associated protein 4 (MFAP4) is an extracellular matrix (ECM) protein involved in the induction of vascular remodeling. This study aimed to investigate if MFAP4 facilitates the development of AAA and characterize the underlying MFAP4-mediated mechanisms.

Approach and Results: Double apolipoprotein E- and Mfap4-deficient (ApoE−/−Mfap4−/−) and control apolipoprotein E-deficient (ApoE−/−) mice were infused subcutaneously with angiotensin II (Ang II) for 28 days. Mfap4 expression was localized within the adventitial and medial layers and was upregulated after Ang II treatment. While Ang II-induced blood pressure increase was independent of Mfap4 genotype, ApoE−/−Mfap4−/− mice exhibited significantly lower AAA incidence and reduced maximal aortic diameter compared to ApoE−/− littermates. The ApoE−/−Mfap4−/− AAAs were further characterized by reduced macrophage infiltration, matrix metalloproteinase (MMP)-2 and MMP-9 activity, proliferative activity, collagen content, and elastic membrane disruption. MFAP4 deficiency also attenuated activation of integrin- and TGF-β-related signaling within the adventitial layer of AAA tissues. Finally, MFAP4 stimulation promoted human monocyte migration and significantly upregulated MMP-9 activity in macrophage-like THP-1 cells.

Conclusion: This study demonstrates that MFAP4 induces macrophage-rich inflammation, MMP activity, and maladaptive remodeling of the ECM within the vessel wall, leading to an acceleration of AAA development and progression. Collectively, our findings suggest that MFAP4 is an essential aggravator of AAA pathology that acts through regulation of monocyte influx and MMP production.
Adrenocortical Tumors in Children With Constitutive Chromosome 11p15 Paternal Uniparental Disomy: Implications for Diagnosis and Treatment
Authors: Pinto Emilia Modolo , Rodriguez-Galindo Carlos , Lam Catherine G. , Ruiz Robert E. , Zambetti Gerard P. , Ribeiro Raul C.
Published: November 2021

Pediatric adrenocortical tumors (ACTs) are rare and heterogeneous. Approximately 50% of children with ACT carry a germline TP53 variant; however, the genetic underpinning of remaining cases has not been elucidated. In patients having germline TP53 variants, loss of maternal chromosome 11 and duplication of the paternal copy [paternal uniparental disomy, (UPD)] occurs early in tumorigenesis and explains the overexpression of IGF2, the hallmark of pediatric ACT. Beckwith-Wiedemann syndrome (BWS) is also associated with overexpression of IGF2 due to disruption of the 11p15 loci, including segmental UPD. Here, we report six children with ACT with wild type TP53 and germline paternal 11p15 UPD. Median age of five girls and one boy was 3.2 years (range 0.5-11 years). Two patients met the criteria for BWS before diagnosis of ACT. However, ACT was the first and only manifestation of paternal 11p15 UPD in four children. Tumor weight ranged from 21.5 g to 550 g. Despite poor prognostic features at presentation, such as pulmonary metastasis, bilateral adrenal involvement, and large tumors, all patients are alive 8-21 years after cancer diagnosis. Our observations suggest that children with ACT and wild type TP53, irrespective of their age, should be screened for germline abnormalities in chromosome 11p15.
The Transgenerational Transmission of the Paternal Type 2 Diabetes-Induced Subfertility Phenotype
Authors: Zatecka Eva , Bohuslavova Romana , Valaskova Eliska , Margaryan Hasmik , Elzeinova Fatima , Kubatova Alena , Hylmarova Simona , Peknicova Jana , Pavlinkova Gabriela
Published: November 2021

Diabetes is a chronic metabolic disorder characterized by hyperglycemia and associated with many health complications due to the long-term damage and dysfunction of various organs. A consequential complication of diabetes in men is reproductive dysfunction, reduced fertility, and poor reproductive outcomes. However, the molecular mechanisms responsible for diabetic environment-induced sperm damage and overall decreased reproductive outcomes are not fully established. We evaluated the effects of type 2 diabetes exposure on the reproductive system and the reproductive outcomes of males and their male offspring, using a mouse model. We demonstrate that paternal exposure to type 2 diabetes mediates intergenerational and transgenerational effects on the reproductive health of the offspring, especially on sperm quality, and on metabolic characteristics. Given the transgenerational impairment of reproductive and metabolic parameters through two generations, these changes likely take the form of inherited epigenetic marks through the germline. Our results emphasize the importance of improving metabolic health not only in women of reproductive age, but also in potential fathers, in order to reduce the negative impacts of diabetes on subsequent generations.
Unravelling Checkpoint Inhibitor Associated Autoimmune Diabetes: From Bench to Bedside
Authors: Wu Linda , Tsang Venessa H. M. , Sasson Sarah C. , Menzies Alexander M. , Carlino Matteo S. , Brown David A. , Clifton-Bligh Roderick , Gunton Jenny E.
Published: November 2021

