bluuebunny/crossref_metadata_2025 huggingface dataset:
Epigenetic Regulation of Angiogenesis in Development and Tumors Progression: Potential Implications for Cancer Treatment
Authors: Aspriţoiu Veronica Mãdãlina , Stoica Ileana , Bleotu Coralia , Diaconu Carmen Cristina
Published: September 2021

Angiogenesis is a multi-stage process of new blood vessel development from pre-existing vessels toward an angiogenic stimulus. The process is essential for tissue maintenance and homeostasis during embryonic development and adult life as well as tumor growth. Under normal conditions, angiogenesis is involved in physiological processes, such as wound healing, cyclic regeneration of the endometrium, placental development and repairing certain cardiac damage, in pathological conditions, it is frequently associated with cancer development and metastasis. The control mechanisms of angiogenesis in carcinogenesis are tightly regulated at the genetic and epigenetic level. While genetic alterations are the critical part of gene silencing in cancer cells, epigenetic dysregulation can lead to repression of tumor suppressor genes or oncogene activation, becoming an important event in early development and the late stages of tumor development, as well. The global alteration of the epigenetic spectrum, which includes DNA methylation, histone modification, chromatin remodeling, microRNAs, and other chromatin components, is considered one of the hallmarks of cancer, and the efforts are concentrated on the discovery of molecular epigenetic markers that identify cancerous precursor lesions or early stage cancer. This review aims to highlight recent findings on the genetic and epigenetic changes that can occur in physiological and pathological angiogenesis and analyze current knowledge on how deregulation of epigenetic modifiers contributes to tumorigenesis and tumor maintenance. Also, we will evaluate the clinical relevance of epigenetic markers of angiogenesis and the potential use of “epi-drugs” in modulating the responsiveness of cancer cells to anticancer therapy through chemotherapy, radiotherapy, immunotherapy and hormone therapy as anti-angiogenic strategies in cancer.
Molecular Features of Polycystic Ovary Syndrome Revealed by Transcriptome Analysis of Oocytes and Cumulus Cells
Authors: Li Jie , Chen Haixia , Gou Mo , Tian Chenglei , Wang Huasong , Song Xueru , Keefe David L. , Bai Xiaohong , Liu Lin
Published: September 2021

Polycystic ovary syndrome (PCOS) is typically characterized by a polycystic ovarian morphology, hyperandrogenism, ovulatory dysfunction, and infertility. Furthermore, PCOS patients undergoing ovarian stimulation have more oocytes; however, the poor quality of oocytes leads to lower fertilization and implantation rates, decreased pregnancy rates, and increased miscarriage rates. The complex molecular mechanisms underlying PCOS and the poor quality of oocytes remain to be elucidated. We obtained matched oocytes and cumulus cells (CCs) from PCOS patients, compared them with age-matched controls, and performed RNA sequencing analysis to explore the transcriptional characteristics of their oocytes and CCs. Moreover, we validated our newly confirmed candidate genes for PCOS by immunofluorescence. Unsupervised clustering analysis showed that the overall global gene expression patterns and transposable element (TE) expression profiles of PCOS patients tightly clustered together, clearly distinct from those of controls. Abnormalities in functionally important pathways are found in PCOS oocytes. Notably, genes involved in microtubule processes, TUBB8 and TUBA1C, are overexpressed in PCOS oocytes. The metabolic and oxidative phosphorylation pathways are also dysregulated in both oocytes and CCs from PCOS patients. Moreover, in oocytes, differentially expressed TEs are not uniformly dispersed in human chromosomes. Endogenous retrovirus 1 (ERV1) elements located on chromosomes 2, 3, 4, and 5 are rather highly upregulated. Interestingly, these correlate with the most highly expressed protein-coding genes, including tubulin-associated genes TUBA1C, TUBB8P8, and TUBB8, linking the ERV1 elements to the occurrence of PCOS. Our comprehensive analysis of gene expression in oocytes and CCs, including TE expression, revealed the specific molecular features of PCOS. The aberrantly elevated expression of TUBB8 and TUBA1C and ERV1 provides additional markers for PCOS and may contribute to the compromised oocyte developmental competence in PCOS patients. Our findings may also have implications for treatment strategies to improve oocyte maturation and the pregnancy outcomes for women with PCOS.
Lanthanide-Doped Luminescent Nanophosphors via Ionic Liquids
Authors: Sharma Rahul Kumar , Ghosh Pushpal
Published: September 2021