Immune checkpoint inhibitors have transformed the landscape of oncological therapy, but at the price of a new array of immune related adverse events. Among these is β-cell failure, leading to checkpoint inhibitor-related autoimmune diabetes (CIADM) which entails substantial long-term morbidity. As our understanding of this novel disease grows, parallels and differences between CIADM and classic type 1 diabetes (T1D) may provide insights into the development of diabetes and identify novel potential therapeutic strategies. In this review, we outline the knowledge across the disciplines of endocrinology, oncology and immunology regarding the pathogenesis of CIADM and identify possible management strategies.
Mate Choice, Sex Roles and Sexual Cognition in Vertebrates: Mate Choice Turns Cognition or Cognition Turns Mate Choice?
Authors: Fuss Theodora
Published: November 2021

The idea of “smart is sexy,” meaning superior cognition provides competitive benefits in mate choice and, therefore, evolutionary advantages in terms of reproductive fitness, is both exciting and captivating. Cognitively flexible individuals perceive and adapt more dynamically to (unpredictable) environmental changes. The sex roles that females and males adopt within their populations can vary greatly in response to the prevalent mating system. Based on how cognition determines these grossly divergent sex roles, different selection pressures could possibly shape the (progressive) evolution of cognitive abilities, suggesting the potential to induce sexual dimorphisms in superior cognitive abilities. Associations between an individual’s mating success, sexual traits and its cognitive abilities have been found consistently across vertebrate species and taxa, providing evidence that sexual selection may well shape the supporting cognitive prerequisites. Yet, while superior cognitive abilities provide benefits such as higher feeding success, improved antipredator behavior, or more favorable mate choice, they also claim costs such as higher energy levels and metabolic rates, which in turn may reduce fecundity, growth, or immune response. There is compelling evidence in a variety of vertebrate taxa that females appear to prefer skilled problem-solver males, i.e., they prefer those that appear to have better cognitive abilities. Consequently, cognition is also likely to have substantial effects on sexual selection processes. How the choosing sex assesses the cognitive abilities of potential mates has not been explored conclusively yet. Do cognitive skills guide an individual’s mate choice and does learning change an individual’s mate choice decisions? How and to which extent do individuals use their own cognitive skills to assess those of their conspecifics when choosing a mate? How does an individual’s role within a mating system influence the choice of the choosing sex in this context? Drawing on several examples from the vertebrate world, this review aims to elucidate various aspects associated with cognitive sex differences, the different roles of males and females in social and sexual interactions, and the potential influence of cognition on mate choice decisions. Finally, future perspectives aim to identify ways to answer the central question of how the triad of sex, cognition, and mate choice interacts.
Genome-Wide Identification of Circular RNAs Potentially Involved in the Biosynthesis of Secondary Metabolites in Salvia miltiorrhiza
Authors: Jiang Mei , Chen Haimei , Du Qing , Wang Liqiang , Liu Xinyue , Liu Chang
Published: November 2021

Circular RNAs (circRNAs) play various roles in cellular functions. However, no studies have been reported on the potential involvement of circRNAs in the biosynthesis of secondary metabolites in plants. Here, we performed a genome-wide discovery of circRNAs from root, stem and leaf samples of Salvia miltiorrhiza using RNA-Seq. We predicted a total of 2,476 circRNAs with at least two junction reads using circRNA_finder and CIRI, of which 2,096, 151 and 229 were exonic, intronic and intergenic circRNAs, respectively. Sequence similarity analysis showed that 294 out of 2,476 circRNAs were conserved amongst multiple plants. Of the 55 predicted circRNAs, 31 (56%) were validated successfully by PCR and Sanger sequencing using convergent and divergent primer pairs. Alternative circularisation analysis showed that most parental genes produced two circRNAs. Functional enrichment analyses of the parental genes showed that the primary metabolism pathways were significantly enriched, particularly the carbon metabolism. Differential expression analysis showed that the expression profiles of circRNAs were tissue-specific. Co-expression analysis showed 275 circRNAs, and their parental genes had significantly positive correlations. However, 14 had significantly negative correlations. Weighted gene co-expression network analysis showed that nine circRNAs were co-expressed with four modules of protein-coding genes. Next, we found 416 exonic circRNAs with miRNA-binding sites, suggesting possible interactions between circRNAs and miRNAs. Lastly, we found six validated circRNAs, namely, SMscf2473-46693-46978, SMscf3091-29256-29724, SMscf16-111773-112193, SMscf432-13232-13866, SMscf7007-10563-10888 and SMscf1730-1749-2013, which were originated from the genes involved in the biosynthesis of secondary metabolites. Their parental genes were acetyl-CoA C-acetyltransferase 1 (SmAACT1), 1-deoxy-d-xylulose-5-phosphate synthase 2 (SmDXS2), 4-hydroxy-3-methylbut-2-enyl diphosphate reductase 1 (SmHDR1), kaurene synthase-like 2 (SmKSL2), DWF4 and CYP88A3, respectively. In particular, the correlation coefficient of SMscf2473-46693-46978 and SmDXS2 gene was 0.86 (p = 0.003), indicating a potential interaction between this pair of circRNA and its parent gene. Our results provided the first comprehensive catalogue of circRNAs in S. miltiorrhiza and identified one circRNA that might play important roles in the biosynthesis of secondary metabolites.
Hsa_circRNA_103124 Upregulation in Crohn’s Disease Promotes Cell Proliferation and Inhibits Autophagy by Regulating the Hsa-miR-650/AKT2 Signaling Pathway
Authors: Yin Juan , Tong Fuyi , Ye Yulan , Hu Tong , Xu Lijuan , Zhang Liping , Zhu Jianyun , Pang Zhi
Published: November 2021

Circular RNAs (circRNAs) play important roles in the pathogenesis of Crohn’s disease (CD). We discovered that hsa_circRNA_103124 was upregulated in CD patients in our previous study. Nonetheless, the function of hsa_circRNA_103124 is unclear. In this study, hsa_circRNA_103124 was predicted to interact with hsa-miR-650. Gene Ontology (GO) and pathway analyses identified AKT serine/threonine kinase 2 (AKT2) as the downstream target protein of hsa-miR-650. Activated AKT2 inhibits autophagy, but promotes cell proliferation. Recent studies suggest that the inhibition of autophagy is one of the mechanisms of CD pathogenesis. Therefore, we inferred that hsa_circRNA_103124 might regulate autophagy and proliferation by targeting AKT2 as a sponge for hsa-miR-650. Here, quantitative reverse transcription PCR (RT-QPCR) results revealed that upregulated hsa_circRNA_103124 expression in patients with CD was negatively correlated with hsa-miR-650 expression but positively correlated with the white blood cell count and calprotectin levels. TSC complex subunit 1 (TSC1), one of the proteins upstream of autophagy was downregulated in patients with CD. Consisting with the bioinformatics prediction, it was verified that hsa_circRNA_103124 targeted to hsa-miR650 by fluorescence in situ hybridization (FISH) and luciferase reporter assays. A hsa-miR-650 inhibitor reversed the promotion of rapamycin-induced autophagy and the inhibition of cell proliferation by the hsa_circRNA_103124 siRNA. However, hsa-miR-650 mimics reversed the inhibition of rapamycin-induced autophagy and the promotion of cell proliferation through hsa_circRNA_103124 overexpression. These results indicate that hsa_circRNA_103124 upregulation in patients with CD promotes cell proliferation and inhibits autophagy by regulating the hsa-miR-650/AKT2 signaling pathway.
Metallothionein 1: A New Spotlight on Inflammatory Diseases
Authors: Dai Hanying , Wang Lu , Li Lingyun , Huang Zhong , Ye Liang
Published: November 2021