Lanthanide (Ln3+) ion(s)-doped or rare-earth ion(s)-doped nanomaterials have been considered a very important class of nanophosphors for various photonic and biophotonic applications. Unlike semiconductors and organic-based luminescent particles, the optical properties of Ln3+-doped nanophosphors are independent of the size of the nanoparticles. However, by varying the crystal phase, morphology, and lattice strain of the host materials along with making core-shell structure, the relaxation dynamics of dopant Ln3+ ions can be effectively tuned. Interestingly, a judicious choice of dopant ions leads to unparallel photophysical dynamics, such as quantum cutting, upconversion, and energy transfer. Recently, ionic liquids (ILs) have drawn tremendous attention in the field of nanomaterials synthesis due to their unique properties like negligible vapor pressure, nonflammability, and, most importantly, tunability; thus, they are often called “green” and “designer” solvents. This review article provides a critical overview of the latest developments in the ILs-assisted synthesis of rare-earth-doped nanomaterials and their subsequent photonic/biophotonic applications, such as energy-efficient lighting and solar cell applications, photodynamic therapy, and in vivo and in vitro bioimaging. This article will emphasize how luminescence dynamics of dopant rare-earth ions can be tuned by changing the basic properties of the host materials like crystal phase, morphology, and lattice strain, which can be eventually tuned by various properties of ILs such as cation/anion combination, alkyl chain length, and viscosity. Last but not least, different aspects of ILs like their ability to act as templating agents, solvents, and reaction partners and sometimes their “three-in-one” use in nanomaterials synthesis are highlighted along with various photoluminescence mechanisms of Ln3+ ion like up- and downconversion (UC and DC).
Theoretical Insight Into the Ultralong Room-Temperature Phosphorescence of Nonplanar Aromatic Hydrocarbon
Authors: Qin Ke , Gong Wenqi , Gao Jia , Hu Deping , Shi Huifang , Yao Wei , An Zhongfu , Ma Huili
Published: September 2021

Purely aromatic hydrocarbon materials with ultralong room-temperature phosphorescence (RTP) were reported recently, but which is universally recognized as unobservable. To reveal the inherent luminescent mechanism, two compounds, i.e., PT with a faint RTP and HD with strong RTP featured by nonplanar geometry, were chosen as a prototype to study their excited-state electronic structures by using quantum mechanics/molecular mechanics (QM/MM) model. It is demonstrated that the nonplanar ethylene brides can offer σ-electron to strengthen spin-orbit coupling (SOC) between singlet and triplet excited states, which can not only promote intersystem crossing (ISC) of S1→Tn to increase the population of triplet excitons, but also accelerate the radiative decay rate of T1→S0, and thus improving RTP. Impressively, the nonradiative decay rate only has a small increase, owing to the synergistic effect between the increase of SOC and the reduction of reorganization energy of T1→S0 caused by the restricted torsional motions of aromatic rings. Therefore, a bright and long-lived RTP was obtained in aromatic hydrocarbon materials with twisted structure. This work provided a new insight into the ultralong RTP in pure organic materials.
The Use of CRISPR/Cas9 as a Tool to Study Human Infectious Viruses
Authors: Lin Huafeng , Li Gang , Peng Xiangwen , Deng Aimin , Ye Lei , Shi Lei , Wang Tuanmei , He Jun
Published: September 2021

Clustered regularly interspaced short palindromic repeats (CRISPR) systems are a set of versatile gene-editing toolkit that perform diverse revolutionary functions in various fields of application such as agricultural practices, food industry, biotechnology, biomedicine, and clinical research. Specially, as a novel antiviral method of choice, CRISPR/Cas9 system has been extensively and effectively exploited to fight against human infectious viruses. Infectious diseases including human immunodeficiency virus (HIV), hepatitis B virus (HBV), human papillomavirus (HPV), and other viruses are still global threats with persistent potential to probably cause pandemics. To facilitate virus removals, the CRISPR/Cas9 system has already been customized to confer new antiviral capabilities into host animals either by modifying host genome or by directly targeting viral inherent factors in the form of DNA. Although several limitations and difficulties still need to be conquered, this technology holds great promises in the treatment of human viral infectious diseases. In this review, we will first present a brief biological feature of CRISPR/Cas9 systems, which includes a description of CRISPR/Cas9 structure and composition; thereafter, we will focus on the investigations and applications that employ CRISPR/Cas9 system to combat several human infectious viruses and discuss challenges and future perspectives of using this new platform in the preclinical and clinical settings as an antiviral strategy.
Prevalence and Characterization of Cryptosporidium Species in Tibetan Antelope (Pantholops hodgsonii)
Authors: Qin Si-Yuan , Sun He-Ting , Lyu Chuang , Zhu Jun-Hui , Wang Zhen-Jun , Ma Tao , Zhao Quan , Lan Yun-Gang , He Wen-Qi
Published: September 2021

Cryptosporidium is an enteric apicomplexan parasite, which can infect multiple mammals including livestock and wildlife. Tibetan Antelope (Pantholops hodgsonii) is one of the most famous wildlife species, that belongs to the first class protected wild animals in China. However, it has not been known whether Tibetan Antelope is infected with Cryptosporidium so far. The objective of the present study was to determine the prevalence and characterization of Cryptosporidium species infection in Tibetan Antelope and the corresponding species by using molecular biological method. In the current study, a total of 627 fecal samples were randomly collected from Tibetan Antelope in the Tibet Autonomous Region (2019–2020), and were examined by PCR amplification of the small subunit ribosomal RNA (SSU rRNA) gene. Among 627 samples, 19 (3.03%, 19/627) were examined as Cryptosporidium-positive, with 7 (2.33%, 7/300) in females and 12 (3.67%, 12/327) in males. The analysis of SSU rRNA gene sequence suggested that only two Cryptosporidium species, namely, C. xiaoi and C. ubiquitum, were identified in this study. This is the first evidence for an existence of Cryptosporidium in Tibetan Antelope. These findings extend the host range for Cryptosporidium spp. and also provide important data support for prevention and control of Cryptosporidium infection in Tibetan Antelope.
Myeloid-Derived Suppressor Cells in Trypanosoma cruzi Infection
Authors: Fresno Manuel , Gironès Núria
Published: September 2021