MT1 has been demonstrated to be an essential stress protein in maintaining physiological balance and regulating immune homeostasis. While the immunological involvement of MT1 in central nervous system disorders and cancer has been extensively investigated, mounting evidence suggests that MT1 has a broader role in inflammatory diseases and can shape innate and adaptive immunity. In this review, we will first summarize the biological features of MT1 and the regulators that influence MT1 expression, emphasizing metal, inflammation, and immunosuppressive factors. We will then focus on the immunoregulatory function of MT1 on diverse immune cells and the signaling pathways regulated by MT1. Finally, we will discuss recent advances in our knowledge of the biological role of MT1 in several inflammatory diseases to develop novel therapeutic strategies.
Open-Label Placebo Treatment for Acute Postoperative Pain (OLP-POP Study): Study Protocol of a Randomized Controlled Trial
Authors: Sezer Dilan , de Leeuw Matthijs , Netzer Cordula , Dieterle Markus , Meyer Andrea , Buergler Sarah , Locher Cosima , Ruppen Wilhelm , Gaab Jens , Schneider Tobias
Published: November 2021

Introduction: Open-label placebos have been proposed as way of using long recognized analgesic placebo effects in an ethical manner. Recent evidence shows efficacy of open-label placebos for clinical conditions, but there is need for more research on open-label placebos in acute pain. In the treatment of acute postoperative pain, minimization of opioid related side effects remains one of the key challenges. Therefore, this study aims at investigating the potential of adding unconditioned open-label placebos to treatment as usual as a means of reducing opioid consumption and its related side effects in patients with acute postoperative pain.

Methods and Analysis: This is the protocol of an ongoing single site randomized controlled trial. The first patient was enrolled in May 2020. In total, 70 patients suffering from acute postoperative pain following dorsal lumbar interbody fusion are randomized to either a treatment as usual group or an experimental intervention group. The treatment as usual group consists of participants receiving a patient-controlled morphine pump. On day 1 and 2 post-surgery, patients in the intervention group receive, in addition to treatment as usual, two open-label placebo injections per day along with an evidence-based treatment rationale explaining the mechanisms of placebos. The primary outcome is measured by means of self-administered morphine during day 1 and 2 post-surgery. Several other outcome measures including pain intensity and adverse events as well as potential predictors of placebo response are assessed. Analysis of covariance will be used to answer the primary research question and additional statistical techniques such as generalized linear mixed models will be applied to model the temporal course of morphine consumption.

Discussion: This study will provide valuable insights into the efficacy of open-label placebos in acute pain and will potentially constitute an important step toward the implementation of open-label placebos in the clinical management of acute postoperative pain. In addition, it will shed light on a cost-efficient and patient-centered strategy to reduce opioid consumption and its related side effects, without any loss in pain management efficacy.

Ethics and Dissemination: The “Ethikkommission Nordwest- und Zentralschweiz” (BASEC2020-00099) approved the study protocol. Results of the analysis will be submitted for publication in a peer-reviewed journal.

Clinical Trial Registration: The study is registered at ClinicalTrials.gov (NCT04339023) and is listed in the Swiss national registry at kofam.ch (SNCTP000003720).
Crosstalk Between ER Stress, Autophagy and Inflammation
Authors: Chipurupalli Sandhya , Samavedam Unni , Robinson Nirmal
Published: November 2021

The endoplasmic reticulum (ER) is not only responsible for protein synthesis and folding but also plays a critical role in sensing cellular stress and maintaining cellular homeostasis. Upon sensing the accumulation of unfolded proteins due to perturbation in protein synthesis or folding, specific intracellular signaling pathways are activated, which are collectively termed as unfolded protein response (UPR). UPR expands the capacity of the protein folding machinery, decreases protein synthesis and enhances ER-associated protein degradation (ERAD) which degrades misfolded proteins through the proteasomes. More recent evidences suggest that UPR also amplifies cytokines-mediated inflammatory responses leading to pathogenesis of inflammatory diseases. UPR signaling also activates autophagy; a lysosome-dependent degradative pathwaythat has an extended capacity to degrade misfolded proteins and damaged ER. Thus, activation of autophagy limits inflammatory response and provides cyto-protection by attenuating ER-stress. Here we review the mechanisms that couple UPR, autophagy and cytokine-induced inflammation that can facilitate the development of novel therapeutic strategies to mitigate cellular stress and inflammation associated with various pathologies.
Insight Into the Roles of Non-coding RNA in Bronchopulmonary Dysplasia
Authors: Xi Yufeng , Wang Yujia
Published: November 2021

Bronchopulmonary dysplasia (BPD) is a chronic lung disease most commonly occurring in premature infants, and its pathological manifestations are alveolar hypoplasia and dysregulation of pulmonary vasculature development. The effective treatment for BPD has not yet been established. Non-coding RNAs, including microRNAs and long non-coding RNAs do not encode proteins, but can perform its biological functions at the RNA level. Non-coding RNAs play an important role in the incidence and development of BPD by regulating the expression of genes related to proliferation, apoptosis, angiogenesis, inflammation and other cell activities of alveolar epithelial cells and vascular endothelial cells. Here we summarize the role of non-coding RNAs in BPD, which provides possible molecular marker and therapeutic target for the diagnosis and treatment of BPD.
Curiosity in Online Video Concept Learning and Short-Term Outcomes in Blended Medical Education
Authors: Ho Cheng-Maw , Yeh Chi-Chuan , Wang Jann-Yuan , Hu Rey-Heng , Lee Po-Huang
Published: November 2021

Background: A student's level of curiosity in a subject after learning about it through online videos has not been addressed well in the medical education field. The purpose of this study, therefore, was to investigate online learning's effect on the stimulation of curiosity and short-term learning outcomes in a blended framework of precision medical education.

Methods: A mixed-methods research design was used. During the 2020 academic year, all fifth-year medical students who, prior to class, viewed 6 video clips that presented 6 core concepts were invited to complete a survey and self-reflection on their learning process to assess their level of curiosity in each concept. For each group of medical students, teaching assistants helped collect anonymous survey data and summative assessment scores representing the students' learning outcomes. Video-viewing patterns, attained through an action log transformation, were also coded for analysis. Mann–Whitney U and Kruskal–Wallis tests were employed to compare differences between groups, and multiple linear regression was used to select the factors affecting learning outcomes. Qualitative data were content-coded through a descriptive approach using thematic analysis.

Results: Of 142 medical students, 136 watched the online videos, 124 responded to the questionnaires, and 92 provided comments. Students' curiosity levels after learning about each concept through online videos significantly correlated with the degree to which a concept was learned. Medical students spent a median of 1.6 h online, and pause frequency correlated with curiosity in certain concepts. Aroused curiosity was associated with short-term learning outcomes in inconsistent effect sizes and directions. Students' feedback revealed various dimensions of curiosity, including novelty acknowledgment, recognition of an information gap, and information-seeking requests.

Conclusions: Curiosity can be induced through online video learning platforms and has a role in short-term learning outcomes in medical education.
Comparison of the Efficacy and Safety of Minimally Invasive Simple Prostatectomy and Endoscopic Enucleation of Prostate for Large Benign Prostatic Hyperplasia
Authors: Li Jinze , Cao Dehong , Meng Chunyang , Xia Zhongyou , Peng Lei , Li Yunxiang , Wei Qiang
Published: November 2021

Background: Minimally invasive simple prostatectomy (MISP) and endoscopic enucleation of the prostate (EEP) are the two most commonly used methods for large benign prostatic hyperplasia (BPH), but it remains unclear which of the two is superior. This study aims to perform a pooled analysis to compare efficacy and safety profiles between MISP and EEP.

Methods: We conducted a comprehensive search of PubMed, Embase, Web of Science, and ClinicalTrials.gov databases to identify eligible studies comparing MISP with EEP. Parameters including efficacy and safety outcomes were compared using Stata 14.0 version.

Results: Eight comparative trials with 1,504 patients were included. Compared to MISP, EEP demonstrated shorter operative time (mean difference [MD] 46.37, 95% confidence interval [CI] 19.92 to 72.82, p = 0.0006), lesser hemoglobin decrease (standardized MD [SMD] 0.59, 95% CI 0.23 to 0.95, p = 0.001), lower catheterization time (SMD 4.13, 95% CI 2.16 to 6.10, p < 0.001), and shorter length of stay (SMD 2.38, 95% CI 1.40 to 3.36, p < 0.001). However, overall complications and blood transfusions did not differ between the two groups. Moreover, EEP had better postvoid residual volume (PVR) at 6-month (MD 14.39, 95% CI 11.06 to 17.72, p < 0.001) and comparable 3- and 6-month International Prostate Symptom Score, 3- and 6-month maximum flow rate, 3-month PVR, and 3-month quality of life compared with MISP.