Myeloid-derived suppressor cells (MDSCs) are immature heterogeneous myeloid cells that expand in pathologic conditions as cancer, trauma, and infection. Although characterization of MDSCs is continuously revisited, the best feature is their suppressor activity. There are many markers for MDSC identification, it is distinctive that they express inducible nitric oxide synthase (iNOS) and arginase 1, which can mediate immune suppression. MDSCs can have a medullary origin as a result of emergency myelopoiesis, but also can have an extramedullary origin. Early studies onTrypanosoma cruziinfection showed severe immunosuppression, and several mechanisms involving parasite antigens and host cell mediators were described as inhibition of IL-2 and IL-2R. Another mechanism of immunosuppression involving tumor necrosis factor/interferon γ-dependent nitric oxide production by inducible nitric oxide synthase was also described. Moreover, other studies showed that nitric oxide was produced by CD11b+Gr-1+MDSCs in the spleen, and later iNOS and arginase 1 expressed in CD11b+Ly6C+Ly6Glomonocytic MDSC were found in spleen and heart ofT. cruziinfected mice that suppressed T cell proliferation. Uncontrolled expansion of monocytic MDSCs leads to L-arginine depletion which hinders nitric oxide production leading to death. Supplement of L-arginine partially reverts L-arginine depletion and survival, suggesting that L-arginine could be administered along with anti-parasitical drugs. On the other hand, pharmacological inhibition of MDSCs leads to death in mice, suggesting that some expansion of MDSCs is needed for an efficient immune response. The role of signaling molecules mediating immune suppression as reactive oxygen species, reactive nitrogen species, as well as prostaglandin E2, characteristics of MDSCs, inT. cruziinfection is not fully understood. We review and discuss the role of these reactive species mediators produced by MDSCs. Finally, we discuss the latest results that link the SLAMF1 immune receptor with reactive oxygen species. Interaction of the parasite with the SLAMF1 modulates parasite virulence through myeloid cell infectivity and reactive oxygen species production. We discuss the possible strategies for targeting MDSCs and SLAMF1 receptor in acuteTrypanosoma cruziinfection in mice, to evaluate a possible translational application in human acute infections.
3 Challenges, 3 Errors, and 3 Solutions to Integrate Frontline Communities in Climate Change Policy and Research: Lessons From California
Authors: Fernandez-Bou Angel Santiago , Ortiz-Partida J. Pablo , Classen-Rodriguez Leticia M. , Pells Chantelise , Dobbin Kristin B. , Espinoza Vicky , Rodríguez-Flores José Manuel , Thao Chia , Hammond Wagner Courtney R. , Fencl Amanda , Flores-Landeros Humberto , Maskey Mahesh L. , Cole Spencer A. , Azamian Shayda , Gamiño Eliseo , Guzman Alexander , Alvarado Ana Grace F. , Campos-Martínez Miriam S. , Weintraub Coreen , Sandoval Espi , Dahlquist-Willard Ruth M. , Bernacchi Leigh A. , Naughton Colleen C. , DeLugan Robin M. , Medellín-Azuara Josué
Published: September 2021

Frontline communities of California experience disproportionate social, economic, and environmental injustices, and climate change is exacerbating the root causes of inequity in those areas. Yet, climate adaptation and mitigation strategies often fail to meaningfully address the experience of frontline community stakeholders. Here, we present three challenges, three errors, and three solutions to better integrate frontline communities' needs in climate change research and to create more impactful policies. We base our perspective on our collective firsthand experiences and on scholarship to bridge local knowledge with hydroclimatic research and policymaking. Unawareness of local priorities (Challenge 1) is a consequence of Ignoring local knowledge (Error 1) that can be, in part, resolved with Information exchange and expansion of community-based participatory research (Solution 1). Unequal access to natural resources (Challenge 2) is often due to Top-down decision making (Error 2), but Buffer zones for environmental protection, green areas, air quality, and water security can help achieve environmental justice (Solution 2). Unequal access to public services (Challenge 3) is a historical issue that persists because of System abuse and tokenism (Error 3), and it may be partially resolved with Multi-benefit projects to create socioeconomic and environmental opportunities within frontline communities that include positive externalities for other stakeholders and public service improvements (Solution 3). The path forward in climate change policy decision-making must be grounded in collaboration with frontline community members and practitioners trained in working with vulnerable stakeholders. Addressing co-occurring inequities exacerbated by climate change requires transdisciplinary efforts to identify technical, policy, and engineering solutions.
Case Report: Congenital Coronary Artery Ring With Single Left Coronary Ostium and Fistula: A Previously Unreported Anatomy
Authors: Tang Shiyuan , Tang Mi , Daniel Iroegbu Chukwuemeka , Yang Jinfu , Fan Chengming
Published: September 2021

Background: Single coronary ostium concomitant with coronary artery fistula is a very rare congenital anomaly. Apart from that, the combination of a closed loop of the coronary artery has never been reported.

Case presentation: Herein, we present a 7-year-old girl diagnosed as single left coronary ostium with a giant coronary trunk, coronary artery to right ventricle fistula, and coronary artery ring. The coronary fistula was surgically ligated with off-pump strategy and the patient discharged on postoperative day 5 and free of symptoms during the 3 years of follow-up.

Conclusion: To our knowledge, the presented congenital coronary anomaly is the first to be reported in the literature with the name of congenital coronary artery ring with single left coronary ostium and fistula.
Digital Mental Health for Young People: A Scoping Review of Ethical Promises and Challenges
Authors: Wies Blanche , Landers Constantin , Ienca Marcello
Published: September 2021

Mental health disorders are complex disorders of the nervous system characterized by a behavioral or mental pattern that causes significant distress or impairment of personal functioning. Mental illness is of particular concern for younger people. The WHO estimates that around 20% of the world's children and adolescents have a mental health condition, a rate that is almost double compared to the general population. One approach toward mitigating the medical and socio-economic effects of mental health disorders is leveraging the power of digital health technology to deploy assistive, preventative, and therapeutic solutions for people in need. We define “digital mental health” as any application of digital health technology for mental health assessment, support, prevention, and treatment. However, there is only limited evidence that digital mental health tools can be successfully implemented in clinical settings. Authors have pointed to a lack of technical and medical standards for digital mental health apps, personalized neurotechnology, and assistive cognitive technology as a possible cause of suboptimal adoption and implementation in the clinical setting. Further, ethical concerns have been raised related to insufficient effectiveness, lack of adequate clinical validation, and user-centered design as well as data privacy vulnerabilities of current digital mental health products. The aim of this paper is to report on a scoping review we conducted to capture and synthesize the growing literature on the promises and ethical challenges of digital mental health for young people aged 0–25. This review seeks to survey the scope and focus of the relevant literature, identify major benefits and opportunities of ethical significance (e.g., reducing suffering and improving well-being), and provide a comprehensive mapping of the emerging ethical challenges. Our findings provide a comprehensive synthesis of the current literature and offer a detailed informative basis for any stakeholder involved in the development, deployment, and management of ethically-aligned digital mental health solutions for young people.
Vegetation History in a Peat Succession Over the Past 8,000 years in the ISM-Controlled Kedarnath Region, Garhwal Himalaya: Reconstruction Using Molecular Fossils
Authors: Bhattacharya Sharmila , Kishor Harsh , Ankit Yadav , Mishra Praveen K. , Srivastava Pradeep
Published: September 2021

The Holocene epoch has witnessed several natural climate variations and these are well encoded in various geological archives. The present biomarker investigation in conjunction with previously published multi-proxy records was applied to reconstruct organic matter (OM) sources forming the peat succession spanning the last 8000 cal yr BP and shift in hydrological conditions from the Kedarnath region, Garhwal Himalaya. Intensified monsoon prevailed from ∼7515 until ∼2300 cal yr BP but with reversal to transient arid period particularly between ∼5200 and ∼3600 cal yr BP as revealed by the variability in n-C23/n-C31, ACL (average chain length of n-alkanes) and Paq (P-aqueous) values. A prolonged arid phase is recognizable during the interval between ∼2200 and ∼370 cal yr BP suggested by the n-alkane proxies. Regional scale heterogeneity in the monsoonal pattern is known in the studied temporal range of mid to late Holocene across the Indian subcontinent that is probably a result of complex climate dynamics, sensitivity of proxies and impact of teleconnections. The biomarker signatures deduced from gas chromatography mass spectrometry (GCMS) analysis are suggestive of a mixed biotic input that includes prokaryotes, Sphagnum spp. and gymnosperm flora. The mid chain alkanes viz. n-C23 and n-C25 denote the presence of typical peat forming Sphagnum moss that preferentially grows in humid and waterlogged conditions. Diterpane marker such as ent-kaurane indicates contribution of gymnosperms, whereas the hopanes are signatures of microbial input. The preservation of organic matter is attributed to little microbial degradation in a largely suboxic depositional environment. Our study strengthens the applicability of organic geochemical proxies for the reconstruction of past climate history and indicates their suitability for use on longer timescales given the high preservation potential of the molecular remains.
Sp1-Induced lncRNA Rmrp Promotes Mesangial Cell Proliferation and Fibrosis in Diabetic Nephropathy by Modulating the miR-1a-3p/JunD Pathway
Authors: Yang Hansen , Wang Jia , Zhang Zheng , Peng Rui , Lv Dan , Liu Handeng , Sun Yan
Published: September 2021

Diabetic nephropathy (DN) is a serious complication of diabetes mellitus. Long non-coding RNAs (lncRNAs) are regulators in DN progression. However, the regulatory mechanisms of multiple lncRNAs in DN remain to be determined. Our aim was to investigate the function and molecular mechanism of lncRNA RNA component of mitochondrial RNAase P (Rmrp) in DN. Here, we observed that the expression of Rmrp was up-regulated in the kidney of db/db DN mice and high glucose induced glomerular mesangial cells (MC). More importantly, the abnormal transcription of Rmrp was induced by nuclear transcription factor Sp1, which promotes the proliferation and production of fibrotic markers in MC. Subsequently, we screened the miRNAs related to Rmrp and found that Rmrp and miR-1a-3p are co-localized at the subcellular level of MC, and Rmrp could directly binds to miR-1a-3p. Further mechanism research demonstrated that the elevated miR-1a-3p significantly attenuated the proliferation and fibrosis-promoting effects induced by up-regulation of Rmrp. At the same time, we also investigated that miR-1a-3p can directly bind to Jun D proto-oncogene (JunD), thereby regulating the protein level of JunD. Rmrp-induced proliferation and fibrogenesis were reversed by co-transfection with JunD siRNA. In summary, Sp1 induced lncRNA Rmrp could drive the expression of JunD via sponging miR-1a-3p in DN progression.
Diffusion Tensor Imaging in Rat Models of Preclinical Diabetic Nephropathy: A Preliminary Study
Authors: Hu Xiaoyan , Kuang Min , Peng Bo , Yang Yang , Lin Wei , Li Wenbo , Wu Yinghua
Published: September 2021

Purpose

This study aimed to investigate the value of diffusion tensor imaging to assess renal injury in a rat model of preclinical diabetic nephropathy.