Conclusion: Both MISP and EEP are effective and safe surgical procedures for the treatment of large BPH. EEP appears to have a superior perioperative profile compared to MISP. This should be interpreted with caution due to the significant heterogeneity between studies. Hence, treatment selection should be based on the surgeon's experience and availability.
Niche Differentiation of Arsenic-Transforming Microbial Groups in the Rice Rhizosphere Compartments as Impacted by Water Management and Soil-Arsenic Concentrations
Authors: Somenahally Anil C. , Loeppert Richard H. , Zhou Jizhong , Gentry Terry J.
Published: November 2021

Arsenic (As) bioavailability in the rice rhizosphere is influenced by many microbial interactions, particularly by metal-transforming functional groups at the root-soil interface. This study was conducted to examine As-transforming microbes and As-speciation in the rice rhizosphere compartments, in response to two different water management practices (continuous and intermittently flooded), established on fields with high to low soil-As concentration. Microbial functional gene composition in the rhizosphere and root-plaque compartments were characterized using the GeoChip 4.0 microarray. Arsenic speciation and concentrations were analyzed in the rhizosphere soil, root-plaque, pore water, and grain samples. Results confirmed several As-biotransformation processes in the rice rhizosphere compartments, and distinct assemblage of As-reducing and methylating bacteria was observed between the root-plaque and rhizosphere. Results confirmed higher potential for microbial As-reduction and As-methylation in continuously flooded, long term As-contaminated fields, which accumulated highest concentrations of AsIIIand methyl-As concentrations in pore water and rice grains. Water management treatment significantly altered As-speciation in the rhizosphere, and intermittent flooding reduced methyl-As and AsIIIconcentrations in the pore water, root-plaque and rice grain. Ordination and taxonomic analysis of detected gene-probes indicated that root-plaque and rhizosphere assembled significantly different microbial functional groups demonstrating niche separation. Taxonomic non-redundancy was evident, suggesting that As-reduction, -oxidation and -methylation processes were performed by different microbial functional groups. It was also evident that As transformation was coupled to different biogeochemical cycling processes (nutrient assimilation, carbon metabolism etc.) in the compartments and between treatments, revealing functional non-redundancy of rice-rhizosphere microbiome in response to local biogeochemical conditions and As contamination. This study provided novel insights on As-biotransformation processes and their implications on As-chemistry at the root-soil interface and their responses to water management, which could be applied for mitigating As-bioavailability and accumulation in rice grains.
ASPP2κ Is Expressed In Human Colorectal Carcinoma And Promotes Chemotherapy Resistance And Tumorigenesis
Authors: Rieger Ingmar , Tsintari Vasileia , Overkamp Mathis , Fend Falko , Lopez Charles D. , Schittenhelm Marcus M. , Kampa-Schittenhelm Kerstin M.
Published: November 2021

Alternative splicing is a common physiologic mechanism to generate numerous distinct gene products from one gene locus, which can result in unique gene products with differing important functional outcomes depending on cell context. Aberrant alternative splicing is a hallmark of cancer that can contribute to oncogenesis and aggressiveness of the disease as well as resistance to therapy. However, aberrant splicing might also result in novel targets for cancer therapy. ASPP2 is a haplo-insufficient tumor suppressor, that functions through both p53-dependent as well as p53-independent mechanisms to enhance cell death after stress. Interestingly, the common human tumor TP53 mutations result in a loss of the binding sites to ASPP2, leading to impaired induction of apoptosis. Vice versa, attenuation of ASPP2 has been described to be associated with high-risk disease, therapy failure and poor clinical outcome especially in tumors harboring the TP53 wildtype (WT) isoform. We have recently identified a novel, dominant-negative splicing variant of ASPP2, named ASPP2κ, with oncogenic potential. Exon-skipping results in a reading-frame shift with a premature translation stop, omitting most of the ASPP2 C-terminus - which harbors the p53-binding domain. Consequently, the ASPP2-p53 interaction is abrogated, which in part impacts on oncogenesis, aggressiveness of disease and response to therapy. Since ASPP2κ has been shown in hematologic malignancies to promote tumorigenesis, we further wished to determine if aberrant ASPP2κ expression plays a role in human solid tumors. In this report, we find that ASPP2κ is frequently expressed in human colorectal tumors (CRC). Using ASPP2κ overexpressing and interference CRC models, we demonstrate a functional role of ASPP2κ in contributing to oncogenesis and resistance to therapy in CRC by 1) enhancing proliferation, 2) promoting cell migration and, 3) conferring resistance to chemotherapy induced apoptosis. Our findings have far-reaching consequences for future diagnostic and therapeutic strategies for ASPP2κ expressing colorectal cancer patients and provide proof-of-principle to further explore ASPP2κ as potential predictive marker and target for therapy in clinical trials.
Hepatitis B Virus Promotes Hepatocellular Carcinoma Progression Synergistically With Hepatic Stellate Cells via Facilitating the Expression and Secretion of ENPP2
Authors: Deng Wanyu , Chen Fu , Zhou Ziyu , Huang Yipei , Lin Junlong , Zhang Fapeng , Xiao Gang , Liu Chaoqun , Liu Chao , Xu Leibo
Published: November 2021