Methods

Twenty-eight male Sprague Dawley rats were divided into two groups: the normal control (NC) group of 10 rats and the diabetic nephropathy (DN) group of 18 rats. Eight weeks after diabetes induction by streptozotocin, 3.0-T magnetic resonance (MR) imaging (b = 0 and 600 s/mm2, 15 diffusion directions) using a 32-channel knee coil was performed. After MR imaging, we measured serum creatinine, and collected double kidney tissues for pathology. The apparent diffusion coefficients(ADC) and fractional anisotropy(FA) values of the renal cortex and medulla were calculated for all kidneys. Physiological parameters, laboratory parameters, and imaging results were compared between the two groups.

Results

All DN group animals developed hyperglycemia, polyuria, and emaciation. Serum creatinine was not significantly different between the groups (P > 0.05). Urinary albumin at 2, 4, and 8 weeks was higher in the DN group than in the NC group but <20 µg/min (P < 0.05). Pathologically, renal damage in the DN rats was observed. The ADC value was significantly increased in DN animals in the cortex (1.75×10-3mm2/s),medulla(1.53×10-3mm2/s)compared with NC group(cortex, 1.52×10-3mm2/s; medulla,1.35×10-3mm2/s). The FA value was significantly reduced in DN animals in the cortex (0.21),medulla(0.25)compared with NC group(cortex,0.26;medulla,0.3).

Conclusions

Increased apparent diffusion coefficients and decreased fractional anisotropy values on diffusion tensor imaging were associated with preclinical DN. Diffusion tensor imaging may be useful in early, non-invasive, quantitative detection, and therapy monitoring of DN.
Neck Circumference Is Associated With Hyperuricemia in Women With Polycystic Ovary Syndrome
Authors: Yang Haiyan , Liu Chang , Jin Congcong , Yu Rong , Ding Lin , Mu Liangshan
Published: September 2021

Objective

To evaluate the association between neck circumference (NC) and hyperuricemia in women with polycystic ovary syndrome (PCOS).

Methods

This is a cross-sectional study that recruited 601 women with PCOS from January 2018 to January 2021. PCOS was diagnosed according to the Rotterdam definition. Hyperuricemia was defined as serum uric acid level of at least 357 μmol/L.

Results

PCOS females with hyperuricemia had significantly greater values of NC, body mass index (BMI), waist circumference (WC) and hip circumference (HC). NC was positively associated with serum uric acid levels, with a standardized regression coefficient of 0.34 after adjusting for confounding factors. Furthermore, logistic regression analysis showed that NC was significantly associated with an increased risk of hyperuricemia, with an adjusted odds ratio of 1.36. The associations between NC and serum uric acid levels were more considerable in those with medium/high BMI (BMI ≥ 21.63 kg/m2), all ranges of WC or medium/high HC (HC ≥ 90 cm). The optimal cut-off point of NC in predicting hyperuricemia was 32.0 cm (Youden index = 0.48), with the sensitivity and negative predictive value of 84.81% and 92.08%, respectively.

Conclusions

NC was positively correlated with serum uric acid levels and the prevalence of hyperuricemia in women with PCOS. Therefore, we suggest NC as a simple, novel, and reliable anthropometric measure to be used in the routine clinical assessment of women with PCOS to screen those at high risk of hyperuricemia.
Therapeutic Strategy in Low-Risk Papillary Thyroid Carcinoma – Long-Term Results of the First Single-Center Prospective Non-Randomized Trial Between 2011 and 2015
Authors: Czarniecka Agnieszka , Zeman Marcin , Wozniak Grzegorz , Maciejewski Adam , Stobiecka Ewa , Chmielik Ewa , Oczko-Wojciechowska Malgorzata , Krajewska Jolanta , Handkiewicz-Junak Daria , Jarzab Barbara
Published: September 2021

Optimal therapeutic strategy in low advanced papillary thyroid carcinoma (PTC) is still a matter of debate. The management differs depending on the country.

A prospective non-randomized study was performed to evaluate whether less extensive surgery could be a safe, acceptable, and sufficient therapeutic option in PTC cT1N0M0 patients. The present paper summarizes the results of over a 5-year follow-up

Material

Our prospective group (PG) treated between 2011 and 2015 consisted of 139 patients with cT1aN0M0 PTC who underwent lobectomy (LT) as initial surgical treatment (PGcT1aN0M0 group) and 102 cT1bN0M0 patients in whom total thyroidectomy (TT) with unilateral central neck dissection (CND) was performed (PGcT1bN0M0). PG was compared with the retrospective group (RG) of patients who underwent TT with bilateral CND between 2004 and 2006: 103 cT1aN0M0 patients (RGcT1aN0M0) and 91cT1bN0M0 (RGcT1bN0M0). The risks of reoperation, cancer relapse and postoperative complications were analyzed.