Background: Hepatitis B virus (HBV) infection is a major risk factor causing hepatocellular carcinoma (HCC) development, but the molecular mechanisms are not fully elucidated. It has been reported that virus infection induces ectonucleotide pyrophosphatase-phosphodiesterase 2 (ENPP2) expression, the latter participates in tumor progression. Therefore, the aim of the present study was to investigate whether HBV induced HCC malignancy via ENPP2.

Methods: HCC patient clinical data were collected and prognosis was analyzed. Transient transfection and stable ectopic expression of the HBV genome were established in hepatoma cell lines. Immunohistochemical staining, RT-qPCR, western blot, and ELISA assays were used to detect the expression and secretion of ENPP2. Finally, CCK-8, colony formation, and migration assays as well as a subcutaneous xenograft mouse model were used to investigate the influence of HBV infection, ENPP2 expression, and activated hepatic stellate cells (aHSCs) on HCC progression in vitro and in vivo.

Results: The data from cancer databases indicated that the level of ENPP2 was significant higher in HCC compared within normal liver tissues. Clinical relevance analysis using 158 HCC patients displayed that ENPP2 expression was positively correlated with poor overall survival and disease-free survival. Statistical analysis revealed that compared to HBV-negative HCC tissues, HBV-positive tissues expressed a higher level of ENPP2. In vitro, HBV upregulated ENPP2 expression and secretion in hepatoma cells and promoted hepatoma cell proliferation, colony formation, and migration via enhancement of ENPP2; downregulation of ENPP2 expression or inhibition of its function suppressed HCC progression. In addition, aHSCs strengthened hepatoma cell proliferation, migration in vitro, and promoted tumorigenesis synergistically with HBV in vivo; a loss-function assay further verified that ENPP2 is essential for HBV/aHSC-induced HCC progression.

Conclusion: HBV enhanced the expression and secretion of ENPP2 in hepatoma cells, combined with aHSCs to promote HCC progression via ENPP2.
Impact of Andropause on Multiple Sclerosis
Authors: Ysrraelit Maria C. , Correale Jorge
Published: November 2021

Andropause results from the natural decrease in testosterone levels that occurs with age. In contrast to menopause, which is a universal, well-characterized process associated with absolute gonadal failure, andropause ensues after gradual decline of both hypothalamic-pituitary-gonadal axis activity, as well as of testicular function, a process which usually develops over a period of many years. Increasing evidence on greater risk of Multiple sclerosis (MS) associated with lower testosterone levels is being reported. Likewise, epidemiological studies have shown a later age of onset of MS in men, relative to women, which could perhaps respond to the decline in protective testosterone levels. In this review, we will discuss the role of androgens in the development and function of the innate and adaptive immune response, as well as in neuroprotective mechanisms relevant to MS. Testosterone effects observed in different animal models and in epidemiological studies in humans will be discussed, as well as their correlation with physical disability and cognitive function levels. Finally, published and ongoing clinical trials exploring the role of androgens, particularly at key stages of sexual maturation, will be reviewed.
Resting State Networks Related to the Maintenance of Good Cognitive Performance During Healthy Aging
Authors: Maesawa Satoshi , Mizuno Satomi , Bagarinao Epifanio , Watanabe Hirohisa , Kawabata Kazuya , Hara Kazuhiro , Ohdake Reiko , Ogura Aya , Mori Daisuke , Nakatsubo Daisuke , Isoda Haruo , Hoshiyama Minoru , Katsuno Masahisa , Saito Ryuta , Ozaki Norio , Sobue Gen
Published: November 2021

Purpose: Maintenance of cognitive performance is important for healthy aging. This study aims to elucidate the relationship between brain networks and cognitive function in subjects maintaining relatively good cognitive performance.