Results

Only 12 cT1aN0M0 patients (7.6%) withdrew from the trial and underwent TT with bilateral CND. Over 90% of patients accepted less extensive surgery. In 4 cT1aN0M0 cases, TT with CND was performed due to lymph node metastases found intraoperatively. The initial clinical stage according to the TNM/AJCC 7th edition was confirmed histologically in 77% of cases in PGT1aN0M0 and in 72% in PGT1bN0M0, respectively. 24 PGcT1aN0M0 patients were reoperated on. In this group, cancer lesions in the postoperative histological specimens were found in 8 cases (32%). Five-year disease-free survival (DFS) was excellent. However, no statistically significant differences were found between PG and RG groups (99.3% in PGcT1aN0M0 and 99.0%, in RGcT1aN0M0; p = 0.41 and 98%, in PGcT1bN0M0 and 94.4% in RGcT1bN0M0; p=0.19). No significant differences were observed in the incidence of early paresis of the recurrent laryngeal nerves between PG and RG. However, as predicted, LT completely eliminated the risk of postoperative hypoparathyroidism.

The results of the prospective clinical trial confirm that less extensive surgery in adequately selected low-advanced PTC patients is both safe and sufficient.
Debates in Pancreatic Beta Cell Biology: Proliferation Versus Progenitor Differentiation and Transdifferentiation in Restoring β Cell Mass
Authors: Spears Erick , Serafimidis Ioannis , Powers Alvin C. , Gavalas Anthony
Published: September 2021

In all forms of diabetes, β cell mass or function is reduced and therefore the capacity of the pancreatic cells for regeneration or replenishment is a critical need. Diverse lines of research have shown the capacity of endocrine as well as acinar, ductal and centroacinar cells to generate new β cells. Several experimental approaches using injury models, pharmacological or genetic interventions, isolation and in vitro expansion of putative progenitors followed by transplantations or a combination thereof have suggested several pathways for β cell neogenesis or regeneration. The experimental results have also generated controversy related to the limitations and interpretation of the experimental approaches and ultimately their physiological relevance, particularly when considering differences between mouse, the primary animal model, and human. As a result, consensus is lacking regarding the relative importance of islet cell proliferation or progenitor differentiation and transdifferentiation of other pancreatic cell types in generating new β cells. In this review we summarize and evaluate recent experimental approaches and findings related to islet regeneration and address their relevance and potential clinical application in the fight against diabetes.
The Role of River Flooding as an Environmental Filter for Amazonian Butterfly Assemblages
Authors: Rabelo Rafael M. , Pereira Geanne C. N. , Valsecchi João , Magnusson William E.
Published: September 2021

Amazonian flooded (várzea) and upland (terra firme) forests harbor distinct assemblages of most taxonomic groups. These differences are mainly attributed to flooding, which may affect directly or indirectly the persistence of species. Here, we compare the abundance, richness and composition of butterfly assemblages invárzeaandterra firmeforests, and evaluate whether environmental gradients between and within these forest types can be used to predict patterns of assemblage structure. We found that both total abundance and number of species per plot are higher invárzeathan interra firmeforests.Várzeaassemblages had a higher dominance of abundant species thanterra firmeassemblages, in which butterfly abundances were more equitable. Rarefied species richness forvárzeaandterra firmeforests was similar. There was a strong turnover in species composition fromvárzeatoterra firmeforests associated with environmental change between these forest types, but with little evidence for an effect of the environmental gradients within forest types. Despite a smaller total area in the Amazon basin, less defined vegetation strata and the shorter existence over geological time of floodplain forests, Nymphalid-butterfly assemblages were not more species-poor invárzeaforests than in unflooded forests. We highlight the role of flooding as a primary environmental filter in Amazonian floodplain forests, which strongly determines the composition of butterfly assemblages.
Testing the Interspecific Function of Female Common Cuckoo “Bubbling” Call
Authors: Wang Yanyi , Tian Miao , Liu Jingpeng , Lu Xingyu , Møller Anders Pape , Xia Canwei
Published: September 2021

Female common cuckoo (Cuculus canorous) predator-like “bubbling” calls distract host parental attention and reduce the egg rejection rate. Such “bubbling” calls are also frequently used to attract males and deter territorial rivals in intraspecies contact, and these calls are an ancestral character in many cuckoo species. Although hosts have had sufficient time to become familiar with this call and evolve anti-parasitic strategies, why are the hosts fooled by this “bubbling” call? We propose two hypotheses. The first hypothesis proposes that call variation reduces the opportunity for host species to correctly assess cuckoo tricks. In contrast, the second hypothesis proposes that the cost of behavior may prevent the antiparasitic strategy from evolving. In the study, we tested the prerequisites of these hypotheses, by investigating whether cuckoo calls vary during the day and testing whether the predator-like calls suppress bird activities. Based on field recordings from three different areas, we found high overlap in the calls generated during different periods. Oriental great reed warblers (Acrocephalus orientalis), a host species, did not show different responses toward the playback of female common cuckoo calls generated before noon or afternoon. Based on bird count data, we found that predator-like call playback is insufficient for suppressing bird activities. Therefore, none of the prerequisites were supported by our field data. We discuss the potential reasons for our findings and hope to inspire more research examining female cuckoo vocalizations.
Patient-Specific Cell Communication Networks Associate With Disease Progression in Cancer
Authors: Gibbs David L. , Aguilar Boris , Thorsson Vésteinn , Ratushny Alexander V. , Shmulevich Ilya
Published: September 2021

The maintenance and function of tissues in health and disease depends on cell–cell communication. This work shows how high-level features, representing cell–cell communication, can be defined and used to associate certain signaling “axes” with clinical outcomes. We generated a scaffold of cell–cell interactions and defined a probabilistic method for creating per-patient weighted graphs based on gene expression and cell deconvolution results. With this method, we generated over 9,000 graphs for The Cancer Genome Atlas (TCGA) patient samples, each representing likely channels of intercellular communication in the tumor microenvironment (TME). It was shown that cell–cell edges were strongly associated with disease severity and progression, in terms of survival time and tumor stage. Within individual tumor types, there are predominant cell types, and the collection of associated edges were found to be predictive of clinical phenotypes. Additionally, genes associated with differentially weighted edges were enriched in Gene Ontology terms associated with tissue structure and immune response. Code, data, and notebooks are provided to enable the application of this method to any expression dataset (https://github.com/IlyaLab/Pan-Cancer-Cell-Cell-Comm-Net).
Epigenetic Regulation of the Wnt/β-Catenin Signaling Pathway in Cancer
Authors: Sharma Ankita , Mir Rafeeq , Galande Sanjeev
Published: September 2021

Studies over the past four decades have elucidated the role of Wnt/β-catenin mediated regulation in cell proliferation, differentiation and migration. These processes are fundamental to embryonic development, regeneration potential of tissues, as well as cancer initiation and progression. In this review, we focus on the epigenetic players which influence the Wnt/β-catenin pathway via modulation of its components and coordinated regulation of the Wnt target genes. The role played by crosstalk with other signaling pathways mediating tumorigenesis is also elaborated. The Hippo/YAP pathway is particularly emphasized due to its extensive crosstalk via the Wnt destruction complex. Further, we highlight the recent advances in developing potential therapeutic interventions targeting the epigenetic machinery based on the characterization of these regulatory networks for effective treatment of various cancers and also for regenerative therapies.
A Robust Seven-Gene Signature Associated With Tumor Microenvironment to Predict Survival Outcomes of Patients With Stage III–IV Lung Adenocarcinoma
Authors: Zhao Hao , Zhang Xuening , Guo Lan , Shi Songhe , Lu Ciyong
Published: September 2021

Background

Due to the relatively insidious early symptoms of lung adenocarcinoma (LUAD), most LUAD patients are at an advanced stage at the time of diagnosis and lose the best chance of surgical resection. Mounting evidence suggested that the tumor microenvironment (TME) was highly correlated with tumor occurrence, progress, and prognosis. However, TME in advanced LUAD remained to be studied and reliable prognostic signatures based on TME in advanced LUAD also had not been well-established. This study aimed to understand the cell composition and function of TME and construct a gene signature associated with TME in advanced LUAD.

Methods

The immune, stromal, and ESTIMATE scores of each sample from The Cancer Genome Atlas (TCGA) database were, respectively, calculated using an ESTIMATE algorithm. The LASSO and Cox regression model were applied to select prognostic genes and to construct a gene signature associated with TME. Two independent datasets from the Gene Expression Omnibus (GEO) were used for external validation. Twenty-two subsets of tumor-infiltrating immune cells (Tiics) were analyzed using the CIBERSORT algorithm.

Results

Favorable overall survival (OS) and progression-free survival (PFS) were found in patients with high immune score (p = 0.048 and p = 0.028; respectively) and stromal score (p = 0.024 and p = 0.025; respectively). Based on the immune and stromal scores, 453 differentially expressed genes (DEGs) were identified. Using the LASSO and Cox regression model, a seven-gene signature containing AFAP1L2, CAMK1D, LOXL2, PIK3CG, PLEKHG1, RARRES2, and SPP1 was identified to construct a risk stratification model. The OS and PFS of the high-risk group were significantly worse than that of the low-risk group (p < 0.001 and p < 0.001; respectively). The receiver operating characteristic (ROC) curve analysis confirmed the good potency of the seven-gene signature. Similar findings were validated in two independent cohorts. In addition, the proportion of macrophages M2 and Tregs was higher in high-risk patients (p = 0.041 and p = 0.022, respectively).

Conclusion

Our study established and validated a seven-gene signature associated with TME, which might serve as a prognosis stratification tool to predict survival outcomes of advanced LUAD patients. In addition, macrophages M2 polarization may lead to worse prognosis in patients with advanced LUAD.
Interspecific Sample Prioritization Can Improve QTL Detection With Tree-Based Predictive Models
Authors: Shin Min-Gyoung , Nuzhdin Sergey V.
Published: September 2021

Due to increasing demand for new advanced crops, considerable efforts have been made to explore the improvement of stress and disease resistance cultivar traits through the study of wild crops. When both wild and interspecific hybrid materials are available, a common approach has been to study two types of materials separately and simply compare the quantitative trait locus (QTL) regions. However, combining the two types of materials can potentially create a more efficient method of finding predictive QTLs. In this simulation study, we focused on scenarios involving causal marker expression suppressed by trans-regulatory mechanisms, where the otherwise easily lost associated signals benefit the most from combining the two types of data. A probabilistic sampling approach was used to prioritize consistent genotypic phenotypic patterns across both types of data sets. We chose random forest and gradient boosting to apply the prioritization scheme and found that both facilitated the investigation of predictive causal markers in most of the biological scenarios simulated.
Structural Analysis of SARS-CoV-2 ORF8 Protein: Pathogenic and Therapeutic Implications
Authors: Valcarcel Antonio , Bensussen Antonio , Álvarez-Buylla Elena R. , Díaz José
Published: September 2021