Methods: A total of 120 subjects, with equal number of participants from each age group between 20 and 70 years, were included in this study. Only participants with Addenbrooke’s Cognitive Examination – Revised (ACE-R) total score greater than 83 were included. Anatomical T1-weighted MR images and resting-state functional MR images (rsfMRIs) were taken from all participants using a 3-tesla MRI scanner. After preprocessing, several factors associated with age including the ACE-R total score, scores of five domains, sub-scores of ACE-R, and brain volumes were tested. Morphometric changes associated with age were analyzed using voxel based morphometry (VBM) and changes in resting state networks (RSNs) were examined using dual regression analysis.

Results: Significant negative correlations with age were seen in the total gray matter volume (GMV, r = −0.58), and in the memory, attention, and visuospatial domains. Among the different sub-scores, the score of the delayed recall (DR) showed the highest negative correlation with age (r = −0.55, p < 0.001). In VBM analysis, widespread regions demonstrated negative correlation with age, but none with any of the cognitive scores. Quadratic approximations of cognitive scores as functions of age showed relatively delayed decline compared to total GMV loss. In dual regression analysis, some cognitive networks, including the dorsal default mode network, the lateral dorsal attention network, the right / left executive control network, the posterior salience network, and the language network, did not demonstrate negative correlation with age. Some regions in the sensorimotor networks showed positive correlation with the DR, memory, and fluency scores.

Conclusion: Some domains of the cognitive test did not correlate with age, and even the highly correlated sub-scores such as the DR score, showed delayed decline compared to the loss of total GMV. Some RSNs, especially involving cognitive control regions, were relatively maintained with age. Furthermore, the scores of memory, fluency, and the DR were correlated with the within-network functional connectivity values of the sensorimotor network, which supported the importance of exercise for maintenance of cognition.
Sustainable Agriculture Development in Northwest China Under the Impacts of Global Climate Change
Authors: Liu Dachuan , Li Yan , Wang Pengfei , Zhong Huaqi , Wang Pu
Published: November 2021

Northwest China has one of the most vulnerable agricultural systems in the context of global climate change. We argue that sustainable agriculture development in this region requires a systematic approach toward climate change adaptation, and propose a schematic framework for strategic thinking. We first briefly review the impacts of climate change on various agricultural environmental factors, including light, temperature, water, and atmosphere, and explores the effects of climate change on agricultural practices, such as disaster response, pests and weeds control, fertilizer application, and species selection. The study shows that climate change has increased extreme climate disasters such as drought and heat waves, and has expanded the scope and severity of pests and weeds, which in turn requires a series of changes in farming practices. These effects have profound impacts on farmland management, as well as the sustainability of the agricultural system. Based on the findings, the authors argue that the key adaptation strategies should include: (1) optimizing the geographic distribution of agriculture, (2) cultivating new crop varieties that can better adapt to the changing environment, (3) adjusting cropping timing and structure, (4) developing water-saving irrigation systems, (5) improving capacities of disaster prevention and mitigation at both household and government levels, and (6) strengthening the sciences, technology, and human resources to mitigate the adverse effects of climate change.
Primary Giant Cell Tumor of the Breast With Pulmonary Metastasis: A Case Report and Review of the Literature
Authors: Zhang Wenxiang , Kong Xiangyi , Qi Yihang , Wang Xiangyu , Liu Qiang , Fang Yi , Song Yan , Wang Jing
Published: November 2021

Giant cell tumor of soft tissue (GCT-ST) is an extremely rare tumor that is similar in morphology and immunohistochemistry to giant cell tumor of the bone. Almost 80% of these tumors occur in the upper and lower extremities, and the breast is a very rare location. Here, we report a case of a 65-year-old female patient with a small mobile palpable lump in the left breast. Although the left breast tumor was considered malignant on preoperative imaging, no evidence of malignant tumor was found by ultrasound-guided core needle biopsy (CNB). Subsequently, the left breast tumor was confirmed as a malignant tumor by intraoperative rapid pathological examination. The initial treatment of the tumor was wide local excision and sentinel lymph node biopsy, and it was confirmed to be GCT-ST by histopathology and immunohistochemistry. Despite surgical treatment achieving clear surgical margins, the patient experienced lung metastases within a year of her initial treatment. Fortunately, the patient underwent surgical treatment of lung metastases, and at the last follow-up, the patient was still alive. This is the first case of a primary soft tissue tumor of the breast that has undergone surgical intervention after lung metastasis. This case report highlights the complexity of the clinical diagnosis and treatment of GCT-ST arising from the breast. Surgery may be another good treatment when the patient develops lung metastases.