Current therapeutic strategies and vaccines against SARS-CoV-2 are mainly focused on the Spike protein despite there are other viral proteins with important roles in COVID-19 pathogenicity. For example, ORF8 restructures vesicular trafficking in the host cell, impacts intracellular immunity through the IFN-I signaling, and growth pathways through the mitogen-activated protein kinases (MAPKs). In this mini-review, we analyze the main structural similarities of ORF8 with immunological molecules such as IL−1, contributing to the immunological deregulation observed in COVID-19. We also propose that the blockage of some effector functions of ORF8 with Rapamycin, such as the mTORC1 activation through MAPKs 40 pathway, with Rapamycin, can be a promising approach to reduce COVID-19 mortality.
Establishment of an Endocytosis-Related Prognostic Signature for Patients With Low-Grade Glioma
Authors: Wang Dawei , Liu Shiguang , Wang Guangxin
Published: September 2021

Background

Low-grade glioma (LGG) is a heterogeneous tumor that might develop into high-grade malignant glioma, which markedly reduces patient survival time. Endocytosis is a cellular process responsible for the internalization of cell surface proteins or external materials into the cytosol. Dysregulated endocytic pathways have been linked to all steps of oncogenesis, from initial transformation to late invasion and metastasis. However, endocytosis-related gene (ERG) signatures have not been used to study the correlations between endocytosis and prognosis in cancer. Therefore, it is essential to develop a prognostic model for LGG based on the expression profiles of ERGs.

Methods

The Cancer Genome Atlas and the Genotype-Tissue Expression database were used to identify differentially expressed ERGs in LGG patients. Gene ontology, Kyoto Encyclopedia of Genes and Genomes, and Gene set enrichment analysis methodologies were adopted for functional analysis. A protein-protein interaction (PPI) network was constructed and hub genes were identified based on the Search Tool for the Retrieval of Interacting Proteins database. Univariate and multivariate Cox regression analyses were used to develop an ERG signature to predict the overall survival (OS) of LGG patients. Finally, the association between the ERG signature and gene mutation status was further analyzed.

Results

Sixty-two ERGs showed distinct mRNA expression patterns between normal brain tissues and LGG tissues. Functional analysis indicated that these ERGs were strikingly enriched in endosomal trafficking pathways. The PPI network indicated that EGFR was the most central protein. We then built a 29-gene signature, dividing patients into high-risk and low-risk groups with significantly different OS times. The prognostic performance of the 29-gene signature was validated in another LGG cohort. Additionally, we found that the mutation scores calculated based on the TTN, PIK3CA, NF1, and IDH1 mutation status were significantly correlated with the endocytosis-related prognostic signature. Finally, a clinical nomogram with a concordance index of 0.881 predicted the survival probability of LGG patients by integrating clinicopathologic features and ERG signatures.

Conclusion

Our ERG-based prediction models could serve as an independent prognostic tool to accurately predict the outcomes of LGG.
Deep Sequencing of MHC-Adapted Viral Lines Reveals Complex Recombinational Exchanges With Endogenous Retroviruses Leading to High-Frequency Variants
Authors: Middlebrook Earl A. , Stark Derek L. , Cornwall Douglas H. , Kubinak Jason L. , Potts Wayne K.
Published: September 2021

Experimental evolution (serial passage) of Friend virus complex (FVC) in mice demonstrates phenotypic adaptation to specific host major histocompatibility complex (MHC) genotypes. These evolved viral lines show increased fitness and virulence in their host-genotype-of-passage, but display fitness and virulence tradeoffs when infecting unfamiliar host MHC genotypes. Here, we deep sequence these viral lines in an attempt to discover the genetic basis of FVC adaptation. The principal prediction for genotype-specific adaptation is that unique mutations would rise to high frequency in viral lines adapted to each host MHC genotype. This prediction was not supported by our sequencing data as most observed high-frequency variants were present in each of our independently evolved viral lines. However, using a multi-variate approach to measure divergence between viral populations, we show that populations of replicate evolved viral lines from the same MHC congenic mouse strain were more similar to one another than to lines derived from different MHC congenic mouse strains, suggesting that MHC genotype does predictably act on viral evolution in our model. Sequence analysis also revealed rampant recombination with endogenous murine leukemia virus sequences (EnMuLVs) that are encoded within the BALB/c mouse genome. The highest frequency variants in all six lines contained a 12 bp insertion from a recombinant EnMuLV source, suggesting such recombinants were either being favored by selection or were contained in a recombinational hotspot. Interestingly, they did not reach fixation, as if they are low fitness. The amount of background mutations linked to FVC/EnMuLV variable sites indicated that FVC/EnMuLV recombinants had not reached mutation selection equilibrium and thus, that EnMuLV sequences are likely continuously introgressing into the replicating viral population. These discoveries raise the question: is the expression of EnMuLV sequences in mouse splenocytes that permit recombination with exogenous FVC a pathogen or host adaptation?